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curl -X POST \
  'http://laksa120.int.ahrefs:8124/' \
  -H 'Content-Type: text/plain' \
  -H 'X-ClickHouse-Database: crawler3' \
  -H 'Authorization: Basic YXBpOg==' \
  -d 'SELECT getAhrefsURLFromUnparsed(src_unparsed) AS found_url, ifNull(toUnixTimestamp(download_stamp), 0) AS crawl_time, ifNull(toUnixTimestamp(props_url_first_seen), 0) AS first_indexed_time, download_http_code AS http_code, src_unparsed AS src_unparsed, src_root_hash AS src_root_hash, history_drop_reason AS history_drop_reason, meta_title AS meta_title, meta_descriptions AS meta_descriptions, attrs_boilerpipe_text AS attrs_boilerpipe_text, attrs_markdown AS attrs_markdown, attrs_readable_markdown AS attrs_readable_markdown, meta_canonical AS meta_canonical FROM crawler3.page_info_local FINAL PREWHERE (src_root_hash, src_unparsed) IN ((getAhrefsRootHashFromUnparsed(getAhrefsUnparsedNoserviceFromURL(\'https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(21)00224-3/fulltext\')), getAhrefsUnparsedNoserviceFromURL(\'https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(21)00224-3/fulltext\'))) FORMAT JSONEachRow'

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{"found_url":"https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099(21)00224-3\/fulltext","crawl_time":1769511503,"first_indexed_time":1619568963,"http_code":200,"src_unparsed":"com,thelancet!www,\/journals\/laninf\/article\/PIIS1473-3099(21)00224-3\/fulltext s443","src_root_hash":"16469721507011418920","history_drop_reason":null,"meta_title":"Vaccine side-effects and SARS-CoV-2 infection after vaccination in users of the COVID Symptom Study app in the UK: a prospective observational study - The Lancet Infectious Diseases","meta_descriptions":[],"attrs_boilerpipe_text":"Summary\nBackground\nThe Pfizer-BioNTech (BNT162b2) and the Oxford-AstraZeneca (ChAdOx1 nCoV-19) COVID-19 vaccines have shown excellent safety and efficacy in phase 3 trials. We aimed to investigate the safety and effectiveness of these vaccines in a UK community setting.\nMethods\nIn this prospective observational study, we examined the proportion and probability of self-reported systemic and local side-effects within 8 days of vaccination in individuals using the COVID Symptom Study app who received one or two doses of the BNT162b2 vaccine or one dose of the ChAdOx1 nCoV-19 vaccine. We also compared infection rates in a subset of vaccinated individuals subsequently tested for SARS-CoV-2 with PCR or lateral flow tests with infection rates in unvaccinated controls. All analyses were adjusted by age (≤55 years\nvs\n>55 years), sex, health-care worker status (binary variable), obesity (BMI <30 kg\/m\n2\nvs\n≥30 kg\/m\n2\n), and comorbidities (binary variable, with or without comorbidities).\nFindings\nBetween Dec 8, and March 10, 2021, 627 383 individuals reported being vaccinated with 655 590 doses: 282 103 received one dose of BNT162b2, of whom 28 207 received a second dose, and 345 280 received one dose of ChAdOx1 nCoV-19. Systemic side-effects were reported by 13·5% (38 155 of 282 103) of individuals after the first dose of BNT162b2, by 22·0% (6216 of 28 207) after the second dose of BNT162b2, and by 33·7% (116 473 of 345 280) after the first dose of ChAdOx1 nCoV-19. Local side-effects were reported by 71·9% (150 023 of 208 767) of individuals after the first dose of BNT162b2, by 68·5% (9025 of 13 179) after the second dose of BNT162b2, and by 58·7% (104 282 of 177 655) after the first dose of ChAdOx1 nCoV-19. Systemic side-effects were more common (1·6 times after the first dose of ChAdOx1 nCoV-19 and 2·9 times after the first dose of BNT162b2) among individuals with previous SARS-CoV-2 infection than among those without known past infection. Local effects were similarly higher in individuals previously infected than in those without known past infection (1·4 times after the first dose of ChAdOx1 nCoV-19 and 1·2 times after the first dose of BNT162b2). 3106 of 103 622 vaccinated individuals and 50 340 of 464 356 unvaccinated controls tested positive for SARS-CoV-2 infection. Significant reductions in infection risk were seen starting at 12 days after the first dose, reaching 60% (95% CI 49–68) for ChAdOx1 nCoV-19 and 69% (66–72) for BNT162b2 at 21–44 days and 72% (63–79) for BNT162b2 after 45–59 days.\nInterpretation\nSystemic and local side-effects after BNT162b2 and ChAdOx1 nCoV-19 vaccination occur at frequencies lower than reported in phase 3 trials. Both vaccines decrease the risk of SARS-CoV-2 infection after 12 days.\nFunding\nZOE Global, National Institute for Health Research, Chronic Disease Research Foundation, National Institutes of Health, UK Medical Research Council, Wellcome Trust, UK Research and Innovation, American Gastroenterological Association.\nIntroduction\nThe UK's Medicines and Healthcare products Regulatory Agency has given emergency use authorisation to three COVID-19 vaccines: the Pfizer-BioNTech mRNA vaccine (BNT162b2), the Oxford-AstraZeneca adenovirus-vectored vaccine (ChAdOx1 nCoV-19), and the Moderna mRNA vaccine (mRNA-1273). The first two vaccines have been rolled out across the UK since Dec 8, 2020, and Jan 4, 2021, respectively.\n1\n1.\nPublic Health England\nCOVID-19 vaccination programme\nIn late December, 2020, based on advice from the Joint Committee on Vaccination and Immunisation,\n2\n2.\nDepartment of Health and Social Care\nPriority groups for coronavirus (COVID-19) vaccination: advice from the JCVI, 30 December 2020\nthe UK Government decided to delay the administration of second doses.\nPhase 3 trials reported the BNT162b2 vaccine to have an efficacy of 52% at 12 days after the first dose and of 95% after the second dose if administered 3–4 weeks apart in participants without previous SARS-CoV-2 infection.\n3\n3.\nPolack, FP ∙ Thomas, SJ ∙ Kitchin, N ∙ et al.\nSafety and efficacy of the BNT162b2 mRNA COVID-19 vaccine\nN Engl J Med.\n2020;\n383\n:2603-2615\nThe effectiveness of this vaccine in reducing infection, severe disease, hospitalisation, and death with COVID-19 has been reported for the whole of Israel,\n4\n4.\nDagan, N ∙ Barda, N ∙ Kepten, E ∙ et al.\nBNT162b2 mRNA COVID-19 vaccine in a nationwide mass vaccination setting\nN Engl J Med.\n2021;\nwith reanalysis of the data from Israel revealing it to be 90% effective 2 weeks after the first dose.\n5\n5.\nHunter, PR ∙ Brainard, J\nEstimating the effectiveness of the Pfizer COVID-19 BNT162b2 vaccine after a single dose. A reanalysis of a study of “real-world” vaccination outcomes from Israel\nmedRxiv.\n2021;\n(preprint).\nThe ChAdOx1 nCoV-19 trial found efficacy against symptomatic disease of 76% at 22–90 days after at least one standard dose.\n6–8\n6.\nVoysey, M ∙ Clemens, SAC ∙ Madhi, SA ∙ et al.\nSafety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK\nLancet.\n2021;\n397\n:99-111\n7.\nRamasamy, MN ∙ Minassian, AM ∙ Ewer, KJ ∙ et al.\nSafety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2\/3 trial\nLancet.\n2021;\n396\n:1979-1993\n8.\nVoysey, M ∙ Clemens, SAC ∙ Madhi, SA ∙ et al.\nSingle-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials\nLancet.\n2021;\n397\n:881-891\nResearch in context\nEvidence before this study\nWe searched PubMed for articles published up to March 10, 2021, using the terms (“BNT162b2“ OR “mRNA Covid-19 Vaccine” OR “ChAdOx1 nCoV-19” OR “adenovirus-vectored Covid-19 vaccine”) AND (“effectiveness” OR “reinfection” OR “side-effects” OR “adverse effects” OR “reactogenicity” OR “phase IV”). We did not restrict our search by language or type of publication. Besides the original phase 1–3 trials, we found one published article and two preprints on data from Israel investigating the effectiveness of the Pfizer-BioNTech vaccine (BNT162b2), a preprint from the UK exploring the effectiveness of both the BNT162b2 and Oxford-AstraZeneca (ChAdOx1 nCoV-19) vaccines in individuals aged 70 years or older in the community, and a study that linked health records for all vaccinated people in Scotland to investigate COVID-19 hospitalisation and mortality after vaccination. No study investigated the prevalence of adverse effects of the vaccines and all studies reported both vaccines to be highly effective.\nAdded value of this study\nIn this large prospective observational study, we assessed adverse effects from the two COVID-19 vaccines in use in the UK at the time of writing (BNT162b2 and ChAdOx1 nCoV-19), as well as self-reported infection rates following one dose or two doses of BNT162b2 and one dose of ChAdOx1 nCoV-19. Reported side-effects were minor in severity and of short duration. Headache and fatigue were more common in women than in men, in people aged 55 years or younger than in people older than 55 years, and after the second than after the first dose. Individuals with known past SARS-CoV-2 infection were more likely to have adverse effects after the first dose than were those without known past infection. We found, in a community setting, that self-reported infection rates of those vaccinated with the BNT162b2 or ChAdOx1 nCoV-19 vaccines were significantly lower than infection rates in unvaccinated controls. Documented infection rates in our app after a single vaccine dose decreased by 58% (95% CI 54–62) at 12–20 days, 69% (66–72) at 21–44 days, and 72% (63–79) after 45–59 days following BNT162b2, and 39% (21–53) at 12–20 days and 60% (49–68) at 21–44 days following ChAdOx1 nCoV-19, compared with unvaccinated controls.\nImplications of all the available evidence\nLocalised and systemic side-effects after vaccination are less common in a real-world community setting than reported in phase 3 trials, mostly minor in severity, and self-limiting. Our data will enable prediction of side-effects based on age, sex, and past COVID-19 status to help update guidance to health professionals to reassure the population about the safety of vaccines.\nSurveillance in the general population is necessary at this stage during vaccination rollout.\n9\n9.\nPublic Health England\nCOVID-19: vaccine surveillance strategy\nThe OpenSAFELY collaboration\n10\n10.\nThe OpenSAFELY Collaborative ∙ MacKenna, B ∙ Curtis, HJ ∙ et al.\nTrends, regional variation, and clinical characteristics of COVID-19 vaccine recipients: a retrospective cohort study in 23·4 million patients using OpenSAFELY\nmedRxiv.\n2021;\n(preprint).\nimplemented a framework for monitoring vaccine rollout and coverage in the UK via record linkage, Public Health England has reported early data on effectiveness in the older population prioritised for vaccination,\n11\n11.\nLopez Bernal, J ∙ Andrews, N ∙ Gower, C ∙ et al.\nEarly effectiveness of COVID-19 vaccination with BNT162b2 mRNA vaccine and ChAdOx1 adenovirus vector vaccine on symptomatic disease, hospitalisations and mortality in older adults in England\nmedRxiv.\n2021;\n(preprint).\nand a prospective observational study investigated the association between the rollout of the first vaccine dose and COVID-19 hospital admission in Scotland.\n12\n12.\nVasileiou, E ∙ Simpson, CR ∙ Shi, T ∙ et al.\nInterim findings from first-dose mass COVID-19 vaccination roll-out and COVID-19 hospital admissions in Scotland: a national prospective cohort study\nLancet.\n2021;\nOther surveys, such as the SIREN study\n13\n13.\nHall, VJ ∙ Foulkes, S ∙ Saei, A ∙ et al.\nCOVID-19 vaccine coverage in health-care workers in England and effectiveness of BNT162b2 mRNA vaccine against infection (SIREN): a prospective, multicentre, cohort study\nLancet.\n2021;\nin health-care workers, will also link directly to health records to assess the real-life effectiveness and safety of the various phases of vaccine rollout. However, it takes time for such studies to come to fruition. Real-time data from app users can provide a faster view of the safety and effectiveness of COVID-19 vaccines.\nThe aim of this study was to investigate the adverse effects and infection rate of vaccinated people in a community (general population app users) scenario. We used data from 627 383 individuals who received the BNT162b2 or ChAdOx1 nCoV-19 vaccines between December, 2020, and March, 2021, and reported symptoms in real-time via the COVID Symptom Study app.\n14\n14.\nMenni, C ∙ Valdes, AM ∙ Freidin, MB ∙ et al.\nReal-time tracking of self-reported symptoms to predict potential COVID-19\nNat Med.\n2020;\n26\n:1037-1040\nA subset of individuals also reported receiving a PCR or lateral flow test.\nMethods\nStudy design and participants\nThe COVID Symptom Study app\n14\n14.\nMenni, C ∙ Valdes, AM ∙ Freidin, MB ∙ et al.\nReal-time tracking of self-reported symptoms to predict potential COVID-19\nNat Med.\n2020;\n26\n:1037-1040\nwas developed by health data company ZOE Global, with input from King's College London (London, UK), the Massachusetts General Hospital (Boston, MA, USA), Lund University (Lund, Sweden), and Uppsala University (Uppsala, Sweden). In the UK, it was launched in English on March 24, 2020. The app enables self-reported information related to SARS-CoV-2 infection to be captured. Individuals older than 18 years can sign up to the app without any restrictions. Individuals can also record information for dependents younger than 18 years. Use of the app was driven by referrals or word of mouth, the media, and eventually partnerships with charities and the Welsh and Scottish Governments.\n15\n15.\nDrew, DA ∙ Nguyen, LH ∙ Steves, CJ ∙ et al.\nRapid implementation of mobile technology for real-time epidemiology of COVID-19\nScience.\n2020;\n368\n:1362-1367\nOn first use, the app records self-reported location, age, and core health risk factors (body-mass index [BMI], smoking status, race or ethnicity, and presence of comorbidities, including cancer, diabetes, eczema, heart disease, lung disease, kidney disease, and hay fever), as well as employment status, such as being a health-care worker. With continued use, participants provide daily updates on symptoms experienced, SARS-CoV-2 test results (negative, pending, or positive), vaccines administered, and whether they are self-quarantining or seeking health care, including the level of intervention and related outcomes. Individuals without symptoms are encouraged to report through the app every day. Through direct updates to the app, new or modified questions are added in real time to capture data to test emerging hypotheses about COVID-19 symptoms and treatments. Versions 2.1.0–2.4.0 of the app were in use during the study period.\nParticipants were asked if they had been vaccinated for COVID-19 and, if so, to record the type of vaccine and date of administration. We included all UK app users reporting having received at least one dose of the two available vaccines (\nappendix p 2\n). Users reporting vaccination were then asked daily for the following 8 days whether they experienced adverse effects, including both systemic (whole body) and local effects. Systemic solicited side-effects included headache, fatigue, chills and shiver, diarrhoea, fever, arthralgia, myalgia, and nausea; solicited local side-effects included local pain, swelling, tenderness, redness, itch, warmth, and swollen armpit glands (\nappendix p 6\n). Users were also permitted to report no symptoms by leaving the box unchecked.\nEthical approval for use of the app for research purposes in the UK was obtained from King's College London Ethics Committee (review reference LRS-19\/20-18210), and all users provided consent for non-commercial use of their data.\nOutcomes\nOur primary outcome was the proportion of app users reporting adverse effects within 8 days after vaccination and the probability of having an adverse event. Our secondary outcome was infection rates in individuals after receiving a first dose of either the BNT162b2 or ChAdOx1 nCoV-19 vaccines. We did not collect information on why individuals were tested, so not all tested individuals were necessarily experiencing COVID-19-associated symptoms at testing, and some individuals might have been routinely tested while being asymptomatic.\nStatistical analysis\nWe used χ\n2\nand Student's\nt\ntests to compare the demographic characteristics of individuals who received BNT162b2 versus those who received ChAdOx1 nCoV-19. We investigated the evolution of systemic and local adverse effects within 8 days from the vaccination date, computing the percentage of users experiencing side-effects after having received the vaccine. Vaccinated individuals who logged their systemic or local effects (or the absence of them) at least once within 8 days from the vaccination date were included in the adverse effects analysis (\nappendix p 2\n). We estimated the ratio of the daily number of users reporting at least one adverse effect (systemic or local) after vaccination to the total number of vaccinated users logging into the app that day. The occurrence of adverse effects was studied for both BNT162b2 doses and the first ChAdOx1 nCoV-19 dose.\nWe compared the probability of having adverse effects between the first and second BNT162b2 doses, the first BNT162b2 and the first ChAdOx1 nCoV-19 doses, and the second BNT162b2 and the first ChAdOx1 nCoV-19 doses. As different people received different vaccines, we used Pearl's back-door adjustment\n16\n16.\nPearl, J\nCausality\nCambridge University Press, Cambridge, 2009\nto account for differences within the populations. Backdoor adjustments are used when there are both causal and non-causal paths between predictors (eg, vaccine treatment [\nV\n]) and an outcome. Because of the observational (non-interventional) nature of the study, the non-causal paths between outcomes and predictors that might involve age, sex, BMI, or health status need to be adjusted statistically. Backdoor adjustment methods essentially condition on these variables, cutting out the non-causal (indirect) links between a predictor and an outcome:\nwhere\nR\nis adverse effects,\nS\nis stratum, and\nP\n(\nR | S,V\n) is the probability of having adverse effects in a given stratum after receiving a vaccine.\nWe used the following strata: age (≤55 years\nvs\n>55 years), in line with stratification in the BNT162b2 and ChAdOx1 nCoV-19 phase 3 trials,\n3\n3.\nPolack, FP ∙ Thomas, SJ ∙ Kitchin, N ∙ et al.\nSafety and efficacy of the BNT162b2 mRNA COVID-19 vaccine\nN Engl J Med.\n2020;\n383\n:2603-2615\nsex, health-care worker status (binary variable), obesity (BMI <30 kg\/m\n2\nvs\n≥30 kg\/m\n2\n), and comorbidities (binary variable, with or without comorbidities). Adjusted odds ratios (ORs) were computed after Pearl's back-door adjustment was applied to the raw rates (see\nappendix p 15\nfor the formula). 95% CIs for ORs were obtained by bootstrapping 50 times on the vaccinated population.\nLogistic regressions were used for each of the specified strata to investigate whether adverse effects varied across different participant groups, and in individuals who had previously reported a positive test for COVID-19 (PCR or lateral flow positive at least 6 months before vaccination, PCR or lateral flow positive within the 6 months before vaccination, and no previously detected infection).\nFinally, in a subanalysis of vaccinated participants who reported having had the first dose of the BNT162b2 vaccine or one dose of the ChAdOx1 nCoV-19 vaccine and were then subsequently tested for SARS-CoV-2 infection, we investigated the change in infection rates after the first vaccine dose. We compared the outcomes of PCR or lateral flow tests in individuals who had been vaccinated with the first dose with those of unvaccinated individuals who reported having a COVID-19 test in the same week as a vaccinated app user. We computed the difference in days between when participants had the vaccine and when they were tested, and we used this metric to group users. If a person reported more than one PCR test or lateral flow result after being vaccinated, we selected the positive test, or if none were positive, the latest negative test. Since the BNT162b2 phase 3 trial showed a decrease in infections from 12 days after vaccination,\n3\n3.\nPolack, FP ∙ Thomas, SJ ∙ Kitchin, N ∙ et al.\nSafety and efficacy of the BNT162b2 mRNA COVID-19 vaccine\nN Engl J Med.\n2020;\n383\n:2603-2615\nwe analysed infection rates at 0–4, 5–11, 12–20, 21–44, and 45–59 days after vaccination. For each of the vaccines and for different timepoints from the vaccination date, we used Poisson regressions to model the rates of positive tests in vaccinated individuals compared with those in the unvaccinated population, adjusting for the number of tests. This model allowed us to control for the number of follow-up days for each group. Moreover, as there was a two-times increase in daily incidence in England followed by a decrease of a similar proportion during the data collection period,\n17\n17.\nOffice for National Statistics\nCoronavirus (COVID-19) Infection Survey\nwe also included incidence as a covariate in the Poisson regression model, with incidence calculated as previously described.\n18\n18.\nVarsavsky, T ∙ Graham, MS ∙ Canas, LS ∙ et al.\nDetecting COVID-19 infection hotspots in England using large-scale self-reported data from a mobile application: a prospective, observational study\nLancet Public Health.\n2021;\n6\n:e21-e29\nWe defined the adjusted infection risk reduction (RR) as follows:\nwhere\ni\nis BNT162b2 or ChAdOx1 nCoV-19 vaccine,\nn\nis the number of days since vaccination (0–4, 5–11, 12–20, 21–44, 45–59), and the risk ratio is the coefficient of the vaccine status variables in the Poisson regression model.\nWe further tested the role of covariates in risk of infection after vaccination by running stratified Poisson models (adjusted for confounders). For this analysis, we considered all app responders who were vaccinated with BNT162b2 or ChAdOx1 nCoV-19 vaccines at least 12 days before having a test for SARS-CoV-2 positivity. Due to a relatively small sample size in some of the strata, we did not differentiate between vaccine types but pooled all vaccinated contributors.\nData were extracted and preprocessed using ExeTera version 0.3.2,\n19\n19.\nMurray, B ∙ Kerfoot, E ∙ Graham, MS ∙ et al.\nAccessible data curation and analytics for international-scale citizen science datasets\narXiv.\n2020;\n(preprint).\na Python library developed at King's College London, and we did statistical analysis using Python version 3.7 (pandas, NumPy, and SciPy).\nRole of the funding source\nZOE Global developed the app for data collection as a not-for-profit endeavour. The funder had no role in study design, data analysis, data interpretation, or writing of the report.\nResults\nBetween Dec 8, 2020, and March 10, 2021, 655 590 vaccine doses were logged in the app in the UK, corresponding to 282 103 individuals (aged 16–99 years) who reported having received the first dose of the BNT162b2 vaccine, of whom 28 207 reported having had both doses of the BNT162b2 vaccine (a median of 41 days [IQR 21–63] apart), and 345 280 individuals who reported having had the first dose of ChAdOx1 nCoV-19. Participants joined the COVID Symptom Study app a mean of 288 days (SD 96) before being vaccinated. Users started logging adverse effects reports 0·79 days (SD 1·2) after they had the vaccine. 1 607 620 users were active in the app during the study period (logged at least an assessment since Dec 8), which represents 2·4% of the UK population. The mean age of app users was 50·6 years (SD 19·2), and 77 683 (4·8%) of them were health-care workers.\nUsers who reported receiving a BNT162b2 vaccine were slightly younger, had more comorbidities, and were more frequently female than users who reported receiving a ChAdOx1 nCoV-19 inoculation (\ntable\n). Moreover, health-care workers were more likely to receive a BNT162b2 vaccine than ChAdOx1 nCoV-19 (\nappendix p 8\n). The age distribution of the included individuals is presented in the\nappendix (p 3)\n.\n \n \nBNT162b2\nChAdOx1 nCoV-19\n \n \nFirst dose (N=282 103)\nSecond dose (N=28 207)\nFirst dose (N=345 280)\nSex\n*\n \nFemale\n173 866 (61·6%)\n19 640 (69·6%)\n199 269 (57·7%)\n \nMale\n108 237 (38·4%)\n8567 (30·4%)\n146 011 (42·3%)\nAge, years\n*\n†\n62·0 (14·3); 64 (54–72)\n61·0 (17·3); 59 (49–76)\n63·3 (11·5); 65 (59–71)\nBody-mass index, kg\/m\n2\n‡\n26·8 (5·5)\n26·5 (5·3)\n26·8 (5·3)\nHealth-care workers\n*\n31 996 (11·3%)\n8828 (31·3%)\n9746 (2·8%)\nComorbidities\n*\n77 433 (27·4%)\n7617 (27·0%)\n88 453 (25·6%)\nPrevious COVID-19\n*\n14 369 (5·1%)\n2251 (8·0%)\n14 231 (4·1%)\nSystemic side-effects\n \nAny\n38 155 (13·5%)\n6216 (22·0%)\n116 473 (33·7%)\n \nHeadache\n21 910 (7·8%)\n3731 (13·2%)\n78 734 (22·8%)\n \nFatigue\n23 674 (8·4%)\n4064 (14·4%)\n72 924 (21·1%)\n \nChills and shiver\n7166 (2·5%)\n1812 (6·4%)\n50 761 (14·7%)\n \nDiarrhoea\n3885 (1·4%)\n416 (1·5%)\n7546 (2·2%)\n \nFever\n4236 (1·5%)\n1076 (3·8%)\n28 268 (8·2%)\n \nArthralgia\n9021 (3·2%)\n1978 (7·0%)\n39 648 (11·5%)\n \nMyalgia\n6479 (2·3%)\n1415 (5·0%)\n24 274 (7·0%)\n \nNausea\n5926 (2·1%)\n981 (3·5%)\n19 509 (5·7%)\nLocal side-effects\n§\n \nAny\n150 023 (71·9%)\n9025 (68·5%)\n104 282 (58·7%)\n \nPain\n61 016 (29·2%)\n4515 (34·3%)\n33 939 (19·1%)\n \nSwelling\n13 264 (6·4%)\n1285 (9·8%)\n9769 (5·5%)\n \nTenderness\n119 431 (57·2%)\n6705 (50·9%)\n87 609 (49·3%)\n \nItch\n6242 (3·0%)\n840 (6·4%)\n6934 (3·9%)\n \nSwollen armpit glands\n2278 (1·1%)\n549 (4·2%)\n1994 (1·1%)\n \nRedness\n7891 (3·8%)\n953 (7·2%)\n7431 (4·2%)\n \nWarmth\n14 024 (6·7%)\n1245 (9·4%)\n14 033 (7·9%)\n \nBruising\n1872 (0·9%)\n64 (0·5%)\n4269 (2·4%)\nAllergic reactions\n \nRash\n682 (0·2%)\n103 (0·4%)\n1432 (0·4%)\n \nSkin burning\n2075 (0·7%)\n324 (1·1%)\n5940 (1·7%)\n \nRed welts on face and lips\n469 (0·2%)\n59 (0·2%)\n846 (0·2%)\nTable\nDemographic characteristics of the study population\nData are n (%), unless otherwise indicated.\n*\np<0·05 for the difference between the first dose of BNT162b2 and the first dose of ChAdOx1 nCoV-19 (Student's\nt\ntest for continuous variables and χ\n2\ntest for categorical variables).\n†\nData are mean (SD); median (IQR).\n‡\nData are mean (SD).\n§\nDenominators are 208 767 for the first BNT162b2 dose, 13 179 for the second BNT162b2 dose, and 177 655 for the first ChAdOx1 nCoV-19 dose.\nOpen table in a new tab\nAmong vaccinated app users, 159 101 (25·4%) of 627 383 indicated having one or more systemic adverse effect, and 257 209 (66·2%) of 388 430 reported one or more local adverse effect (\ntable\n). The most commonly reported systemic side-effects were fatigue and headache overall (\ntable\n) and by strata (\nappendix p 9\n). These were most frequently reported within the first 24 h after vaccination and lasted a mean of 1·01 days (SD 0·1;\nfigure 1\n). Tenderness and local pain around the injection site were the most frequently reported local effects (\ntable\n), occurring most often on the day after injection and lasting a mean of 1·02 days (SD 0·15;\nfigure 1\n). Other side-effects, including allergic skin reactions such as skin burning, rashes, and red welts on the lips and face, were reported by 10 860 (1·7%) of 627 383 users across both types of vaccine (\ntable\n;\nappendix p 9\n). In an exploratory analysis, we assessed the association between symptom reporting and socioeconomic status measured as index of multiple deprivation,\n20\n20.\nMinistry of Housing, Communities, and Local Government\nEnglish indices of deprivation 2019\nand we found a modest association (\nr\n=0·021 [95% CI 0·019–0·025]), corresponding to 0·04% of the variance in symptoms reporting.\nFigure 1\nProportion of participants self-reporting adverse effects to the COVID Symptom Study app within 8 days after vaccination\nIn the 28 207 individuals who reported having two BNT162b2 doses, 3325 (11·7%) reported at least one systemic effect after the first dose compared with 6216 (22·0%) after the second dose (p<0·0001;\nfigure 2\n). When comparing systemic effects after one dose of each vaccine, reactogenicity was significantly higher in individuals who had one dose of the ChAdOx1 nCoV-19 vaccine than in those who had one dose of the BNT162b2 vaccine (116 473 [33·7%] of 345 280 compared with 38 155 [13·5%] of 282 103; adjusted p<0·0001).\nFigure 2\nComparison of adverse effects self-reported to the COVID Symptom Study app between vaccine types and doses\nBy contrast, local effects were less commonly reported after the second dose than after the first dose of BNT162b2 (9025 [68·5%] of 13 179\nvs\n150 023 [71·9%] of 208 767; p<0·0001). Moreover, local effects were less commonly reported after the first ChAdOx1 nCoV-19 injection (104 282 [58·7%] of 177 655) than after the first BNT162b2 injection (adjusted p<0·0001;\nfigure 2\n).\nWhen comparing the second BNT162b2 dose with the first ChAdOx1 nCoV-19 dose, we found that systemic effects occurred more frequently after the first ChAdOx1 nCoV-19 dose than after the second BNT162b2 dose (adjusted p<0·0001;\nfigure 2\n), whereas local effects were less likely to appear after the first ChAdOx1 nCoV-19 injection than after the second BNT162b2 dose (adjusted p<0·0001;\nfigure 2\n).\nWe then tested whether adverse effects varied across individuals' characteristics, such as age and BMI groups, sex, and health status. The proportion of participants who reported at least one systemic effect after the first dose was significantly higher among people aged 55 years or younger than among those older than 55 years for both vaccines. After the first dose of BNT162b2, 16 733 (20·7%) of 80 879 people aged 55 years or younger reported at least one systemic effect compared with 21 422 (10·6%) of 201 224 people older than 55 years (OR 2·19 [95% CI 2·14–2·24]; p<0·0001). For ChAdOx1 nCoV-19, 30 487 (46·9%) of 65 034 people aged 55 years or younger reported at least one systemic effect after the first dose compared with 85 986 (30·7%) of 280 243 older than 55 years (1·99 [1·96–2·03]; p<0·0001). Women were more likely to report adverse effects than men (28 140 [16·2%] of 173 866\nvs\n10 015 [9·3%] of 108 237 after the first dose of BNT162b2, OR 1·89 [95% CI 1·85–1·94], p<0·0001; 78 222 [39·3%] of 199 269\nvs\n38 251 [26·2%] of 146 011 after the first dose of ChAdOx1 nCoV-19, 1·82 [1·79–1·85], p<0·0001). Although there were some differences between strata of BMI and co-morbidities, there was no clear trend across vaccines and doses (\nfigure 3\n).\nFigure 3\nAdverse effects self-reported to the COVID Symptom Study app after COVID-19 vaccination, stratified by sex, age, BMI, health status, and previous SARS-CoV-2 test status\nWe observed the same trend for local effects as for systemic effects, whereby app users aged 55 years or younger reported more local side-effects than participants older than 55 years (\nfigure 3\n), and women were more likely to report local side-effects than men (\nfigure 3\n;\nappendix p 11\n). Similar levels of side-effects were seen regardless of the levels of completeness of reporting by app users (\nappendix p 12\n).\nGiven preliminary evidence from small studies\n21–23\n21.\nSaadat, S ∙ Rikhtegaran-Tehrani, Z ∙ Logue, J ∙ et al.\nSingle dose vaccination in healthcare workers previously infected with SARS-CoV-2\nmedRxiv.\n2021;\n(preprint).\n22.\nKrammer, F ∙ Srivastava, K ∙ Simon, V\nRobust spike antibody responses and increased reactogenicity in seropositive individuals after a single dose of SARS-CoV-2 mRNA vaccine\nmedRxiv.\n2021;\n(preprint).\n23.\nWise, J\nCOVID-19: people who have had infection might only need one dose of mRNA vaccine\nBMJ.\n2021;\n372\n:n308\nsuggesting that reactogenicity is higher among individuals previously infected with SARS-CoV-2, we investigated the extent to which previous SARS-CoV-2 infection (based on self-reported previous positive PCR or lateral flow result) was associated with reports of adverse effects. Individuals vaccinated with a single dose of BNT162b2 were more likely to report systemic effects if they had a previous SARS-CoV-2 positive test than were those without known past infection (5148 [35·8%] of 14 369\nvs\n33 007 [12·3%] of 267 734; OR 3·97 [95% CI 3·83–4·12], p<0·0001). A similar effect was seen for ChAdOx1 nCoV-19 first dose inoculation (7551 [53·1%] of 14 231 with past infection\nvs\n108 922 [32·9%] of 331 049 without past infection; 2·31 [2·23–2·38], p<0·0001;\nfigure 3\n) and BNT162b2 second dose inoculation (859 [38·2%] of 2251\nvs\n5357 [20·6%] of 25 956; 2·37 [2·17–2·60], p<0·0001). Local effects were similarly higher in individuals previously infected than in those without known past infection for both vaccines (\nfigure 3\n). No consistent difference in occurrence of systemic or local adverse effects was observed between individuals who reported a positive test result within the past 6 months and those who reported they received a positive test result at least 6 months ago (\nfigure 3\n).\nWe also investigated infection rates after the first vaccine dose in a subset of 67 293 app users who received BNT162b2 and 36 329 who received ChAdOx1 nCoV-19 in the study period and logged at least one PCR or lateral flow test after vaccination. We compared the test results of this population with those of 464 356 unvaccinated app users who had a PCR or lateral flow test result between Jan 4, and March 10, 2021 (\nappendix pp 4, 8\n). 3106 of 103 622 vaccinated individuals and 50 340 of 464 356 unvaccinated controls tested positive for SARS-CoV-2 infection. As UK guidelines stipulate that individuals need to be free of symptoms to be vaccinated, we found vaccinated participants to have a lower infection risk at the time of the vaccination than unvaccinated participants (RR for BNT162b2 −64% [95% CI −69 to −59]; RR for ChAdOx1 nCoV-19 −52% [95% CI −65 to −34]). We observed that 5–11 days after vaccination, the infection rates in the vaccinated group were only slightly below those of the unvaccinated group (\nfigure 4\n), whereas 12–20 days after vaccination, infection risk in the vaccinated group was significantly lower than in the unvaccinated group (RR for BNT162b2 −58% [95% CI −62 to −54]; RR for ChAdOx1 nCoV-19 −39% [95% CI −53 to −21]), after adjusting for population differences in the vaccinated groups using Poisson regressions. We observed a further reduction in infection risk after one dose of the BNT162b2 vaccine when compared with unvaccinated controls at 21–44 days after vaccination (RR −69% [95% CI −72 to −66]) and at 45–59 days after vaccination (−72% [–79 to −63];\nfigure 4\n). The RR after one dose of ChAdOx1 nCoV-19 compared with unvaccinated controls was −60% (95% CI −68 to −49) at 21–44 days after vaccination.\nFigure 4\nInfection risk reduction after the first dose in app users who have been vaccinated and subsequently tested, as a function of days since vac\nFinally, we tested the role of covariates in risk of infection after vaccination. We observed a larger risk reduction in vaccinated participants aged 55 years or younger (RR −70% [95% CI −72 to −68) than in those older than 55 years (−61% [–64 to −57]). Similarly, individuals without comorbidities had a larger risk reduction (−69% [–71 to −68]) than those with at least one comorbidity (−54% [–59 to −48]). Borderline differences were observed for BMI (RR for BMI <30 kg\/m\n2\n−69% [95% CI −71 to −67]; RR for BMI ≥30 kg\/m\n2\n−63% [−67 to −59]) and sex (RR for female −69% [95% CI −71 to −67]; RR for male −61% [–66 to −57];\nappendix p 5\n).\nDiscussion\nIn this large-scale, community-based study in the UK, we have investigated adverse effects and infection rates following administration of the two COVID-19 vaccines that are in use in the UK. The overall mean age of the vaccinated app users was higher than that of the general population (40·3 years)\n24\n24.\nOffice for National Statistics\nPopulation estimates for the UK, England and Wales, Scotland and Northern Ireland, provisional: mid-2019\nyet was lower than those of the samples within other UK COVID-19 effectiveness studies,\n11,12\n11.\nLopez Bernal, J ∙ Andrews, N ∙ Gower, C ∙ et al.\nEarly effectiveness of COVID-19 vaccination with BNT162b2 mRNA vaccine and ChAdOx1 adenovirus vector vaccine on symptomatic disease, hospitalisations and mortality in older adults in England\nmedRxiv.\n2021;\n(preprint).\n12.\nVasileiou, E ∙ Simpson, CR ∙ Shi, T ∙ et al.\nInterim findings from first-dose mass COVID-19 vaccination roll-out and COVID-19 hospital admissions in Scotland: a national prospective cohort study\nLancet.\n2021;\nlargely because of the presence of a small proportion of health-care workers among the participants of this study. However, our study population was considerably older than the study populations of the phase 3 trials.\n3,6,7\n3.\nPolack, FP ∙ Thomas, SJ ∙ Kitchin, N ∙ et al.\nSafety and efficacy of the BNT162b2 mRNA COVID-19 vaccine\nN Engl J Med.\n2020;\n383\n:2603-2615\n6.\nVoysey, M ∙ Clemens, SAC ∙ Madhi, SA ∙ et al.\nSafety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK\nLancet.\n2021;\n397\n:99-111\n7.\nRamasamy, MN ∙ Minassian, AM ∙ Ewer, KJ ∙ et al.\nSafety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2\/3 trial\nLancet.\n2021;\n396\n:1979-1993\nWe found that systemic adverse effects, including headache and fatigue, affected fewer than one in four people and were less common in the community than expected from clinical trials. For example, in phase 3 clinical trials of the BNT162b2 vaccine,\n3\n3.\nPolack, FP ∙ Thomas, SJ ∙ Kitchin, N ∙ et al.\nSafety and efficacy of the BNT162b2 mRNA COVID-19 vaccine\nN Engl J Med.\n2020;\n383\n:2603-2615\nthe most common events after the first dose were injection-site pain (71–83%), fatigue (34–47%), and headache (25–42%). However, in our community analysis, less than 30% of users complained of injection-site pain and less than 25% of fatigue and headache after the first dose. Although side-effects were significantly more prevalent in women than in men, in people aged 55 years or younger than in those older than 55 years, and after the second than after the first dose, they occurred at much lower frequencies than expected from the published literature. For instance, whereas 51–59% of participants reported fatigue after the second BNT162b2 dose in the phase 3 trial of that vaccine,\n3\n3.\nPolack, FP ∙ Thomas, SJ ∙ Kitchin, N ∙ et al.\nSafety and efficacy of the BNT162b2 mRNA COVID-19 vaccine\nN Engl J Med.\n2020;\n383\n:2603-2615\nfatigue was reported by less than 15% of participants after the second dose in our study. Additionally, our data provide evidence from the community to support early reports of higher frequency of side-effects in younger than in older individuals.\n3,7\n3.\nPolack, FP ∙ Thomas, SJ ∙ Kitchin, N ∙ et al.\nSafety and efficacy of the BNT162b2 mRNA COVID-19 vaccine\nN Engl J Med.\n2020;\n383\n:2603-2615\n7.\nRamasamy, MN ∙ Minassian, AM ∙ Ewer, KJ ∙ et al.\nSafety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2\/3 trial\nLancet.\n2021;\n396\n:1979-1993\nSimilarly, rates of side-effects following the ChAdOx1 nCoV-19 vaccine were lower than expected.\n7\n7.