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Meta TitlePersistent False Positive Covid-19 Rapid Antigen Tests - PMC
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To the Editor: Rapid antigen tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are effective tools for the diagnosis of acute infection, particularly when used serially. 1 The percentage of rapid antigen tests with false positive results is reported to be less than 1%. 2 However, we have observed persons who repeatedly test positive with rapid antigen tests despite concurrent negative molecular tests; this infrequent phenomenon occurs predominantly among women and persons with autoimmune disorders. Our report is based on two longitudinal cohort studies in which participants underwent serial, paired rapid antigen testing and reverse-transcriptase–polymerase-chain-reaction (RT-PCR) testing for SARS-CoV-2. 1 , 3 Participants were considered to have a false positive result if they reported a positive rapid antigen test with a corresponding negative RT-PCR test of samples obtained within 48 hours of each other. All tests were performed with anterior nasal samples, and RT-PCR tests were performed with the Roche Cobas 6800 SARS-CoV-2 assay (see the Methods section in the Supplementary Appendix , available with the full text of this letter at NEJM.org). False positive tests were classified as incidental false positives (in participants with at least one negative rapid antigen test during the study period) or persistent false positives (in participants with at least 5 days of positive rapid antigen tests and no negative rapid antigen test during the study period) (Fig. S1 in the Supplementary Appendix ). Among 11,297 participants who performed 76,610 days of testing, 1.7% had at least one false positive rapid antigen test. Of the 191 participants with false positive results, 13 had persistent false positives ( Table 1 ). Most of the participants with persistent false positive results were women (12 of 13) and used the Quidel QuickVue rapid antigen test (12 of 13). We found a higher prevalence of participant-reported autoimmune disorders among participants with persistent false positives than among those with incidental false positives (in 6 of 13 vs. 10 of 178; crude odds ratio, 14.4; 95% confidence interval, 3.2 to 59.9). Persistent false positive results were obtained with tests from different lots and were not likely to be related to issues with test quality. 4 Table 1. Demographic and Testing Characteristics of Participants with Persistently Positive Tests. Participant No. Sex Age Autoimmune Disorder * Rapid Antigen Test † Days of Rapid Antigen Test Positivity ‡ No. of Rapid Antigen Tests Taken yr 1 Female 20 None Quidel 14 8 2 Female 40 Rheumatoid arthritis Quidel 14 8 3 Female 58 None Quidel 12 7 4 Female 19 None Abbott 14 8 5 Female 33 None Quidel 13 7 6 Female 50 None Quidel 13 4 7 Female 68 Sjögren’s syndrome Quidel 53 15 8 Male 57 Rheumatoid arthritis Quidel 14 8 9 Female 48 Lupus and antisynthetase syndrome Quidel 16 9 10 Female 27 None Quidel 12 7 11 Female 43 Unidentified disorder Quidel 14 8 12 Female 46 None Quidel 9 10 13 Female 55 Unidentified disorder Quidel 14 7 * Autoimmune disorders were reported by the participants. † Quidel refers to the Quidel QuickVue At-Home OTC COVID-19 Test, and Abbott refers to the Abbott BinaxNOW COVID-19 Antigen Self Test. ‡ Participants were considered to be positive on the days between two positive tests unless the tests were more than 7 days apart. This finding has substantial clinical relevance. The persistent false positivity may be a result of cross-reactivity of test antibodies with rheumatoid factor and could potentially occur in any patient who has a condition characterized by circulating rheumatoid factor. 5 Because testing for SARS-CoV-2 is commonly performed among symptomatic patients, false positive results may be unrecognized clinically. However, persons who encounter persistent positive tests after infection or in the absence of symptoms may find reassurance in the recognition of this uncommon but known phenomenon. We suggest that patients with persistent false positive results and a history of autoimmune disease with rheumatoid factor may benefit from repeat testing with a different brand of rapid antigen test. Finally, this report may help public health officials and health care providers to distinguish between cross-reactive false positivity and SARS-CoV-2 rebound. Supplementary Appendix Disclosure Forms The views expressed in this letter are those of the authors and do not necessarily represent the views of the National Institute of Biomedical Imaging and Bioengineering; the National Heart, Lung, and Blood Institute; the National Institutes of Health (NIH); or the U.S. Department of Health and Human Services. Footnotes Supported by a grant (3U54HL143541-02S2) from the NIH RADx Tech Initiative and by an NIH Clinical and Translational Science Award (UL1TR001453). Disclosure forms provided by the authors are available with the full text of this letter at NEJM.org. References 1. Soni A, Herbert C, Lin H, et al. Performance of rapid antigen tests to detect symptomatic and asymptomatic SARS-CoV-2 infection: a prospective cohort study. Ann Intern Med 2023;176:975-982. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 2. Gans JS, Goldfarb A, Agrawal AK, Sennik S, Stein J, Rosella L. False-positive results in rapid antigen tests for SARS-CoV-2. JAMA 2022;327:485-486. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 3. Herbert C, Kheterpal V, Suvarna T, et al. Design and preliminary findings of adherence to the Self-Testing for Our Protection from COVID-19 (STOP COVID-19) risk-based testing protocol: prospective digital study. JMIR Form Res 2022;6(6):e38113-e38113. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 4. Carter AM, Viloria Winnett A, Romano AE, Akana R, Shelby N, Ismagilov RF. Laboratory evaluation links some false-positive COVID-19 antigen test results observed in a field study to a specific lot of test strips. Open Forum Infect Dis 2023;10(1):ofac701-ofac701. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 5. Vinyé Bausà M, Bausà Peris R, Corominas H. Cross-reactions between rheumatoid factor and IgM SARS-CoV-2. Med Clin (Engl Ed) 2020;155:417-418. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] Associated Data This section collects any data citations, data availability statements, or supplementary materials included in this article. Supplementary Materials Articles from The New England Journal of Medicine are provided here courtesy of Massachusetts Medical Society
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Inclusion in an NLM database does not imply endorsement of, or agreement with, the contents by NLM or the National Institutes of Health. Learn more: [PMC Disclaimer](https://pmc.ncbi.nlm.nih.gov/about/disclaimer/) \| [PMC Copyright Notice](https://pmc.ncbi.nlm.nih.gov/about/copyright/) ![NEJM Group COVID-19 Collection logo](https://cdn.ncbi.nlm.nih.gov/pmc/banners/logo-phenejm.png) letter N Engl J Med . 2024 Feb 22;390(8):764–765. doi: [10\.1056/NEJMc2313517](https://doi.org/10.1056/NEJMc2313517) - [Search in PMC](https://pmc.ncbi.nlm.nih.gov/search/?term="N%20Engl%20J%20Med"[jour]) - [Search in PubMed](https://pubmed.ncbi.nlm.nih.gov/?term="N%20Engl%20J%20Med"[jour]) - [View in NLM Catalog](https://www.ncbi.nlm.nih.gov/nlmcatalog?term="N%20Engl%20J%20Med"[Title%20Abbreviation]) - [Add to search](https://pmc.ncbi.nlm.nih.gov/articles/PMC11156185/?term="N%20Engl%20J%20Med"[jour]) # Persistent False Positive Covid-19 Rapid Antigen Tests [Carly Herbert](https://pubmed.ncbi.nlm.nih.gov/?term="Herbert%20C"[Author]) ### Carly Herbert, B.A. 1University of Massachusetts Chan Medical School, Worcester, MA apurv.soni@umassmed.edu Find articles by [Carly Herbert](https://pubmed.ncbi.nlm.nih.gov/?term="Herbert%20C"[Author]) 1, [David D McManus](https://pubmed.ncbi.nlm.nih.gov/?term="McManus%20DD"[Author]) ### David D McManus, M.D. 1University of Massachusetts Chan Medical School, Worcester, MA apurv.soni@umassmed.edu Find articles by [David D McManus](https://pubmed.ncbi.nlm.nih.gov/?term="McManus%20DD"[Author]) 1, [Apurv Soni](https://pubmed.ncbi.nlm.nih.gov/?term="Soni%20A"[Author]) ### Apurv Soni, M.D., Ph.D. 1University of Massachusetts Chan Medical School, Worcester, MA apurv.soni@umassmed.edu Find articles by [Apurv Soni](https://pubmed.ncbi.nlm.nih.gov/?term="Soni%20A"[Author]) 1,✉ - Author information - Copyright and License information 1University of Massachusetts Chan Medical School, Worcester, MA apurv.soni@umassmed.edu ✉ Corresponding author. Copyright © 2024 Massachusetts Medical Society. All rights reserved. This article is made available via the PMC Open Access Subset for unrestricted re-use, except commercial resale, and analyses in any form or by any means with acknowledgment of the original source. PMC is granted a license to make this article available via PMC and Europe PMC, subject to existing copyright protections. [PMC Copyright notice](https://pmc.ncbi.nlm.nih.gov/about/copyright/) PMCID: PMC11156185 PMID: [38381681](https://pubmed.ncbi.nlm.nih.gov/38381681/) See letter "[False Positive Covid-19 Rapid Antigen Tests](https://pmc.ncbi.nlm.nih.gov/articles/PMC11156229/)" on page 1835. *** *To the Editor:* Rapid antigen tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are effective tools for the diagnosis of acute infection, particularly when used serially.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC11156185/#r1) The percentage of rapid antigen tests with false positive results is reported to be less than 1%.[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC11156185/#r2) However, we have observed persons who repeatedly test positive with rapid antigen tests despite concurrent negative molecular tests; this infrequent phenomenon occurs predominantly among women and persons with autoimmune disorders. Our report is based on two longitudinal cohort studies in which participants underwent serial, paired rapid antigen testing and reverse-transcriptase–polymerase-chain-reaction (RT-PCR) testing for SARS-CoV-2.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC11156185/#r1),[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC11156185/#r3) Participants were considered to have a false positive result if they reported a positive rapid antigen test with a corresponding negative RT-PCR test of samples obtained within 48 hours of each other. All tests were performed with anterior nasal samples, and RT-PCR tests were performed with the Roche Cobas 6800 SARS-CoV-2 assay (see the Methods section in the [Supplementary Appendix](https://pmc