\nRamasamy, MN ∙ Minassian, AM ∙ Ewer, KJ ∙ et al.\nSafety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2\/3 trial\nLancet.\n2021;\n396\n:1979-1993\nThe phase 2–3 trial of the ChAdOx1 nCoV-19 vaccine\n7\n7.\nRamasamy, MN ∙ Minassian, AM ∙ Ewer, KJ ∙ et al.\nSafety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2\/3 trial\nLancet.\n2021;\n396\n:1979-1993\nreported systemic adverse effects in 88% of participants aged 18–55 years who received the first injection, whereas we found a lower rate of 33·7% after the first dose in the overall sample and 46·9% in individuals aged 18–55 years (data not shown). Individuals vaccinated with the ChAdOx1 nCoV-19 vaccine were more likely to experience systemic side-effects than those who had been given the BNT162b2 vaccine, but in our study 89% of respondents who logged at least one systemic effect after the ChAdOx1 nCoV-19 vaccine did not report any systemic effects after 3 days, and 98·3% did not report any after 1 week.\nIndividuals with evidence of past SARS-CoV-2 infection were also more likely to have adverse effects than those without evidence of past infection with both vaccines. It is possible, although it remains to be tested, that this increased reactogenicity relates to increased immunogenicity. It has been shown that vaccines have increased immunogenicity in individuals with past infection and these people have higher antibody titres than those without previous infection.\n22,23,25\n22.\nKrammer, F ∙ Srivastava, K ∙ Simon, V\nRobust spike antibody responses and increased reactogenicity in seropositive individuals after a single dose of SARS-CoV-2 mRNA vaccine\nmedRxiv.\n2021;\n(preprint).\n23.\nWise, J\nCOVID-19: people who have had infection might only need one dose of mRNA vaccine\nBMJ.\n2021;\n372\n:n308\n25.\nManisty, C ∙ Otter, AD ∙ Treibel, TA ∙ et al.\nAntibody response to first BNT162b2 dose in previously SARS-CoV-2-infected individuals\nLancet.\n2021;\n397\n:1057-1058\nWe observed an infection risk reduction at 21–44 days after vaccination in all vaccinated users compared with unvaccinated controls (RR was −69% [95% CI −72 to −66] for BNT162b2 and −60% [–68 to −49] for ChAdOx1 nCoV-19). The reduction of infection was lower in individuals older than 55 years than those aged 55 years or younger, in those with one or more comorbidities than in those without comorbidities, and in individuals with a BMI of 30 kg\/m\n2\nor higher than in those with a BMI of less than 30 kg\/m\n2\n(\nappendix p 5\n). A preprint based on data from Israel suggested that a single dose of BNT162b2 might not provide enough protection;\n26\n26.\nChodick, G ∙ Tene, L ∙ Patalon, T ∙ et al.\nThe effectiveness of the first dose of BNT162b2 vaccine in reducing SARS-CoV-2 infection 13–24 days after immunization: real-world evidence\nmedRxiv.\n2021;\n(preprint).\nhowever, a re-analysis of the same dataset indicated that after 14 days the effectiveness of a single dose of vaccine was about 90%.\n5\n5.\nHunter, PR ∙ Brainard, J\nEstimating the effectiveness of the Pfizer COVID-19 BNT162b2 vaccine after a single dose. A reanalysis of a study of “real-world” vaccination outcomes from Israel\nmedRxiv.\n2021;\n(preprint).\nAlthough our data, due to their observational nature, does not allow us to comment directly on effectiveness, the observed decrease of infection over time seems to be in line with efficacy reported in the BNT162b2 phase 3 trial\n3\n3.\nPolack, FP ∙ Thomas, SJ ∙ Kitchin, N ∙ et al.\nSafety and efficacy of the BNT162b2 mRNA COVID-19 vaccine\nN Engl J Med.\n2020;\n383\n:2603-2615\nand supports the UK Government's decision to delay the timing of the second injection to 12 weeks to maximise the number of people receiving at least one dose. Long-term surveillance for SARS-CoV-2 protection in individuals who have received delayed second doses of BNT162b2 compared with those receiving second doses according to initial guidelines (ie, 21 days after the first dose) will be required to determine whether these initial protection estimates persist.\nStrengths of our study include its large sample size; capture of data on SARS-CoV-2 RT-PCR or lateral flow test results, regardless of symptoms; the prospective real-time capture of information on symptoms; and the availability of both BNT162b2 and ChAdOx1 nCoV-19 vaccines in the UK, which allowed cross-vaccine comparison. Our study also has several limitations. We used self-reported data, which can introduce information bias, including misclassification, or effect bias exposure. Also, some participants might be more likely to report symptoms than others, and there is the potential for users to drop out of reporting in the app. Participants using the app were a self-selected group and not representative of the general population, as has been observed in other digital platform studies.\n27\n27.\nBaltrusaitis, K ∙ Santillana, M ∙ Crawley, AW ∙ et al.\nDeterminants of participants' follow-up and characterization of representativeness in flu near you, a participatory disease surveillance system\nJMIR Public Health Surveill.\n2017;\n3\n:e18\nUsers of a participatory platform (as well as participants in all voluntary studies, including clinical trials) are likely to be more interested in health, and might behave differently to the general population as a result. Previous work has shown that data from our app is able to produce estimates of population-level disease prevalence that agree well with surveys with random, representative designs,\n18,28\n18.\nVarsavsky, T ∙ Graham, MS ∙ Canas, LS ∙ et al.\nDetecting COVID-19 infection hotspots in England using large-scale self-reported data from a mobile application: a prospective, observational study\nLancet Public Health.\n2021;\n6\n:e21-e29\n28.\nBowyer, RCE ∙ Varsavsky, T ∙ Thompson, EJ ∙ et al.\nGeo-social gradients in predicted COVID-19 prevalence in Great Britain: results from 1 960 242 users of the COVID-19 Symptoms Study app\nThorax.\n2020;\nsuggesting that behavioural issues are not substantially biasing our app population. As with other studies examining COVID-19 vaccine effects in the general community, our data are limited by the vaccine rollout's focus on health-care workers, elderly people, and people who are clinically vulnerable.\n2\n2.\nDepartment of Health and Social Care\nPriority groups for coronavirus (COVID-19) vaccination: advice from the JCVI, 30 December 2020\nMoreover, our results might have been affected by collider bias (ie, when a risk factor and an outcome both affect the likelihood of being sampled)\n29\n29.\nGriffith, GJ ∙ Morris, TT ∙ Tudball, MJ ∙ et al.\nCollider bias undermines our understanding of COVID-19 disease risk and severity\nNat Commun.\n2020;\n11\n, 5749\nif both vaccination status and COVID positivity influenced the probability of participation in the app. However, given that strong reductions in COVID hospitalisations after vaccination were observed in nationwide studies in Scotland\n12\n12.\nVasileiou, E ∙ Simpson, CR ∙ Shi, T ∙ et al.\nInterim findings from first-dose mass COVID-19 vaccination roll-out and COVID-19 hospital admissions in Scotland: a national prospective cohort study\nLancet.\n2021;\nand England,\n11\n11.\nLopez Bernal, J ∙ Andrews, N ∙ Gower, C ∙ et al.\nEarly effectiveness of COVID-19 vaccination with BNT162b2 mRNA vaccine and ChAdOx1 adenovirus vector vaccine on symptomatic disease, hospitalisations and mortality in older adults in England\nmedRxiv.\n2021;\n(preprint).\nwe believe that collider bias is unlikely to underlie the reduction in infections seen in our data. Recipients of the ChAdOx1 nCoV-19 vaccine might differ from recipients of the BNT162b2 vaccine by age or dependency. Although we adjusted for population differences across the BNT162b2, ChAdOx1 nCoV-19, and unvaccinated control groups, our estimates of infection rates after vaccination might not have fully adjusted for case-mix and therefore are preliminary. Furthermore, because the ChAdOx1 nCoV-19 vaccine started being rolled out in January, 2021, and the second dose is to be administered at 12 weeks, no app users had received two doses of ChAdOx1 nCoV-19 at the time of this report. The completeness of reporting was higher for systemic effects than for local effects, which might have introduced some bias (\nappendix p 12\n). Some severe side-effects might have been missed if app users experiencing them were unable to use the app to report side-effects. However, we saw substantially lower rates of severe and mild side-effects than observed in phase 3 trials, making the missing of severe side-effects an unlikely explanation for the lower prevalence of side-effects seen in our data. Furthermore, we cannot rule out the presence of selection bias in who was tested after vaccination, as we know that health-care workers are tested more frequently than people in the general population, even if they are asymptomatic. This is an observational study, with data captured during a specific timeframe, and our study design does not allow an inference of causality. Also, we evaluated only short-term adverse effects, and long-term surveillance in the general population will be required to investigate possible future effects. Finally, the systemic side-effects were collected from daily reports within 1 week from the injection date, so we cannot rule out that these effects might not be vaccine related. We also had insufficient power to assess differential rates by ethnic group.\nIn conclusion, short-term adverse effects of both vaccines are moderate in frequency, mild in severity, and short-lived. Adverse effects are more frequently reported in younger individuals, women, and among those who previously had COVID-19. The post-vaccine symptoms (both systemic and local) often last 1–2 days from the injection. Our data could be used to inform people on the likelihood of side-effects on the basis of their age and sex and the type of vaccine being administered. Furthermore, our data support results from randomised controlled trials in a large community-based scenario showing evidence of reduction in infection after 12 days and substantial protection after 3 weeks.\nContributors\nJW and TDS acquired funding. CM and TDS conceptualised the study. KK, AM, LP, and JC analysed the data. BM and JC curated the data. PL, CHS, LHN, DAD, JM, MA, LSC, EM, MSG, MMo, ADJ, MMa, AH, ATC, CJS, SO, SS, and CH contributed data and software. CM, JC, and TDS verified the underlying data. CM, KK, AM, LP, AMV, ALG, and TDS wrote the first draft of the manuscript. All authors reviewed and edited revisions of the manuscript, had full access to all the data in the study, and had final responsibility for the decision to submit for publication.\nData sharing\nAnonymised research data are shared with third parties via Health Data Research UK (HDRUK.ac.uk). US investigators are encouraged to coordinate data requests through the Coronavirus Pandemic Epidemiology (COPE) consortium (\nwww.monganinstitute.org\/cope-consortium\n). Data updates can be found at\nhttps:\/\/covid.joinzoe.com\n.\nDeclaration of interests\nCM reports grants from Chronic Disease Research Foundation (CDRF) during the conduct of the study. JW, AM, LP, CH, SS, and JC report being employees of ZOE Global during the conduct of the study. ATC reports grants from Massachusetts Consortium on Pathogen Readiness during the conduct of the study, and personal fees from Bayer Pharma, Pfizer, and Boehringer Ingelheim, outside the submitted work. DAD reports grants from National Institutes of Health (NIH), Massachusetts Consortium on Pathogen Readiness, and American Gastroenterological Association, during the conduct of the study, and that he served as a co-investigator on an unrelated nutrition trial sponsored by ZOE Global. CHS reports grants from Alzheimer's Society during the conduct of the study. AMV reports grants from Medical Research Council (MRC) and personal fees from ZOE Global, during the conduct of the study. ALG reports having shares in AstraZeneca and receiving grants from Novavax, outside the submitted work. CJS reports grants from CDRF, MRC, and Wellcome Trust, during the conduct of the study. SO reports grants from Wellcome Trust, UK Research and Innovation (UKRI), and CDRF, during the conduct of the study. TDS reports being a consultant for ZOE Global, during the conduct of the study. All other authors declare no competing interests.\nAcknowledgments\nZOE Global provided in-kind support for all aspects of building, running, and supporting the app and service to all users worldwide. The Department of Twin Research & Genetic Epidemiology at King's College London receives grant support from the Wellcome Trust (212904\/Z\/18\/Z), the MRC British Heart Foundation Ancestry and Biological Informative Markers for Stratification of Hypertension (AIMHY; MR\/M016560\/1), the European Union, CDRF, ZOE Global, NIH, the National Institute for Health Research (NIHR)-funded BioResource, and Clinical Research Facility and Biomedical Research Centre based at Guy's and St Thomas' National Health Service (NHS) Foundation Trust, in partnership with King's College London. SO is funded by the Wellcome Engineering and Physical Sciences Research Council (EPSRC) Centre for Medical Engineering (WT203148\/Z\/16\/Z) and the Wellcome Flagship Programme (WT213038\/Z\/18\/Z). CM is funded by the CDRF and the MRC AIMHY project grant. CHS is an Alzheimer's Society junior fellow (AS-JF-17-011). The School of Biomedical Engineering & Imaging Sciences is supported by the Wellcome EPSRC Centre for Medical Engineering at King's College London (WT203148\/Z\/16\/Z) and the Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St Thomas' NHS Foundation Trust, in partnership with King's College London and King's College Hospital NHS Foundation Trust. ATC is a Stuart and Suzanne Steele MGH Research Scholar. LHN is supported by an NIH K23DK125838 award, the American Gastroenterological Association Research Scholar Award, and the Crohn's and Colitis Foundation Career Development Award. DAD and LHN are supported by the American Gastroenterological Association-Takeda COVID-19 Rapid Response Research Award (AGA2021-5102). DAD is supported by NIH\/National Institute of Health Diabetes and Digestive and Kidney Diseases (K01DK120742). ATC, LHN, and DAD are supported by the Massachusetts Consortium on Pathogen Readiness. JM is partially supported by the NIH (DK40561) and the American Diabetes Association (7-21-JDFM-005). PL is funded by the CDRF. AMV is funded by a UKRI and MRC Covid-Rapid Response grant (MR\/V027883\/1). We thank all participants, including study volunteers enrolled in cohorts within the COPE consortium. We thank the staff of ZOE Global, the Department of Twin Research & Genetic Epidemiology at King's College London, the Clinical & Translational Epidemiology Unit at Massachusetts General Hospital, and researchers and staff at Lund University in Sweden for their tireless work in contributing to the running of the study and data collection.\nSupplementary Material (1)\nSupplementary appendix\nReferences\nPublic Health England\nCOVID-19 vaccination programme\nDepartment of Health and Social Care\nPriority groups for coronavirus (COVID-19) vaccination: advice from the JCVI, 30 December 2020\nPolack, FP ∙ Thomas, SJ ∙ Kitchin, N ∙ et al.\nSafety and efficacy of the BNT162b2 mRNA COVID-19 vaccine\nN Engl J Med.\n2020;\n383\n:2603-2615\nDagan, N ∙ Barda, N ∙ Kepten, E ∙ et al.\nBNT162b2 mRNA COVID-19 vaccine in a nationwide mass vaccination setting\nN Engl J Med.\n2021;\nHunter, PR ∙ Brainard, J\nEstimating the effectiveness of the Pfizer COVID-19 BNT162b2 vaccine after a single dose. A reanalysis of a study of “real-world” vaccination outcomes from Israel\nmedRxiv.\n2021;\n(preprint).\nVoysey, M ∙ Clemens, SAC ∙ Madhi, SA ∙ et al.\nSafety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK\nLancet.\n2021;\n397\n:99-111\nRamasamy, MN ∙ Minassian, AM ∙ Ewer, KJ ∙ et al.\nSafety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2\/3 trial\nLancet.\n2021;\n396\n:1979-1993\nVoysey, M ∙ Clemens, SAC ∙ Madhi, SA ∙ et al.\nSingle-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials\nLancet.\n2021;\n397\n:881-891\nPublic Health England\nCOVID-19: vaccine surveillance strategy\nThe OpenSAFELY Collaborative ∙ MacKenna, B ∙ Curtis, HJ ∙ et al.\nTrends, regional variation, and clinical characteristics of COVID-19 vaccine recipients: a retrospective cohort study in 23·4 million patients using OpenSAFELY\nmedRxiv.\n2021;\n(preprint).\nLopez Bernal, J ∙ Andrews, N ∙ Gower, C ∙ et al.\nEarly effectiveness of COVID-19 vaccination with BNT162b2 mRNA vaccine and ChAdOx1 adenovirus vector vaccine on symptomatic disease, hospitalisations and mortality in older adults in England\nmedRxiv.\n2021;\n(preprint).\nVasileiou, E ∙ Simpson, CR ∙ Shi, T ∙ et al.\nInterim findings from first-dose mass COVID-19 vaccination roll-out and COVID-19 hospital admissions in Scotland: a national prospective cohort study\nLancet.\n2021;\nHall, VJ ∙ Foulkes, S ∙ Saei, A ∙ et al.\nCOVID-19 vaccine coverage in health-care workers in England and effectiveness of BNT162b2 mRNA vaccine against infection (SIREN): a prospective, multicentre, cohort study\nLancet.\n2021;\nMenni, C ∙ Valdes, AM ∙ Freidin, MB ∙ et al.\nReal-time tracking of self-reported symptoms to predict potential COVID-19\nNat Med.\n2020;\n26\n:1037-1040\nDrew, DA ∙ Nguyen, LH ∙ Steves, CJ ∙ et al.\nRapid implementation of mobile technology for real-time epidemiology of COVID-19\nScience.\n2020;\n368\n:1362-1367\nPearl, J\nCausality\nCambridge University Press, Cambridge, 2009\nOffice for National Statistics\nCoronavirus (COVID-19) Infection Survey\nVarsavsky, T ∙ Graham, MS ∙ Canas, LS ∙ et al.\nDetecting COVID-19 infection hotspots in England using large-scale self-reported data from a mobile application: a prospective, observational study\nLancet Public Health.\n2021;\n6\n:e21-e29\nMurray, B ∙ Kerfoot, E ∙ Graham, MS ∙ et al.\nAccessible data curation and analytics for international-scale citizen science datasets\narXiv.\n2020;\n(preprint).\nMinistry of Housing, Communities, and Local Government\nEnglish indices of deprivation 2019\nSaadat, S ∙ Rikhtegaran-Tehrani, Z ∙ Logue, J ∙ et al.\nSingle dose vaccination in healthcare workers previously infected with SARS-CoV-2\nmedRxiv.\n2021;\n(preprint).\nKrammer, F ∙ Srivastava, K ∙ Simon, V\nRobust spike antibody responses and increased reactogenicity in seropositive individuals after a single dose of SARS-CoV-2 mRNA vaccine\nmedRxiv.\n2021;\n(preprint).\nWise, J\nCOVID-19: people who have had infection might only need one dose of mRNA vaccine\nBMJ.\n2021;\n372\n:n308\nOffice for National Statistics\nPopulation estimates for the UK, England and Wales, Scotland and Northern Ireland, provisional: mid-2019\nManisty, C ∙ Otter, AD ∙ Treibel, TA ∙ et al.\nAntibody response to first BNT162b2 dose in previously SARS-CoV-2-infected individuals\nLancet.\n2021;\n397\n:1057-1058\nChodick, G ∙ Tene, L ∙ Patalon, T ∙ et al.\nThe effectiveness of the first dose of BNT162b2 vaccine in reducing SARS-CoV-2 infection 13–24 days after immunization: real-world evidence\nmedRxiv.\n2021;\n(preprint).\nBaltrusaitis, K ∙ Santillana, M ∙ Crawley, AW ∙ et al.\nDeterminants of participants' follow-up and characterization of representativeness in flu near you, a participatory disease surveillance system\nJMIR Public Health Surveill.\n2017;\n3\n:e18\nBowyer, RCE ∙ Varsavsky, T ∙ Thompson, EJ ∙ et al.\nGeo-social gradients in predicted COVID-19 prevalence in Great Britain: results from 1 960 242 users of the COVID-19 Symptoms Study app\nThorax.\n2020;\nGriffith, GJ ∙ Morris, TT ∙ Tudball, MJ ∙ et al.\nCollider bias undermines our understanding of COVID-19 disease risk and severity\nNat Commun.\n2020;\n11\n, 5749","attrs_markdown":"[Skip to Main Content](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#page-body-id \"Skip to Main Content\") [Skip to Main Menu](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#mega-menu-nav \"Skip to Main Menu\")\n\n## Login to your account\nDon’t have an account?\n\n[Create a Free 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started\n\n[Ok](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext)\n# Vaccine side-effects and SARS-CoV-2 infection after vaccination in users of the COVID Symptom Study app in the UK: a prospective observational study\n[Cristina Menni, PhD](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext)\n\nCristina Menni, PhD\n\nCorrespondence\n\nCorrespondence to: Dr Cristina Menni, Department of Twin Research & Genetic Epidemiology, King's College London, London SE1 7EH, UK\n\n[cristina.menni@kcl.ac.uk](mailto:cristina.menni@kcl.ac.uk \"Send email to Cristina Menni\")\n\nFootnotes\n\n†\n\nContributed equally\n\nAffiliations\n\nDepartment of Twin Research & Genetic Epidemiology, King's College London, London, UK\n\n[Search for articles by this author](https:\/\/www.thelancet.com\/authored-by\/Menni\/Cristina)\n\n[a](),[†]() [cristina.menni@kcl.ac.uk](mailto:cristina.menni@kcl.ac.uk \"Send email to Cristina Menni\")\n\n∙\n\n[Kerstin Klaser, MSc](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext)\n\nKerstin Klaser, MSc\n\nFootnotes\n\n†\n\nContributed equally\n\nAffiliations\n\nSchool of Biomedical Engineering & Imaging Sciences, King's College London, London, UK\n\n[Search for articles by this author](https:\/\/www.thelancet.com\/authored-by\/Klaser\/Kerstin)\n\n[b](),[†]()\n\n∙\n\n[Anna May, MA](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext)\n\nAnna May, MA\n\nAffiliations\n\nZOE Global, London, UK\n\n[Search for articles by this author](https:\/\/www.thelancet.com\/authored-by\/May\/Anna)\n\n[c]()\n\n∙\n\n[Lorenzo Polidori, MSc](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext)\n\nLorenzo Polidori, MSc\n\nAffiliations\n\nZOE Global, London, UK\n\n[Search for articles by this author](https:\/\/www.thelancet.com\/authored-by\/Polidori\/Lorenzo)\n\n[c]()\n\n∙\n\n[Joan Capdevila, PhD](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext)\n\nJoan Capdevila, PhD\n\nAffiliations\n\nZOE Global, London, UK\n\n[Search for articles by this author](https:\/\/www.thelancet.com\/authored-by\/Capdevila\/Joan)\n\n[c]()\n\n∙\n\n[Panayiotis Louca, MSc](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext)\n\nPanayiotis Louca, MSc\n\nAffiliations\n\nDepartment of Twin Research & Genetic Epidemiology, King's College London, London, UK\n\n[Search for articles by this author](https:\/\/www.thelancet.com\/authored-by\/Louca\/Panayiotis)\n\n[a]()\n\n∙\n\n[Carole H Sudre, PhD](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext)\n\nCarole H Sudre, PhD\n\nAffiliations\n\nSchool of Biomedical Engineering & Imaging Sciences, King's College London, London, UK\n\nMedical Research Council Unit for Lifelong Health and Ageing, Department of Population Science and Experimental Medicine, and Centre for Medical Image Computing, Department of Computer Science, University College London, London, UK\n\n[Search for articles by this author](https:\/\/www.thelancet.com\/authored-by\/Sudre\/Carole+H)\n\n[b](),[d]()\n\n∙\n\n[Long H Nguyen, MD](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext)\n\nLong H Nguyen, MD\n\nAffiliations\n\nClinical & Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA\n\nDivision of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA\n\n[Search for articles by this author](https:\/\/www.thelancet.com\/authored-by\/Nguyen\/Long+H)\n\n[e](),[f]()\n\n∙\n\n[David A Drew, PhD](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext)\n\nDavid A Drew, PhD\n\nAffiliations\n\nClinical & Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA\n\nDivision of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA\n\n[Search for articles by this author](https:\/\/www.thelancet.com\/authored-by\/Drew\/David+A)\n\n[e](),[f]()\n\n∙\n\n[Jordi Merino, PhD](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext)\n\nJordi Merino, PhD\n\nAffiliations\n\nDiabetes Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA\n\nDepartment of Medicine, Harvard Medical School, Boston, MA, USA\n\nProgram in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA\n\n[Search for articles by this 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MD\n\nAffiliations\n\nClinical & Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA\n\nDivision of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA\n\n[Search for articles by this author](https:\/\/www.thelancet.com\/authored-by\/Chan\/Andrew+T)\n\n[e](),[f]()\n\n∙\n\n[Jonathan Wolf, MA](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext)\n\nJonathan Wolf, MA\n\nAffiliations\n\nZOE Global, London, UK\n\n[Search for articles by this author](https:\/\/www.thelancet.com\/authored-by\/Wolf\/Jonathan)\n\n[c]()\n\n∙\n\n[Claire J Steves, PhD](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext)\n\nClaire J Steves, PhD\n\nAffiliations\n\nDepartment of Twin Research & Genetic Epidemiology, King's College London, London, UK\n\n[Search for articles by this 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Spector, MD](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext)\n\nProf Tim D Spector, MD\n\nAffiliations\n\nDepartment of Twin Research & Genetic Epidemiology, King's College London, London, UK\n\n[Search for articles by this author](https:\/\/www.thelancet.com\/authored-by\/Spector\/Tim+D)\n\n[a]()\n\n∙ et al. Show more Show less\n\nAffiliations & Notes\n\nArticle Info\n\nLinked Articles (1)\n\naDepartment of Twin Research & Genetic Epidemiology, King's College London, London, UK\n\nbSchool of Biomedical Engineering & Imaging Sciences, King's College London, London, UK\n\ncZOE Global, London, UK\n\ndMedical Research Council Unit for Lifelong Health and Ageing, Department of Population Science and Experimental Medicine, and Centre for Medical Image Computing, Department of Computer Science, University College London, London, UK\n\neClinical & Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA\n\nfDivision of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA\n\ngDiabetes Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA\n\nhDepartment of Medicine, Harvard Medical School, Boston, MA, USA\n\niProgram in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA\n\njNational Institute for Health Research (NIHR) Biomedical Research Centre at Guy's and St Thomas' Foundation Trust, London, UK\n\nkNottingham NIHR Biomedical Research Centre at the School of Medicine, University of Nottingham, Nottingham City Hospital, Nottingham, UK\n\nlDepartment of Infection, Guy's and St Thomas' Foundation Trust, St Thomas Hospital, London, UK\n\n†\n\nContributed equally\n\nPublication History:\n\nPublished April 27, 2021\n\nDOI: [10\\.1016\/S1473-3099(21)00224-3 External Link](https:\/\/doi.org\/10.1016\/S1473-3099\\(21\\)00224-3)Also available on [ScienceDirect External Link](https:\/\/www.sciencedirect.com\/science\/article\/pii\/S1473309921002243)\n\nCopyright: © 2021 The Author(s). Published by Elsevier Ltd.\n\nUser License: [Creative Commons Attribution (CC BY 4.0)](http:\/\/creativecommons.org\/licenses\/by\/4.0\/) \\| [Elsevier's open access license policy](https:\/\/www.elsevier.com\/open-access)\n\n- Comment\n  [Symptom study app provides real-world data on COVID-19 vaccines](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00264-4\/fulltext \"Symptom study app provides real-world data on COVID-19 vaccines\")\n  - Drury et al.\n  *The Lancet Infectious Diseases*April 27, 2021\n\n[![Cover Image - The Lancet Infectious Diseases, Volume 21, Issue 7](https:\/\/www.thelancet.com\/cms\/asset\/23c68d6a-1234-448a-b73c-a4f31e48f53d\/cov200h.gif)](https:\/\/www.thelancet.com\/journals\/laninf\/issue\/vol21no7\/PIIS1473-3099\\(21\\)X0007-2)\n\n[Download PDFDownload PDF](https:\/\/www.thelancet.com\/action\/showPdf?pii=S1473-3099%2821%2900224-3 \"Standard PDF (opens in a new tab)\")\n\nOutline\n\nOutline\n\n- [Summary](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#author-abstract)\n- [Introduction](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#sec-1)\n- [Methods](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#sec-2)\n- [Results](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#sec-3)\n- [Discussion](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#sec-4)\n- [Data sharing](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#sec-5)\n- [Declaration of interests](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#conflict)\n- [Supplementary Material (1)](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#supplementary-material)\n- [References](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#references)\n- [Article metrics](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#core-collateral-metrics)\n\nShare\n\n#### Share\nShare on\n\n- [Email](https:\/\/www.thelancet.com\/#email \"Email\")\n- [X](https:\/\/www.thelancet.com\/#twitter \"formerly known as Twitter\")\n- [Facebook](https:\/\/www.thelancet.com\/#facebook \"Facebook\")\n- [LinkedIn](https:\/\/www.thelancet.com\/#linkedin \"LinkedIn\")\n- [Sina Weibo](https:\/\/www.thelancet.com\/#sina_weibo \"Sina Weibo\")\n- [Mendeley](https:\/\/www.thelancet.com\/#mendeley \"Mendeley\")\n- [Bluesky](https:\/\/www.thelancet.com\/#bluesky \"Bluesky\")\n\n[Add to my reading list](https:\/\/www.thelancet.com\/personalize\/addFavoritePublication?doi=10.1016\/S1473-3099\\(21\\)00224-3)\n\nMore\n\nMore\n\n- [Download PDFDownload PDF](https:\/\/www.thelancet.com\/action\/showPdf?pii=S1473-3099%2821%2900224-3 \"Standard PDF (opens in a new tab)\")\n- [Cite](https:\/\/www.thelancet.com\/action\/showCitFormats?doi=10.1016%2FS1473-3099%2821%2900224-3&pii=S1473-3099%2821%2900224-3 \"Cite\")\n- Share\n  \n  #### Share\n  Share on\n  \n  - 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We aimed to investigate the safety and effectiveness of these vaccines in a UK community setting.\n\n### Methods\nIn this prospective observational study, we examined the proportion and probability of self-reported systemic and local side-effects within 8 days of vaccination in individuals using the COVID Symptom Study app who received one or two doses of the BNT162b2 vaccine or one dose of the ChAdOx1 nCoV-19 vaccine. We also compared infection rates in a subset of vaccinated individuals subsequently tested for SARS-CoV-2 with PCR or lateral flow tests with infection rates in unvaccinated controls. All analyses were adjusted by age (≤55 years *vs* \\>55 years), sex, health-care worker status (binary variable), obesity (BMI \\<30 kg\/m2*vs* ≥30 kg\/m2), and comorbidities (binary variable, with or without comorbidities).\n\n### Findings\nBetween Dec 8, and March 10, 2021, 627 383 individuals reported being vaccinated with 655 590 doses: 282 103 received one dose of BNT162b2, of whom 28 207 received a second dose, and 345 280 received one dose of ChAdOx1 nCoV-19. Systemic side-effects were reported by 13·5% (38 155 of 282 103) of individuals after the first dose of BNT162b2, by 22·0% (6216 of 28 207) after the second dose of BNT162b2, and by 33·7% (116 473 of 345 280) after the first dose of ChAdOx1 nCoV-19. Local side-effects were reported by 71·9% (150 023 of 208 767) of individuals after the first dose of BNT162b2, by 68·5% (9025 of 13 179) after the second dose of BNT162b2, and by 58·7% (104 282 of 177 655) after the first dose of ChAdOx1 nCoV-19. Systemic side-effects were more common (1·6 times after the first dose of ChAdOx1 nCoV-19 and 2·9 times after the first dose of BNT162b2) among individuals with previous SARS-CoV-2 infection than among those without known past infection. Local effects were similarly higher in individuals previously infected than in those without known past infection (1·4 times after the first dose of ChAdOx1 nCoV-19 and 1·2 times after the first dose of BNT162b2). 3106 of 103 622 vaccinated individuals and 50 340 of 464 356 unvaccinated controls tested positive for SARS-CoV-2 infection. Significant reductions in infection risk were seen starting at 12 days after the first dose, reaching 60% (95% CI 49–68) for ChAdOx1 nCoV-19 and 69% (66–72) for BNT162b2 at 21–44 days and 72% (63–79) for BNT162b2 after 45–59 days.\n\n### Interpretation\nSystemic and local side-effects after BNT162b2 and ChAdOx1 nCoV-19 vaccination occur at frequencies lower than reported in phase 3 trials. Both vaccines decrease the risk of SARS-CoV-2 infection after 12 days.\n\n### Funding\nZOE Global, National Institute for Health Research, Chronic Disease Research Foundation, National Institutes of Health, UK Medical Research Council, Wellcome Trust, UK Research and Innovation, American Gastroenterological Association.\n\n## Introduction\nThe UK's Medicines and Healthcare products Regulatory Agency has given emergency use authorisation to three COVID-19 vaccines: the Pfizer-BioNTech mRNA vaccine (BNT162b2), the Oxford-AstraZeneca adenovirus-vectored vaccine (ChAdOx1 nCoV-19), and the Moderna mRNA vaccine (mRNA-1273). The first two vaccines have been rolled out across the UK since Dec 8, 2020, and Jan 4, 2021, respectively.\n\n[1](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext)\n\n1\\.\n\nPublic Health England\n\n**COVID-19 vaccination programme**\n\n<https:\/\/www.gov.uk\/government\/collections\/covid-19-vaccination-programme>\n\nDate: Nov 27, 2020\n\nDate accessed: February 18, 2021\n\n[Google Scholar](https:\/\/scholar.google.com\/scholar?q=Public+Health+EnglandCOVID-19+vaccination+programmehttps%3A%2F%2Fwww.gov.uk%2Fgovernment%2Fcollections%2Fcovid-19-vaccination-programmeNov+27%2C+2020)\n\nIn late December, 2020, based on advice from the Joint Committee on Vaccination and Immunisation,\n\n[2](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext)\n\n2\\.\n\nDepartment of Health and Social Care\n\n**Priority groups for coronavirus (COVID-19) vaccination: advice from the JCVI, 30 December 2020**\n\n<https:\/\/www.gov.uk\/government\/publications\/priority-groups-for-coronavirus-covid-19-vaccination-advice-from-the-jcvi-30-december-2020?utm_source=f1de4cd1-935e-4a5e-b539-3b37cd92e598>\n\nDate: Dec 30, 2020\n\nDate accessed: February 18, 2021\n\n[Google Scholar](https:\/\/scholar.google.com\/scholar?q=Department+of+Health+and+Social+CarePriority+groups+for+coronavirus+%28COVID-19%29+vaccination%3A+advice+from+the+JCVI%2C+30+December+2020https%3A%2F%2Fwww.gov.uk%2Fgovernment%2Fpublications%2Fpriority-groups-for-coronavirus-covid-19-vaccination-advice-from-the-jcvi-30-december-2020%3Futm_source%3Df1de4cd1-935e-4a5e-b539-3b37cd92e598Dec+30%2C+2020)\n\nthe UK Government decided to delay the administration of second doses.\n\nPhase 3 trials reported the BNT162b2 vaccine to have an efficacy of 52% at 12 days after the first dose and of 95% after the second dose if administered 3–4 weeks apart in participants without previous SARS-CoV-2 infection.\n\n[3](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext)\n\n3\\.\n\nPolack, FP ∙ Thomas, SJ ∙ Kitchin, N ∙ et al.\n\n**Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine**\n\n*N Engl J Med.* 2020; **383**:2603-2615\n\n[Crossref](https:\/\/doi.org\/10.1056\/NEJMoa2034577)\n\n[Scopus (10099)](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_3_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85098117107)\n\n[PubMed](https:\/\/pubmed.ncbi.nlm.nih.gov\/33301246\/)\n\n[Google Scholar](https:\/\/scholar.google.com\/scholar_lookup?doi=10.1056%2FNEJMoa2034577&pmid=33301246)\n\nThe effectiveness of this vaccine in reducing infection, severe disease, hospitalisation, and death with COVID-19 has been reported for the whole of Israel,\n\n[4](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext)\n\n4\\.\n\nDagan, N ∙ Barda, N ∙ Kepten, E ∙ et al.\n\n**BNT162b2 mRNA COVID-19 vaccine in a nationwide mass vaccination setting**\n\n*N Engl J Med.* 2021;\n\npublished online Feb 24. <https:\/\/doi.org\/10.1056\/nejmoa2101765>\n\n[Scopus (1814)](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_4_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85103719376)\n\n[PubMed](https:\/\/pubmed.ncbi.nlm.nih.gov\/33626250\/)\n\n[Google Scholar](https:\/\/scholar.google.com\/scholar_lookup?doi=10.1056%2FNEJMoa2101765&pmid=33626250)\n\nwith reanalysis of the data from Israel revealing it to be 90% effective 2 weeks after the first dose.\n\n[5](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext)\n\n5\\.\n\nHunter, PR ∙ Brainard, J\n\n**Estimating the effectiveness of the Pfizer COVID-19 BNT162b2 vaccine after a single dose. A reanalysis of a study of “real-world” vaccination outcomes from Israel**\n\n*medRxiv.* 2021;\n\npublished online Feb 3. <https:\/\/doi.org\/10.1101\/2021.02.01.21250957>\n\n(preprint).\n\n[Google Scholar](https:\/\/scholar.google.com\/scholar?q=PRHunterJBrainardEstimating+the+effectiveness+of+the+Pfizer+COVID-19+BNT162b2+vaccine+after+a+single+dose.+A+reanalysis+of+a+study+of+%E2%80%9Creal-world%E2%80%9D+vaccination+outcomes+from+IsraelmedRxiv2021published+online+Feb+3.https%3A%2F%2Fdoi.org%2F10.1101%2F2021.02.01.21250957%28preprint%29.)\n\nThe ChAdOx1 nCoV-19 trial found efficacy against symptomatic disease of 76% at 22–90 days after at least one standard dose.\n\n[6–8](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext)\n\n6\\.\n\nVoysey, M ∙ Clemens, SAC ∙ Madhi, SA ∙ et al.\n\n**Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK**\n\n*Lancet.* 2021; **397**:99-111\n\n[Full Text](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_6_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS0140-6736%2820%2932661-1&cf=fulltext&site=lancet-site)\n\n[Full Text (PDF)](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_6_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS0140-6736%2820%2932661-1&cf=pdf&site=lancet-site)\n\n[Scopus (3425)](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_6_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85097463811)\n\n[PubMed](https:\/\/pubmed.ncbi.nlm.nih.gov\/33306989\/)\n\n[Google Scholar](https:\/\/scholar.google.com\/scholar_lookup?doi=10.1016%2FS0140-6736%2820%2932661-1&pmid=33306989)\n\n7\\.\n\nRamasamy, MN ∙ Minassian, AM ∙ Ewer, KJ ∙ et al.\n\n**Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2\/3 trial**\n\n*Lancet.* 2021; **396**:1979-1993\n\n[Full Text](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_7_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS0140-6736%2820%2932466-1&cf=fulltext&site=lancet-site)\n\n[Full Text (PDF)](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_7_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS0140-6736%2820%2932466-1&cf=pdf&site=lancet-site)\n\n[Scopus (1091)](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_7_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85097243389)\n\n[PubMed](https:\/\/pubmed.ncbi.nlm.nih.gov\/33220855\/)\n\n[Google Scholar](https:\/\/scholar.google.com\/scholar_lookup?doi=10.1016%2FS0140-6736%2820%2932466-1&pmid=33220855)\n\n8\\.\n\nVoysey, M ∙ Clemens, SAC ∙ Madhi, SA ∙ et al.\n\n**Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials**\n\n*Lancet.* 2021; **397**:881-891\n\n[Full Text](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_8_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS0140-6736%2821%2900432-3&cf=fulltext&site=lancet-site)\n\n[Full Text (PDF)](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_8_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS0140-6736%2821%2900432-3&cf=pdf&site=lancet-site)\n\n[Scopus (828)](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_8_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85101846197)\n\n[PubMed](https:\/\/pubmed.ncbi.nlm.nih.gov\/33617777\/)\n\n[Google Scholar](https:\/\/scholar.google.com\/scholar_lookup?doi=10.1016%2FS0140-6736%2821%2900432-3&pmid=33617777)\n\nResearch in context\n\n**Evidence before this study**\n\nWe searched PubMed for articles published up to March 10, 2021, using the terms (“BNT162b2“ OR “mRNA Covid-19 Vaccine” OR “ChAdOx1 nCoV-19” OR “adenovirus-vectored Covid-19 vaccine”) AND (“effectiveness” OR “reinfection” OR “side-effects” OR “adverse effects” OR “reactogenicity” OR “phase IV”). We did not restrict our search by language or type of publication. Besides the original phase 1–3 trials, we found one published article and two preprints on data from Israel investigating the effectiveness of the Pfizer-BioNTech vaccine (BNT162b2), a preprint from the UK exploring the effectiveness of both the BNT162b2 and Oxford-AstraZeneca (ChAdOx1 nCoV-19) vaccines in individuals aged 70 years or older in the community, and a study that linked health records for all vaccinated people in Scotland to investigate COVID-19 hospitalisation and mortality after vaccination. No study investigated the prevalence of adverse effects of the vaccines and all studies reported both vaccines to be highly effective.\n\n**Added value of this study**\n\nIn this large prospective observational study, we assessed adverse effects from the two COVID-19 vaccines in use in the UK at the time of writing (BNT162b2 and ChAdOx1 nCoV-19), as well as self-reported infection rates following one dose or two doses of BNT162b2 and one dose of ChAdOx1 nCoV-19. Reported side-effects were minor in severity and of short duration. Headache and fatigue were more common in women than in men, in people aged 55 years or younger than in people older than 55 years, and after the second than after the first dose. Individuals with known past SARS-CoV-2 infection were more likely to have adverse effects after the first dose than were those without known past infection. We found, in a community setting, that self-reported infection rates of those vaccinated with the BNT162b2 or ChAdOx1 nCoV-19 vaccines were significantly lower than infection rates in unvaccinated controls. Documented infection rates in our app after a single vaccine dose decreased by 58% (95% CI 54–62) at 12–20 days, 69% (66–72) at 21–44 days, and 72% (63–79) after 45–59 days following BNT162b2, and 39% (21–53) at 12–20 days and 60% (49–68) at 21–44 days following ChAdOx1 nCoV-19, compared with unvaccinated controls.\n\n**Implications of all the available evidence**\n\nLocalised and systemic side-effects after vaccination are less common in a real-world community setting than reported in phase 3 trials, mostly minor in severity, and self-limiting. Our data will enable prediction of side-effects based on age, sex, and past COVID-19 status to help update guidance to health professionals to reassure the population about the safety of vaccines.\n\nSurveillance in the general population is necessary at this stage during vaccination rollout.\n\n[9](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext)\n\n9\\.\n\nPublic Health England\n\n**COVID-19: vaccine surveillance strategy**\n\n<https:\/\/www.gov.uk\/government\/publications\/covid-19-vaccine-surveillance-strategy>\n\nDate: Jan 11, 2021\n\nDate accessed: March 17, 2021\n\n[Google Scholar](https:\/\/scholar.google.com\/scholar?q=Public+Health+EnglandCOVID-19%3A+vaccine+surveillance+strategyhttps%3A%2F%2Fwww.gov.uk%2Fgovernment%2Fpublications%2Fcovid-19-vaccine-surveillance-strategyJan+11%2C+2021)\n\nThe OpenSAFELY collaboration\n\n[10](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext)\n\n10\\.\n\nThe OpenSAFELY Collaborative ∙ MacKenna, B ∙ Curtis, HJ ∙ et al.\n\n**Trends, regional variation, and clinical characteristics of COVID-19 vaccine recipients: a retrospective cohort study in 23·4 million patients using OpenSAFELY**\n\n*medRxiv.* 2021;\n\npublished online Jan 26. <https:\/\/doi.org\/10.1101\/2021.01.25.21250356>\n\n(preprint).\n\n[Google Scholar](https:\/\/scholar.google.com\/scholar?q=The+OpenSAFELY+CollaborativeBMacKennaHJCurtisTrends%2C+regional+variation%2C+and+clinical+characteristics+of+COVID-19+vaccine+recipients%3A+a+retrospective+cohort+study+in+23%C2%B74+million+patients+using+OpenSAFELYmedRxiv2021published+online+Jan+26.https%3A%2F%2Fdoi.org%2F10.1101%2F2021.01.25.21250356%28preprint%29.)\n\nimplemented a framework for monitoring vaccine rollout and coverage in the UK via record linkage, Public Health England has reported early data on effectiveness in the older population prioritised for vaccination,\n\n[11](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext)\n\n11\\.\n\nLopez Bernal, J ∙ Andrews, N ∙ Gower, C ∙ et al.\n\n**Early effectiveness of COVID-19 vaccination with BNT162b2 mRNA vaccine and ChAdOx1 adenovirus vector vaccine on symptomatic disease, hospitalisations and mortality in older adults in England**\n\n*medRxiv.* 2021;\n\npublished online March 2. <https:\/\/doi.org\/10.1101\/2021.03.01.21252652>\n\n(preprint).\n\n[Google Scholar](https:\/\/scholar.google.com\/scholar?q=JLopez+BernalNAndrewsCGowerEarly+effectiveness+of+COVID-19+vaccination+with+BNT162b2+mRNA+vaccine+and+ChAdOx1+adenovirus+vector+vaccine+on+symptomatic+disease%2C+hospitalisations+and+mortality+in+older+adults+in+EnglandmedRxiv2021published+online+March+2.https%3A%2F%2Fdoi.org%2F10.1101%2F2021.03.01.21252652%28preprint%29.)\n\nand a prospective observational study investigated the association between the rollout of the first vaccine dose and COVID-19 hospital admission in Scotland.\n\n[12](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext)\n\n12\\.\n\nVasileiou, E ∙ Simpson, CR ∙ Shi, T ∙ et al.\n\n**Interim findings from first-dose mass COVID-19 vaccination roll-out and COVID-19 hospital admissions in Scotland: a national prospective cohort study**\n\n*Lancet.* 2021;\n\npublished online April 23. <https:\/\/doi.org\/10.1016\/S0140-6736(21)00677-2>\n\n[Full Text](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_12_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS0140-6736%2821%2900677-2&cf=fulltext&site=lancet-site)\n\n[Full Text (PDF)](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_12_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS0140-6736%2821%2900677-2&cf=pdf&site=lancet-site)\n\n[Scopus (391)](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_12_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85104923342)\n\n[PubMed](https:\/\/pubmed.ncbi.nlm.nih.gov\/33901420\/)\n\n[Google Scholar](https:\/\/scholar.google.com\/scholar_lookup?doi=10.1016%2FS0140-6736%2821%2900677-2&pmid=33901420)\n\nOther surveys, such as the SIREN study\n\n[13](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext)\n\n13\\.\n\nHall, VJ ∙ Foulkes, S ∙ Saei, A ∙ et al.\n\n**COVID-19 vaccine coverage in health-care workers in England and effectiveness of BNT162b2 mRNA vaccine against infection (SIREN): a prospective, multicentre, cohort study**\n\n*Lancet.* 2021;\n\npublished online April 23. <https:\/\/doi.org\/10.1016\/S0140-6736(21)00790-X>\n\n[Full Text](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_13_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS0140-6736%2821%2900675-9&cf=fulltext&site=lancet-site)\n\n[Full Text (PDF)](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_13_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS0140-6736%2821%2900675-9&cf=pdf&site=lancet-site)\n\n[Scopus (443)](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_13_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85104104418)\n\n[PubMed](https:\/\/pubmed.ncbi.nlm.nih.gov\/33844963\/)\n\n[Google Scholar](https:\/\/scholar.google.com\/scholar_lookup?doi=10.1016%2FS0140-6736%2821%2900675-9&pmid=33844963)\n\nin health-care workers, will also link directly to health records to assess the real-life effectiveness and safety of the various phases of vaccine rollout. However, it takes time for such studies to come to fruition. Real-time data from app users can provide a faster view of the safety and effectiveness of COVID-19 vaccines.\n\nThe aim of this study was to investigate the adverse effects and infection rate of vaccinated people in a community (general population app users) scenario. We used data from 627 383 individuals who received the BNT162b2 or ChAdOx1 nCoV-19 vaccines between December, 2020, and March, 2021, and reported symptoms in real-time via the COVID Symptom Study app.\n\n[14](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext)\n\n14\\.\n\nMenni, C ∙ Valdes, AM ∙ Freidin, MB ∙ et al.\n\n**Real-time tracking of self-reported symptoms to predict potential COVID-19**\n\n*Nat Med.* 2020; **26**:1037-1040\n\n[Crossref](https:\/\/doi.org\/10.1038\/s41591-020-0916-2)\n\n[Scopus (944)](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_14_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85084445397)\n\n[PubMed](https:\/\/pubmed.ncbi.nlm.nih.gov\/32393804\/)\n\n[Google Scholar](https:\/\/scholar.google.com\/scholar_lookup?doi=10.1038%2Fs41591-020-0916-2&pmid=32393804)\n\nA subset of individuals also reported receiving a PCR or lateral flow test.\n\n## Methods\n### Study design and participants\nThe COVID Symptom Study app\n\n[14](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext)\n\n14\\.\n\nMenni, C ∙ Valdes, AM ∙ Freidin, MB ∙ et al.\n\n**Real-time tracking of self-reported symptoms to predict potential COVID-19**\n\n*Nat Med.* 2020; **26**:1037-1040\n\n[Crossref](https:\/\/doi.org\/10.1038\/s41591-020-0916-2)\n\n[Scopus (944)](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_14_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85084445397)\n\n[PubMed](https:\/\/pubmed.ncbi.nlm.nih.gov\/32393804\/)\n\n[Google Scholar](https:\/\/scholar.google.com\/scholar_lookup?doi=10.1038%2Fs41591-020-0916-2&pmid=32393804)\n\nwas developed by health data company ZOE Global, with input from King's College London (London, UK), the Massachusetts General Hospital (Boston, MA, USA), Lund University (Lund, Sweden), and Uppsala University (Uppsala, Sweden). In the UK, it was launched in English on March 24, 2020. The app enables self-reported information related to SARS-CoV-2 infection to be captured. Individuals older than 18 years can sign up to the app without any restrictions. Individuals can also record information for dependents younger than 18 years. Use of the app was driven by referrals or word of mouth, the media, and eventually partnerships with charities and the Welsh and Scottish Governments.\n\n[15](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext)\n\n15\\.\n\nDrew, DA ∙ Nguyen, LH ∙ Steves, CJ ∙ et al.\n\n**Rapid implementation of mobile technology for real-time epidemiology of COVID-19**\n\n*Science.* 2020; **368**:1362-1367\n\n[Crossref](https:\/\/doi.org\/10.1126\/science.abc0473)\n\n[Scopus (266)](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_15_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85086031247)\n\n[PubMed](https:\/\/pubmed.ncbi.nlm.nih.gov\/32371477\/)\n\n[Google Scholar](https:\/\/scholar.google.com\/scholar_lookup?doi=10.1126%2Fscience.abc0473&pmid=32371477)\n\nOn first use, the app records self-reported location, age, and core health risk factors (body-mass index \\[BMI\\], smoking status, race or ethnicity, and presence of comorbidities, including cancer, diabetes, eczema, heart disease, lung disease, kidney disease, and hay fever), as well as employment status, such as being a health-care worker. With continued use, participants provide daily updates on symptoms experienced, SARS-CoV-2 test results (negative, pending, or positive), vaccines administered, and whether they are self-quarantining or seeking health care, including the level of intervention and related outcomes. Individuals without symptoms are encouraged to report through the app every day. Through direct updates to the app, new or modified questions are added in real time to capture data to test emerging hypotheses about COVID-19 symptoms and treatments. Versions 2.1.0–2.4.0 of the app were in use during the study period.\n\nParticipants were asked if they had been vaccinated for COVID-19 and, if so, to record the type of vaccine and date of administration. We included all UK app users reporting having received at least one dose of the two available vaccines ([appendix p 2](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#supplementary-material)). Users reporting vaccination were then asked daily for the following 8 days whether they experienced adverse effects, including both systemic (whole body) and local effects. Systemic solicited side-effects included headache, fatigue, chills and shiver, diarrhoea, fever, arthralgia, myalgia, and nausea; solicited local side-effects included local pain, swelling, tenderness, redness, itch, warmth, and swollen armpit glands ([appendix p 6](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#supplementary-material)). Users were also permitted to report no symptoms by leaving the box unchecked.\n\nEthical approval for use of the app for research purposes in the UK was obtained from King's College London Ethics Committee (review reference LRS-19\/20-18210), and all users provided consent for non-commercial use of their data.\n\n### Outcomes\nOur primary outcome was the proportion of app users reporting adverse effects within 8 days after vaccination and the probability of having an adverse event. Our secondary outcome was infection rates in individuals after receiving a first dose of either the BNT162b2 or ChAdOx1 nCoV-19 vaccines. We did not collect information on why individuals were tested, so not all tested individuals were necessarily experiencing COVID-19-associated symptoms at testing, and some individuals might have been routinely tested while being asymptomatic.\n\n### Statistical analysis\nWe used χ2 and Student's *t* tests to compare the demographic characteristics of individuals who received BNT162b2 versus those who received ChAdOx1 nCoV-19. We investigated the evolution of systemic and local adverse effects within 8 days from the vaccination date, computing the percentage of users experiencing side-effects after having received the vaccine. Vaccinated individuals who logged their systemic or local effects (or the absence of them) at least once within 8 days from the vaccination date were included in the adverse effects analysis ([appendix p 2](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#supplementary-material)). We estimated the ratio of the daily number of users reporting at least one adverse effect (systemic or local) after vaccination to the total number of vaccinated users logging into the app that day. The occurrence of adverse effects was studied for both BNT162b2 doses and the first ChAdOx1 nCoV-19 dose.\n\nWe compared the probability of having adverse effects between the first and second BNT162b2 doses, the first BNT162b2 and the first ChAdOx1 nCoV-19 doses, and the second BNT162b2 and the first ChAdOx1 nCoV-19 doses. As different people received different vaccines, we used Pearl's back-door adjustment\n\n[16](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext)\n\n16\\.\n\nPearl, J\n\n**Causality**\n\nCambridge University Press, Cambridge, 2009\n\n[Crossref](https:\/\/doi.org\/10.1017\/CBO9780511803161)\n\n[Scopus (618)](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_16_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-84922937176)\n\n[Google Scholar](https:\/\/scholar.google.com\/scholar_lookup?doi=10.1017%2FCBO9780511803161)\n\nto account for differences within the populations. Backdoor adjustments are used when there are both causal and non-causal paths between predictors (eg, vaccine treatment \\[*V*\\]) and an outcome. Because of the observational (non-interventional) nature of the study, the non-causal paths between outcomes and predictors that might involve age, sex, BMI, or health status need to be adjusted statistically. Backdoor adjustment methods essentially condition on these variables, cutting out the non-causal (indirect) links between a predictor and an outcome:\n\n𝑃\n\n⁡\n\n(\n\n𝑅\n\n\\|\n\n𝑑\n\n⁢\n\n𝑜\n\n⁡\n\n\\[\n\n𝑉\n\n\\]\n\n)\n\n\\=\n\n∑\n\n𝑃\n\n⁡\n\n(\n\n𝑅\n\n\\|\n\n𝑆\n\n,\n\n𝑉\n\n)\n\n⁢\n\n𝑃\n\n⁡\n\n(\n\n𝑆\n\n)\n\nwhere *R* is adverse effects, *S* is stratum, and *P*(*R \\| S,V*) is the probability of having adverse effects in a given stratum after receiving a vaccine.\n\nWe used the following strata: age (≤55 years *vs* \\>55 years), in line with stratification in the BNT162b2 and ChAdOx1 nCoV-19 phase 3 trials,\n\n[3](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext)\n\n3\\.\n\nPolack, FP ∙ Thomas, SJ ∙ Kitchin, N ∙ et al.\n\n**Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine**\n\n*N Engl J Med.* 2020; **383**:2603-2615\n\n[Crossref](https:\/\/doi.org\/10.1056\/NEJMoa2034577)\n\n[Scopus (10099)](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_3_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85098117107)\n\n[PubMed](https:\/\/pubmed.ncbi.nlm.nih.gov\/33301246\/)\n\n[Google Scholar](https:\/\/scholar.google.com\/scholar_lookup?doi=10.1056%2FNEJMoa2034577&pmid=33301246)\n\nsex, health-care worker status (binary variable), obesity (BMI \\<30 kg\/m2 *vs* ≥30 kg\/m2), and comorbidities (binary variable, with or without comorbidities). Adjusted odds ratios (ORs) were computed after Pearl's back-door adjustment was applied to the raw rates (see [appendix p 15](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#supplementary-material) for the formula). 95% CIs for ORs were obtained by bootstrapping 50 times on the vaccinated population.\n\nLogistic regressions were used for each of the specified strata to investigate whether adverse effects varied across different participant groups, and in individuals who had previously reported a positive test for COVID-19 (PCR or lateral flow positive at least 6 months before vaccination, PCR or lateral flow positive within the 6 months before vaccination, and no previously detected infection).\n\nFinally, in a subanalysis of vaccinated participants who reported having had the first dose of the BNT162b2 vaccine or one dose of the ChAdOx1 nCoV-19 vaccine and were then subsequently tested for SARS-CoV-2 infection, we investigated the change in infection rates after the first vaccine dose. We compared the outcomes of PCR or lateral flow tests in individuals who had been vaccinated with the first dose with those of unvaccinated individuals who reported having a COVID-19 test in the same week as a vaccinated app user. We computed the difference in days between when participants had the vaccine and when they were tested, and we used this metric to group users. If a person reported more than one PCR test or lateral flow result after being vaccinated, we selected the positive test, or if none were positive, the latest negative test. Since the BNT162b2 phase 3 trial showed a decrease in infections from 12 days after vaccination,\n\n[3](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext)\n\n3\\.\n\nPolack, FP ∙ Thomas, SJ ∙ Kitchin, N ∙ et al.\n\n**Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine**\n\n*N Engl J Med.* 2020; **383**:2603-2615\n\n[Crossref](https:\/\/doi.org\/10.1056\/NEJMoa2034577)\n\n[Scopus (10099)](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_3_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85098117107)\n\n[PubMed](https:\/\/pubmed.ncbi.nlm.nih.gov\/33301246\/)\n\n[Google Scholar](https:\/\/scholar.google.com\/scholar_lookup?doi=10.1056%2FNEJMoa2034577&pmid=33301246)\n\nwe analysed infection rates at 0–4, 5–11, 12–20, 21–44, and 45–59 days after vaccination. For each of the vaccines and for different timepoints from the vaccination date, we used Poisson regressions to model the rates of positive tests in vaccinated individuals compared with those in the unvaccinated population, adjusting for the number of tests. This model allowed us to control for the number of follow-up days for each group. Moreover, as there was a two-times increase in daily incidence in England followed by a decrease of a similar proportion during the data collection period,\n\n[17](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext)\n\n17\\.\n\nOffice for National Statistics\n\n**Coronavirus (COVID-19) Infection Survey**\n\n<https:\/\/www.ons.gov.uk\/peoplepopulationandcommunity\/healthandsocialcare\/conditionsanddiseases\/datasets\/coronaviruscovid19infectionsurveydata\/2021>\n\nDate: March 12, 2021\n\nDate accessed: March 16, 2021\n\n[Google Scholar](https:\/\/scholar.google.com\/scholar?q=Office+for+National+StatisticsCoronavirus+%28COVID-19%29+Infection+Surveyhttps%3A%2F%2Fwww.ons.gov.uk%2Fpeoplepopulationandcommunity%2Fhealthandsocialcare%2Fconditionsanddiseases%2Fdatasets%2Fcoronaviruscovid19infectionsurveydata%2F2021March+12%2C+2021)\n\nwe also included incidence as a covariate in the Poisson regression model, with incidence calculated as previously described.\n\n[18](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext)\n\n18\\.\n\nVarsavsky, T ∙ Graham, MS ∙ Canas, LS ∙ et al.\n\n**Detecting COVID-19 infection hotspots in England using large-scale self-reported data from a mobile application: a prospective, observational study**\n\n*Lancet Public Health.* 2021; **6**:e21-e29\n\n[Full Text](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_18_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS2468-2667%2820%2930269-3&cf=fulltext&site=lancet-site)\n\n[Full Text (PDF)](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_18_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS2468-2667%2820%2930269-3&cf=pdf&site=lancet-site)\n\n[Scopus (54)](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_18_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85099010576)\n\n[PubMed](https:\/\/pubmed.ncbi.nlm.nih.gov\/33278917\/)\n\n[Google Scholar](https:\/\/scholar.google.com\/scholar_lookup?doi=10.1016%2FS2468-2667%2820%2930269-3&pmid=33278917)\n\nWe defined the adjusted infection risk reduction (RR) as follows:\n\nR\n\nR\n\n\\=\n\nr\n\ni\n\ns\n\nk\n\nr\n\na\n\nt\n\ni\n\no\n\n𝑖\n\n,\n\n𝑛\n\n−\n\n1\n\nwhere *i* is BNT162b2 or ChAdOx1 nCoV-19 vaccine, *n* is the number of days since vaccination (0–4, 5–11, 12–20, 21–44, 45–59), and the risk ratio is the coefficient of the vaccine status variables in the Poisson regression model.\n\nWe further tested the role of covariates in risk of infection after vaccination by running stratified Poisson models (adjusted for confounders). For this analysis, we considered all app responders who were vaccinated with BNT162b2 or ChAdOx1 nCoV-19 vaccines at least 12 days before having a test for SARS-CoV-2 positivity. Due to a relatively small sample size in some of the strata, we did not differentiate between vaccine types but pooled all vaccinated contributors.\n\nData were extracted and preprocessed using ExeTera version 0.3.2,\n\n[19](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext)\n\n19\\.\n\nMurray, B ∙ Kerfoot, E ∙ Graham, MS ∙ et al.\n\n**Accessible data curation and analytics for international-scale citizen science datasets**\n\n*arXiv.* 2020;\n\npublished online Nov 2. <http:\/\/arxiv.org\/abs\/2011.00867>\n\n(preprint).\n\n[PubMed](https:\/\/pubmed.ncbi.nlm.nih.gov\/32550252\/)\n\n[Google Scholar](https:\/\/scholar.google.com\/scholar_lookup?pmid=32550252)\n\na Python library developed at King's College London, and we did statistical analysis using Python version 3.7 (pandas, NumPy, and SciPy).\n\n### Role of the funding source\nZOE Global developed the app for data collection as a not-for-profit endeavour. The funder had no role in study design, data analysis, data interpretation, or writing of the report.\n\n## Results\nBetween Dec 8, 2020, and March 10, 2021, 655 590 vaccine doses were logged in the app in the UK, corresponding to 282 103 individuals (aged 16–99 years) who reported having received the first dose of the BNT162b2 vaccine, of whom 28 207 reported having had both doses of the BNT162b2 vaccine (a median of 41 days \\[IQR 21–63\\] apart), and 345 280 individuals who reported having had the first dose of ChAdOx1 nCoV-19. Participants joined the COVID Symptom Study app a mean of 288 days (SD 96) before being vaccinated. Users started logging adverse effects reports 0·79 days (SD 1·2) after they had the vaccine. 1 607 620 users were active in the app during the study period (logged at least an assessment since Dec 8), which represents 2·4% of the UK population. The mean age of app users was 50·6 years (SD 19·2), and 77 683 (4·8%) of them were health-care workers.\n\nUsers who reported receiving a BNT162b2 vaccine were slightly younger, had more comorbidities, and were more frequently female than users who reported receiving a ChAdOx1 nCoV-19 inoculation ([table](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#tbl1)). Moreover, health-care workers were more likely to receive a BNT162b2 vaccine than ChAdOx1 nCoV-19 ([appendix p 8](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#supplementary-material)). The age distribution of the included individuals is presented in the [appendix (p 3)](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#supplementary-material).\n\n|   |   |   |   |   |\n|---|---|---|---|---|\n|   |   | **BNT162b2** | **ChAdOx1 nCoV-19** |   |\n|   |   | First dose (N=282 103) | Second dose (N=28 207) | First dose (N=345 280) |\n| Sex[\\*](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#tbl1fn1) |   |   |   |   |\n|   | Female | 173 866 (61·6%) | 19 640 (69·6%) | 199 269 (57·7%) |\n|   | Male | 108 237 (38·4%) | 8567 (30·4%) | 146 011 (42·3%) |\n| Age, years[\\*](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#tbl1fn1)[†](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#tbl1fn2) | 62·0 (14·3); 64 (54–72) | 61·0 (17·3); 59 (49–76) | 63·3 (11·5); 65 (59–71) |   |\n| Body-mass index, kg\/m2[‡](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#tbl1fn3) | 26·8 (5·5) | 26·5 (5·3) | 26·8 (5·3) |   |\n| Health-care workers[\\*](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#tbl1fn1) | 31 996 (11·3%) | 8828 (31·3%) | 9746 (2·8%) |   |\n| Comorbidities[\\*](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#tbl1fn1) | 77 433 (27·4%) | 7617 (27·0%) | 88 453 (25·6%) |   |\n| Previous COVID-19[\\*](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#tbl1fn1) | 14 369 (5·1%) | 2251 (8·0%) | 14 231 (4·1%) |   |\n| Systemic side-effects |   |   |   |   |\n|   | Any | 38 155 (13·5%) | 6216 (22·0%) | 116 473 (33·7%) |\n|   | Headache | 21 910 (7·8%) | 3731 (13·2%) | 78 734 (22·8%) |\n|   | Fatigue | 23 674 (8·4%) | 4064 (14·4%) | 72 924 (21·1%) |\n|   | Chills and shiver | 7166 (2·5%) | 1812 (6·4%) | 50 761 (14·7%) |\n|   | Diarrhoea | 3885 (1·4%) | 416 (1·5%) | 7546 (2·2%) |\n|   | Fever | 4236 (1·5%) | 1076 (3·8%) | 28 268 (8·2%) |\n|   | Arthralgia | 9021 (3·2%) | 1978 (7·0%) | 39 648 (11·5%) |\n|   | Myalgia | 6479 (2·3%) | 1415 (5·0%) | 24 274 (7·0%) |\n|   | Nausea | 5926 (2·1%) | 981 (3·5%) | 19 509 (5·7%) |\n| Local side-effects[§](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#tbl1fn4) |   |   |   |   |\n|   | Any | 150 023 (71·9%) | 9025 (68·5%) | 104 282 (58·7%) |\n|   | Pain | 61 016 (29·2%) | 4515 (34·3%) | 33 939 (19·1%) |\n|   | Swelling | 13 264 (6·4%) | 1285 (9·8%) | 9769 (5·5%) |\n|   | Tenderness | 119 431 (57·2%) | 6705 (50·9%) | 87 609 (49·3%) |\n|   | Itch | 6242 (3·0%) | 840 (6·4%) | 6934 (3·9%) |\n|   | Swollen armpit glands | 2278 (1·1%) | 549 (4·2%) | 1994 (1·1%) |\n|   | Redness | 7891 (3·8%) | 953 (7·2%) | 7431 (4·2%) |\n|   | Warmth | 14 024 (6·7%) | 1245 (9·4%) | 14 033 (7·9%) |\n|   | Bruising | 1872 (0·9%) | 64 (0·5%) | 4269 (2·4%) |\n| Allergic reactions |   |   |   |   |\n|   | Rash | 682 (0·2%) | 103 (0·4%) | 1432 (0·4%) |\n|   | Skin burning | 2075 (0·7%) | 324 (1·1%) | 5940 (1·7%) |\n|   | Red welts on face and lips | 469 (0·2%) | 59 (0·2%) | 846 (0·2%) |\n\nTable\n\nDemographic characteristics of the study population\n\nData are n (%), unless otherwise indicated.\n\n\\*\n\np\\<0·05 for the difference between the first dose of BNT162b2 and the first dose of ChAdOx1 nCoV-19 (Student's *t* test for continuous variables and χ2 test for categorical variables).\n\n†\n\nData are mean (SD); median (IQR).\n\n‡\n\nData are mean (SD).\n\n§\n\nDenominators are 208 767 for the first BNT162b2 dose, 13 179 for the second BNT162b2 dose, and 177 655 for the first ChAdOx1 nCoV-19 dose.\n\n- [Open table in a new tab](https:\/\/www.thelancet.com\/action\/showFullTableHTML?isHtml=true&tableId=tbl1&pii=S1473-3099%2821%2900224-3)\n\nAmong vaccinated app users, 159 101 (25·4%) of 627 383 indicated having one or more systemic adverse effect, and 257 209 (66·2%) of 388 430 reported one or more local adverse effect ([table](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#tbl1)). The most commonly reported systemic side-effects were fatigue and headache overall ([table](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#tbl1)) and by strata ([appendix p 9](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#supplementary-material)). These were most frequently reported within the first 24 h after vaccination and lasted a mean of 1·01 days (SD 0·1; [figure 1](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#fig1)). Tenderness and local pain around the injection site were the most frequently reported local effects ([table](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#tbl1)), occurring most often on the day after injection and lasting a mean of 1·02 days (SD 0·15; [figure 1](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#fig1)). Other side-effects, including allergic skin reactions such as skin burning, rashes, and red welts on the lips and face, were reported by 10 860 (1·7%) of 627 383 users across both types of vaccine ([table](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#tbl1); [appendix p 9](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#supplementary-material)). In an exploratory analysis, we assessed the association between symptom reporting and socioeconomic status measured as index of multiple deprivation,\n\n[20](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext)\n\n20\\.\n\nMinistry of Housing, Communities, and Local Government\n\n**English indices of deprivation 2019**\n\n<https:\/\/www.gov.uk\/government\/statistics\/english-indices-of-deprivation-2019>\n\nDate: Sept 26, 2019\n\nDate accessed: February 12, 2021\n\n[Google Scholar](https:\/\/scholar.google.com\/scholar?q=Ministry+of+Housing%2C+Communities%2C+and+Local+GovernmentEnglish+indices+of+deprivation+2019https%3A%2F%2Fwww.gov.uk%2Fgovernment%2Fstatistics%2Fenglish-indices-of-deprivation-2019Sept+26%2C+2019)\n\nand we found a modest association (*r*\\=0·021 \\[95% CI 0·019–0·025\\]), corresponding to 0·04% of the variance in symptoms reporting.\n\n[![](https:\/\/www.thelancet.com\/cms\/10.1016\/S1473-3099\\(21\\)00224-3\/asset\/7936827d-8890-464f-9165-30c98891fdfa\/main.assets\/gr1.jpg)](https:\/\/www.thelancet.com\/cms\/10.1016\/S1473-3099\\(21\\)00224-3\/asset\/b3402ef0-4ec3-437b-85c1-4ac3705e6fe3\/main.assets\/gr1_lrg.jpg \"View full size image in a new tab\")\n\nFigure 1 Proportion of participants self-reporting adverse effects to the COVID Symptom Study app within 8 days after vaccination\n\nShow full caption\n\nFigure viewer\n\nThe top row shows systemic effects and the bottom row shows local effects within 8 days after receipt of the first dose (A, D) or second dose (B, E) of the BNT162b2 vaccine or the first dose of the ChAdOx1 nCoV-19 vaccine (C, F). Shading indicates 95% CIs.\n\nIn the 28 207 individuals who reported having two BNT162b2 doses, 3325 (11·7%) reported at least one systemic effect after the first dose compared with 6216 (22·0%) after the second dose (p\\<0·0001; [figure 2](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#fig2)). When comparing systemic effects after one dose of each vaccine, reactogenicity was significantly higher in individuals who had one dose of the ChAdOx1 nCoV-19 vaccine than in those who had one dose of the BNT162b2 vaccine (116 473 \\[33·7%\\] of 345 280 compared with 38 155 \\[13·5%\\] of 282 103; adjusted p\\<0·0001).\n\n[![](https:\/\/www.thelancet.com\/cms\/10.1016\/S1473-3099\\(21\\)00224-3\/asset\/9e20a8bb-e4f1-4d2e-957e-7b1f55c55e39\/main.assets\/gr2.jpg)](https:\/\/www.thelancet.com\/cms\/10.1016\/S1473-3099\\(21\\)00224-3\/asset\/6f6277f8-7df4-467b-b39b-9cdb977504c1\/main.assets\/gr2_lrg.jpg \"View full size image in a new tab\")\n\nFigure 2 Comparison of adverse effects self-reported to the COVID Symptom Study app between vaccine types and doses\n\nShow full caption\n\nFigure viewer\n\nORs for comparisons of the first or second doses of BNT162b2 versus the first dose of ChAdOx1 nCoV-19 were adjusted using Pearl's back-door method.\n\n[16](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext)\n\n16\\.\n\nPearl, J\n\n**Causality**\n\nCambridge University Press, Cambridge, 2009\n\n[Crossref](https:\/\/doi.org\/10.1017\/CBO9780511803161)\n\n[Scopus (618)](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_16_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-84922937176)\n\n[Google Scholar](https:\/\/scholar.google.com\/scholar_lookup?doi=10.1017%2FCBO9780511803161)\n\nOR=odds ratio.\n\nBy contrast, local effects were less commonly reported after the second dose than after the first dose of BNT162b2 (9025 \\[68·5%\\] of 13 179 *vs* 150 023 \\[71·9%\\] of 208 767; p\\<0·0001). Moreover, local effects were less commonly reported after the first ChAdOx1 nCoV-19 injection (104 282 \\[58·7%\\] of 177 655) than after the first BNT162b2 injection (adjusted p\\<0·0001; [figure 2](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#fig2)).\n\nWhen comparing the second BNT162b2 dose with the first ChAdOx1 nCoV-19 dose, we found that systemic effects occurred more frequently after the first ChAdOx1 nCoV-19 dose than after the second BNT162b2 dose (adjusted p\\<0·0001; [figure 2](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#fig2)), whereas local effects were less likely to appear after the first ChAdOx1 nCoV-19 injection than after the second BNT162b2 dose (adjusted p\\<0·0001; [figure 2](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#fig2)).\n\nWe then tested whether adverse effects varied across individuals' characteristics, such as age and BMI groups, sex, and health status. The proportion of participants who reported at least one systemic effect after the first dose was significantly higher among people aged 55 years or younger than among those older than 55 years for both vaccines. After the first dose of BNT162b2, 16 733 (20·7%) of 80 879 people aged 55 years or younger reported at least one systemic effect compared with 21 422 (10·6%) of 201 224 people older than 55 years (OR 2·19 \\[95% CI 2·14–2·24\\]; p\\<0·0001). For ChAdOx1 nCoV-19, 30 487 (46·9%) of 65 034 people aged 55 years or younger reported at least one systemic effect after the first dose compared with 85 986 (30·7%) of 280 243 older than 55 years (1·99 \\[1·96–2·03\\]; p\\<0·0001). Women were more likely to report adverse effects than men (28 140 \\[16·2%\\] of 173 866 *vs* 10 015 \\[9·3%\\] of 108 237 after the first dose of BNT162b2, OR 1·89 \\[95% CI 1·85–1·94\\], p\\<0·0001; 78 222 \\[39·3%\\] of 199 269 *vs* 38 251 \\[26·2%\\] of 146 011 after the first dose of ChAdOx1 nCoV-19, 1·82 \\[1·79–1·85\\], p\\<0·0001). Although there were some differences between strata of BMI and co-morbidities, there was no clear trend across vaccines and doses ([figure 3](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#fig3)).\n\n[![](https:\/\/www.thelancet.com\/cms\/10.1016\/S1473-3099\\(21\\)00224-3\/asset\/6a3373a7-6236-4245-b406-f3eadf207a33\/main.assets\/gr3.jpg)](https:\/\/www.thelancet.com\/cms\/10.1016\/S1473-3099\\(21\\)00224-3\/asset\/6d50aaf8-8e12-4c05-b5c0-e80f7b10b8b5\/main.assets\/gr3_lrg.jpg \"View full size image in a new tab\")\n\nFigure 3 Adverse effects self-reported to the COVID Symptom Study app after COVID-19 vaccination, stratified by sex, age, BMI, health status, and previous SARS-CoV-2 test status\n\nShow full caption\n\nFigure viewer\n\nProportions with systemic adverse effects (A, C, E) and local adverse effects (B, D, F) are shown. Error bars represent 95% CIs. Numbers in each strata are reported in the [appendix (pp 13–14](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#supplementary-material)). BMI=body-mass index. \\*p\\<0·01. †p\\<0·05.\n\nWe observed the same trend for local effects as for systemic effects, whereby app users aged 55 years or younger reported more local side-effects than participants older than 55 years ([figure 3](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#fig3)), and women were more likely to report local side-effects than men ([figure 3](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#fig3); [appendix p 11](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#supplementary-material)). Similar levels of side-effects were seen regardless of the levels of completeness of reporting by app users ([appendix p 12](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#supplementary-material)).\n\nGiven preliminary evidence from small studies\n\n[21–23](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext)\n\n21\\.\n\nSaadat, S ∙ Rikhtegaran-Tehrani, Z ∙ Logue, J ∙ et al.\n\n**Single dose vaccination in healthcare workers previously infected with SARS-CoV-2**\n\n*medRxiv.* 2021;\n\npublished online Feb 1. <https:\/\/doi.org\/10.1101\/2021.01.30.21250843>\n\n(preprint).\n\n[Google Scholar](https:\/\/scholar.google.com\/scholar?q=SSaadatZRikhtegaran-TehraniJLogueSingle+dose+vaccination+in+healthcare+workers+previously+infected+with+SARS-CoV-2medRxiv2021published+online+Feb+1.https%3A%2F%2Fdoi.org%2F10.1101%2F2021.01.30.21250843%28preprint%29.)\n\n22\\.\n\nKrammer, F ∙ Srivastava, K ∙ Simon, V\n\n**Robust spike antibody responses and increased reactogenicity in seropositive individuals after a single dose of SARS-CoV-2 mRNA vaccine**\n\n*medRxiv.* 2021;\n\npublished online Feb 1. <https:\/\/doi.org\/10.1101\/2021.01.29.21250653>\n\n(preprint).\n\n[Google Scholar](https:\/\/scholar.google.com\/scholar?q=FKrammerKSrivastavaVSimonRobust+spike+antibody+responses+and+increased+reactogenicity+in+seropositive+individuals+after+a+single+dose+of+SARS-CoV-2+mRNA+vaccinemedRxiv2021published+online+Feb+1.https%3A%2F%2Fdoi.org%2F10.1101%2F2021.01.29.21250653%28preprint%29.)\n\n23\\.\n\nWise, J\n\n**COVID-19: people who have had infection might only need one dose of mRNA vaccine**\n\n*BMJ.* 2021; **372**:n308\n\n[Crossref](https:\/\/doi.org\/10.1136\/bmj.n308)\n\n[Scopus (43)](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_23_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85101276843)\n\n[PubMed](https:\/\/pubmed.ncbi.nlm.nih.gov\/33531333\/)\n\n[Google Scholar](https:\/\/scholar.google.com\/scholar_lookup?doi=10.1136%2Fbmj.n308&pmid=33531333)\n\nsuggesting that reactogenicity is higher among individuals previously infected with SARS-CoV-2, we investigated the extent to which previous SARS-CoV-2 infection (based on self-reported previous positive PCR or lateral flow result) was associated with reports of adverse effects. Individuals vaccinated with a single dose of BNT162b2 were more likely to report systemic effects if they had a previous SARS-CoV-2 positive test than were those without known past infection (5148 \\[35·8%\\] of 14 369 *vs* 33 007 \\[12·3%\\] of 267 734; OR 3·97 \\[95% CI 3·83–4·12\\], p\\<0·0001). A similar effect was seen for ChAdOx1 nCoV-19 first dose inoculation (7551 \\[53·1%\\] of 14 231 with past infection *vs* 108 922 \\[32·9%\\] of 331 049 without past infection; 2·31 \\[2·23–2·38\\], p\\<0·0001; [figure 3](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#fig3)) and BNT162b2 second dose inoculation (859 \\[38·2%\\] of 2251 *vs* 5357 \\[20·6%\\] of 25 956; 2·37 \\[2·17–2·60\\], p\\<0·0001). Local effects were similarly higher in individuals previously infected than in those without known past infection for both vaccines ([figure 3](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#fig3)). No consistent difference in occurrence of systemic or local adverse effects was observed between individuals who reported a positive test result within the past 6 months and those who reported they received a positive test result at least 6 months ago ([figure 3](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#fig3)).\n\nWe also investigated infection rates after the first vaccine dose in a subset of 67 293 app users who received BNT162b2 and 36 329 who received ChAdOx1 nCoV-19 in the study period and logged at least one PCR or lateral flow test after vaccination. We compared the test results of this population with those of 464 356 unvaccinated app users who had a PCR or lateral flow test result between Jan 4, and March 10, 2021 ([appendix pp 4, 8](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#supplementary-material)). 3106 of 103 622 vaccinated individuals and 50 340 of 464 356 unvaccinated controls tested positive for SARS-CoV-2 infection. As UK guidelines stipulate that individuals need to be free of symptoms to be vaccinated, we found vaccinated participants to have a lower infection risk at the time of the vaccination than unvaccinated participants (RR for BNT162b2 −64% \\[95% CI −69 to −59\\]; RR for ChAdOx1 nCoV-19 −52% \\[95% CI −65 to −34\\]). We observed that 5–11 days after vaccination, the infection rates in the vaccinated group were only slightly below those of the unvaccinated group ([figure 4](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#fig4)), whereas 12–20 days after vaccination, infection risk in the vaccinated group was significantly lower than in the unvaccinated group (RR for BNT162b2 −58% \\[95% CI −62 to −54\\]; RR for ChAdOx1 nCoV-19 −39% \\[95% CI −53 to −21\\]), after adjusting for population differences in the vaccinated groups using Poisson regressions. We observed a further reduction in infection risk after one dose of the BNT162b2 vaccine when compared with unvaccinated controls at 21–44 days after vaccination (RR −69% \\[95% CI −72 to −66\\]) and at 45–59 days after vaccination (−72% \\[–79 to −63\\]; [figure 4](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#fig4)). The RR after one dose of ChAdOx1 nCoV-19 compared with unvaccinated controls was −60% (95% CI −68 to −49) at 21–44 days after vaccination.\n\n[![](https:\/\/www.thelancet.com\/cms\/10.1016\/S1473-3099\\(21\\)00224-3\/asset\/5655fb5d-b246-4163-823f-026f58635080\/main.assets\/gr4.jpg)](https:\/\/www.thelancet.com\/cms\/10.1016\/S1473-3099\\(21\\)00224-3\/asset\/b46338e4-7cd4-41fc-8bc7-fe477a858f32\/main.assets\/gr4_lrg.jpg \"View full size image in a new tab\")\n\nFigure 4 Infection risk reduction after the first dose in app users who have been vaccinated and subsequently tested, as a function of days since vac\n\nShow full caption\n\nFigure viewer\n\nThe bar chart represents the risk reduction for infection of the vaccinated groups (those who logged at least one PCR or lateral flow test result after vaccination) compared with the unvaccinated group, by vaccine type and days since vaccination. The black lines show 95% CIs.\n\nFinally, we tested the role of covariates in risk of infection after vaccination. We observed a larger risk reduction in vaccinated participants aged 55 years or younger (RR −70% \\[95% CI −72 to −68) than in those older than 55 years (−61% \\[–64 to −57\\]). Similarly, individuals without comorbidities had a larger risk reduction (−69% \\[–71 to −68\\]) than those with at least one comorbidity (−54% \\[–59 to −48\\]). Borderline differences were observed for BMI (RR for BMI \\<30 kg\/m2 −69% \\[95% CI −71 to −67\\]; RR for BMI ≥30 kg\/m2 −63% \\[−67 to −59\\]) and sex (RR for female −69% \\[95% CI −71 to −67\\]; RR for male −61% \\[–66 to −57\\]; [appendix p 5](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#supplementary-material)).\n\n## Discussion\nIn this large-scale, community-based study in the UK, we have investigated adverse effects and infection rates following administration of the two COVID-19 vaccines that are in use in the UK. The overall mean age of the vaccinated app users was higher than that of the general population (40·3 years)\n\n[24](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext)\n\n24\\.\n\nOffice for National Statistics\n\n**Population estimates for the UK, England and Wales, Scotland and Northern Ireland, provisional: mid-2019**\n\n<https:\/\/www.ons.gov.uk\/peoplepopulationandcommunity\/populationandmigration\/populationestimates\/bulletins\/annualmidyearpopulationestimates\/mid2019>\n\nDate: May 6, 2020\n\nDate accessed: March 16, 2021\n\n[Google Scholar](https:\/\/scholar.google.com\/scholar?q=Office+for+National+StatisticsPopulation+estimates+for+the+UK%2C+England+and+Wales%2C+Scotland+and+Northern+Ireland%2C+provisional%3A+mid-2019https%3A%2F%2Fwww.ons.gov.uk%2Fpeoplepopulationandcommunity%2Fpopulationandmigration%2Fpopulationestimates%2Fbulletins%2Fannualmidyearpopulationestimates%2Fmid2019May+6%2C+2020)\n\nyet was lower than those of the samples within other UK COVID-19 effectiveness studies,\n\n[11,12](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext)\n\n11\\.\n\nLopez Bernal, J ∙ Andrews, N ∙ Gower, C ∙ et al.\n\n**Early effectiveness of COVID-19 vaccination with BNT162b2 mRNA vaccine and ChAdOx1 adenovirus vector vaccine on symptomatic disease, hospitalisations and mortality in older adults in England**\n\n*medRxiv.* 2021;\n\npublished online March 2. <https:\/\/doi.org\/10.1101\/2021.03.01.21252652>\n\n(preprint).\n\n[Google Scholar](https:\/\/scholar.google.com\/scholar?q=JLopez+BernalNAndrewsCGowerEarly+effectiveness+of+COVID-19+vaccination+with+BNT162b2+mRNA+vaccine+and+ChAdOx1+adenovirus+vector+vaccine+on+symptomatic+disease%2C+hospitalisations+and+mortality+in+older+adults+in+EnglandmedRxiv2021published+online+March+2.https%3A%2F%2Fdoi.org%2F10.1101%2F2021.03.01.21252652%28preprint%29.)\n\n12\\.\n\nVasileiou, E ∙ Simpson, CR ∙ Shi, T ∙ et al.\n\n**Interim findings from first-dose mass COVID-19 vaccination roll-out and COVID-19 hospital admissions in Scotland: a national prospective cohort study**\n\n*Lancet.* 2021;\n\npublished online April 23. <https:\/\/doi.org\/10.1016\/S0140-6736(21)00677-2>\n\n[Full Text](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_12_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS0140-6736%2821%2900677-2&cf=fulltext&site=lancet-site)\n\n[Full Text (PDF)](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_12_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS0140-6736%2821%2900677-2&cf=pdf&site=lancet-site)\n\n[Scopus (391)](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_12_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85104923342)\n\n[PubMed](https:\/\/pubmed.ncbi.nlm.nih.gov\/33901420\/)\n\n[Google Scholar](https:\/\/scholar.google.com\/scholar_lookup?doi=10.1016%2FS0140-6736%2821%2900677-2&pmid=33901420)\n\nlargely because of the presence of a small proportion of health-care workers among the participants of this study. However, our study population was considerably older than the study populations of the phase 3 trials.\n\n[3,6,7](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext)\n\n3\\.\n\nPolack, FP ∙ Thomas, SJ ∙ Kitchin, N ∙ et al.\n\n**Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine**\n\n*N Engl J Med.* 2020; **383**:2603-2615\n\n[Crossref](https:\/\/doi.org\/10.1056\/NEJMoa2034577)\n\n[Scopus (10099)](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_3_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85098117107)\n\n[PubMed](https:\/\/pubmed.ncbi.nlm.nih.gov\/33301246\/)\n\n[Google Scholar](https:\/\/scholar.google.com\/scholar_lookup?doi=10.1056%2FNEJMoa2034577&pmid=33301246)\n\n6\\.\n\nVoysey, M ∙ Clemens, SAC ∙ Madhi, SA ∙ et al.\n\n**Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK**\n\n*Lancet.* 2021; **397**:99-111\n\n[Full Text](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_6_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS0140-6736%2820%2932661-1&cf=fulltext&site=lancet-site)\n\n[Full Text (PDF)](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_6_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS0140-6736%2820%2932661-1&cf=pdf&site=lancet-site)\n\n[Scopus (3425)](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_6_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85097463811)\n\n[PubMed](https:\/\/pubmed.ncbi.nlm.nih.gov\/33306989\/)\n\n[Google Scholar](https:\/\/scholar.google.com\/scholar_lookup?doi=10.1016%2FS0140-6736%2820%2932661-1&pmid=33306989)\n\n7\\.\n\nRamasamy, MN ∙ Minassian, AM ∙ Ewer, KJ ∙ et al.\n\n**Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2\/3 trial**\n\n*Lancet.* 2021; **396**:1979-1993\n\n[Full Text](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_7_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS0140-6736%2820%2932466-1&cf=fulltext&site=lancet-site)\n\n[Full Text (PDF)](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_7_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS0140-6736%2820%2932466-1&cf=pdf&site=lancet-site)\n\n[Scopus (1091)](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_7_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85097243389)\n\n[PubMed](https:\/\/pubmed.ncbi.nlm.nih.gov\/33220855\/)\n\n[Google Scholar](https:\/\/scholar.google.com\/scholar_lookup?doi=10.1016%2FS0140-6736%2820%2932466-1&pmid=33220855)\n\nWe found that systemic adverse effects, including headache and fatigue, affected fewer than one in four people and were less common in the community than expected from clinical trials. For example, in phase 3 clinical trials of the BNT162b2 vaccine,\n\n[3](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext)\n\n3\\.\n\nPolack, FP ∙ Thomas, SJ ∙ Kitchin, N ∙ et al.\n\n**Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine**\n\n*N Engl J Med.* 2020; **383**:2603-2615\n\n[Crossref](https:\/\/doi.org\/10.1056\/NEJMoa2034577)\n\n[Scopus (10099)](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_3_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85098117107)\n\n[PubMed](https:\/\/pubmed.ncbi.nlm.nih.gov\/33301246\/)\n\n[Google Scholar](https:\/\/scholar.google.com\/scholar_lookup?doi=10.1056%2FNEJMoa2034577&pmid=33301246)\n\nthe most common events after the first dose were injection-site pain (71–83%), fatigue (34–47%), and headache (25–42%). However, in our community analysis, less than 30% of users complained of injection-site pain and less than 25% of fatigue and headache after the first dose. Although side-effects were significantly more prevalent in women than in men, in people aged 55 years or younger than in those older than 55 years, and after the second than after the first dose, they occurred at much lower frequencies than expected from the published literature. For instance, whereas 51–59% of participants reported fatigue after the second BNT162b2 dose in the phase 3 trial of that vaccine,\n\n[3](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext)\n\n3\\.\n\nPolack, FP ∙ Thomas, SJ ∙ Kitchin, N ∙ et al.\n\n**Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine**\n\n*N Engl J Med.* 2020; **383**:2603-2615\n\n[Crossref](https:\/\/doi.org\/10.1056\/NEJMoa2034577)\n\n[Scopus (10099)](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_3_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85098117107)\n\n[PubMed](https:\/\/pubmed.ncbi.nlm.nih.gov\/33301246\/)\n\n[Google Scholar](https:\/\/scholar.google.com\/scholar_lookup?doi=10.1056%2FNEJMoa2034577&pmid=33301246)\n\nfatigue was reported by less than 15% of participants after the second dose in our study. Additionally, our data provide evidence from the community to support early reports of higher frequency of side-effects in younger than in older individuals.\n\n[3,7](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext)\n\n3\\.\n\nPolack, FP ∙ Thomas, SJ ∙ Kitchin, N ∙ et al.\n\n**Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine**\n\n*N Engl J Med.* 2020; **383**:2603-2615\n\n[Crossref](https:\/\/doi.org\/10.1056\/NEJMoa2034577)\n\n[Scopus (10099)](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_3_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85098117107)\n\n[PubMed](https:\/\/pubmed.ncbi.nlm.nih.gov\/33301246\/)\n\n[Google Scholar](https:\/\/scholar.google.com\/scholar_lookup?doi=10.1056%2FNEJMoa2034577&pmid=33301246)\n\n7\\.\n\nRamasamy, MN ∙ Minassian, AM ∙ Ewer, KJ ∙ et al.\n\n**Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2\/3 trial**\n\n*Lancet.* 2021; **396**:1979-1993\n\n[Full Text](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_7_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS0140-6736%2820%2932466-1&cf=fulltext&site=lancet-site)\n\n[Full Text (PDF)](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_7_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS0140-6736%2820%2932466-1&cf=pdf&site=lancet-site)\n\n[Scopus (1091)](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_7_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85097243389)\n\n[PubMed](https:\/\/pubmed.ncbi.nlm.nih.gov\/33220855\/)\n\n[Google Scholar](https:\/\/scholar.google.com\/scholar_lookup?doi=10.1016%2FS0140-6736%2820%2932466-1&pmid=33220855)\n\nSimilarly, rates of side-effects following the ChAdOx1 nCoV-19 vaccine were lower than expected.\n\n[7](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext)\n\n7\\.\n\nRamasamy, MN ∙ Minassian, AM ∙ Ewer, KJ ∙ et al.\n\n**Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2\/3 trial**\n\n*Lancet.* 2021; **396**:1979-1993\n\n[Full Text](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_7_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS0140-6736%2820%2932466-1&cf=fulltext&site=lancet-site)\n\n[Full Text (PDF)](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_7_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS0140-6736%2820%2932466-1&cf=pdf&site=lancet-site)\n\n[Scopus (1091)](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_7_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85097243389)\n\n[PubMed](https:\/\/pubmed.ncbi.nlm.nih.gov\/33220855\/)\n\n[Google Scholar](https:\/\/scholar.google.com\/scholar_lookup?doi=10.1016%2FS0140-6736%2820%2932466-1&pmid=33220855)\n\nThe phase 2–3 trial of the ChAdOx1 nCoV-19 vaccine\n\n[7](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext)\n\n7\\.\n\nRamasamy, MN ∙ Minassian, AM ∙ Ewer, KJ ∙ et al.\n\n**Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2\/3 trial**\n\n*Lancet.* 2021; **396**:1979-1993\n\n[Full Text](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_7_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS0140-6736%2820%2932466-1&cf=fulltext&site=lancet-site)\n\n[Full Text (PDF)](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_7_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS0140-6736%2820%2932466-1&cf=pdf&site=lancet-site)\n\n[Scopus (1091)](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_7_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85097243389)\n\n[PubMed](https:\/\/pubmed.ncbi.nlm.nih.gov\/33220855\/)\n\n[Google Scholar](https:\/\/scholar.google.com\/scholar_lookup?doi=10.1016%2FS0140-6736%2820%2932466-1&pmid=33220855)\n\nreported systemic adverse effects in 88% of participants aged 18–55 years who received the first injection, whereas we found a lower rate of 33·7% after the first dose in the overall sample and 46·9% in individuals aged 18–55 years (data not shown). Individuals vaccinated with the ChAdOx1 nCoV-19 vaccine were more likely to experience systemic side-effects than those who had been given the BNT162b2 vaccine, but in our study 89% of respondents who logged at least one systemic effect after the ChAdOx1 nCoV-19 vaccine did not report any systemic effects after 3 days, and 98·3% did not report any after 1 week.\n\nIndividuals with evidence of past SARS-CoV-2 infection were also more likely to have adverse effects than those without evidence of past infection with both vaccines. It is possible, although it remains to be tested, that this increased reactogenicity relates to increased immunogenicity. It has been shown that vaccines have increased immunogenicity in individuals with past infection and these people have higher antibody titres than those without previous infection.\n\n[22,23,25](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext)\n\n22\\.\n\nKrammer, F ∙ Srivastava, K ∙ Simon, V\n\n**Robust spike antibody responses and increased reactogenicity in seropositive individuals after a single dose of SARS-CoV-2 mRNA vaccine**\n\n*medRxiv.* 2021;\n\npublished online Feb 1. <https:\/\/doi.org\/10.1101\/2021.01.29.21250653>\n\n(preprint).\n\n[Google Scholar](https:\/\/scholar.google.com\/scholar?q=FKrammerKSrivastavaVSimonRobust+spike+antibody+responses+and+increased+reactogenicity+in+seropositive+individuals+after+a+single+dose+of+SARS-CoV-2+mRNA+vaccinemedRxiv2021published+online+Feb+1.https%3A%2F%2Fdoi.org%2F10.1101%2F2021.01.29.21250653%28preprint%29.)\n\n23\\.\n\nWise, J\n\n**COVID-19: people who have had infection might only need one dose of mRNA vaccine**\n\n*BMJ.* 2021; **372**:n308\n\n[Crossref](https:\/\/doi.org\/10.1136\/bmj.n308)\n\n[Scopus (43)](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_23_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85101276843)\n\n[PubMed](https:\/\/pubmed.ncbi.nlm.nih.gov\/33531333\/)\n\n[Google Scholar](https:\/\/scholar.google.com\/scholar_lookup?doi=10.1136%2Fbmj.n308&pmid=33531333)\n\n25\\.\n\nManisty, C ∙ Otter, AD ∙ Treibel, TA ∙ et al.\n\n**Antibody response to first BNT162b2 dose in previously SARS-CoV-2-infected individuals**\n\n*Lancet.* 2021; **397**:1057-1058\n\n[Full Text](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_25_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS0140-6736%2821%2900501-8&cf=fulltext&site=lancet-site)\n\n[Full Text (PDF)](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_25_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS0140-6736%2821%2900501-8&cf=pdf&site=lancet-site)\n\n[Scopus (292)](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_25_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85102625202)\n\n[PubMed](https:\/\/pubmed.ncbi.nlm.nih.gov\/33640038\/)\n\n[Google Scholar](https:\/\/scholar.google.com\/scholar_lookup?doi=10.1016%2FS0140-6736%2821%2900501-8&pmid=33640038)\n\nWe observed an infection risk reduction at 21–44 days after vaccination in all vaccinated users compared with unvaccinated controls (RR was −69% \\[95% CI −72 to −66\\] for BNT162b2 and −60% \\[–68 to −49\\] for ChAdOx1 nCoV-19). The reduction of infection was lower in individuals older than 55 years than those aged 55 years or younger, in those with one or more comorbidities than in those without comorbidities, and in individuals with a BMI of 30 kg\/m2 or higher than in those with a BMI of less than 30 kg\/m2 ([appendix p 5](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#supplementary-material)). A preprint based on data from Israel suggested that a single dose of BNT162b2 might not provide enough protection;\n\n[26](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext)\n\n26\\.\n\nChodick, G ∙ Tene, L ∙ Patalon, T ∙ et al.\n\n**The effectiveness of the first dose of BNT162b2 vaccine in reducing SARS-CoV-2 infection 13–24 days after immunization: real-world evidence**\n\n*medRxiv.* 2021;\n\npublished online Jan 29. <https:\/\/doi.org\/10.1101\/2021.01.27.21250612>\n\n(preprint).\n\n[Google Scholar](https:\/\/scholar.google.com\/scholar?q=GChodickLTeneTPatalonThe+effectiveness+of+the+first+dose+of+BNT162b2+vaccine+in+reducing+SARS-CoV-2+infection+13%E2%80%9324+days+after+immunization%3A+real-world+evidencemedRxiv2021published+online+Jan+29.https%3A%2F%2Fdoi.org%2F10.1101%2F2021.01.27.21250612%28preprint%29.)\n\nhowever, a re-analysis of the same dataset indicated that after 14 days the effectiveness of a single dose of vaccine was about 90%.\n\n[5](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext)\n\n5\\.\n\nHunter, PR ∙ Brainard, J\n\n**Estimating the effectiveness of the Pfizer COVID-19 BNT162b2 vaccine after a single dose. A reanalysis of a study of “real-world” vaccination outcomes from Israel**\n\n*medRxiv.* 2021;\n\npublished online Feb 3. <https:\/\/doi.org\/10.1101\/2021.02.01.21250957>\n\n(preprint).\n\n[Google Scholar](https:\/\/scholar.google.com\/scholar?q=PRHunterJBrainardEstimating+the+effectiveness+of+the+Pfizer+COVID-19+BNT162b2+vaccine+after+a+single+dose.+A+reanalysis+of+a+study+of+%E2%80%9Creal-world%E2%80%9D+vaccination+outcomes+from+IsraelmedRxiv2021published+online+Feb+3.https%3A%2F%2Fdoi.org%2F10.1101%2F2021.02.01.21250957%28preprint%29.)\n\nAlthough our data, due to their observational nature, does not allow us to comment directly on effectiveness, the observed decrease of infection over time seems to be in line with efficacy reported in the BNT162b2 phase 3 trial\n\n[3](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext)\n\n3\\.\n\nPolack, FP ∙ Thomas, SJ ∙ Kitchin, N ∙ et al.\n\n**Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine**\n\n*N Engl J Med.* 2020; **383**:2603-2615\n\n[Crossref](https:\/\/doi.org\/10.1056\/NEJMoa2034577)\n\n[Scopus (10099)](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_3_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85098117107)\n\n[PubMed](https:\/\/pubmed.ncbi.nlm.nih.gov\/33301246\/)\n\n[Google Scholar](https:\/\/scholar.google.com\/scholar_lookup?doi=10.1056%2FNEJMoa2034577&pmid=33301246)\n\nand supports the UK Government's decision to delay the timing of the second injection to 12 weeks to maximise the number of people receiving at least one dose. Long-term surveillance for SARS-CoV-2 protection in individuals who have received delayed second doses of BNT162b2 compared with those receiving second doses according to initial guidelines (ie, 21 days after the first dose) will be required to determine whether these initial protection estimates persist.\n\nStrengths of our study include its large sample size; capture of data on SARS-CoV-2 RT-PCR or lateral flow test results, regardless of symptoms; the prospective real-time capture of information on symptoms; and the availability of both BNT162b2 and ChAdOx1 nCoV-19 vaccines in the UK, which allowed cross-vaccine comparison. Our study also has several limitations. We used self-reported data, which can introduce information bias, including misclassification, or effect bias exposure. Also, some participants might be more likely to report symptoms than others, and there is the potential for users to drop out of reporting in the app. Participants using the app were a self-selected group and not representative of the general population, as has been observed in other digital platform studies.\n\n[27](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext)\n\n27\\.\n\nBaltrusaitis, K ∙ Santillana, M ∙ Crawley, AW ∙ et al.\n\n**Determinants of participants' follow-up and characterization of representativeness in flu near you, a participatory disease surveillance system**\n\n*JMIR Public Health Surveill.* 2017; **3**:e18\n\n[Crossref](https:\/\/doi.org\/10.2196\/publichealth.7304)\n\n[Scopus (39)](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_27_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85041028925)\n\n[PubMed](https:\/\/pubmed.ncbi.nlm.nih.gov\/28389417\/)\n\n[Google Scholar](https:\/\/scholar.google.com\/scholar_lookup?doi=10.2196%2Fpublichealth.7304&pmid=28389417)\n\nUsers of a participatory platform (as well as participants in all voluntary studies, including clinical trials) are likely to be more interested in health, and might behave differently to the general population as a result. Previous work has shown that data from our app is able to produce estimates of population-level disease prevalence that agree well with surveys with random, representative designs,\n\n[18,28](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext)\n\n18\\.\n\nVarsavsky, T ∙ Graham, MS ∙ Canas, LS ∙ et al.\n\n**Detecting COVID-19 infection hotspots in England using large-scale self-reported data from a mobile application: a prospective, observational study**\n\n*Lancet Public Health.* 2021; **6**:e21-e29\n\n[Full Text](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_18_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS2468-2667%2820%2930269-3&cf=fulltext&site=lancet-site)\n\n[Full Text (PDF)](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_18_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS2468-2667%2820%2930269-3&cf=pdf&site=lancet-site)\n\n[Scopus (54)](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_18_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85099010576)\n\n[PubMed](https:\/\/pubmed.ncbi.nlm.nih.gov\/33278917\/)\n\n[Google Scholar](https:\/\/scholar.google.com\/scholar_lookup?doi=10.1016%2FS2468-2667%2820%2930269-3&pmid=33278917)\n\n28\\.\n\nBowyer, RCE ∙ Varsavsky, T ∙ Thompson, EJ ∙ et al.\n\n**Geo-social gradients in predicted COVID-19 prevalence in Great Britain: results from 1 960 242 users of the COVID-19 Symptoms Study app**\n\n*Thorax.* 2020;\n\npublished online Dec 29. <http:\/\/dx.doi.org\/10.1136\/thoraxjnl-2020-215119>\n\n[Crossref](https:\/\/doi.org\/10.1136\/thoraxjnl-2020-215119)\n\n[Scopus (8)](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_28_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85098646607)\n\n[PubMed](https:\/\/pubmed.ncbi.nlm.nih.gov\/33376145\/)\n\n[Google Scholar](https:\/\/scholar.google.com\/scholar_lookup?doi=10.1136%2Fthoraxjnl-2020-215119&pmid=33376145)\n\nsuggesting that behavioural issues are not substantially biasing our app population. As with other studies examining COVID-19 vaccine effects in the general community, our data are limited by the vaccine rollout's focus on health-care workers, elderly people, and people who are clinically vulnerable.\n\n[2](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext)\n\n2\\.\n\nDepartment of Health and Social Care\n\n**Priority groups for coronavirus (COVID-19) vaccination: advice from the JCVI, 30 December 2020**\n\n<https:\/\/www.gov.uk\/government\/publications\/priority-groups-for-coronavirus-covid-19-vaccination-advice-from-the-jcvi-30-december-2020?utm_source=f1de4cd1-935e-4a5e-b539-3b37cd92e598>\n\nDate: Dec 30, 2020\n\nDate accessed: February 18, 2021\n\n[Google Scholar](https:\/\/scholar.google.com\/scholar?q=Department+of+Health+and+Social+CarePriority+groups+for+coronavirus+%28COVID-19%29+vaccination%3A+advice+from+the+JCVI%2C+30+December+2020https%3A%2F%2Fwww.gov.uk%2Fgovernment%2Fpublications%2Fpriority-groups-for-coronavirus-covid-19-vaccination-advice-from-the-jcvi-30-december-2020%3Futm_source%3Df1de4cd1-935e-4a5e-b539-3b37cd92e598Dec+30%2C+2020)\n\nMoreover, our results might have been affected by collider bias (ie, when a risk factor and an outcome both affect the likelihood of being sampled)\n\n[29](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext)\n\n29\\.\n\nGriffith, GJ ∙ Morris, TT ∙ Tudball, MJ ∙ et al.\n\n**Collider bias undermines our understanding of COVID-19 disease risk and severity**\n\n*Nat Commun.* 2020; **11**, 5749\n\n[Crossref](https:\/\/doi.org\/10.1038\/s41467-020-19478-2)\n\n[Scopus (490)](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_29_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85095945843)\n\n[PubMed](https:\/\/pubmed.ncbi.nlm.nih.gov\/33184277\/)\n\n[Google Scholar](https:\/\/scholar.google.com\/scholar_lookup?doi=10.1038%2Fs41467-020-19478-2&pmid=33184277)\n\nif both vaccination status and COVID positivity influenced the probability of participation in the app. However, given that strong reductions in COVID hospitalisations after vaccination were observed in nationwide studies in Scotland\n\n[12](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext)\n\n12\\.\n\nVasileiou, E ∙ Simpson, CR ∙ Shi, T ∙ et al.\n\n**Interim findings from first-dose mass COVID-19 vaccination roll-out and COVID-19 hospital admissions in Scotland: a national prospective cohort study**\n\n*Lancet.* 2021;\n\npublished online April 23. <https:\/\/doi.org\/10.1016\/S0140-6736(21)00677-2>\n\n[Full Text](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_12_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS0140-6736%2821%2900677-2&cf=fulltext&site=lancet-site)\n\n[Full Text (PDF)](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_12_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS0140-6736%2821%2900677-2&cf=pdf&site=lancet-site)\n\n[Scopus (391)](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_12_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85104923342)\n\n[PubMed](https:\/\/pubmed.ncbi.nlm.nih.gov\/33901420\/)\n\n[Google Scholar](https:\/\/scholar.google.com\/scholar_lookup?doi=10.1016%2FS0140-6736%2821%2900677-2&pmid=33901420)\n\nand England,\n\n[11](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext)\n\n11\\.\n\nLopez Bernal, J ∙ Andrews, N ∙ Gower, C ∙ et al.\n\n**Early effectiveness of COVID-19 vaccination with BNT162b2 mRNA vaccine and ChAdOx1 adenovirus vector vaccine on symptomatic disease, hospitalisations and mortality in older adults in England**\n\n*medRxiv.* 2021;\n\npublished online March 2. <https:\/\/doi.org\/10.1101\/2021.03.01.21252652>\n\n(preprint).\n\n[Google Scholar](https:\/\/scholar.google.com\/scholar?q=JLopez+BernalNAndrewsCGowerEarly+effectiveness+of+COVID-19+vaccination+with+BNT162b2+mRNA+vaccine+and+ChAdOx1+adenovirus+vector+vaccine+on+symptomatic+disease%2C+hospitalisations+and+mortality+in+older+adults+in+EnglandmedRxiv2021published+online+March+2.https%3A%2F%2Fdoi.org%2F10.1101%2F2021.03.01.21252652%28preprint%29.)\n\nwe believe that collider bias is unlikely to underlie the reduction in infections seen in our data. Recipients of the ChAdOx1 nCoV-19 vaccine might differ from recipients of the BNT162b2 vaccine by age or dependency. Although we adjusted for population differences across the BNT162b2, ChAdOx1 nCoV-19, and unvaccinated control groups, our estimates of infection rates after vaccination might not have fully adjusted for case-mix and therefore are preliminary. Furthermore, because the ChAdOx1 nCoV-19 vaccine started being rolled out in January, 2021, and the second dose is to be administered at 12 weeks, no app users had received two doses of ChAdOx1 nCoV-19 at the time of this report. The completeness of reporting was higher for systemic effects than for local effects, which might have introduced some bias ([appendix p 12](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#supplementary-material)). Some severe side-effects might have been missed if app users experiencing them were unable to use the app to report side-effects. However, we saw substantially lower rates of severe and mild side-effects than observed in phase 3 trials, making the missing of severe side-effects an unlikely explanation for the lower prevalence of side-effects seen in our data. Furthermore, we cannot rule out the presence of selection bias in who was tested after vaccination, as we know that health-care workers are tested more frequently than people in the general population, even if they are asymptomatic. This is an observational study, with data captured during a specific timeframe, and our study design does not allow an inference of causality. Also, we evaluated only short-term adverse effects, and long-term surveillance in the general population will be required to investigate possible future effects. Finally, the systemic side-effects were collected from daily reports within 1 week from the injection date, so we cannot rule out that these effects might not be vaccine related. We also had insufficient power to assess differential rates by ethnic group.\n\nIn conclusion, short-term adverse effects of both vaccines are moderate in frequency, mild in severity, and short-lived. Adverse effects are more frequently reported in younger individuals, women, and among those who previously had COVID-19. The post-vaccine symptoms (both systemic and local) often last 1–2 days from the injection. Our data could be used to inform people on the likelihood of side-effects on the basis of their age and sex and the type of vaccine being administered. Furthermore, our data support results from randomised controlled trials in a large community-based scenario showing evidence of reduction in infection after 12 days and substantial protection after 3 weeks.\n\n**Contributors**\n\nJW and TDS acquired funding. CM and TDS conceptualised the study. KK, AM, LP, and JC analysed the data. BM and JC curated the data. PL, CHS, LHN, DAD, JM, MA, LSC, EM, MSG, MMo, ADJ, MMa, AH, ATC, CJS, SO, SS, and CH contributed data and software. CM, JC, and TDS verified the underlying data. CM, KK, AM, LP, AMV, ALG, and TDS wrote the first draft of the manuscript. All authors reviewed and edited revisions of the manuscript, had full access to all the data in the study, and had final responsibility for the decision to submit for publication.\n\n## Data sharing\nAnonymised research data are shared with third parties via Health Data Research UK (HDRUK.ac.uk). US investigators are encouraged to coordinate data requests through the Coronavirus Pandemic Epidemiology (COPE) consortium ([www.monganinstitute.org\/cope-consortium](http:\/\/www.monganinstitute.org\/cope-consortium)). Data updates can be found at <https:\/\/covid.joinzoe.com>.\n\n## Declaration of interests\nCM reports grants from Chronic Disease Research Foundation (CDRF) during the conduct of the study. JW, AM, LP, CH, SS, and JC report being employees of ZOE Global during the conduct of the study. ATC reports grants from Massachusetts Consortium on Pathogen Readiness during the conduct of the study, and personal fees from Bayer Pharma, Pfizer, and Boehringer Ingelheim, outside the submitted work. DAD reports grants from National Institutes of Health (NIH), Massachusetts Consortium on Pathogen Readiness, and American Gastroenterological Association, during the conduct of the study, and that he served as a co-investigator on an unrelated nutrition trial sponsored by ZOE Global. CHS reports grants from Alzheimer's Society during the conduct of the study. AMV reports grants from Medical Research Council (MRC) and personal fees from ZOE Global, during the conduct of the study. ALG reports having shares in AstraZeneca and receiving grants from Novavax, outside the submitted work. CJS reports grants from CDRF, MRC, and Wellcome Trust, during the conduct of the study. SO reports grants from Wellcome Trust, UK Research and Innovation (UKRI), and CDRF, during the conduct of the study. TDS reports being a consultant for ZOE Global, during the conduct of the study. All other authors declare no competing interests.\n\n## Acknowledgments\nZOE Global provided in-kind support for all aspects of building, running, and supporting the app and service to all users worldwide. The Department of Twin Research & Genetic Epidemiology at King's College London receives grant support from the Wellcome Trust (212904\/Z\/18\/Z), the MRC British Heart Foundation Ancestry and Biological Informative Markers for Stratification of Hypertension (AIMHY; MR\/M016560\/1), the European Union, CDRF, ZOE Global, NIH, the National Institute for Health Research (NIHR)-funded BioResource, and Clinical Research Facility and Biomedical Research Centre based at Guy's and St Thomas' National Health Service (NHS) Foundation Trust, in partnership with King's College London. SO is funded by the Wellcome Engineering and Physical Sciences Research Council (EPSRC) Centre for Medical Engineering (WT203148\/Z\/16\/Z) and the Wellcome Flagship Programme (WT213038\/Z\/18\/Z). CM is funded by the CDRF and the MRC AIMHY project grant. CHS is an Alzheimer's Society junior fellow (AS-JF-17-011). The School of Biomedical Engineering & Imaging Sciences is supported by the Wellcome EPSRC Centre for Medical Engineering at King's College London (WT203148\/Z\/16\/Z) and the Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St Thomas' NHS Foundation Trust, in partnership with King's College London and King's College Hospital NHS Foundation Trust. ATC is a Stuart and Suzanne Steele MGH Research Scholar. LHN is supported by an NIH K23DK125838 award, the American Gastroenterological Association Research Scholar Award, and the Crohn's and Colitis Foundation Career Development Award. DAD and LHN are supported by the American Gastroenterological Association-Takeda COVID-19 Rapid Response Research Award (AGA2021-5102). DAD is supported by NIH\/National Institute of Health Diabetes and Digestive and Kidney Diseases (K01DK120742). ATC, LHN, and DAD are supported by the Massachusetts Consortium on Pathogen Readiness. JM is partially supported by the NIH (DK40561) and the American Diabetes Association (7-21-JDFM-005). PL is funded by the CDRF. AMV is funded by a UKRI and MRC Covid-Rapid Response grant (MR\/V027883\/1). We thank all participants, including study volunteers enrolled in cohorts within the COPE consortium. We thank the staff of ZOE Global, the Department of Twin Research & Genetic Epidemiology at King's College London, the Clinical & Translational Epidemiology Unit at Massachusetts General Hospital, and researchers and staff at Lund University in Sweden for their tireless work in contributing to the running of the study and data collection.\n\n## Supplementary Material (1)\n[PDF (923.33 KB)](https:\/\/www.thelancet.com\/cms\/10.1016\/S1473-3099\\(21\\)00224-3\/attachment\/05d885cc-88b3-43a5-be70-912e3dd2f3a6\/mmc1.pdf)\n\nSupplementary appendix\n\n## References\n[1\\.](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#body-ref-sbref10 \"View in article\")\n\nPublic Health England\n\n**COVID-19 vaccination programme**\n\n<https:\/\/www.gov.uk\/government\/collections\/covid-19-vaccination-programme>\n\nDate: Nov 27, 2020\n\nDate accessed: February 18, 2021\n\n[Google Scholar](https:\/\/scholar.google.com\/scholar?q=Public+Health+EnglandCOVID-19+vaccination+programmehttps%3A%2F%2Fwww.gov.uk%2Fgovernment%2Fcollections%2Fcovid-19-vaccination-programmeNov+27%2C+2020)\n\n[2\\.](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#body-ref-sbref20-1 \"View in article\")\n\nDepartment of Health and Social Care\n\n**Priority groups for coronavirus (COVID-19) vaccination: advice from the JCVI, 30 December 2020**\n\n<https:\/\/www.gov.uk\/government\/publications\/priority-groups-for-coronavirus-covid-19-vaccination-advice-from-the-jcvi-30-december-2020?utm_source=f1de4cd1-935e-4a5e-b539-3b37cd92e598>\n\nDate: Dec 30, 2020\n\nDate accessed: February 18, 2021\n\n[Google Scholar](https:\/\/scholar.google.com\/scholar?q=Department+of+Health+and+Social+CarePriority+groups+for+coronavirus+%28COVID-19%29+vaccination%3A+advice+from+the+JCVI%2C+30+December+2020https%3A%2F%2Fwww.gov.uk%2Fgovernment%2Fpublications%2Fpriority-groups-for-coronavirus-covid-19-vaccination-advice-from-the-jcvi-30-december-2020%3Futm_source%3Df1de4cd1-935e-4a5e-b539-3b37cd92e598Dec+30%2C+2020)\n\n[3\\.](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#body-ref-sbref30-1 \"View in article\")\n\nPolack, FP ∙ Thomas, SJ ∙ Kitchin, N ∙ et al.\n\n**Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine**\n\n*N Engl J Med.* 2020; **383**:2603-2615\n\n[Crossref](https:\/\/doi.org\/10.1056\/NEJMoa2034577)\n\n[Scopus (10099)](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_3_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85098117107)\n\n[PubMed](https:\/\/pubmed.ncbi.nlm.nih.gov\/33301246\/)\n\n[Google Scholar](https:\/\/scholar.google.com\/scholar_lookup?doi=10.1056%2FNEJMoa2034577&pmid=33301246)\n\n[4\\.](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#body-ref-sbref40 \"View in article\")\n\nDagan, N ∙ Barda, N ∙ Kepten, E ∙ et al.\n\n**BNT162b2 mRNA COVID-19 vaccine in a nationwide mass vaccination setting**\n\n*N Engl J Med.* 2021;\n\npublished online Feb 24. <https:\/\/doi.org\/10.1056\/nejmoa2101765>\n\n[Scopus (1814)](https:\/\/www.thelancet.com\/servlet\/linkout?suffix=e_1_5_1_2_4_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85103719376)\n\n[PubMed](https:\/\/pubmed.ncbi.nlm.nih.gov\/33626250\/)\n\n[Google Scholar](https:\/\/scholar.google.com\/scholar_lookup?doi=10.1056%2FNEJMoa2101765&pmid=33626250)\n\n[5\\.](https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099\\(21\\)00224-3\/fulltext#body-ref-sbref50-1 \"View in article\")\n\nHunter, PR ∙ Brainard, J\n\n**Estimating the effectiveness of the Pfizer COVID-19 BNT162b2 vaccine after a single dose. 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Meta Title	Vaccine side-effects and SARS-CoV-2 infection after vaccination in users of the COVID Symptom Study app in the UK: a prospective observational study - The Lancet Infectious Diseases
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Boilerpipe Text	Summary Background The Pfizer-BioNTech (BNT162b2) and the Oxford-AstraZeneca (ChAdOx1 nCoV-19) COVID-19 vaccines have shown excellent safety and efficacy in phase 3 trials. We aimed to investigate the safety and effectiveness of these vaccines in a UK community setting. Methods In this prospective observational study, we examined the proportion and probability of self-reported systemic and local side-effects within 8 days of vaccination in individuals using the COVID Symptom Study app who received one or two doses of the BNT162b2 vaccine or one dose of the ChAdOx1 nCoV-19 vaccine. We also compared infection rates in a subset of vaccinated individuals subsequently tested for SARS-CoV-2 with PCR or lateral flow tests with infection rates in unvaccinated controls. All analyses were adjusted by age (≤55 years vs >55 years), sex, health-care worker status (binary variable), obesity (BMI <30 kg/m 2 vs ≥30 kg/m 2 ), and comorbidities (binary variable, with or without comorbidities). Findings Between Dec 8, and March 10, 2021, 627 383 individuals reported being vaccinated with 655 590 doses: 282 103 received one dose of BNT162b2, of whom 28 207 received a second dose, and 345 280 received one dose of ChAdOx1 nCoV-19. Systemic side-effects were reported by 13·5% (38 155 of 282 103) of individuals after the first dose of BNT162b2, by 22·0% (6216 of 28 207) after the second dose of BNT162b2, and by 33·7% (116 473 of 345 280) after the first dose of ChAdOx1 nCoV-19. Local side-effects were reported by 71·9% (150 023 of 208 767) of individuals after the first dose of BNT162b2, by 68·5% (9025 of 13 179) after the second dose of BNT162b2, and by 58·7% (104 282 of 177 655) after the first dose of ChAdOx1 nCoV-19. Systemic side-effects were more common (1·6 times after the first dose of ChAdOx1 nCoV-19 and 2·9 times after the first dose of BNT162b2) among individuals with previous SARS-CoV-2 infection than among those without known past infection. Local effects were similarly higher in individuals previously infected than in those without known past infection (1·4 times after the first dose of ChAdOx1 nCoV-19 and 1·2 times after the first dose of BNT162b2). 3106 of 103 622 vaccinated individuals and 50 340 of 464 356 unvaccinated controls tested positive for SARS-CoV-2 infection. Significant reductions in infection risk were seen starting at 12 days after the first dose, reaching 60% (95% CI 49–68) for ChAdOx1 nCoV-19 and 69% (66–72) for BNT162b2 at 21–44 days and 72% (63–79) for BNT162b2 after 45–59 days. Interpretation Systemic and local side-effects after BNT162b2 and ChAdOx1 nCoV-19 vaccination occur at frequencies lower than reported in phase 3 trials. Both vaccines decrease the risk of SARS-CoV-2 infection after 12 days. Funding ZOE Global, National Institute for Health Research, Chronic Disease Research Foundation, National Institutes of Health, UK Medical Research Council, Wellcome Trust, UK Research and Innovation, American Gastroenterological Association. Introduction The UK's Medicines and Healthcare products Regulatory Agency has given emergency use authorisation to three COVID-19 vaccines: the Pfizer-BioNTech mRNA vaccine (BNT162b2), the Oxford-AstraZeneca adenovirus-vectored vaccine (ChAdOx1 nCoV-19), and the Moderna mRNA vaccine (mRNA-1273). The first two vaccines have been rolled out across the UK since Dec 8, 2020, and Jan 4, 2021, respectively. 1 1. Public Health England COVID-19 vaccination programme In late December, 2020, based on advice from the Joint Committee on Vaccination and Immunisation, 2 2. Department of Health and Social Care Priority groups for coronavirus (COVID-19) vaccination: advice from the JCVI, 30 December 2020 the UK Government decided to delay the administration of second doses. Phase 3 trials reported the BNT162b2 vaccine to have an efficacy of 52% at 12 days after the first dose and of 95% after the second dose if administered 3–4 weeks apart in participants without previous SARS-CoV-2 infection. 3 3. Polack, FP ∙ Thomas, SJ ∙ Kitchin, N ∙ et al. Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine N Engl J Med. 2020; 383 :2603-2615 The effectiveness of this vaccine in reducing infection, severe disease, hospitalisation, and death with COVID-19 has been reported for the whole of Israel, 4 4. Dagan, N ∙ Barda, N ∙ Kepten, E ∙ et al. BNT162b2 mRNA COVID-19 vaccine in a nationwide mass vaccination setting N Engl J Med. 2021; with reanalysis of the data from Israel revealing it to be 90% effective 2 weeks after the first dose. 5 5. Hunter, PR ∙ Brainard, J Estimating the effectiveness of the Pfizer COVID-19 BNT162b2 vaccine after a single dose. A reanalysis of a study of “real-world” vaccination outcomes from Israel medRxiv. 2021; (preprint). The ChAdOx1 nCoV-19 trial found efficacy against symptomatic disease of 76% at 22–90 days after at least one standard dose. 6–8 6. Voysey, M ∙ Clemens, SAC ∙ Madhi, SA ∙ et al. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK Lancet. 2021; 397 :99-111 7. Ramasamy, MN ∙ Minassian, AM ∙ Ewer, KJ ∙ et al. Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial Lancet. 2021; 396 :1979-1993 8. Voysey, M ∙ Clemens, SAC ∙ Madhi, SA ∙ et al. Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials Lancet. 2021; 397 :881-891 Research in context Evidence before this study We searched PubMed for articles published up to March 10, 2021, using the terms (“BNT162b2“ OR “mRNA Covid-19 Vaccine” OR “ChAdOx1 nCoV-19” OR “adenovirus-vectored Covid-19 vaccine”) AND (“effectiveness” OR “reinfection” OR “side-effects” OR “adverse effects” OR “reactogenicity” OR “phase IV”). We did not restrict our search by language or type of publication. Besides the original phase 1–3 trials, we found one published article and two preprints on data from Israel investigating the effectiveness of the Pfizer-BioNTech vaccine (BNT162b2), a preprint from the UK exploring the effectiveness of both the BNT162b2 and Oxford-AstraZeneca (ChAdOx1 nCoV-19) vaccines in individuals aged 70 years or older in the community, and a study that linked health records for all vaccinated people in Scotland to investigate COVID-19 hospitalisation and mortality after vaccination. No study investigated the prevalence of adverse effects of the vaccines and all studies reported both vaccines to be highly effective. Added value of this study In this large prospective observational study, we assessed adverse effects from the two COVID-19 vaccines in use in the UK at the time of writing (BNT162b2 and ChAdOx1 nCoV-19), as well as self-reported infection rates following one dose or two doses of BNT162b2 and one dose of ChAdOx1 nCoV-19. Reported side-effects were minor in severity and of short duration. Headache and fatigue were more common in women than in men, in people aged 55 years or younger than in people older than 55 years, and after the second than after the first dose. Individuals with known past SARS-CoV-2 infection were more likely to have adverse effects after the first dose than were those without known past infection. We found, in a community setting, that self-reported infection rates of those vaccinated with the BNT162b2 or ChAdOx1 nCoV-19 vaccines were significantly lower than infection rates in unvaccinated controls. Documented infection rates in our app after a single vaccine dose decreased by 58% (95% CI 54–62) at 12–20 days, 69% (66–72) at 21–44 days, and 72% (63–79) after 45–59 days following BNT162b2, and 39% (21–53) at 12–20 days and 60% (49–68) at 21–44 days following ChAdOx1 nCoV-19, compared with unvaccinated controls. Implications of all the available evidence Localised and systemic side-effects after vaccination are less common in a real-world community setting than reported in phase 3 trials, mostly minor in severity, and self-limiting. Our data will enable prediction of side-effects based on age, sex, and past COVID-19 status to help update guidance to health professionals to reassure the population about the safety of vaccines. Surveillance in the general population is necessary at this stage during vaccination rollout. 9 9. Public Health England COVID-19: vaccine surveillance strategy The OpenSAFELY collaboration 10 10. The OpenSAFELY Collaborative ∙ MacKenna, B ∙ Curtis, HJ ∙ et al. Trends, regional variation, and clinical characteristics of COVID-19 vaccine recipients: a retrospective cohort study in 23·4 million patients using OpenSAFELY medRxiv. 2021; (preprint). implemented a framework for monitoring vaccine rollout and coverage in the UK via record linkage, Public Health England has reported early data on effectiveness in the older population prioritised for vaccination, 11 11. Lopez Bernal, J ∙ Andrews, N ∙ Gower, C ∙ et al. Early effectiveness of COVID-19 vaccination with BNT162b2 mRNA vaccine and ChAdOx1 adenovirus vector vaccine on symptomatic disease, hospitalisations and mortality in older adults in England medRxiv. 2021; (preprint). and a prospective observational study investigated the association between the rollout of the first vaccine dose and COVID-19 hospital admission in Scotland. 12 12. Vasileiou, E ∙ Simpson, CR ∙ Shi, T ∙ et al. Interim findings from first-dose mass COVID-19 vaccination roll-out and COVID-19 hospital admissions in Scotland: a national prospective cohort study Lancet. 2021; Other surveys, such as the SIREN study 13 13. Hall, VJ ∙ Foulkes, S ∙ Saei, A ∙ et al. COVID-19 vaccine coverage in health-care workers in England and effectiveness of BNT162b2 mRNA vaccine against infection (SIREN): a prospective, multicentre, cohort study Lancet. 2021; in health-care workers, will also link directly to health records to assess the real-life effectiveness and safety of the various phases of vaccine rollout. However, it takes time for such studies to come to fruition. Real-time data from app users can provide a faster view of the safety and effectiveness of COVID-19 vaccines. The aim of this study was to investigate the adverse effects and infection rate of vaccinated people in a community (general population app users) scenario. We used data from 627 383 individuals who received the BNT162b2 or ChAdOx1 nCoV-19 vaccines between December, 2020, and March, 2021, and reported symptoms in real-time via the COVID Symptom Study app. 14 14. Menni, C ∙ Valdes, AM ∙ Freidin, MB ∙ et al. Real-time tracking of self-reported symptoms to predict potential COVID-19 Nat Med. 2020; 26 :1037-1040 A subset of individuals also reported receiving a PCR or lateral flow test. Methods Study design and participants The COVID Symptom Study app 14 14. Menni, C ∙ Valdes, AM ∙ Freidin, MB ∙ et al. Real-time tracking of self-reported symptoms to predict potential COVID-19 Nat Med. 2020; 26 :1037-1040 was developed by health data company ZOE Global, with input from King's College London (London, UK), the Massachusetts General Hospital (Boston, MA, USA), Lund University (Lund, Sweden), and Uppsala University (Uppsala, Sweden). In the UK, it was launched in English on March 24, 2020. The app enables self-reported information related to SARS-CoV-2 infection to be captured. Individuals older than 18 years can sign up to the app without any restrictions. Individuals can also record information for dependents younger than 18 years. Use of the app was driven by referrals or word of mouth, the media, and eventually partnerships with charities and the Welsh and Scottish Governments. 15 15. Drew, DA ∙ Nguyen, LH ∙ Steves, CJ ∙ et al. Rapid implementation of mobile technology for real-time epidemiology of COVID-19 Science. 2020; 368 :1362-1367 On first use, the app records self-reported location, age, and core health risk factors (body-mass index [BMI], smoking status, race or ethnicity, and presence of comorbidities, including cancer, diabetes, eczema, heart disease, lung disease, kidney disease, and hay fever), as well as employment status, such as being a health-care worker. With continued use, participants provide daily updates on symptoms experienced, SARS-CoV-2 test results (negative, pending, or positive), vaccines administered, and whether they are self-quarantining or seeking health care, including the level of intervention and related outcomes. Individuals without symptoms are encouraged to report through the app every day. Through direct updates to the app, new or modified questions are added in real time to capture data to test emerging hypotheses about COVID-19 symptoms and treatments. Versions 2.1.0–2.4.0 of the app were in use during the study period. Participants were asked if they had been vaccinated for COVID-19 and, if so, to record the type of vaccine and date of administration. We included all UK app users reporting having received at least one dose of the two available vaccines ( appendix p 2 ). Users reporting vaccination were then asked daily for the following 8 days whether they experienced adverse effects, including both systemic (whole body) and local effects. Systemic solicited side-effects included headache, fatigue, chills and shiver, diarrhoea, fever, arthralgia, myalgia, and nausea; solicited local side-effects included local pain, swelling, tenderness, redness, itch, warmth, and swollen armpit glands ( appendix p 6 ). Users were also permitted to report no symptoms by leaving the box unchecked. Ethical approval for use of the app for research purposes in the UK was obtained from King's College London Ethics Committee (review reference LRS-19/20-18210), and all users provided consent for non-commercial use of their data. Outcomes Our primary outcome was the proportion of app users reporting adverse effects within 8 days after vaccination and the probability of having an adverse event. Our secondary outcome was infection rates in individuals after receiving a first dose of either the BNT162b2 or ChAdOx1 nCoV-19 vaccines. We did not collect information on why individuals were tested, so not all tested individuals were necessarily experiencing COVID-19-associated symptoms at testing, and some individuals might have been routinely tested while being asymptomatic. Statistical analysis We used χ 2 and Student's t tests to compare the demographic characteristics of individuals who received BNT162b2 versus those who received ChAdOx1 nCoV-19. We investigated the evolution of systemic and local adverse effects within 8 days from the vaccination date, computing the percentage of users experiencing side-effects after having received the vaccine. Vaccinated individuals who logged their systemic or local effects (or the absence of them) at least once within 8 days from the vaccination date were included in the adverse effects analysis ( appendix p 2 ). We estimated the ratio of the daily number of users reporting at least one adverse effect (systemic or local) after vaccination to the total number of vaccinated users logging into the app that day. The occurrence of adverse effects was studied for both BNT162b2 doses and the first ChAdOx1 nCoV-19 dose. We compared the probability of having adverse effects between the first and second BNT162b2 doses, the first BNT162b2 and the first ChAdOx1 nCoV-19 doses, and the second BNT162b2 and the first ChAdOx1 nCoV-19 doses. As different people received different vaccines, we used Pearl's back-door adjustment 16 16. Pearl, J Causality Cambridge University Press, Cambridge, 2009 to account for differences within the populations. Backdoor adjustments are used when there are both causal and non-causal paths between predictors (eg, vaccine treatment [ V ]) and an outcome. Because of the observational (non-interventional) nature of the study, the non-causal paths between outcomes and predictors that might involve age, sex, BMI, or health status need to be adjusted statistically. Backdoor adjustment methods essentially condition on these variables, cutting out the non-causal (indirect) links between a predictor and an outcome: where R is adverse effects, S is stratum, and P ( R \| S,V ) is the probability of having adverse effects in a given stratum after receiving a vaccine. We used the following strata: age (≤55 years vs >55 years), in line with stratification in the BNT162b2 and ChAdOx1 nCoV-19 phase 3 trials, 3 3. Polack, FP ∙ Thomas, SJ ∙ Kitchin, N ∙ et al. Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine N Engl J Med. 2020; 383 :2603-2615 sex, health-care worker status (binary variable), obesity (BMI <30 kg/m 2 vs ≥30 kg/m 2 ), and comorbidities (binary variable, with or without comorbidities). Adjusted odds ratios (ORs) were computed after Pearl's back-door adjustment was applied to the raw rates (see appendix p 15 for the formula). 95% CIs for ORs were obtained by bootstrapping 50 times on the vaccinated population. Logistic regressions were used for each of the specified strata to investigate whether adverse effects varied across different participant groups, and in individuals who had previously reported a positive test for COVID-19 (PCR or lateral flow positive at least 6 months before vaccination, PCR or lateral flow positive within the 6 months before vaccination, and no previously detected infection). Finally, in a subanalysis of vaccinated participants who reported having had the first dose of the BNT162b2 vaccine or one dose of the ChAdOx1 nCoV-19 vaccine and were then subsequently tested for SARS-CoV-2 infection, we investigated the change in infection rates after the first vaccine dose. We compared the outcomes of PCR or lateral flow tests in individuals who had been vaccinated with the first dose with those of unvaccinated individuals who reported having a COVID-19 test in the same week as a vaccinated app user. We computed the difference in days between when participants had the vaccine and when they were tested, and we used this metric to group users. If a person reported more than one PCR test or lateral flow result after being vaccinated, we selected the positive test, or if none were positive, the latest negative test. Since the BNT162b2 phase 3 trial showed a decrease in infections from 12 days after vaccination, 3 3. Polack, FP ∙ Thomas, SJ ∙ Kitchin, N ∙ et al. Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine N Engl J Med. 2020; 383 :2603-2615 we analysed infection rates at 0–4, 5–11, 12–20, 21–44, and 45–59 days after vaccination. For each of the vaccines and for different timepoints from the vaccination date, we used Poisson regressions to model the rates of positive tests in vaccinated individuals compared with those in the unvaccinated population, adjusting for the number of tests. This model allowed us to control for the number of follow-up days for each group. Moreover, as there was a two-times increase in daily incidence in England followed by a decrease of a similar proportion during the data collection period, 17 17. Office for National Statistics Coronavirus (COVID-19) Infection Survey we also included incidence as a covariate in the Poisson regression model, with incidence calculated as previously described. 18 18. Varsavsky, T ∙ Graham, MS ∙ Canas, LS ∙ et al. Detecting COVID-19 infection hotspots in England using large-scale self-reported data from a mobile application: a prospective, observational study Lancet Public Health. 2021; 6 :e21-e29 We defined the adjusted infection risk reduction (RR) as follows: where i is BNT162b2 or ChAdOx1 nCoV-19 vaccine, n is the number of days since vaccination (0–4, 5–11, 12–20, 21–44, 45–59), and the risk ratio is the coefficient of the vaccine status variables in the Poisson regression model. We further tested the role of covariates in risk of infection after vaccination by running stratified Poisson models (adjusted for confounders). For this analysis, we considered all app responders who were vaccinated with BNT162b2 or ChAdOx1 nCoV-19 vaccines at least 12 days before having a test for SARS-CoV-2 positivity. Due to a relatively small sample size in some of the strata, we did not differentiate between vaccine types but pooled all vaccinated contributors. Data were extracted and preprocessed using ExeTera version 0.3.2, 19 19. Murray, B ∙ Kerfoot, E ∙ Graham, MS ∙ et al. Accessible data curation and analytics for international-scale citizen science datasets arXiv. 2020; (preprint). a Python library developed at King's College London, and we did statistical analysis using Python version 3.7 (pandas, NumPy, and SciPy). Role of the funding source ZOE Global developed the app for data collection as a not-for-profit endeavour. The funder had no role in study design, data analysis, data interpretation, or writing of the report. Results Between Dec 8, 2020, and March 10, 2021, 655 590 vaccine doses were logged in the app in the UK, corresponding to 282 103 individuals (aged 16–99 years) who reported having received the first dose of the BNT162b2 vaccine, of whom 28 207 reported having had both doses of the BNT162b2 vaccine (a median of 41 days [IQR 21–63] apart), and 345 280 individuals who reported having had the first dose of ChAdOx1 nCoV-19. Participants joined the COVID Symptom Study app a mean of 288 days (SD 96) before being vaccinated. Users started logging adverse effects reports 0·79 days (SD 1·2) after they had the vaccine. 1 607 620 users were active in the app during the study period (logged at least an assessment since Dec 8), which represents 2·4% of the UK population. The mean age of app users was 50·6 years (SD 19·2), and 77 683 (4·8%) of them were health-care workers. Users who reported receiving a BNT162b2 vaccine were slightly younger, had more comorbidities, and were more frequently female than users who reported receiving a ChAdOx1 nCoV-19 inoculation ( table ). Moreover, health-care workers were more likely to receive a BNT162b2 vaccine than ChAdOx1 nCoV-19 ( appendix p 8 ). The age distribution of the included individuals is presented in the appendix (p 3) . BNT162b2 ChAdOx1 nCoV-19 First dose (N=282 103) Second dose (N=28 207) First dose (N=345 280) Sex * Female 173 866 (61·6%) 19 640 (69·6%) 199 269 (57·7%) Male 108 237 (38·4%) 8567 (30·4%) 146 011 (42·3%) Age, years * † 62·0 (14·3); 64 (54–72) 61·0 (17·3); 59 (49–76) 63·3 (11·5); 65 (59–71) Body-mass index, kg/m 2 ‡ 26·8 (5·5) 26·5 (5·3) 26·8 (5·3) Health-care workers * 31 996 (11·3%) 8828 (31·3%) 9746 (2·8%) Comorbidities * 77 433 (27·4%) 7617 (27·0%) 88 453 (25·6%) Previous COVID-19 * 14 369 (5·1%) 2251 (8·0%) 14 231 (4·1%) Systemic side-effects Any 38 155 (13·5%) 6216 (22·0%) 116 473 (33·7%) Headache 21 910 (7·8%) 3731 (13·2%) 78 734 (22·8%) Fatigue 23 674 (8·4%) 4064 (14·4%) 72 924 (21·1%) Chills and shiver 7166 (2·5%) 1812 (6·4%) 50 761 (14·7%) Diarrhoea 3885 (1·4%) 416 (1·5%) 7546 (2·2%) Fever 4236 (1·5%) 1076 (3·8%) 28 268 (8·2%) Arthralgia 9021 (3·2%) 1978 (7·0%) 39 648 (11·5%) Myalgia 6479 (2·3%) 1415 (5·0%) 24 274 (7·0%) Nausea 5926 (2·1%) 981 (3·5%) 19 509 (5·7%) Local side-effects § Any 150 023 (71·9%) 9025 (68·5%) 104 282 (58·7%) Pain 61 016 (29·2%) 4515 (34·3%) 33 939 (19·1%) Swelling 13 264 (6·4%) 1285 (9·8%) 9769 (5·5%) Tenderness 119 431 (57·2%) 6705 (50·9%) 87 609 (49·3%) Itch 6242 (3·0%) 840 (6·4%) 6934 (3·9%) Swollen armpit glands 2278 (1·1%) 549 (4·2%) 1994 (1·1%) Redness 7891 (3·8%) 953 (7·2%) 7431 (4·2%) Warmth 14 024 (6·7%) 1245 (9·4%) 14 033 (7·9%) Bruising 1872 (0·9%) 64 (0·5%) 4269 (2·4%) Allergic reactions Rash 682 (0·2%) 103 (0·4%) 1432 (0·4%) Skin burning 2075 (0·7%) 324 (1·1%) 5940 (1·7%) Red welts on face and lips 469 (0·2%) 59 (0·2%) 846 (0·2%) Table Demographic characteristics of the study population Data are n (%), unless otherwise indicated. * p<0·05 for the difference between the first dose of BNT162b2 and the first dose of ChAdOx1 nCoV-19 (Student's t test for continuous variables and χ 2 test for categorical variables). † Data are mean (SD); median (IQR). ‡ Data are mean (SD). § Denominators are 208 767 for the first BNT162b2 dose, 13 179 for the second BNT162b2 dose, and 177 655 for the first ChAdOx1 nCoV-19 dose. Open table in a new tab Among vaccinated app users, 159 101 (25·4%) of 627 383 indicated having one or more systemic adverse effect, and 257 209 (66·2%) of 388 430 reported one or more local adverse effect ( table ). The most commonly reported systemic side-effects were fatigue and headache overall ( table ) and by strata ( appendix p 9 ). These were most frequently reported within the first 24 h after vaccination and lasted a mean of 1·01 days (SD 0·1; figure 1 ). Tenderness and local pain around the injection site were the most frequently reported local effects ( table ), occurring most often on the day after injection and lasting a mean of 1·02 days (SD 0·15; figure 1 ). Other side-effects, including allergic skin reactions such as skin burning, rashes, and red welts on the lips and face, were reported by 10 860 (1·7%) of 627 383 users across both types of vaccine ( table ; appendix p 9 ). In an exploratory analysis, we assessed the association between symptom reporting and socioeconomic status measured as index of multiple deprivation, 20 20. Ministry of Housing, Communities, and Local Government English indices of deprivation 2019 and we found a modest association ( r =0·021 [95% CI 0·019–0·025]), corresponding to 0·04% of the variance in symptoms reporting. Figure 1 Proportion of participants self-reporting adverse effects to the COVID Symptom Study app within 8 days after vaccination In the 28 207 individuals who reported having two BNT162b2 doses, 3325 (11·7%) reported at least one systemic effect after the first dose compared with 6216 (22·0%) after the second dose (p<0·0001; figure 2 ). When comparing systemic effects after one dose of each vaccine, reactogenicity was significantly higher in individuals who had one dose of the ChAdOx1 nCoV-19 vaccine than in those who had one dose of the BNT162b2 vaccine (116 473 [33·7%] of 345 280 compared with 38 155 [13·5%] of 282 103; adjusted p<0·0001). Figure 2 Comparison of adverse effects self-reported to the COVID Symptom Study app between vaccine types and doses By contrast, local effects were less commonly reported after the second dose than after the first dose of BNT162b2 (9025 [68·5%] of 13 179 vs 150 023 [71·9%] of 208 767; p<0·0001). Moreover, local effects were less commonly reported after the first ChAdOx1 nCoV-19 injection (104 282 [58·7%] of 177 655) than after the first BNT162b2 injection (adjusted p<0·0001; figure 2 ). When comparing the second BNT162b2 dose with the first ChAdOx1 nCoV-19 dose, we found that systemic effects occurred more frequently after the first ChAdOx1 nCoV-19 dose than after the second BNT162b2 dose (adjusted p<0·0001; figure 2 ), whereas local effects were less likely to appear after the first ChAdOx1 nCoV-19 injection than after the second BNT162b2 dose (adjusted p<0·0001; figure 2 ). We then tested whether adverse effects varied across individuals' characteristics, such as age and BMI groups, sex, and health status. The proportion of participants who reported at least one systemic effect after the first dose was significantly higher among people aged 55 years or younger than among those older than 55 years for both vaccines. After the first dose of BNT162b2, 16 733 (20·7%) of 80 879 people aged 55 years or younger reported at least one systemic effect compared with 21 422 (10·6%) of 201 224 people older than 55 years (OR 2·19 [95% CI 2·14–2·24]; p<0·0001). For ChAdOx1 nCoV-19, 30 487 (46·9%) of 65 034 people aged 55 years or younger reported at least one systemic effect after the first dose compared with 85 986 (30·7%) of 280 243 older than 55 years (1·99 [1·96–2·03]; p<0·0001). Women were more likely to report adverse effects than men (28 140 [16·2%] of 173 866 vs 10 015 [9·3%] of 108 237 after the first dose of BNT162b2, OR 1·89 [95% CI 1·85–1·94], p<0·0001; 78 222 [39·3%] of 199 269 vs 38 251 [26·2%] of 146 011 after the first dose of ChAdOx1 nCoV-19, 1·82 [1·79–1·85], p<0·0001). Although there were some differences between strata of BMI and co-morbidities, there was no clear trend across vaccines and doses ( figure 3 ). Figure 3 Adverse effects self-reported to the COVID Symptom Study app after COVID-19 vaccination, stratified by sex, age, BMI, health status, and previous SARS-CoV-2 test status We observed the same trend for local effects as for systemic effects, whereby app users aged 55 years or younger reported more local side-effects than participants older than 55 years ( figure 3 ), and women were more likely to report local side-effects than men ( figure 3 ; appendix p 11 ). Similar levels of side-effects were seen regardless of the levels of completeness of reporting by app users ( appendix p 12 ). Given preliminary evidence from small studies 21–23 21. Saadat, S ∙ Rikhtegaran-Tehrani, Z ∙ Logue, J ∙ et al. Single dose vaccination in healthcare workers previously infected with SARS-CoV-2 medRxiv. 2021; (preprint). 22. Krammer, F ∙ Srivastava, K ∙ Simon, V Robust spike antibody responses and increased reactogenicity in seropositive individuals after a single dose of SARS-CoV-2 mRNA vaccine medRxiv. 2021; (preprint). 23. Wise, J COVID-19: people who have had infection might only need one dose of mRNA vaccine BMJ. 2021; 372 :n308 suggesting that reactogenicity is higher among individuals previously infected with SARS-CoV-2, we investigated the extent to which previous SARS-CoV-2 infection (based on self-reported previous positive PCR or lateral flow result) was associated with reports of adverse effects. Individuals vaccinated with a single dose of BNT162b2 were more likely to report systemic effects if they had a previous SARS-CoV-2 positive test than were those without known past infection (5148 [35·8%] of 14 369 vs 33 007 [12·3%] of 267 734; OR 3·97 [95% CI 3·83–4·12], p<0·0001). A similar effect was seen for ChAdOx1 nCoV-19 first dose inoculation (7551 [53·1%] of 14 231 with past infection vs 108 922 [32·9%] of 331 049 without past infection; 2·31 [2·23–2·38], p<0·0001; figure 3 ) and BNT162b2 second dose inoculation (859 [38·2%] of 2251 vs 5357 [20·6%] of 25 956; 2·37 [2·17–2·60], p<0·0001). Local effects were similarly higher in individuals previously infected than in those without known past infection for both vaccines ( figure 3 ). No consistent difference in occurrence of systemic or local adverse effects was observed between individuals who reported a positive test result within the past 6 months and those who reported they received a positive test result at least 6 months ago ( figure 3 ). We also investigated infection rates after the first vaccine dose in a subset of 67 293 app users who received BNT162b2 and 36 329 who received ChAdOx1 nCoV-19 in the study period and logged at least one PCR or lateral flow test after vaccination. We compared the test results of this population with those of 464 356 unvaccinated app users who had a PCR or lateral flow test result between Jan 4, and March 10, 2021 ( appendix pp 4, 8 ). 3106 of 103 622 vaccinated individuals and 50 340 of 464 356 unvaccinated controls tested positive for SARS-CoV-2 infection. As UK guidelines stipulate that individuals need to be free of symptoms to be vaccinated, we found vaccinated participants to have a lower infection risk at the time of the vaccination than unvaccinated participants (RR for BNT162b2 −64% [95% CI −69 to −59]; RR for ChAdOx1 nCoV-19 −52% [95% CI −65 to −34]). We observed that 5–11 days after vaccination, the infection rates in the vaccinated group were only slightly below those of the unvaccinated group ( figure 4 ), whereas 12–20 days after vaccination, infection risk in the vaccinated group was significantly lower than in the unvaccinated group (RR for BNT162b2 −58% [95% CI −62 to −54]; RR for ChAdOx1 nCoV-19 −39% [95% CI −53 to −21]), after adjusting for population differences in the vaccinated groups using Poisson regressions. We observed a further reduction in infection risk after one dose of the BNT162b2 vaccine when compared with unvaccinated controls at 21–44 days after vaccination (RR −69% [95% CI −72 to −66]) and at 45–59 days after vaccination (−72% [–79 to −63]; figure 4 ). The RR after one dose of ChAdOx1 nCoV-19 compared with unvaccinated controls was −60% (95% CI −68 to −49) at 21–44 days after vaccination. Figure 4 Infection risk reduction after the first dose in app users who have been vaccinated and subsequently tested, as a function of days since vac Finally, we tested the role of covariates in risk of infection after vaccination. We observed a larger risk reduction in vaccinated participants aged 55 years or younger (RR −70% [95% CI −72 to −68) than in those older than 55 years (−61% [–64 to −57]). Similarly, individuals without comorbidities had a larger risk reduction (−69% [–71 to −68]) than those with at least one comorbidity (−54% [–59 to −48]). Borderline differences were observed for BMI (RR for BMI <30 kg/m 2 −69% [95% CI −71 to −67]; RR for BMI ≥30 kg/m 2 −63% [−67 to −59]) and sex (RR for female −69% [95% CI −71 to −67]; RR for male −61% [–66 to −57]; appendix p 5 ). Discussion In this large-scale, community-based study in the UK, we have investigated adverse effects and infection rates following administration of the two COVID-19 vaccines that are in use in the UK. The overall mean age of the vaccinated app users was higher than that of the general population (40·3 years) 24 24. Office for National Statistics Population estimates for the UK, England and Wales, Scotland and Northern Ireland, provisional: mid-2019 yet was lower than those of the samples within other UK COVID-19 effectiveness studies, 11,12 11. Lopez Bernal, J ∙ Andrews, N ∙ Gower, C ∙ et al. Early effectiveness of COVID-19 vaccination with BNT162b2 mRNA vaccine and ChAdOx1 adenovirus vector vaccine on symptomatic disease, hospitalisations and mortality in older adults in England medRxiv. 2021; (preprint). 12. Vasileiou, E ∙ Simpson, CR ∙ Shi, T ∙ et al. Interim findings from first-dose mass COVID-19 vaccination roll-out and COVID-19 hospital admissions in Scotland: a national prospective cohort study Lancet. 2021; largely because of the presence of a small proportion of health-care workers among the participants of this study. However, our study population was considerably older than the study populations of the phase 3 trials. 3,6,7 3. Polack, FP ∙ Thomas, SJ ∙ Kitchin, N ∙ et al. Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine N Engl J Med. 2020; 383 :2603-2615 6. Voysey, M ∙ Clemens, SAC ∙ Madhi, SA ∙ et al. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK Lancet. 2021; 397 :99-111 7. Ramasamy, MN ∙ Minassian, AM ∙ Ewer, KJ ∙ et al. Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial Lancet. 2021; 396 :1979-1993 We found that systemic adverse effects, including headache and fatigue, affected fewer than one in four people and were less common in the community than expected from clinical trials. For example, in phase 3 clinical trials of the BNT162b2 vaccine, 3 3. Polack, FP ∙ Thomas, SJ ∙ Kitchin, N ∙ et al. Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine N Engl J Med. 2020; 383 :2603-2615 the most common events after the first dose were injection-site pain (71–83%), fatigue (34–47%), and headache (25–42%). However, in our community analysis, less than 30% of users complained of injection-site pain and less than 25% of fatigue and headache after the first dose. Although side-effects were significantly more prevalent in women than in men, in people aged 55 years or younger than in those older than 55 years, and after the second than after the first dose, they occurred at much lower frequencies than expected from the published literature. For instance, whereas 51–59% of participants reported fatigue after the second BNT162b2 dose in the phase 3 trial of that vaccine, 3 3. Polack, FP ∙ Thomas, SJ ∙ Kitchin, N ∙ et al. Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine N Engl J Med. 2020; 383 :2603-2615 fatigue was reported by less than 15% of participants after the second dose in our study. Additionally, our data provide evidence from the community to support early reports of higher frequency of side-effects in younger than in older individuals. 3,7 3. Polack, FP ∙ Thomas, SJ ∙ Kitchin, N ∙ et al. Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine N Engl J Med. 2020; 383 :2603-2615 7. Ramasamy, MN ∙ Minassian, AM ∙ Ewer, KJ ∙ et al. Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial Lancet. 2021; 396 :1979-1993 Similarly, rates of side-effects following the ChAdOx1 nCoV-19 vaccine were lower than expected. 7 7. Ramasamy, MN ∙ Minassian, AM ∙ Ewer, KJ ∙ et al. Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial Lancet. 2021; 396 :1979-1993 The phase 2–3 trial of the ChAdOx1 nCoV-19 vaccine 7 7. Ramasamy, MN ∙ Minassian, AM ∙ Ewer, KJ ∙ et al. Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial Lancet. 2021; 396 :1979-1993 reported systemic adverse effects in 88% of participants aged 18–55 years who received the first injection, whereas we found a lower rate of 33·7% after the first dose in the overall sample and 46·9% in individuals aged 18–55 years (data not shown). Individuals vaccinated with the ChAdOx1 nCoV-19 vaccine were more likely to experience systemic side-effects than those who had been given the BNT162b2 vaccine, but in our study 89% of respondents who logged at least one systemic effect after the ChAdOx1 nCoV-19 vaccine did not report any systemic effects after 3 days, and 98·3% did not report any after 1 week. Individuals with evidence of past SARS-CoV-2 infection were also more likely to have adverse effects than those without evidence of past infection with both vaccines. It is possible, although it remains to be tested, that this increased reactogenicity relates to increased immunogenicity. It has been shown that vaccines have increased immunogenicity in individuals with past infection and these people have higher antibody titres than those without previous infection. 22,23,25 22. Krammer, F ∙ Srivastava, K ∙ Simon, V Robust spike antibody responses and increased reactogenicity in seropositive individuals after a single dose of SARS-CoV-2 mRNA vaccine medRxiv. 2021; (preprint). 23. Wise, J COVID-19: people who have had infection might only need one dose of mRNA vaccine BMJ. 2021; 372 :n308 25. Manisty, C ∙ Otter, AD ∙ Treibel, TA ∙ et al. Antibody response to first BNT162b2 dose in previously SARS-CoV-2-infected individuals Lancet. 2021; 397 :1057-1058 We observed an infection risk reduction at 21–44 days after vaccination in all vaccinated users compared with unvaccinated controls (RR was −69% [95% CI −72 to −66] for BNT162b2 and −60% [–68 to −49] for ChAdOx1 nCoV-19). The reduction of infection was lower in individuals older than 55 years than those aged 55 years or younger, in those with one or more comorbidities than in those without comorbidities, and in individuals with a BMI of 30 kg/m 2 or higher than in those with a BMI of less than 30 kg/m 2 ( appendix p 5 ). A preprint based on data from Israel suggested that a single dose of BNT162b2 might not provide enough protection; 26 26. Chodick, G ∙ Tene, L ∙ Patalon, T ∙ et al. The effectiveness of the first dose of BNT162b2 vaccine in reducing SARS-CoV-2 infection 13–24 days after immunization: real-world evidence medRxiv. 2021; (preprint). however, a re-analysis of the same dataset indicated that after 14 days the effectiveness of a single dose of vaccine was about 90%. 5 5. Hunter, PR ∙ Brainard, J Estimating the effectiveness of the Pfizer COVID-19 BNT162b2 vaccine after a single dose. A reanalysis of a study of “real-world” vaccination outcomes from Israel medRxiv. 2021; (preprint). Although our data, due to their observational nature, does not allow us to comment directly on effectiveness, the observed decrease of infection over time seems to be in line with efficacy reported in the BNT162b2 phase 3 trial 3 3. Polack, FP ∙ Thomas, SJ ∙ Kitchin, N ∙ et al. Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine N Engl J Med. 2020; 383 :2603-2615 and supports the UK Government's decision to delay the timing of the second injection to 12 weeks to maximise the number of people receiving at least one dose. Long-term surveillance for SARS-CoV-2 protection in individuals who have received delayed second doses of BNT162b2 compared with those receiving second doses according to initial guidelines (ie, 21 days after the first dose) will be required to determine whether these initial protection estimates persist. Strengths of our study include its large sample size; capture of data on SARS-CoV-2 RT-PCR or lateral flow test results, regardless of symptoms; the prospective real-time capture of information on symptoms; and the availability of both BNT162b2 and ChAdOx1 nCoV-19 vaccines in the UK, which allowed cross-vaccine comparison. Our study also has several limitations. We used self-reported data, which can introduce information bias, including misclassification, or effect bias exposure. Also, some participants might be more likely to report symptoms than others, and there is the potential for users to drop out of reporting in the app. Participants using the app were a self-selected group and not representative of the general population, as has been observed in other digital platform studies. 27 27. Baltrusaitis, K ∙ Santillana, M ∙ Crawley, AW ∙ et al. Determinants of participants' follow-up and characterization of representativeness in flu near you, a participatory disease surveillance system JMIR Public Health Surveill. 2017; 3 :e18 Users of a participatory platform (as well as participants in all voluntary studies, including clinical trials) are likely to be more interested in health, and might behave differently to the general population as a result. Previous work has shown that data from our app is able to produce estimates of population-level disease prevalence that agree well with surveys with random, representative designs, 18,28 18. Varsavsky, T ∙ Graham, MS ∙ Canas, LS ∙ et al. Detecting COVID-19 infection hotspots in England using large-scale self-reported data from a mobile application: a prospective, observational study Lancet Public Health. 2021; 6 :e21-e29 28. Bowyer, RCE ∙ Varsavsky, T ∙ Thompson, EJ ∙ et al. Geo-social gradients in predicted COVID-19 prevalence in Great Britain: results from 1 960 242 users of the COVID-19 Symptoms Study app Thorax. 2020; suggesting that behavioural issues are not substantially biasing our app population. As with other studies examining COVID-19 vaccine effects in the general community, our data are limited by the vaccine rollout's focus on health-care workers, elderly people, and people who are clinically vulnerable. 2 2. Department of Health and Social Care Priority groups for coronavirus (COVID-19) vaccination: advice from the JCVI, 30 December 2020 Moreover, our results might have been affected by collider bias (ie, when a risk factor and an outcome both affect the likelihood of being sampled) 29 29. Griffith, GJ ∙ Morris, TT ∙ Tudball, MJ ∙ et al. Collider bias undermines our understanding of COVID-19 disease risk and severity Nat Commun. 2020; 11 , 5749 if both vaccination status and COVID positivity influenced the probability of participation in the app. However, given that strong reductions in COVID hospitalisations after vaccination were observed in nationwide studies in Scotland 12 12. Vasileiou, E ∙ Simpson, CR ∙ Shi, T ∙ et al. Interim findings from first-dose mass COVID-19 vaccination roll-out and COVID-19 hospital admissions in Scotland: a national prospective cohort study Lancet. 2021; and England, 11 11. Lopez Bernal, J ∙ Andrews, N ∙ Gower, C ∙ et al. Early effectiveness of COVID-19 vaccination with BNT162b2 mRNA vaccine and ChAdOx1 adenovirus vector vaccine on symptomatic disease, hospitalisations and mortality in older adults in England medRxiv. 2021; (preprint). we believe that collider bias is unlikely to underlie the reduction in infections seen in our data. Recipients of the ChAdOx1 nCoV-19 vaccine might differ from recipients of the BNT162b2 vaccine by age or dependency. Although we adjusted for population differences across the BNT162b2, ChAdOx1 nCoV-19, and unvaccinated control groups, our estimates of infection rates after vaccination might not have fully adjusted for case-mix and therefore are preliminary. Furthermore, because the ChAdOx1 nCoV-19 vaccine started being rolled out in January, 2021, and the second dose is to be administered at 12 weeks, no app users had received two doses of ChAdOx1 nCoV-19 at the time of this report. The completeness of reporting was higher for systemic effects than for local effects, which might have introduced some bias ( appendix p 12 ). Some severe side-effects might have been missed if app users experiencing them were unable to use the app to report side-effects. However, we saw substantially lower rates of severe and mild side-effects than observed in phase 3 trials, making the missing of severe side-effects an unlikely explanation for the lower prevalence of side-effects seen in our data. Furthermore, we cannot rule out the presence of selection bias in who was tested after vaccination, as we know that health-care workers are tested more frequently than people in the general population, even if they are asymptomatic. This is an observational study, with data captured during a specific timeframe, and our study design does not allow an inference of causality. Also, we evaluated only short-term adverse effects, and long-term surveillance in the general population will be required to investigate possible future effects. Finally, the systemic side-effects were collected from daily reports within 1 week from the injection date, so we cannot rule out that these effects might not be vaccine related. We also had insufficient power to assess differential rates by ethnic group. In conclusion, short-term adverse effects of both vaccines are moderate in frequency, mild in severity, and short-lived. Adverse effects are more frequently reported in younger individuals, women, and among those who previously had COVID-19. The post-vaccine symptoms (both systemic and local) often last 1–2 days from the injection. Our data could be used to inform people on the likelihood of side-effects on the basis of their age and sex and the type of vaccine being administered. Furthermore, our data support results from randomised controlled trials in a large community-based scenario showing evidence of reduction in infection after 12 days and substantial protection after 3 weeks. Contributors JW and TDS acquired funding. CM and TDS conceptualised the study. KK, AM, LP, and JC analysed the data. BM and JC curated the data. PL, CHS, LHN, DAD, JM, MA, LSC, EM, MSG, MMo, ADJ, MMa, AH, ATC, CJS, SO, SS, and CH contributed data and software. CM, JC, and TDS verified the underlying data. CM, KK, AM, LP, AMV, ALG, and TDS wrote the first draft of the manuscript. All authors reviewed and edited revisions of the manuscript, had full access to all the data in the study, and had final responsibility for the decision to submit for publication. Data sharing Anonymised research data are shared with third parties via Health Data Research UK (HDRUK.ac.uk). US investigators are encouraged to coordinate data requests through the Coronavirus Pandemic Epidemiology (COPE) consortium ( www.monganinstitute.org/cope-consortium ). Data updates can be found at https://covid.joinzoe.com . Declaration of interests CM reports grants from Chronic Disease Research Foundation (CDRF) during the conduct of the study. JW, AM, LP, CH, SS, and JC report being employees of ZOE Global during the conduct of the study. ATC reports grants from Massachusetts Consortium on Pathogen Readiness during the conduct of the study, and personal fees from Bayer Pharma, Pfizer, and Boehringer Ingelheim, outside the submitted work. DAD reports grants from National Institutes of Health (NIH), Massachusetts Consortium on Pathogen Readiness, and American Gastroenterological Association, during the conduct of the study, and that he served as a co-investigator on an unrelated nutrition trial sponsored by ZOE Global. CHS reports grants from Alzheimer's Society during the conduct of the study. AMV reports grants from Medical Research Council (MRC) and personal fees from ZOE Global, during the conduct of the study. ALG reports having shares in AstraZeneca and receiving grants from Novavax, outside the submitted work. CJS reports grants from CDRF, MRC, and Wellcome Trust, during the conduct of the study. SO reports grants from Wellcome Trust, UK Research and Innovation (UKRI), and CDRF, during the conduct of the study. TDS reports being a consultant for ZOE Global, during the conduct of the study. All other authors declare no competing interests. Acknowledgments ZOE Global provided in-kind support for all aspects of building, running, and supporting the app and service to all users worldwide. The Department of Twin Research & Genetic Epidemiology at King's College London receives grant support from the Wellcome Trust (212904/Z/18/Z), the MRC British Heart Foundation Ancestry and Biological Informative Markers for Stratification of Hypertension (AIMHY; MR/M016560/1), the European Union, CDRF, ZOE Global, NIH, the National Institute for Health Research (NIHR)-funded BioResource, and Clinical Research Facility and Biomedical Research Centre based at Guy's and St Thomas' National Health Service (NHS) Foundation Trust, in partnership with King's College London. SO is funded by the Wellcome Engineering and Physical Sciences Research Council (EPSRC) Centre for Medical Engineering (WT203148/Z/16/Z) and the Wellcome Flagship Programme (WT213038/Z/18/Z). CM is funded by the CDRF and the MRC AIMHY project grant. CHS is an Alzheimer's Society junior fellow (AS-JF-17-011). The School of Biomedical Engineering & Imaging Sciences is supported by the Wellcome EPSRC Centre for Medical Engineering at King's College London (WT203148/Z/16/Z) and the Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St Thomas' NHS Foundation Trust, in partnership with King's College London and King's College Hospital NHS Foundation Trust. ATC is a Stuart and Suzanne Steele MGH Research Scholar. LHN is supported by an NIH K23DK125838 award, the American Gastroenterological Association Research Scholar Award, and the Crohn's and Colitis Foundation Career Development Award. DAD and LHN are supported by the American Gastroenterological Association-Takeda COVID-19 Rapid Response Research Award (AGA2021-5102). DAD is supported by NIH/National Institute of Health Diabetes and Digestive and Kidney Diseases (K01DK120742). ATC, LHN, and DAD are supported by the Massachusetts Consortium on Pathogen Readiness. JM is partially supported by the NIH (DK40561) and the American Diabetes Association (7-21-JDFM-005). PL is funded by the CDRF. AMV is funded by a UKRI and MRC Covid-Rapid Response grant (MR/V027883/1). We thank all participants, including study volunteers enrolled in cohorts within the COPE consortium. We thank the staff of ZOE Global, the Department of Twin Research & Genetic Epidemiology at King's College London, the Clinical & Translational Epidemiology Unit at Massachusetts General Hospital, and researchers and staff at Lund University in Sweden for their tireless work in contributing to the running of the study and data collection. Supplementary Material (1) Supplementary appendix References Public Health England COVID-19 vaccination programme Department of Health and Social Care Priority groups for coronavirus (COVID-19) vaccination: advice from the JCVI, 30 December 2020 Polack, FP ∙ Thomas, SJ ∙ Kitchin, N ∙ et al. Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine N Engl J Med. 2020; 383 :2603-2615 Dagan, N ∙ Barda, N ∙ Kepten, E ∙ et al. BNT162b2 mRNA COVID-19 vaccine in a nationwide mass vaccination setting N Engl J Med. 2021; Hunter, PR ∙ Brainard, J Estimating the effectiveness of the Pfizer COVID-19 BNT162b2 vaccine after a single dose. A reanalysis of a study of “real-world” vaccination outcomes from Israel medRxiv. 2021; (preprint). Voysey, M ∙ Clemens, SAC ∙ Madhi, SA ∙ et al. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK Lancet. 2021; 397 :99-111 Ramasamy, MN ∙ Minassian, AM ∙ Ewer, KJ ∙ et al. Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial Lancet. 2021; 396 :1979-1993 Voysey, M ∙ Clemens, SAC ∙ Madhi, SA ∙ et al. Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials Lancet. 2021; 397 :881-891 Public Health England COVID-19: vaccine surveillance strategy The OpenSAFELY Collaborative ∙ MacKenna, B ∙ Curtis, HJ ∙ et al. Trends, regional variation, and clinical characteristics of COVID-19 vaccine recipients: a retrospective cohort study in 23·4 million patients using OpenSAFELY medRxiv. 2021; (preprint). Lopez Bernal, J ∙ Andrews, N ∙ Gower, C ∙ et al. Early effectiveness of COVID-19 vaccination with BNT162b2 mRNA vaccine and ChAdOx1 adenovirus vector vaccine on symptomatic disease, hospitalisations and mortality in older adults in England medRxiv. 2021; (preprint). Vasileiou, E ∙ Simpson, CR ∙ Shi, T ∙ et al. Interim findings from first-dose mass COVID-19 vaccination roll-out and COVID-19 hospital admissions in Scotland: a national prospective cohort study Lancet. 2021; Hall, VJ ∙ Foulkes, S ∙ Saei, A ∙ et al. COVID-19 vaccine coverage in health-care workers in England and effectiveness of BNT162b2 mRNA vaccine against infection (SIREN): a prospective, multicentre, cohort study Lancet. 2021; Menni, C ∙ Valdes, AM ∙ Freidin, MB ∙ et al. Real-time tracking of self-reported symptoms to predict potential COVID-19 Nat Med. 2020; 26 :1037-1040 Drew, DA ∙ Nguyen, LH ∙ Steves, CJ ∙ et al. Rapid implementation of mobile technology for real-time epidemiology of COVID-19 Science. 2020; 368 :1362-1367 Pearl, J Causality Cambridge University Press, Cambridge, 2009 Office for National Statistics Coronavirus (COVID-19) Infection Survey Varsavsky, T ∙ Graham, MS ∙ Canas, LS ∙ et al. Detecting COVID-19 infection hotspots in England using large-scale self-reported data from a mobile application: a prospective, observational study Lancet Public Health. 2021; 6 :e21-e29 Murray, B ∙ Kerfoot, E ∙ Graham, MS ∙ et al. Accessible data curation and analytics for international-scale citizen science datasets arXiv. 2020; (preprint). Ministry of Housing, Communities, and Local Government English indices of deprivation 2019 Saadat, S ∙ Rikhtegaran-Tehrani, Z ∙ Logue, J ∙ et al. Single dose vaccination in healthcare workers previously infected with SARS-CoV-2 medRxiv. 2021; (preprint). Krammer, F ∙ Srivastava, K ∙ Simon, V Robust spike antibody responses and increased reactogenicity in seropositive individuals after a single dose of SARS-CoV-2 mRNA vaccine medRxiv. 2021; (preprint). Wise, J COVID-19: people who have had infection might only need one dose of mRNA vaccine BMJ. 2021; 372 :n308 Office for National Statistics Population estimates for the UK, England and Wales, Scotland and Northern Ireland, provisional: mid-2019 Manisty, C ∙ Otter, AD ∙ Treibel, TA ∙ et al. Antibody response to first BNT162b2 dose in previously SARS-CoV-2-infected individuals Lancet. 2021; 397 :1057-1058 Chodick, G ∙ Tene, L ∙ Patalon, T ∙ et al. The effectiveness of the first dose of BNT162b2 vaccine in reducing SARS-CoV-2 infection 13–24 days after immunization: real-world evidence medRxiv. 2021; (preprint). Baltrusaitis, K ∙ Santillana, M ∙ Crawley, AW ∙ et al. Determinants of participants' follow-up and characterization of representativeness in flu near you, a participatory disease surveillance system JMIR Public Health Surveill. 2017; 3 :e18 Bowyer, RCE ∙ Varsavsky, T ∙ Thompson, EJ ∙ et al. Geo-social gradients in predicted COVID-19 prevalence in Great Britain: results from 1 960 242 users of the COVID-19 Symptoms Study app Thorax. 2020; Griffith, GJ ∙ Morris, TT ∙ Tudball, MJ ∙ et al. Collider bias undermines our understanding of COVID-19 disease risk and severity Nat Commun. 2020; 11 , 5749
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[Ok](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) # Vaccine side-effects and SARS-CoV-2 infection after vaccination in users of the COVID Symptom Study app in the UK: a prospective observational study [Cristina Menni, PhD](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) Cristina Menni, PhD Correspondence Correspondence to: Dr Cristina Menni, Department of Twin Research & Genetic Epidemiology, King's College London, London SE1 7EH, UK [cristina.menni@kcl.ac.uk](mailto:cristina.menni@kcl.ac.uk "Send email to Cristina Menni") Footnotes † Contributed equally Affiliations Department of Twin Research & Genetic Epidemiology, King's College London, London, UK [Search for articles by this author](https://www.thelancet.com/authored-by/Menni/Cristina) [a](),[†]() [cristina.menni@kcl.ac.uk](mailto:cristina.menni@kcl.ac.uk "Send email to Cristina Menni") ∙ [Kerstin Klaser, MSc](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) Kerstin Klaser, MSc Footnotes † Contributed equally Affiliations School of Biomedical Engineering & Imaging Sciences, King's College London, London, UK [Search for articles by this author](https://www.thelancet.com/authored-by/Klaser/Kerstin) [b](),[†]() ∙ [Anna May, MA](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) Anna May, MA Affiliations ZOE Global, London, UK [Search for articles by this author](https://www.thelancet.com/authored-by/May/Anna) [c]() ∙ [Lorenzo Polidori, MSc](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) Lorenzo Polidori, MSc Affiliations ZOE Global, London, UK [Search for articles by this author](https://www.thelancet.com/authored-by/Polidori/Lorenzo) [c]() ∙ [Joan Capdevila, PhD](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) Joan Capdevila, PhD Affiliations ZOE Global, London, UK [Search for articles by this author](https://www.thelancet.com/authored-by/Capdevila/Joan) [c]() ∙ [Panayiotis Louca, MSc](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) Panayiotis Louca, MSc Affiliations Department of Twin Research & Genetic Epidemiology, King's College London, London, UK [Search for articles by this author](https://www.thelancet.com/authored-by/Louca/Panayiotis) [a]() ∙ [Carole H Sudre, PhD](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) Carole H Sudre, PhD Affiliations School of Biomedical Engineering & Imaging Sciences, King's College London, London, UK Medical Research Council Unit for Lifelong Health and Ageing, Department of Population Science and Experimental Medicine, and Centre for Medical Image Computing, Department of Computer Science, University College London, London, UK [Search for articles by this author](https://www.thelancet.com/authored-by/Sudre/Carole+H) [b](),[d]() ∙ [Long H Nguyen, MD](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) Long H Nguyen, MD Affiliations Clinical & Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA [Search for articles by this author](https://www.thelancet.com/authored-by/Nguyen/Long+H) [e](),[f]() ∙ [David A Drew, PhD](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) David A Drew, PhD Affiliations Clinical & Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA [Search for articles by this 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[Search for articles by this author](https://www.thelancet.com/authored-by/Selvachandran/Somesh) [c]() ∙ [Michela Antonelli, PhD](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) Michela Antonelli, PhD Affiliations School of Biomedical Engineering & Imaging Sciences, King's College London, London, UK [Search for articles by this author](https://www.thelancet.com/authored-by/Antonelli/Michela) [b]() ∙ [Benjamin Murray, MSc](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) Benjamin Murray, MSc Affiliations School of Biomedical Engineering & Imaging Sciences, King's College London, London, UK [Search for articles by this author](https://www.thelancet.com/authored-by/Murray/Benjamin) [b]() ∙ [Liane S Canas, PhD](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) Liane S Canas, PhD Affiliations School of Biomedical Engineering & Imaging Sciences, King's College London, London, UK [Search for articles by this author](https://www.thelancet.com/authored-by/Canas/Liane+S) [b]() ∙ [Erika Molteni, PhD](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) Erika Molteni, PhD Affiliations School of Biomedical Engineering & Imaging Sciences, King's College London, London, UK [Search for articles by this author](https://www.thelancet.com/authored-by/Molteni/Erika) [b]() ∙ [Mark S Graham, PhD](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) Mark S Graham, PhD Affiliations School of Biomedical Engineering & Imaging Sciences, King's College London, London, UK [Search for articles by this author](https://www.thelancet.com/authored-by/Graham/Mark+S) [b]() ∙ [Marc Modat, PhD](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) Marc Modat, PhD Affiliations School of Biomedical Engineering & Imaging Sciences, King's College London, London, UK [Search for articles by this 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Medical School, Boston, MA, USA Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA [Search for articles by this author](https://www.thelancet.com/authored-by/Chan/Andrew+T) [e](),[f]() ∙ [Jonathan Wolf, MA](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) Jonathan Wolf, MA Affiliations ZOE Global, London, UK [Search for articles by this author](https://www.thelancet.com/authored-by/Wolf/Jonathan) [c]() ∙ [Claire J Steves, PhD](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) Claire J Steves, PhD Affiliations Department of Twin Research & Genetic Epidemiology, King's College London, London, UK [Search for articles by this author](https://www.thelancet.com/authored-by/Steves/Claire+J) [a]() ∙ [Prof Ana M Valdes, PhD](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) Prof Ana M Valdes, PhD Affiliations Department of Twin Research & Genetic Epidemiology, King's College London, London, UK Nottingham NIHR Biomedical Research Centre at the School of Medicine, University of Nottingham, Nottingham City Hospital, Nottingham, UK [Search for articles by this author](https://www.thelancet.com/authored-by/Valdes/Ana+M) [a](),[k]() ∙ [Prof Sebastien Ourselin, PhD](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) Prof Sebastien Ourselin, PhD Affiliations School of Biomedical Engineering & Imaging Sciences, King's College London, London, UK [Search for articles by this author](https://www.thelancet.com/authored-by/Ourselin/Sebastien) [b]() ∙ [Prof Tim D Spector, MD](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) Prof Tim D Spector, MD Affiliations Department of Twin Research & Genetic Epidemiology, King's College London, London, UK [Search for articles by this 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Show more Show less Affiliations & Notes Article Info Linked Articles (1) aDepartment of Twin Research & Genetic Epidemiology, King's College London, London, UK bSchool of Biomedical Engineering & Imaging Sciences, King's College London, London, UK cZOE Global, London, UK dMedical Research Council Unit for Lifelong Health and Ageing, Department of Population Science and Experimental Medicine, and Centre for Medical Image Computing, Department of Computer Science, University College London, London, UK eClinical & Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA fDivision of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA gDiabetes Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA hDepartment of Medicine, Harvard Medical School, Boston, MA, USA iProgram in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA jNational Institute for Health Research (NIHR) Biomedical Research Centre at Guy's and St Thomas' Foundation Trust, London, UK kNottingham NIHR Biomedical Research Centre at the School of Medicine, University of Nottingham, Nottingham City Hospital, Nottingham, UK lDepartment of Infection, Guy's and St Thomas' Foundation Trust, St Thomas Hospital, London, UK † Contributed equally Publication History: Published April 27, 2021 DOI: [10\.1016/S1473-3099(21)00224-3 External Link](https://doi.org/10.1016/S1473-3099\(21\)00224-3)Also available on [ScienceDirect External Link](https://www.sciencedirect.com/science/article/pii/S1473309921002243) Copyright: © 2021 The Author(s). Published by Elsevier Ltd. User License: [Creative Commons Attribution (CC BY 4.0)](http://creativecommons.org/licenses/by/4.0/) \\| [Elsevier's open access license policy](https://www.elsevier.com/open-access) - Comment [Symptom study app provides real-world data on COVID-19 vaccines](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00264-4/fulltext "Symptom study app provides real-world data on COVID-19 vaccines") - Drury et al. The Lancet Infectious DiseasesApril 27, 2021 [![Cover Image - The Lancet Infectious Diseases, Volume 21, Issue 7](https://www.thelancet.com/cms/asset/23c68d6a-1234-448a-b73c-a4f31e48f53d/cov200h.gif)](https://www.thelancet.com/journals/laninf/issue/vol21no7/PIIS1473-3099\(21\)X0007-2) [Download PDFDownload PDF](https://www.thelancet.com/action/showPdf?pii=S1473-3099%2821%2900224-3 "Standard PDF (opens in a new tab)") Outline Outline - [Summary](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext#author-abstract) - [Introduction](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext#sec-1) - [Methods](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext#sec-2) - [Results](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext#sec-3) - [Discussion](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext#sec-4) - [Data sharing](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext#sec-5) - 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[Data sharing](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext#sec-5) - [Declaration of interests](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext#conflict) - [Supplementary Material (1)](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext#supplementary-material) - [References](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext#references) - [Article metrics](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext#core-collateral-metrics) ## Summary ### Background The Pfizer-BioNTech (BNT162b2) and the Oxford-AstraZeneca (ChAdOx1 nCoV-19) COVID-19 vaccines have shown excellent safety and efficacy in phase 3 trials. We aimed to investigate the safety and effectiveness of these vaccines in a UK community setting. ### Methods In this prospective observational study, we examined the proportion and probability of self-reported systemic and local side-effects within 8 days of vaccination in individuals using the COVID Symptom Study app who received one or two doses of the BNT162b2 vaccine or one dose of the ChAdOx1 nCoV-19 vaccine. We also compared infection rates in a subset of vaccinated individuals subsequently tested for SARS-CoV-2 with PCR or lateral flow tests with infection rates in unvaccinated controls. All analyses were adjusted by age (≤55 years vs \>55 years), sex, health-care worker status (binary variable), obesity (BMI \<30 kg/m2vs ≥30 kg/m2), and comorbidities (binary variable, with or without comorbidities). ### Findings Between Dec 8, and March 10, 2021, 627 383 individuals reported being vaccinated with 655 590 doses: 282 103 received one dose of BNT162b2, of whom 28 207 received a second dose, and 345 280 received one dose of ChAdOx1 nCoV-19. Systemic side-effects were reported by 13·5% (38 155 of 282 103) of individuals after the first dose of BNT162b2, by 22·0% (6216 of 28 207) after the second dose of BNT162b2, and by 33·7% (116 473 of 345 280) after the first dose of ChAdOx1 nCoV-19. Local side-effects were reported by 71·9% (150 023 of 208 767) of individuals after the first dose of BNT162b2, by 68·5% (9025 of 13 179) after the second dose of BNT162b2, and by 58·7% (104 282 of 177 655) after the first dose of ChAdOx1 nCoV-19. Systemic side-effects were more common (1·6 times after the first dose of ChAdOx1 nCoV-19 and 2·9 times after the first dose of BNT162b2) among individuals with previous SARS-CoV-2 infection than among those without known past infection. Local effects were similarly higher in individuals previously infected than in those without known past infection (1·4 times after the first dose of ChAdOx1 nCoV-19 and 1·2 times after the first dose of BNT162b2). 3106 of 103 622 vaccinated individuals and 50 340 of 464 356 unvaccinated controls tested positive for SARS-CoV-2 infection. Significant reductions in infection risk were seen starting at 12 days after the first dose, reaching 60% (95% CI 49–68) for ChAdOx1 nCoV-19 and 69% (66–72) for BNT162b2 at 21–44 days and 72% (63–79) for BNT162b2 after 45–59 days. ### Interpretation Systemic and local side-effects after BNT162b2 and ChAdOx1 nCoV-19 vaccination occur at frequencies lower than reported in phase 3 trials. Both vaccines decrease the risk of SARS-CoV-2 infection after 12 days. ### Funding ZOE Global, National Institute for Health Research, Chronic Disease Research Foundation, National Institutes of Health, UK Medical Research Council, Wellcome Trust, UK Research and Innovation, American Gastroenterological Association. ## Introduction The UK's Medicines and Healthcare products Regulatory Agency has given emergency use authorisation to three COVID-19 vaccines: the Pfizer-BioNTech mRNA vaccine (BNT162b2), the Oxford-AstraZeneca adenovirus-vectored vaccine (ChAdOx1 nCoV-19), and the Moderna mRNA vaccine (mRNA-1273). The first two vaccines have been rolled out across the UK since Dec 8, 2020, and Jan 4, 2021, respectively. [1](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) 1\. Public Health England COVID-19 vaccination programme <https://www.gov.uk/government/collections/covid-19-vaccination-programme> Date: Nov 27, 2020 Date accessed: February 18, 2021 [Google Scholar](https://scholar.google.com/scholar?q=Public+Health+EnglandCOVID-19+vaccination+programmehttps%3A%2F%2Fwww.gov.uk%2Fgovernment%2Fcollections%2Fcovid-19-vaccination-programmeNov+27%2C+2020) In late December, 2020, based on advice from the Joint Committee on Vaccination and Immunisation, [2](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) 2\. Department of Health and Social Care Priority groups for coronavirus (COVID-19) vaccination: advice from the JCVI, 30 December 2020 <https://www.gov.uk/government/publications/priority-groups-for-coronavirus-covid-19-vaccination-advice-from-the-jcvi-30-december-2020?utm_source=f1de4cd1-935e-4a5e-b539-3b37cd92e598> Date: Dec 30, 2020 Date accessed: February 18, 2021 [Google Scholar](https://scholar.google.com/scholar?q=Department+of+Health+and+Social+CarePriority+groups+for+coronavirus+%28COVID-19%29+vaccination%3A+advice+from+the+JCVI%2C+30+December+2020https%3A%2F%2Fwww.gov.uk%2Fgovernment%2Fpublications%2Fpriority-groups-for-coronavirus-covid-19-vaccination-advice-from-the-jcvi-30-december-2020%3Futm_source%3Df1de4cd1-935e-4a5e-b539-3b37cd92e598Dec+30%2C+2020) the UK Government decided to delay the administration of second doses. Phase 3 trials reported the BNT162b2 vaccine to have an efficacy of 52% at 12 days after the first dose and of 95% after the second dose if administered 3–4 weeks apart in participants without previous SARS-CoV-2 infection. [3](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) 3\. Polack, FP ∙ Thomas, SJ ∙ Kitchin, N ∙ et al. Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine N Engl J Med. 2020; 383:2603-2615 [Crossref](https://doi.org/10.1056/NEJMoa2034577) [Scopus (10099)](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_3_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85098117107) [PubMed](https://pubmed.ncbi.nlm.nih.gov/33301246/) [Google Scholar](https://scholar.google.com/scholar_lookup?doi=10.1056%2FNEJMoa2034577&pmid=33301246) The effectiveness of this vaccine in reducing infection, severe disease, hospitalisation, and death with COVID-19 has been reported for the whole of Israel, [4](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) 4\. Dagan, N ∙ Barda, N ∙ Kepten, E ∙ et al. BNT162b2 mRNA COVID-19 vaccine in a nationwide mass vaccination setting N Engl J Med. 2021; published online Feb 24. <https://doi.org/10.1056/nejmoa2101765> [Scopus (1814)](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_4_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85103719376) [PubMed](https://pubmed.ncbi.nlm.nih.gov/33626250/) [Google Scholar](https://scholar.google.com/scholar_lookup?doi=10.1056%2FNEJMoa2101765&pmid=33626250) with reanalysis of the data from Israel revealing it to be 90% effective 2 weeks after the first dose. [5](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) 5\. Hunter, PR ∙ Brainard, J Estimating the effectiveness of the Pfizer COVID-19 BNT162b2 vaccine after a single dose. A reanalysis of a study of “real-world” vaccination outcomes from Israel medRxiv. 2021; published online Feb 3. <https://doi.org/10.1101/2021.02.01.21250957> (preprint). [Google Scholar](https://scholar.google.com/scholar?q=PRHunterJBrainardEstimating+the+effectiveness+of+the+Pfizer+COVID-19+BNT162b2+vaccine+after+a+single+dose.+A+reanalysis+of+a+study+of+%E2%80%9Creal-world%E2%80%9D+vaccination+outcomes+from+IsraelmedRxiv2021published+online+Feb+3.https%3A%2F%2Fdoi.org%2F10.1101%2F2021.02.01.21250957%28preprint%29.) The ChAdOx1 nCoV-19 trial found efficacy against symptomatic disease of 76% at 22–90 days after at least one standard dose. [6–8](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) 6\. Voysey, M ∙ Clemens, SAC ∙ Madhi, SA ∙ et al. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK Lancet. 2021; 397:99-111 [Full Text](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_6_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS0140-6736%2820%2932661-1&cf=fulltext&site=lancet-site) [Full Text (PDF)](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_6_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS0140-6736%2820%2932661-1&cf=pdf&site=lancet-site) [Scopus (3425)](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_6_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85097463811) [PubMed](https://pubmed.ncbi.nlm.nih.gov/33306989/) [Google Scholar](https://scholar.google.com/scholar_lookup?doi=10.1016%2FS0140-6736%2820%2932661-1&pmid=33306989) 7\. Ramasamy, MN ∙ Minassian, AM ∙ Ewer, KJ ∙ et al. Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial Lancet. 2021; 396:1979-1993 [Full Text](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_7_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS0140-6736%2820%2932466-1&cf=fulltext&site=lancet-site) [Full Text (PDF)](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_7_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS0140-6736%2820%2932466-1&cf=pdf&site=lancet-site) [Scopus (1091)](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_7_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85097243389) [PubMed](https://pubmed.ncbi.nlm.nih.gov/33220855/) [Google Scholar](https://scholar.google.com/scholar_lookup?doi=10.1016%2FS0140-6736%2820%2932466-1&pmid=33220855) 8\. Voysey, M ∙ Clemens, SAC ∙ Madhi, SA ∙ et al. Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials Lancet. 2021; 397:881-891 [Full Text](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_8_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS0140-6736%2821%2900432-3&cf=fulltext&site=lancet-site) [Full Text (PDF)](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_8_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS0140-6736%2821%2900432-3&cf=pdf&site=lancet-site) [Scopus (828)](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_8_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85101846197) [PubMed](https://pubmed.ncbi.nlm.nih.gov/33617777/) [Google Scholar](https://scholar.google.com/scholar_lookup?doi=10.1016%2FS0140-6736%2821%2900432-3&pmid=33617777) Research in context Evidence before this study We searched PubMed for articles published up to March 10, 2021, using the terms (“BNT162b2“ OR “mRNA Covid-19 Vaccine” OR “ChAdOx1 nCoV-19” OR “adenovirus-vectored Covid-19 vaccine”) AND (“effectiveness” OR “reinfection” OR “side-effects” OR “adverse effects” OR “reactogenicity” OR “phase IV”). We did not restrict our search by language or type of publication. Besides the original phase 1–3 trials, we found one published article and two preprints on data from Israel investigating the effectiveness of the Pfizer-BioNTech vaccine (BNT162b2), a preprint from the UK exploring the effectiveness of both the BNT162b2 and Oxford-AstraZeneca (ChAdOx1 nCoV-19) vaccines in individuals aged 70 years or older in the community, and a study that linked health records for all vaccinated people in Scotland to investigate COVID-19 hospitalisation and mortality after vaccination. No study investigated the prevalence of adverse effects of the vaccines and all studies reported both vaccines to be highly effective. Added value of this study In this large prospective observational study, we assessed adverse effects from the two COVID-19 vaccines in use in the UK at the time of writing (BNT162b2 and ChAdOx1 nCoV-19), as well as self-reported infection rates following one dose or two doses of BNT162b2 and one dose of ChAdOx1 nCoV-19. Reported side-effects were minor in severity and of short duration. Headache and fatigue were more common in women than in men, in people aged 55 years or younger than in people older than 55 years, and after the second than after the first dose. Individuals with known past SARS-CoV-2 infection were more likely to have adverse effects after the first dose than were those without known past infection. We found, in a community setting, that self-reported infection rates of those vaccinated with the BNT162b2 or ChAdOx1 nCoV-19 vaccines were significantly lower than infection rates in unvaccinated controls. Documented infection rates in our app after a single vaccine dose decreased by 58% (95% CI 54–62) at 12–20 days, 69% (66–72) at 21–44 days, and 72% (63–79) after 45–59 days following BNT162b2, and 39% (21–53) at 12–20 days and 60% (49–68) at 21–44 days following ChAdOx1 nCoV-19, compared with unvaccinated controls. Implications of all the available evidence Localised and systemic side-effects after vaccination are less common in a real-world community setting than reported in phase 3 trials, mostly minor in severity, and self-limiting. Our data will enable prediction of side-effects based on age, sex, and past COVID-19 status to help update guidance to health professionals to reassure the population about the safety of vaccines. Surveillance in the general population is necessary at this stage during vaccination rollout. [9](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) 9\. Public Health England COVID-19: vaccine surveillance strategy <https://www.gov.uk/government/publications/covid-19-vaccine-surveillance-strategy> Date: Jan 11, 2021 Date accessed: March 17, 2021 [Google Scholar](https://scholar.google.com/scholar?q=Public+Health+EnglandCOVID-19%3A+vaccine+surveillance+strategyhttps%3A%2F%2Fwww.gov.uk%2Fgovernment%2Fpublications%2Fcovid-19-vaccine-surveillance-strategyJan+11%2C+2021) The OpenSAFELY collaboration [10](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) 10\. The OpenSAFELY Collaborative ∙ MacKenna, B ∙ Curtis, HJ ∙ et al. Trends, regional variation, and clinical characteristics of COVID-19 vaccine recipients: a retrospective cohort study in 23·4 million patients using OpenSAFELY medRxiv. 2021; published online Jan 26. <https://doi.org/10.1101/2021.01.25.21250356> (preprint). [Google Scholar](https://scholar.google.com/scholar?q=The+OpenSAFELY+CollaborativeBMacKennaHJCurtisTrends%2C+regional+variation%2C+and+clinical+characteristics+of+COVID-19+vaccine+recipients%3A+a+retrospective+cohort+study+in+23%C2%B74+million+patients+using+OpenSAFELYmedRxiv2021published+online+Jan+26.https%3A%2F%2Fdoi.org%2F10.1101%2F2021.01.25.21250356%28preprint%29.) implemented a framework for monitoring vaccine rollout and coverage in the UK via record linkage, Public Health England has reported early data on effectiveness in the older population prioritised for vaccination, [11](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) 11\. Lopez Bernal, J ∙ Andrews, N ∙ Gower, C ∙ et al. Early effectiveness of COVID-19 vaccination with BNT162b2 mRNA vaccine and ChAdOx1 adenovirus vector vaccine on symptomatic disease, hospitalisations and mortality in older adults in England medRxiv. 2021; published online March 2. <https://doi.org/10.1101/2021.03.01.21252652> (preprint). [Google Scholar](https://scholar.google.com/scholar?q=JLopez+BernalNAndrewsCGowerEarly+effectiveness+of+COVID-19+vaccination+with+BNT162b2+mRNA+vaccine+and+ChAdOx1+adenovirus+vector+vaccine+on+symptomatic+disease%2C+hospitalisations+and+mortality+in+older+adults+in+EnglandmedRxiv2021published+online+March+2.https%3A%2F%2Fdoi.org%2F10.1101%2F2021.03.01.21252652%28preprint%29.) and a prospective observational study investigated the association between the rollout of the first vaccine dose and COVID-19 hospital admission in Scotland. [12](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) 12\. Vasileiou, E ∙ Simpson, CR ∙ Shi, T ∙ et al. Interim findings from first-dose mass COVID-19 vaccination roll-out and COVID-19 hospital admissions in Scotland: a national prospective cohort study Lancet. 2021; published online April 23. <https://doi.org/10.1016/S0140-6736(21)00677-2> [Full Text](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_12_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS0140-6736%2821%2900677-2&cf=fulltext&site=lancet-site) [Full Text (PDF)](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_12_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS0140-6736%2821%2900677-2&cf=pdf&site=lancet-site) [Scopus (391)](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_12_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85104923342) [PubMed](https://pubmed.ncbi.nlm.nih.gov/33901420/) [Google Scholar](https://scholar.google.com/scholar_lookup?doi=10.1016%2FS0140-6736%2821%2900677-2&pmid=33901420) Other surveys, such as the SIREN study [13](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) 13\. Hall, VJ ∙ Foulkes, S ∙ Saei, A ∙ et al. COVID-19 vaccine coverage in health-care workers in England and effectiveness of BNT162b2 mRNA vaccine against infection (SIREN): a prospective, multicentre, cohort study Lancet. 2021; published online April 23. <https://doi.org/10.1016/S0140-6736(21)00790-X> [Full Text](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_13_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS0140-6736%2821%2900675-9&cf=fulltext&site=lancet-site) [Full Text (PDF)](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_13_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS0140-6736%2821%2900675-9&cf=pdf&site=lancet-site) [Scopus (443)](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_13_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85104104418) [PubMed](https://pubmed.ncbi.nlm.nih.gov/33844963/) [Google Scholar](https://scholar.google.com/scholar_lookup?doi=10.1016%2FS0140-6736%2821%2900675-9&pmid=33844963) in health-care workers, will also link directly to health records to assess the real-life effectiveness and safety of the various phases of vaccine rollout. However, it takes time for such studies to come to fruition. Real-time data from app users can provide a faster view of the safety and effectiveness of COVID-19 vaccines. The aim of this study was to investigate the adverse effects and infection rate of vaccinated people in a community (general population app users) scenario. We used data from 627 383 individuals who received the BNT162b2 or ChAdOx1 nCoV-19 vaccines between December, 2020, and March, 2021, and reported symptoms in real-time via the COVID Symptom Study app. [14](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) 14\. Menni, C ∙ Valdes, AM ∙ Freidin, MB ∙ et al. Real-time tracking of self-reported symptoms to predict potential COVID-19 Nat Med. 2020; 26:1037-1040 [Crossref](https://doi.org/10.1038/s41591-020-0916-2) [Scopus (944)](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_14_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85084445397) [PubMed](https://pubmed.ncbi.nlm.nih.gov/32393804/) [Google Scholar](https://scholar.google.com/scholar_lookup?doi=10.1038%2Fs41591-020-0916-2&pmid=32393804) A subset of individuals also reported receiving a PCR or lateral flow test. ## Methods ### Study design and participants The COVID Symptom Study app [14](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) 14\. Menni, C ∙ Valdes, AM ∙ Freidin, MB ∙ et al. Real-time tracking of self-reported symptoms to predict potential COVID-19 Nat Med. 2020; 26:1037-1040 [Crossref](https://doi.org/10.1038/s41591-020-0916-2) [Scopus (944)](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_14_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85084445397) [PubMed](https://pubmed.ncbi.nlm.nih.gov/32393804/) [Google Scholar](https://scholar.google.com/scholar_lookup?doi=10.1038%2Fs41591-020-0916-2&pmid=32393804) was developed by health data company ZOE Global, with input from King's College London (London, UK), the Massachusetts General Hospital (Boston, MA, USA), Lund University (Lund, Sweden), and Uppsala University (Uppsala, Sweden). In the UK, it was launched in English on March 24, 2020. The app enables self-reported information related to SARS-CoV-2 infection to be captured. Individuals older than 18 years can sign up to the app without any restrictions. Individuals can also record information for dependents younger than 18 years. Use of the app was driven by referrals or word of mouth, the media, and eventually partnerships with charities and the Welsh and Scottish Governments. [15](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) 15\. Drew, DA ∙ Nguyen, LH ∙ Steves, CJ ∙ et al. Rapid implementation of mobile technology for real-time epidemiology of COVID-19 Science. 2020; 368:1362-1367 [Crossref](https://doi.org/10.1126/science.abc0473) [Scopus (266)](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_15_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85086031247) [PubMed](https://pubmed.ncbi.nlm.nih.gov/32371477/) [Google Scholar](https://scholar.google.com/scholar_lookup?doi=10.1126%2Fscience.abc0473&pmid=32371477) On first use, the app records self-reported location, age, and core health risk factors (body-mass index \[BMI\], smoking status, race or ethnicity, and presence of comorbidities, including cancer, diabetes, eczema, heart disease, lung disease, kidney disease, and hay fever), as well as employment status, such as being a health-care worker. With continued use, participants provide daily updates on symptoms experienced, SARS-CoV-2 test results (negative, pending, or positive), vaccines administered, and whether they are self-quarantining or seeking health care, including the level of intervention and related outcomes. Individuals without symptoms are encouraged to report through the app every day. Through direct updates to the app, new or modified questions are added in real time to capture data to test emerging hypotheses about COVID-19 symptoms and treatments. Versions 2.1.0–2.4.0 of the app were in use during the study period. Participants were asked if they had been vaccinated for COVID-19 and, if so, to record the type of vaccine and date of administration. We included all UK app users reporting having received at least one dose of the two available vaccines ([appendix p 2](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext#supplementary-material)). Users reporting vaccination were then asked daily for the following 8 days whether they experienced adverse effects, including both systemic (whole body) and local effects. Systemic solicited side-effects included headache, fatigue, chills and shiver, diarrhoea, fever, arthralgia, myalgia, and nausea; solicited local side-effects included local pain, swelling, tenderness, redness, itch, warmth, and swollen armpit glands ([appendix p 6](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext#supplementary-material)). Users were also permitted to report no symptoms by leaving the box unchecked. Ethical approval for use of the app for research purposes in the UK was obtained from King's College London Ethics Committee (review reference LRS-19/20-18210), and all users provided consent for non-commercial use of their data. ### Outcomes Our primary outcome was the proportion of app users reporting adverse effects within 8 days after vaccination and the probability of having an adverse event. Our secondary outcome was infection rates in individuals after receiving a first dose of either the BNT162b2 or ChAdOx1 nCoV-19 vaccines. We did not collect information on why individuals were tested, so not all tested individuals were necessarily experiencing COVID-19-associated symptoms at testing, and some individuals might have been routinely tested while being asymptomatic. ### Statistical analysis We used χ2 and Student's t tests to compare the demographic characteristics of individuals who received BNT162b2 versus those who received ChAdOx1 nCoV-19. We investigated the evolution of systemic and local adverse effects within 8 days from the vaccination date, computing the percentage of users experiencing side-effects after having received the vaccine. Vaccinated individuals who logged their systemic or local effects (or the absence of them) at least once within 8 days from the vaccination date were included in the adverse effects analysis ([appendix p 2](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext#supplementary-material)). We estimated the ratio of the daily number of users reporting at least one adverse effect (systemic or local) after vaccination to the total number of vaccinated users logging into the app that day. The occurrence of adverse effects was studied for both BNT162b2 doses and the first ChAdOx1 nCoV-19 dose. We compared the probability of having adverse effects between the first and second BNT162b2 doses, the first BNT162b2 and the first ChAdOx1 nCoV-19 doses, and the second BNT162b2 and the first ChAdOx1 nCoV-19 doses. As different people received different vaccines, we used Pearl's back-door adjustment [16](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) 16\. Pearl, J Causality Cambridge University Press, Cambridge, 2009 [Crossref](https://doi.org/10.1017/CBO9780511803161) [Scopus (618)](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_16_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-84922937176) [Google Scholar](https://scholar.google.com/scholar_lookup?doi=10.1017%2FCBO9780511803161) to account for differences within the populations. Backdoor adjustments are used when there are both causal and non-causal paths between predictors (eg, vaccine treatment \[V\]) and an outcome. Because of the observational (non-interventional) nature of the study, the non-causal paths between outcomes and predictors that might involve age, sex, BMI, or health status need to be adjusted statistically. Backdoor adjustment methods essentially condition on these variables, cutting out the non-causal (indirect) links between a predictor and an outcome: 𝑃 ⁡ ( 𝑅 \\| 𝑑 ⁢ 𝑜 ⁡ \[ 𝑉 \] ) \= ∑ 𝑃 ⁡ ( 𝑅 \\| 𝑆 , 𝑉 ) ⁢ 𝑃 ⁡ ( 𝑆 ) where R is adverse effects, S is stratum, and P(R \\| S,V) is the probability of having adverse effects in a given stratum after receiving a vaccine. We used the following strata: age (≤55 years vs \>55 years), in line with stratification in the BNT162b2 and ChAdOx1 nCoV-19 phase 3 trials, [3](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) 3\. Polack, FP ∙ Thomas, SJ ∙ Kitchin, N ∙ et al. Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine N Engl J Med. 2020; 383:2603-2615 [Crossref](https://doi.org/10.1056/NEJMoa2034577) [Scopus (10099)](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_3_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85098117107) [PubMed](https://pubmed.ncbi.nlm.nih.gov/33301246/) [Google Scholar](https://scholar.google.com/scholar_lookup?doi=10.1056%2FNEJMoa2034577&pmid=33301246) sex, health-care worker status (binary variable), obesity (BMI \<30 kg/m2 vs ≥30 kg/m2), and comorbidities (binary variable, with or without comorbidities). Adjusted odds ratios (ORs) were computed after Pearl's back-door adjustment was applied to the raw rates (see [appendix p 15](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext#supplementary-material) for the formula). 95% CIs for ORs were obtained by bootstrapping 50 times on the vaccinated population. Logistic regressions were used for each of the specified strata to investigate whether adverse effects varied across different participant groups, and in individuals who had previously reported a positive test for COVID-19 (PCR or lateral flow positive at least 6 months before vaccination, PCR or lateral flow positive within the 6 months before vaccination, and no previously detected infection). Finally, in a subanalysis of vaccinated participants who reported having had the first dose of the BNT162b2 vaccine or one dose of the ChAdOx1 nCoV-19 vaccine and were then subsequently tested for SARS-CoV-2 infection, we investigated the change in infection rates after the first vaccine dose. We compared the outcomes of PCR or lateral flow tests in individuals who had been vaccinated with the first dose with those of unvaccinated individuals who reported having a COVID-19 test in the same week as a vaccinated app user. We computed the difference in days between when participants had the vaccine and when they were tested, and we used this metric to group users. If a person reported more than one PCR test or lateral flow result after being vaccinated, we selected the positive test, or if none were positive, the latest negative test. Since the BNT162b2 phase 3 trial showed a decrease in infections from 12 days after vaccination, [3](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) 3\. Polack, FP ∙ Thomas, SJ ∙ Kitchin, N ∙ et al. Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine N Engl J Med. 2020; 383:2603-2615 [Crossref](https://doi.org/10.1056/NEJMoa2034577) [Scopus (10099)](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_3_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85098117107) [PubMed](https://pubmed.ncbi.nlm.nih.gov/33301246/) [Google Scholar](https://scholar.google.com/scholar_lookup?doi=10.1056%2FNEJMoa2034577&pmid=33301246) we analysed infection rates at 0–4, 5–11, 12–20, 21–44, and 45–59 days after vaccination. For each of the vaccines and for different timepoints from the vaccination date, we used Poisson regressions to model the rates of positive tests in vaccinated individuals compared with those in the unvaccinated population, adjusting for the number of tests. This model allowed us to control for the number of follow-up days for each group. Moreover, as there was a two-times increase in daily incidence in England followed by a decrease of a similar proportion during the data collection period, [17](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) 17\. Office for National Statistics Coronavirus (COVID-19) Infection Survey <https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/datasets/coronaviruscovid19infectionsurveydata/2021> Date: March 12, 2021 Date accessed: March 16, 2021 [Google Scholar](https://scholar.google.com/scholar?q=Office+for+National+StatisticsCoronavirus+%28COVID-19%29+Infection+Surveyhttps%3A%2F%2Fwww.ons.gov.uk%2Fpeoplepopulationandcommunity%2Fhealthandsocialcare%2Fconditionsanddiseases%2Fdatasets%2Fcoronaviruscovid19infectionsurveydata%2F2021March+12%2C+2021) we also included incidence as a covariate in the Poisson regression model, with incidence calculated as previously described. [18](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) 18\. Varsavsky, T ∙ Graham, MS ∙ Canas, LS ∙ et al. Detecting COVID-19 infection hotspots in England using large-scale self-reported data from a mobile application: a prospective, observational study Lancet Public Health. 2021; 6:e21-e29 [Full Text](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_18_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS2468-2667%2820%2930269-3&cf=fulltext&site=lancet-site) [Full Text (PDF)](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_18_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS2468-2667%2820%2930269-3&cf=pdf&site=lancet-site) [Scopus (54)](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_18_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85099010576) [PubMed](https://pubmed.ncbi.nlm.nih.gov/33278917/) [Google Scholar](https://scholar.google.com/scholar_lookup?doi=10.1016%2FS2468-2667%2820%2930269-3&pmid=33278917) We defined the adjusted infection risk reduction (RR) as follows: R R \= r i s k r a t i o 𝑖 , 𝑛 − 1 where i is BNT162b2 or ChAdOx1 nCoV-19 vaccine, n is the number of days since vaccination (0–4, 5–11, 12–20, 21–44, 45–59), and the risk ratio is the coefficient of the vaccine status variables in the Poisson regression model. We further tested the role of covariates in risk of infection after vaccination by running stratified Poisson models (adjusted for confounders). For this analysis, we considered all app responders who were vaccinated with BNT162b2 or ChAdOx1 nCoV-19 vaccines at least 12 days before having a test for SARS-CoV-2 positivity. Due to a relatively small sample size in some of the strata, we did not differentiate between vaccine types but pooled all vaccinated contributors. Data were extracted and preprocessed using ExeTera version 0.3.2, [19](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) 19\. Murray, B ∙ Kerfoot, E ∙ Graham, MS ∙ et al. Accessible data curation and analytics for international-scale citizen science datasets arXiv. 2020; published online Nov 2. <http://arxiv.org/abs/2011.00867> (preprint). [PubMed](https://pubmed.ncbi.nlm.nih.gov/32550252/) [Google Scholar](https://scholar.google.com/scholar_lookup?pmid=32550252) a Python library developed at King's College London, and we did statistical analysis using Python version 3.7 (pandas, NumPy, and SciPy). ### Role of the funding source ZOE Global developed the app for data collection as a not-for-profit endeavour. The funder had no role in study design, data analysis, data interpretation, or writing of the report. ## Results Between Dec 8, 2020, and March 10, 2021, 655 590 vaccine doses were logged in the app in the UK, corresponding to 282 103 individuals (aged 16–99 years) who reported having received the first dose of the BNT162b2 vaccine, of whom 28 207 reported having had both doses of the BNT162b2 vaccine (a median of 41 days \[IQR 21–63\] apart), and 345 280 individuals who reported having had the first dose of ChAdOx1 nCoV-19. Participants joined the COVID Symptom Study app a mean of 288 days (SD 96) before being vaccinated. Users started logging adverse effects reports 0·79 days (SD 1·2) after they had the vaccine. 1 607 620 users were active in the app during the study period (logged at least an assessment since Dec 8), which represents 2·4% of the UK population. The mean age of app users was 50·6 years (SD 19·2), and 77 683 (4·8%) of them were health-care workers. Users who reported receiving a BNT162b2 vaccine were slightly younger, had more comorbidities, and were more frequently female than users who reported receiving a ChAdOx1 nCoV-19 inoculation ([table](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext#tbl1)). Moreover, health-care workers were more likely to receive a BNT162b2 vaccine than ChAdOx1 nCoV-19 ([appendix p 8](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext#supplementary-material)). The age distribution of the included individuals is presented in the [appendix (p 3)](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext#supplementary-material). \| \| \| \| \| \| \|---\|---\|---\|---\|---\| \| \| \| BNT162b2 \| ChAdOx1 nCoV-19 \| \| \| \| \| First dose (N=282 103) \| Second dose (N=28 207) \| First dose (N=345 280) \| \| Sex[\](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext#tbl1fn1) \| \| \| \| \| \| \| Female \| 173 866 (61·6%) \| 19 640 (69·6%) \| 199 269 (57·7%) \| \| \| Male \| 108 237 (38·4%) \| 8567 (30·4%) \| 146 011 (42·3%) \| \| Age, years[\](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext#tbl1fn1)[†](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext#tbl1fn2) \| 62·0 (14·3); 64 (54–72) \| 61·0 (17·3); 59 (49–76) \| 63·3 (11·5); 65 (59–71) \| \| \| Body-mass index, kg/m2[‡](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext#tbl1fn3) \| 26·8 (5·5) \| 26·5 (5·3) \| 26·8 (5·3) \| \| \| Health-care workers[\](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext#tbl1fn1) \| 31 996 (11·3%) \| 8828 (31·3%) \| 9746 (2·8%) \| \| \| Comorbidities[\](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext#tbl1fn1) \| 77 433 (27·4%) \| 7617 (27·0%) \| 88 453 (25·6%) \| \| \| Previous COVID-19[\](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext#tbl1fn1) \| 14 369 (5·1%) \| 2251 (8·0%) \| 14 231 (4·1%) \| \| \| Systemic side-effects \| \| \| \| \| \| \| Any \| 38 155 (13·5%) \| 6216 (22·0%) \| 116 473 (33·7%) \| \| \| Headache \| 21 910 (7·8%) \| 3731 (13·2%) \| 78 734 (22·8%) \| \| \| Fatigue \| 23 674 (8·4%) \| 4064 (14·4%) \| 72 924 (21·1%) \| \| \| Chills and shiver \| 7166 (2·5%) \| 1812 (6·4%) \| 50 761 (14·7%) \| \| \| Diarrhoea \| 3885 (1·4%) \| 416 (1·5%) \| 7546 (2·2%) \| \| \| Fever \| 4236 (1·5%) \| 1076 (3·8%) \| 28 268 (8·2%) \| \| \| Arthralgia \| 9021 (3·2%) \| 1978 (7·0%) \| 39 648 (11·5%) \| \| \| Myalgia \| 6479 (2·3%) \| 1415 (5·0%) \| 24 274 (7·0%) \| \| \| Nausea \| 5926 (2·1%) \| 981 (3·5%) \| 19 509 (5·7%) \| \| Local side-effects[§](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext#tbl1fn4) \| \| \| \| \| \| \| Any \| 150 023 (71·9%) \| 9025 (68·5%) \| 104 282 (58·7%) \| \| \| Pain \| 61 016 (29·2%) \| 4515 (34·3%) \| 33 939 (19·1%) \| \| \| Swelling \| 13 264 (6·4%) \| 1285 (9·8%) \| 9769 (5·5%) \| \| \| Tenderness \| 119 431 (57·2%) \| 6705 (50·9%) \| 87 609 (49·3%) \| \| \| Itch \| 6242 (3·0%) \| 840 (6·4%) \| 6934 (3·9%) \| \| \| Swollen armpit glands \| 2278 (1·1%) \| 549 (4·2%) \| 1994 (1·1%) \| \| \| Redness \| 7891 (3·8%) \| 953 (7·2%) \| 7431 (4·2%) \| \| \| Warmth \| 14 024 (6·7%) \| 1245 (9·4%) \| 14 033 (7·9%) \| \| \| Bruising \| 1872 (0·9%) \| 64 (0·5%) \| 4269 (2·4%) \| \| Allergic reactions \| \| \| \| \| \| \| Rash \| 682 (0·2%) \| 103 (0·4%) \| 1432 (0·4%) \| \| \| Skin burning \| 2075 (0·7%) \| 324 (1·1%) \| 5940 (1·7%) \| \| \| Red welts on face and lips \| 469 (0·2%) \| 59 (0·2%) \| 846 (0·2%) \| Table Demographic characteristics of the study population Data are n (%), unless otherwise indicated. \ p\<0·05 for the difference between the first dose of BNT162b2 and the first dose of ChAdOx1 nCoV-19 (Student's t test for continuous variables and χ2 test for categorical variables). † Data are mean (SD); median (IQR). ‡ Data are mean (SD). § Denominators are 208 767 for the first BNT162b2 dose, 13 179 for the second BNT162b2 dose, and 177 655 for the first ChAdOx1 nCoV-19 dose. - [Open table in a new tab](https://www.thelancet.com/action/showFullTableHTML?isHtml=true&tableId=tbl1&pii=S1473-3099%2821%2900224-3) Among vaccinated app users, 159 101 (25·4%) of 627 383 indicated having one or more systemic adverse effect, and 257 209 (66·2%) of 388 430 reported one or more local adverse effect ([table](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext#tbl1)). The most commonly reported systemic side-effects were fatigue and headache overall ([table](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext#tbl1)) and by strata ([appendix p 9](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext#supplementary-material)). These were most frequently reported within the first 24 h after vaccination and lasted a mean of 1·01 days (SD 0·1; [figure 1](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext#fig1)). Tenderness and local pain around the injection site were the most frequently reported local effects ([table](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext#tbl1)), occurring most often on the day after injection and lasting a mean of 1·02 days (SD 0·15; [figure 1](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext#fig1)). Other side-effects, including allergic skin reactions such as skin burning, rashes, and red welts on the lips and face, were reported by 10 860 (1·7%) of 627 383 users across both types of vaccine ([table](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext#tbl1); [appendix p 9](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext#supplementary-material)). In an exploratory analysis, we assessed the association between symptom reporting and socioeconomic status measured as index of multiple deprivation, [20](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) 20\. Ministry of Housing, Communities, and Local Government English indices of deprivation 2019 <https://www.gov.uk/government/statistics/english-indices-of-deprivation-2019> Date: Sept 26, 2019 Date accessed: February 12, 2021 [Google Scholar](https://scholar.google.com/scholar?q=Ministry+of+Housing%2C+Communities%2C+and+Local+GovernmentEnglish+indices+of+deprivation+2019https%3A%2F%2Fwww.gov.uk%2Fgovernment%2Fstatistics%2Fenglish-indices-of-deprivation-2019Sept+26%2C+2019) and we found a modest association (r\=0·021 \[95% CI 0·019–0·025\]), corresponding to 0·04% of the variance in symptoms reporting. [![](https://www.thelancet.com/cms/10.1016/S1473-3099\(21\)00224-3/asset/7936827d-8890-464f-9165-30c98891fdfa/main.assets/gr1.jpg)](https://www.thelancet.com/cms/10.1016/S1473-3099\(21\)00224-3/asset/b3402ef0-4ec3-437b-85c1-4ac3705e6fe3/main.assets/gr1_lrg.jpg "View full size image in a new tab") Figure 1 Proportion of participants self-reporting adverse effects to the COVID Symptom Study app within 8 days after vaccination Show full caption Figure viewer The top row shows systemic effects and the bottom row shows local effects within 8 days after receipt of the first dose (A, D) or second dose (B, E) of the BNT162b2 vaccine or the first dose of the ChAdOx1 nCoV-19 vaccine (C, F). Shading indicates 95% CIs. In the 28 207 individuals who reported having two BNT162b2 doses, 3325 (11·7%) reported at least one systemic effect after the first dose compared with 6216 (22·0%) after the second dose (p\<0·0001; [figure 2](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext#fig2)). When comparing systemic effects after one dose of each vaccine, reactogenicity was significantly higher in individuals who had one dose of the ChAdOx1 nCoV-19 vaccine than in those who had one dose of the BNT162b2 vaccine (116 473 \[33·7%\] of 345 280 compared with 38 155 \[13·5%\] of 282 103; adjusted p\<0·0001). [![](https://www.thelancet.com/cms/10.1016/S1473-3099\(21\)00224-3/asset/9e20a8bb-e4f1-4d2e-957e-7b1f55c55e39/main.assets/gr2.jpg)](https://www.thelancet.com/cms/10.1016/S1473-3099\(21\)00224-3/asset/6f6277f8-7df4-467b-b39b-9cdb977504c1/main.assets/gr2_lrg.jpg "View full size image in a new tab") Figure 2 Comparison of adverse effects self-reported to the COVID Symptom Study app between vaccine types and doses Show full caption Figure viewer ORs for comparisons of the first or second doses of BNT162b2 versus the first dose of ChAdOx1 nCoV-19 were adjusted using Pearl's back-door method. [16](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) 16\. Pearl, J Causality Cambridge University Press, Cambridge, 2009 [Crossref](https://doi.org/10.1017/CBO9780511803161) [Scopus (618)](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_16_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-84922937176) [Google Scholar](https://scholar.google.com/scholar_lookup?doi=10.1017%2FCBO9780511803161) OR=odds ratio. By contrast, local effects were less commonly reported after the second dose than after the first dose of BNT162b2 (9025 \[68·5%\] of 13 179 vs 150 023 \[71·9%\] of 208 767; p\<0·0001). Moreover, local effects were less commonly reported after the first ChAdOx1 nCoV-19 injection (104 282 \[58·7%\] of 177 655) than after the first BNT162b2 injection (adjusted p\<0·0001; [figure 2](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext#fig2)). When comparing the second BNT162b2 dose with the first ChAdOx1 nCoV-19 dose, we found that systemic effects occurred more frequently after the first ChAdOx1 nCoV-19 dose than after the second BNT162b2 dose (adjusted p\<0·0001; [figure 2](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext#fig2)), whereas local effects were less likely to appear after the first ChAdOx1 nCoV-19 injection than after the second BNT162b2 dose (adjusted p\<0·0001; [figure 2](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext#fig2)). We then tested whether adverse effects varied across individuals' characteristics, such as age and BMI groups, sex, and health status. The proportion of participants who reported at least one systemic effect after the first dose was significantly higher among people aged 55 years or younger than among those older than 55 years for both vaccines. After the first dose of BNT162b2, 16 733 (20·7%) of 80 879 people aged 55 years or younger reported at least one systemic effect compared with 21 422 (10·6%) of 201 224 people older than 55 years (OR 2·19 \[95% CI 2·14–2·24\]; p\<0·0001). For ChAdOx1 nCoV-19, 30 487 (46·9%) of 65 034 people aged 55 years or younger reported at least one systemic effect after the first dose compared with 85 986 (30·7%) of 280 243 older than 55 years (1·99 \[1·96–2·03\]; p\<0·0001). Women were more likely to report adverse effects than men (28 140 \[16·2%\] of 173 866 vs 10 015 \[9·3%\] of 108 237 after the first dose of BNT162b2, OR 1·89 \[95% CI 1·85–1·94\], p\<0·0001; 78 222 \[39·3%\] of 199 269 vs 38 251 \[26·2%\] of 146 011 after the first dose of ChAdOx1 nCoV-19, 1·82 \[1·79–1·85\], p\<0·0001). Although there were some differences between strata of BMI and co-morbidities, there was no clear trend across vaccines and doses ([figure 3](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext#fig3)). [![](https://www.thelancet.com/cms/10.1016/S1473-3099\(21\)00224-3/asset/6a3373a7-6236-4245-b406-f3eadf207a33/main.assets/gr3.jpg)](https://www.thelancet.com/cms/10.1016/S1473-3099\(21\)00224-3/asset/6d50aaf8-8e12-4c05-b5c0-e80f7b10b8b5/main.assets/gr3_lrg.jpg "View full size image in a new tab") Figure 3 Adverse effects self-reported to the COVID Symptom Study app after COVID-19 vaccination, stratified by sex, age, BMI, health status, and previous SARS-CoV-2 test status Show full caption Figure viewer Proportions with systemic adverse effects (A, C, E) and local adverse effects (B, D, F) are shown. Error bars represent 95% CIs. Numbers in each strata are reported in the [appendix (pp 13–14](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext#supplementary-material)). BMI=body-mass index. \p\<0·01. †p\<0·05. We observed the same trend for local effects as for systemic effects, whereby app users aged 55 years or younger reported more local side-effects than participants older than 55 years ([figure 3](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext#fig3)), and women were more likely to report local side-effects than men ([figure 3](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext#fig3); [appendix p 11](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext#supplementary-material)). Similar levels of side-effects were seen regardless of the levels of completeness of reporting by app users ([appendix p 12](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext#supplementary-material)). Given preliminary evidence from small studies [21–23](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) 21\. Saadat, S ∙ Rikhtegaran-Tehrani, Z ∙ Logue, J ∙ et al. Single dose vaccination in healthcare workers previously infected with SARS-CoV-2* medRxiv. 2021; published online Feb 1. <https://doi.org/10.1101/2021.01.30.21250843> (preprint). [Google Scholar](https://scholar.google.com/scholar?q=SSaadatZRikhtegaran-TehraniJLogueSingle+dose+vaccination+in+healthcare+workers+previously+infected+with+SARS-CoV-2medRxiv2021published+online+Feb+1.https%3A%2F%2Fdoi.org%2F10.1101%2F2021.01.30.21250843%28preprint%29.) 22\. Krammer, F ∙ Srivastava, K ∙ Simon, V Robust spike antibody responses and increased reactogenicity in seropositive individuals after a single dose of SARS-CoV-2 mRNA vaccine medRxiv. 2021; published online Feb 1. <https://doi.org/10.1101/2021.01.29.21250653> (preprint). [Google Scholar](https://scholar.google.com/scholar?q=FKrammerKSrivastavaVSimonRobust+spike+antibody+responses+and+increased+reactogenicity+in+seropositive+individuals+after+a+single+dose+of+SARS-CoV-2+mRNA+vaccinemedRxiv2021published+online+Feb+1.https%3A%2F%2Fdoi.org%2F10.1101%2F2021.01.29.21250653%28preprint%29.) 23\. Wise, J COVID-19: people who have had infection might only need one dose of mRNA vaccine BMJ. 2021; 372:n308 [Crossref](https://doi.org/10.1136/bmj.n308) [Scopus (43)](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_23_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85101276843) [PubMed](https://pubmed.ncbi.nlm.nih.gov/33531333/) [Google Scholar](https://scholar.google.com/scholar_lookup?doi=10.1136%2Fbmj.n308&pmid=33531333) suggesting that reactogenicity is higher among individuals previously infected with SARS-CoV-2, we investigated the extent to which previous SARS-CoV-2 infection (based on self-reported previous positive PCR or lateral flow result) was associated with reports of adverse effects. Individuals vaccinated with a single dose of BNT162b2 were more likely to report systemic effects if they had a previous SARS-CoV-2 positive test than were those without known past infection (5148 \[35·8%\] of 14 369 vs 33 007 \[12·3%\] of 267 734; OR 3·97 \[95% CI 3·83–4·12\], p\<0·0001). A similar effect was seen for ChAdOx1 nCoV-19 first dose inoculation (7551 \[53·1%\] of 14 231 with past infection vs 108 922 \[32·9%\] of 331 049 without past infection; 2·31 \[2·23–2·38\], p\<0·0001; [figure 3](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext#fig3)) and BNT162b2 second dose inoculation (859 \[38·2%\] of 2251 vs 5357 \[20·6%\] of 25 956; 2·37 \[2·17–2·60\], p\<0·0001). Local effects were similarly higher in individuals previously infected than in those without known past infection for both vaccines ([figure 3](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext#fig3)). No consistent difference in occurrence of systemic or local adverse effects was observed between individuals who reported a positive test result within the past 6 months and those who reported they received a positive test result at least 6 months ago ([figure 3](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext#fig3)). We also investigated infection rates after the first vaccine dose in a subset of 67 293 app users who received BNT162b2 and 36 329 who received ChAdOx1 nCoV-19 in the study period and logged at least one PCR or lateral flow test after vaccination. We compared the test results of this population with those of 464 356 unvaccinated app users who had a PCR or lateral flow test result between Jan 4, and March 10, 2021 ([appendix pp 4, 8](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext#supplementary-material)). 3106 of 103 622 vaccinated individuals and 50 340 of 464 356 unvaccinated controls tested positive for SARS-CoV-2 infection. As UK guidelines stipulate that individuals need to be free of symptoms to be vaccinated, we found vaccinated participants to have a lower infection risk at the time of the vaccination than unvaccinated participants (RR for BNT162b2 −64% \[95% CI −69 to −59\]; RR for ChAdOx1 nCoV-19 −52% \[95% CI −65 to −34\]). We observed that 5–11 days after vaccination, the infection rates in the vaccinated group were only slightly below those of the unvaccinated group ([figure 4](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext#fig4)), whereas 12–20 days after vaccination, infection risk in the vaccinated group was significantly lower than in the unvaccinated group (RR for BNT162b2 −58% \[95% CI −62 to −54\]; RR for ChAdOx1 nCoV-19 −39% \[95% CI −53 to −21\]), after adjusting for population differences in the vaccinated groups using Poisson regressions. We observed a further reduction in infection risk after one dose of the BNT162b2 vaccine when compared with unvaccinated controls at 21–44 days after vaccination (RR −69% \[95% CI −72 to −66\]) and at 45–59 days after vaccination (−72% \[–79 to −63\]; [figure 4](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext#fig4)). The RR after one dose of ChAdOx1 nCoV-19 compared with unvaccinated controls was −60% (95% CI −68 to −49) at 21–44 days after vaccination. [![](https://www.thelancet.com/cms/10.1016/S1473-3099\(21\)00224-3/asset/5655fb5d-b246-4163-823f-026f58635080/main.assets/gr4.jpg)](https://www.thelancet.com/cms/10.1016/S1473-3099\(21\)00224-3/asset/b46338e4-7cd4-41fc-8bc7-fe477a858f32/main.assets/gr4_lrg.jpg "View full size image in a new tab") Figure 4 Infection risk reduction after the first dose in app users who have been vaccinated and subsequently tested, as a function of days since vac Show full caption Figure viewer The bar chart represents the risk reduction for infection of the vaccinated groups (those who logged at least one PCR or lateral flow test result after vaccination) compared with the unvaccinated group, by vaccine type and days since vaccination. The black lines show 95% CIs. Finally, we tested the role of covariates in risk of infection after vaccination. We observed a larger risk reduction in vaccinated participants aged 55 years or younger (RR −70% \[95% CI −72 to −68) than in those older than 55 years (−61% \[–64 to −57\]). Similarly, individuals without comorbidities had a larger risk reduction (−69% \[–71 to −68\]) than those with at least one comorbidity (−54% \[–59 to −48\]). Borderline differences were observed for BMI (RR for BMI \<30 kg/m2 −69% \[95% CI −71 to −67\]; RR for BMI ≥30 kg/m2 −63% \[−67 to −59\]) and sex (RR for female −69% \[95% CI −71 to −67\]; RR for male −61% \[–66 to −57\]; [appendix p 5](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext#supplementary-material)). ## Discussion In this large-scale, community-based study in the UK, we have investigated adverse effects and infection rates following administration of the two COVID-19 vaccines that are in use in the UK. The overall mean age of the vaccinated app users was higher than that of the general population (40·3 years) [24](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) 24\. Office for National Statistics Population estimates for the UK, England and Wales, Scotland and Northern Ireland, provisional: mid-2019 <https://www.ons.gov.uk/peoplepopulationandcommunity/populationandmigration/populationestimates/bulletins/annualmidyearpopulationestimates/mid2019> Date: May 6, 2020 Date accessed: March 16, 2021 [Google Scholar](https://scholar.google.com/scholar?q=Office+for+National+StatisticsPopulation+estimates+for+the+UK%2C+England+and+Wales%2C+Scotland+and+Northern+Ireland%2C+provisional%3A+mid-2019https%3A%2F%2Fwww.ons.gov.uk%2Fpeoplepopulationandcommunity%2Fpopulationandmigration%2Fpopulationestimates%2Fbulletins%2Fannualmidyearpopulationestimates%2Fmid2019May+6%2C+2020) yet was lower than those of the samples within other UK COVID-19 effectiveness studies, [11,12](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) 11\. Lopez Bernal, J ∙ Andrews, N ∙ Gower, C ∙ et al. Early effectiveness of COVID-19 vaccination with BNT162b2 mRNA vaccine and ChAdOx1 adenovirus vector vaccine on symptomatic disease, hospitalisations and mortality in older adults in England medRxiv. 2021; published online March 2. <https://doi.org/10.1101/2021.03.01.21252652> (preprint). [Google Scholar](https://scholar.google.com/scholar?q=JLopez+BernalNAndrewsCGowerEarly+effectiveness+of+COVID-19+vaccination+with+BNT162b2+mRNA+vaccine+and+ChAdOx1+adenovirus+vector+vaccine+on+symptomatic+disease%2C+hospitalisations+and+mortality+in+older+adults+in+EnglandmedRxiv2021published+online+March+2.https%3A%2F%2Fdoi.org%2F10.1101%2F2021.03.01.21252652%28preprint%29.) 12\. Vasileiou, E ∙ Simpson, CR ∙ Shi, T ∙ et al. Interim findings from first-dose mass COVID-19 vaccination roll-out and COVID-19 hospital admissions in Scotland: a national prospective cohort study Lancet. 2021; published online April 23. <https://doi.org/10.1016/S0140-6736(21)00677-2> [Full Text](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_12_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS0140-6736%2821%2900677-2&cf=fulltext&site=lancet-site) [Full Text (PDF)](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_12_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS0140-6736%2821%2900677-2&cf=pdf&site=lancet-site) [Scopus (391)](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_12_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85104923342) [PubMed](https://pubmed.ncbi.nlm.nih.gov/33901420/) [Google Scholar](https://scholar.google.com/scholar_lookup?doi=10.1016%2FS0140-6736%2821%2900677-2&pmid=33901420) largely because of the presence of a small proportion of health-care workers among the participants of this study. However, our study population was considerably older than the study populations of the phase 3 trials. [3,6,7](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) 3\. Polack, FP ∙ Thomas, SJ ∙ Kitchin, N ∙ et al. Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine N Engl J Med. 2020; 383:2603-2615 [Crossref](https://doi.org/10.1056/NEJMoa2034577) [Scopus (10099)](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_3_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85098117107) [PubMed](https://pubmed.ncbi.nlm.nih.gov/33301246/) [Google Scholar](https://scholar.google.com/scholar_lookup?doi=10.1056%2FNEJMoa2034577&pmid=33301246) 6\. Voysey, M ∙ Clemens, SAC ∙ Madhi, SA ∙ et al. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK Lancet. 2021; 397:99-111 [Full Text](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_6_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS0140-6736%2820%2932661-1&cf=fulltext&site=lancet-site) [Full Text (PDF)](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_6_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS0140-6736%2820%2932661-1&cf=pdf&site=lancet-site) [Scopus (3425)](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_6_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85097463811) [PubMed](https://pubmed.ncbi.nlm.nih.gov/33306989/) [Google Scholar](https://scholar.google.com/scholar_lookup?doi=10.1016%2FS0140-6736%2820%2932661-1&pmid=33306989) 7\. Ramasamy, MN ∙ Minassian, AM ∙ Ewer, KJ ∙ et al. Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial Lancet. 2021; 396:1979-1993 [Full Text](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_7_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS0140-6736%2820%2932466-1&cf=fulltext&site=lancet-site) [Full Text (PDF)](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_7_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS0140-6736%2820%2932466-1&cf=pdf&site=lancet-site) [Scopus (1091)](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_7_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85097243389) [PubMed](https://pubmed.ncbi.nlm.nih.gov/33220855/) [Google Scholar](https://scholar.google.com/scholar_lookup?doi=10.1016%2FS0140-6736%2820%2932466-1&pmid=33220855) We found that systemic adverse effects, including headache and fatigue, affected fewer than one in four people and were less common in the community than expected from clinical trials. For example, in phase 3 clinical trials of the BNT162b2 vaccine, [3](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) 3\. Polack, FP ∙ Thomas, SJ ∙ Kitchin, N ∙ et al. Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine N Engl J Med. 2020; 383:2603-2615 [Crossref](https://doi.org/10.1056/NEJMoa2034577) [Scopus (10099)](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_3_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85098117107) [PubMed](https://pubmed.ncbi.nlm.nih.gov/33301246/) [Google Scholar](https://scholar.google.com/scholar_lookup?doi=10.1056%2FNEJMoa2034577&pmid=33301246) the most common events after the first dose were injection-site pain (71–83%), fatigue (34–47%), and headache (25–42%). However, in our community analysis, less than 30% of users complained of injection-site pain and less than 25% of fatigue and headache after the first dose. Although side-effects were significantly more prevalent in women than in men, in people aged 55 years or younger than in those older than 55 years, and after the second than after the first dose, they occurred at much lower frequencies than expected from the published literature. For instance, whereas 51–59% of participants reported fatigue after the second BNT162b2 dose in the phase 3 trial of that vaccine, [3](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) 3\. Polack, FP ∙ Thomas, SJ ∙ Kitchin, N ∙ et al. Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine N Engl J Med. 2020; 383:2603-2615 [Crossref](https://doi.org/10.1056/NEJMoa2034577) [Scopus (10099)](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_3_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85098117107) [PubMed](https://pubmed.ncbi.nlm.nih.gov/33301246/) [Google Scholar](https://scholar.google.com/scholar_lookup?doi=10.1056%2FNEJMoa2034577&pmid=33301246) fatigue was reported by less than 15% of participants after the second dose in our study. Additionally, our data provide evidence from the community to support early reports of higher frequency of side-effects in younger than in older individuals. [3,7](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) 3\. Polack, FP ∙ Thomas, SJ ∙ Kitchin, N ∙ et al. Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine N Engl J Med. 2020; 383:2603-2615 [Crossref](https://doi.org/10.1056/NEJMoa2034577) [Scopus (10099)](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_3_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85098117107) [PubMed](https://pubmed.ncbi.nlm.nih.gov/33301246/) [Google Scholar](https://scholar.google.com/scholar_lookup?doi=10.1056%2FNEJMoa2034577&pmid=33301246) 7\. Ramasamy, MN ∙ Minassian, AM ∙ Ewer, KJ ∙ et al. Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial Lancet. 2021; 396:1979-1993 [Full Text](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_7_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS0140-6736%2820%2932466-1&cf=fulltext&site=lancet-site) [Full Text (PDF)](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_7_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS0140-6736%2820%2932466-1&cf=pdf&site=lancet-site) [Scopus (1091)](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_7_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85097243389) [PubMed](https://pubmed.ncbi.nlm.nih.gov/33220855/) [Google Scholar](https://scholar.google.com/scholar_lookup?doi=10.1016%2FS0140-6736%2820%2932466-1&pmid=33220855) Similarly, rates of side-effects following the ChAdOx1 nCoV-19 vaccine were lower than expected. [7](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) 7\. Ramasamy, MN ∙ Minassian, AM ∙ Ewer, KJ ∙ et al. Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial Lancet. 2021; 396:1979-1993 [Full Text](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_7_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS0140-6736%2820%2932466-1&cf=fulltext&site=lancet-site) [Full Text (PDF)](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_7_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS0140-6736%2820%2932466-1&cf=pdf&site=lancet-site) [Scopus (1091)](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_7_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85097243389) [PubMed](https://pubmed.ncbi.nlm.nih.gov/33220855/) [Google Scholar](https://scholar.google.com/scholar_lookup?doi=10.1016%2FS0140-6736%2820%2932466-1&pmid=33220855) The phase 2–3 trial of the ChAdOx1 nCoV-19 vaccine [7](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) 7\. Ramasamy, MN ∙ Minassian, AM ∙ Ewer, KJ ∙ et al. Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial Lancet. 2021; 396:1979-1993 [Full Text](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_7_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS0140-6736%2820%2932466-1&cf=fulltext&site=lancet-site) [Full Text (PDF)](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_7_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS0140-6736%2820%2932466-1&cf=pdf&site=lancet-site) [Scopus (1091)](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_7_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85097243389) [PubMed](https://pubmed.ncbi.nlm.nih.gov/33220855/) [Google Scholar](https://scholar.google.com/scholar_lookup?doi=10.1016%2FS0140-6736%2820%2932466-1&pmid=33220855) reported systemic adverse effects in 88% of participants aged 18–55 years who received the first injection, whereas we found a lower rate of 33·7% after the first dose in the overall sample and 46·9% in individuals aged 18–55 years (data not shown). Individuals vaccinated with the ChAdOx1 nCoV-19 vaccine were more likely to experience systemic side-effects than those who had been given the BNT162b2 vaccine, but in our study 89% of respondents who logged at least one systemic effect after the ChAdOx1 nCoV-19 vaccine did not report any systemic effects after 3 days, and 98·3% did not report any after 1 week. Individuals with evidence of past SARS-CoV-2 infection were also more likely to have adverse effects than those without evidence of past infection with both vaccines. It is possible, although it remains to be tested, that this increased reactogenicity relates to increased immunogenicity. It has been shown that vaccines have increased immunogenicity in individuals with past infection and these people have higher antibody titres than those without previous infection. [22,23,25](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) 22\. Krammer, F ∙ Srivastava, K ∙ Simon, V Robust spike antibody responses and increased reactogenicity in seropositive individuals after a single dose of SARS-CoV-2 mRNA vaccine medRxiv. 2021; published online Feb 1. <https://doi.org/10.1101/2021.01.29.21250653> (preprint). [Google Scholar](https://scholar.google.com/scholar?q=FKrammerKSrivastavaVSimonRobust+spike+antibody+responses+and+increased+reactogenicity+in+seropositive+individuals+after+a+single+dose+of+SARS-CoV-2+mRNA+vaccinemedRxiv2021published+online+Feb+1.https%3A%2F%2Fdoi.org%2F10.1101%2F2021.01.29.21250653%28preprint%29.) 23\. Wise, J COVID-19: people who have had infection might only need one dose of mRNA vaccine BMJ. 2021; 372:n308 [Crossref](https://doi.org/10.1136/bmj.n308) [Scopus (43)](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_23_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85101276843) [PubMed](https://pubmed.ncbi.nlm.nih.gov/33531333/) [Google Scholar](https://scholar.google.com/scholar_lookup?doi=10.1136%2Fbmj.n308&pmid=33531333) 25\. Manisty, C ∙ Otter, AD ∙ Treibel, TA ∙ et al. Antibody response to first BNT162b2 dose in previously SARS-CoV-2-infected individuals Lancet. 2021; 397:1057-1058 [Full Text](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_25_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS0140-6736%2821%2900501-8&cf=fulltext&site=lancet-site) [Full Text (PDF)](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_25_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS0140-6736%2821%2900501-8&cf=pdf&site=lancet-site) [Scopus (292)](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_25_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85102625202) [PubMed](https://pubmed.ncbi.nlm.nih.gov/33640038/) [Google Scholar](https://scholar.google.com/scholar_lookup?doi=10.1016%2FS0140-6736%2821%2900501-8&pmid=33640038) We observed an infection risk reduction at 21–44 days after vaccination in all vaccinated users compared with unvaccinated controls (RR was −69% \[95% CI −72 to −66\] for BNT162b2 and −60% \[–68 to −49\] for ChAdOx1 nCoV-19). The reduction of infection was lower in individuals older than 55 years than those aged 55 years or younger, in those with one or more comorbidities than in those without comorbidities, and in individuals with a BMI of 30 kg/m2 or higher than in those with a BMI of less than 30 kg/m2 ([appendix p 5](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext#supplementary-material)). A preprint based on data from Israel suggested that a single dose of BNT162b2 might not provide enough protection; [26](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) 26\. Chodick, G ∙ Tene, L ∙ Patalon, T ∙ et al. The effectiveness of the first dose of BNT162b2 vaccine in reducing SARS-CoV-2 infection 13–24 days after immunization: real-world evidence medRxiv. 2021; published online Jan 29. <https://doi.org/10.1101/2021.01.27.21250612> (preprint). [Google Scholar](https://scholar.google.com/scholar?q=GChodickLTeneTPatalonThe+effectiveness+of+the+first+dose+of+BNT162b2+vaccine+in+reducing+SARS-CoV-2+infection+13%E2%80%9324+days+after+immunization%3A+real-world+evidencemedRxiv2021published+online+Jan+29.https%3A%2F%2Fdoi.org%2F10.1101%2F2021.01.27.21250612%28preprint%29.) however, a re-analysis of the same dataset indicated that after 14 days the effectiveness of a single dose of vaccine was about 90%. [5](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) 5\. Hunter, PR ∙ Brainard, J Estimating the effectiveness of the Pfizer COVID-19 BNT162b2 vaccine after a single dose. A reanalysis of a study of “real-world” vaccination outcomes from Israel medRxiv. 2021; published online Feb 3. <https://doi.org/10.1101/2021.02.01.21250957> (preprint). [Google Scholar](https://scholar.google.com/scholar?q=PRHunterJBrainardEstimating+the+effectiveness+of+the+Pfizer+COVID-19+BNT162b2+vaccine+after+a+single+dose.+A+reanalysis+of+a+study+of+%E2%80%9Creal-world%E2%80%9D+vaccination+outcomes+from+IsraelmedRxiv2021published+online+Feb+3.https%3A%2F%2Fdoi.org%2F10.1101%2F2021.02.01.21250957%28preprint%29.) Although our data, due to their observational nature, does not allow us to comment directly on effectiveness, the observed decrease of infection over time seems to be in line with efficacy reported in the BNT162b2 phase 3 trial [3](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) 3\. Polack, FP ∙ Thomas, SJ ∙ Kitchin, N ∙ et al. Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine N Engl J Med. 2020; 383:2603-2615 [Crossref](https://doi.org/10.1056/NEJMoa2034577) [Scopus (10099)](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_3_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85098117107) [PubMed](https://pubmed.ncbi.nlm.nih.gov/33301246/) [Google Scholar](https://scholar.google.com/scholar_lookup?doi=10.1056%2FNEJMoa2034577&pmid=33301246) and supports the UK Government's decision to delay the timing of the second injection to 12 weeks to maximise the number of people receiving at least one dose. Long-term surveillance for SARS-CoV-2 protection in individuals who have received delayed second doses of BNT162b2 compared with those receiving second doses according to initial guidelines (ie, 21 days after the first dose) will be required to determine whether these initial protection estimates persist. Strengths of our study include its large sample size; capture of data on SARS-CoV-2 RT-PCR or lateral flow test results, regardless of symptoms; the prospective real-time capture of information on symptoms; and the availability of both BNT162b2 and ChAdOx1 nCoV-19 vaccines in the UK, which allowed cross-vaccine comparison. Our study also has several limitations. We used self-reported data, which can introduce information bias, including misclassification, or effect bias exposure. Also, some participants might be more likely to report symptoms than others, and there is the potential for users to drop out of reporting in the app. Participants using the app were a self-selected group and not representative of the general population, as has been observed in other digital platform studies. [27](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) 27\. Baltrusaitis, K ∙ Santillana, M ∙ Crawley, AW ∙ et al. Determinants of participants' follow-up and characterization of representativeness in flu near you, a participatory disease surveillance system JMIR Public Health Surveill. 2017; 3:e18 [Crossref](https://doi.org/10.2196/publichealth.7304) [Scopus (39)](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_27_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85041028925) [PubMed](https://pubmed.ncbi.nlm.nih.gov/28389417/) [Google Scholar](https://scholar.google.com/scholar_lookup?doi=10.2196%2Fpublichealth.7304&pmid=28389417) Users of a participatory platform (as well as participants in all voluntary studies, including clinical trials) are likely to be more interested in health, and might behave differently to the general population as a result. Previous work has shown that data from our app is able to produce estimates of population-level disease prevalence that agree well with surveys with random, representative designs, [18,28](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) 18\. Varsavsky, T ∙ Graham, MS ∙ Canas, LS ∙ et al. Detecting COVID-19 infection hotspots in England using large-scale self-reported data from a mobile application: a prospective, observational study Lancet Public Health. 2021; 6:e21-e29 [Full Text](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_18_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS2468-2667%2820%2930269-3&cf=fulltext&site=lancet-site) [Full Text (PDF)](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_18_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS2468-2667%2820%2930269-3&cf=pdf&site=lancet-site) [Scopus (54)](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_18_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85099010576) [PubMed](https://pubmed.ncbi.nlm.nih.gov/33278917/) [Google Scholar](https://scholar.google.com/scholar_lookup?doi=10.1016%2FS2468-2667%2820%2930269-3&pmid=33278917) 28\. Bowyer, RCE ∙ Varsavsky, T ∙ Thompson, EJ ∙ et al. Geo-social gradients in predicted COVID-19 prevalence in Great Britain: results from 1 960 242 users of the COVID-19 Symptoms Study app Thorax. 2020; published online Dec 29. <http://dx.doi.org/10.1136/thoraxjnl-2020-215119> [Crossref](https://doi.org/10.1136/thoraxjnl-2020-215119) [Scopus (8)](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_28_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85098646607) [PubMed](https://pubmed.ncbi.nlm.nih.gov/33376145/) [Google Scholar](https://scholar.google.com/scholar_lookup?doi=10.1136%2Fthoraxjnl-2020-215119&pmid=33376145) suggesting that behavioural issues are not substantially biasing our app population. As with other studies examining COVID-19 vaccine effects in the general community, our data are limited by the vaccine rollout's focus on health-care workers, elderly people, and people who are clinically vulnerable. [2](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) 2\. Department of Health and Social Care Priority groups for coronavirus (COVID-19) vaccination: advice from the JCVI, 30 December 2020 <https://www.gov.uk/government/publications/priority-groups-for-coronavirus-covid-19-vaccination-advice-from-the-jcvi-30-december-2020?utm_source=f1de4cd1-935e-4a5e-b539-3b37cd92e598> Date: Dec 30, 2020 Date accessed: February 18, 2021 [Google Scholar](https://scholar.google.com/scholar?q=Department+of+Health+and+Social+CarePriority+groups+for+coronavirus+%28COVID-19%29+vaccination%3A+advice+from+the+JCVI%2C+30+December+2020https%3A%2F%2Fwww.gov.uk%2Fgovernment%2Fpublications%2Fpriority-groups-for-coronavirus-covid-19-vaccination-advice-from-the-jcvi-30-december-2020%3Futm_source%3Df1de4cd1-935e-4a5e-b539-3b37cd92e598Dec+30%2C+2020) Moreover, our results might have been affected by collider bias (ie, when a risk factor and an outcome both affect the likelihood of being sampled) [29](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) 29\. Griffith, GJ ∙ Morris, TT ∙ Tudball, MJ ∙ et al. Collider bias undermines our understanding of COVID-19 disease risk and severity Nat Commun. 2020; 11, 5749 [Crossref](https://doi.org/10.1038/s41467-020-19478-2) [Scopus (490)](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_29_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85095945843) [PubMed](https://pubmed.ncbi.nlm.nih.gov/33184277/) [Google Scholar](https://scholar.google.com/scholar_lookup?doi=10.1038%2Fs41467-020-19478-2&pmid=33184277) if both vaccination status and COVID positivity influenced the probability of participation in the app. However, given that strong reductions in COVID hospitalisations after vaccination were observed in nationwide studies in Scotland [12](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) 12\. Vasileiou, E ∙ Simpson, CR ∙ Shi, T ∙ et al. Interim findings from first-dose mass COVID-19 vaccination roll-out and COVID-19 hospital admissions in Scotland: a national prospective cohort study Lancet. 2021; published online April 23. <https://doi.org/10.1016/S0140-6736(21)00677-2> [Full Text](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_12_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS0140-6736%2821%2900677-2&cf=fulltext&site=lancet-site) [Full Text (PDF)](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_12_2&dbid=4&doi=10.1016%2FS1473-3099%2821%2900224-3&key=10.1016%2FS0140-6736%2821%2900677-2&cf=pdf&site=lancet-site) [Scopus (391)](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_12_2&dbid=137438953472&doi=10.1016%2FS1473-3099%2821%2900224-3&key=2-s2.0-85104923342) [PubMed](https://pubmed.ncbi.nlm.nih.gov/33901420/) [Google Scholar](https://scholar.google.com/scholar_lookup?doi=10.1016%2FS0140-6736%2821%2900677-2&pmid=33901420) and England, [11](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext) 11\. Lopez Bernal, J ∙ Andrews, N ∙ Gower, C ∙ et al. Early effectiveness of COVID-19 vaccination with BNT162b2 mRNA vaccine and ChAdOx1 adenovirus vector vaccine on symptomatic disease, hospitalisations and mortality in older adults in England medRxiv. 2021; published online March 2. <https://doi.org/10.1101/2021.03.01.21252652> (preprint). [Google Scholar](https://scholar.google.com/scholar?q=JLopez+BernalNAndrewsCGowerEarly+effectiveness+of+COVID-19+vaccination+with+BNT162b2+mRNA+vaccine+and+ChAdOx1+adenovirus+vector+vaccine+on+symptomatic+disease%2C+hospitalisations+and+mortality+in+older+adults+in+EnglandmedRxiv2021published+online+March+2.https%3A%2F%2Fdoi.org%2F10.1101%2F2021.03.01.21252652%28preprint%29.) we believe that collider bias is unlikely to underlie the reduction in infections seen in our data. Recipients of the ChAdOx1 nCoV-19 vaccine might differ from recipients of the BNT162b2 vaccine by age or dependency. Although we adjusted for population differences across the BNT162b2, ChAdOx1 nCoV-19, and unvaccinated control groups, our estimates of infection rates after vaccination might not have fully adjusted for case-mix and therefore are preliminary. Furthermore, because the ChAdOx1 nCoV-19 vaccine started being rolled out in January, 2021, and the second dose is to be administered at 12 weeks, no app users had received two doses of ChAdOx1 nCoV-19 at the time of this report. The completeness of reporting was higher for systemic effects than for local effects, which might have introduced some bias ([appendix p 12](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext#supplementary-material)). Some severe side-effects might have been missed if app users experiencing them were unable to use the app to report side-effects. However, we saw substantially lower rates of severe and mild side-effects than observed in phase 3 trials, making the missing of severe side-effects an unlikely explanation for the lower prevalence of side-effects seen in our data. Furthermore, we cannot rule out the presence of selection bias in who was tested after vaccination, as we know that health-care workers are tested more frequently than people in the general population, even if they are asymptomatic. This is an observational study, with data captured during a specific timeframe, and our study design does not allow an inference of causality. Also, we evaluated only short-term adverse effects, and long-term surveillance in the general population will be required to investigate possible future effects. Finally, the systemic side-effects were collected from daily reports within 1 week from the injection date, so we cannot rule out that these effects might not be vaccine related. We also had insufficient power to assess differential rates by ethnic group. In conclusion, short-term adverse effects of both vaccines are moderate in frequency, mild in severity, and short-lived. Adverse effects are more frequently reported in younger individuals, women, and among those who previously had COVID-19. The post-vaccine symptoms (both systemic and local) often last 1–2 days from the injection. Our data could be used to inform people on the likelihood of side-effects on the basis of their age and sex and the type of vaccine being administered. Furthermore, our data support results from randomised controlled trials in a large community-based scenario showing evidence of reduction in infection after 12 days and substantial protection after 3 weeks. Contributors JW and TDS acquired funding. CM and TDS conceptualised the study. KK, AM, LP, and JC analysed the data. BM and JC curated the data. PL, CHS, LHN, DAD, JM, MA, LSC, EM, MSG, MMo, ADJ, MMa, AH, ATC, CJS, SO, SS, and CH contributed data and software. CM, JC, and TDS verified the underlying data. CM, KK, AM, LP, AMV, ALG, and TDS wrote the first draft of the manuscript. All authors reviewed and edited revisions of the manuscript, had full access to all the data in the study, and had final responsibility for the decision to submit for publication. ## Data sharing Anonymised research data are shared with third parties via Health Data Research UK (HDRUK.ac.uk). US investigators are encouraged to coordinate data requests through the Coronavirus Pandemic Epidemiology (COPE) consortium ([www.monganinstitute.org/cope-consortium](http://www.monganinstitute.org/cope-consortium)). Data updates can be found at <https://covid.joinzoe.com>. ## Declaration of interests CM reports grants from Chronic Disease Research Foundation (CDRF) during the conduct of the study. JW, AM, LP, CH, SS, and JC report being employees of ZOE Global during the conduct of the study. ATC reports grants from Massachusetts Consortium on Pathogen Readiness during the conduct of the study, and personal fees from Bayer Pharma, Pfizer, and Boehringer Ingelheim, outside the submitted work. DAD reports grants from National Institutes of Health (NIH), Massachusetts Consortium on Pathogen Readiness, and American Gastroenterological Association, during the conduct of the study, and that he served as a co-investigator on an unrelated nutrition trial sponsored by ZOE Global. CHS reports grants from Alzheimer's Society during the conduct of the study. AMV reports grants from Medical Research Council (MRC) and personal fees from ZOE Global, during the conduct of the study. ALG reports having shares in AstraZeneca and receiving grants from Novavax, outside the submitted work. CJS reports grants from CDRF, MRC, and Wellcome Trust, during the conduct of the study. SO reports grants from Wellcome Trust, UK Research and Innovation (UKRI), and CDRF, during the conduct of the study. TDS reports being a consultant for ZOE Global, during the conduct of the study. All other authors declare no competing interests. ## Acknowledgments ZOE Global provided in-kind support for all aspects of building, running, and supporting the app and service to all users worldwide. The Department of Twin Research & Genetic Epidemiology at King's College London receives grant support from the Wellcome Trust (212904/Z/18/Z), the MRC British Heart Foundation Ancestry and Biological Informative Markers for Stratification of Hypertension (AIMHY; MR/M016560/1), the European Union, CDRF, ZOE Global, NIH, the National Institute for Health Research (NIHR)-funded BioResource, and Clinical Research Facility and Biomedical Research Centre based at Guy's and St Thomas' National Health Service (NHS) Foundation Trust, in partnership with King's College London. SO is funded by the Wellcome Engineering and Physical Sciences Research Council (EPSRC) Centre for Medical Engineering (WT203148/Z/16/Z) and the Wellcome Flagship Programme (WT213038/Z/18/Z). CM is funded by the CDRF and the MRC AIMHY project grant. CHS is an Alzheimer's Society junior fellow (AS-JF-17-011). The School of Biomedical Engineering & Imaging Sciences is supported by the Wellcome EPSRC Centre for Medical Engineering at King's College London (WT203148/Z/16/Z) and the Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St Thomas' NHS Foundation Trust, in partnership with King's College London and King's College Hospital NHS Foundation Trust. ATC is a Stuart and Suzanne Steele MGH Research Scholar. LHN is supported by an NIH K23DK125838 award, the American Gastroenterological Association Research Scholar Award, and the Crohn's and Colitis Foundation Career Development Award. DAD and LHN are supported by the American Gastroenterological Association-Takeda COVID-19 Rapid Response Research Award (AGA2021-5102). DAD is supported by NIH/National Institute of Health Diabetes and Digestive and Kidney Diseases (K01DK120742). ATC, LHN, and DAD are supported by the Massachusetts Consortium on Pathogen Readiness. JM is partially supported by the NIH (DK40561) and the American Diabetes Association (7-21-JDFM-005). PL is funded by the CDRF. AMV is funded by a UKRI and MRC Covid-Rapid Response grant (MR/V027883/1). We thank all participants, including study volunteers enrolled in cohorts within the COPE consortium. We thank the staff of ZOE Global, the Department of Twin Research & Genetic Epidemiology at King's College London, the Clinical & Translational Epidemiology Unit at Massachusetts General Hospital, and researchers and staff at Lund University in Sweden for their tireless work in contributing to the running of the study and data collection. ## Supplementary Material (1) [PDF (923.33 KB)](https://www.thelancet.com/cms/10.1016/S1473-3099\(21\)00224-3/attachment/05d885cc-88b3-43a5-be70-912e3dd2f3a6/mmc1.pdf) Supplementary appendix ## References [1\.](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext#body-ref-sbref10 "View in article") Public Health England COVID-19 vaccination programme <https://www.gov.uk/government/collections/covid-19-vaccination-programme> Date: Nov 27, 2020 Date accessed: February 18, 2021 [Google Scholar](https://scholar.google.com/scholar?q=Public+Health+EnglandCOVID-19+vaccination+programmehttps%3A%2F%2Fwww.gov.uk%2Fgovernment%2Fcollections%2Fcovid-19-vaccination-programmeNov+27%2C+2020) [2\.](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext#body-ref-sbref20-1 "View in article") Department of Health and Social Care Priority groups for coronavirus (COVID-19) vaccination: advice from the JCVI, 30 December 2020 <https://www.gov.uk/government/publications/priority-groups-for-coronavirus-covid-19-vaccination-advice-from-the-jcvi-30-december-2020?utm_source=f1de4cd1-935e-4a5e-b539-3b37cd92e598> Date: Dec 30, 2020 Date accessed: February 18, 2021 [Google Scholar](https://scholar.google.com/scholar?q=Department+of+Health+and+Social+CarePriority+groups+for+coronavirus+%28COVID-19%29+vaccination%3A+advice+from+the+JCVI%2C+30+December+2020https%3A%2F%2Fwww.gov.uk%2Fgovernment%2Fpublications%2Fpriority-groups-for-coronavirus-covid-19-vaccination-advice-from-the-jcvi-30-december-2020%3Futm_source%3Df1de4cd1-935e-4a5e-b539-3b37cd92e598Dec+30%2C+2020) [3\.](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(21\)00224-3/fulltext#body-ref-sbref30-1 "View in article") Polack, FP ∙ Thomas, SJ ∙ Kitchin, N ∙ et al. 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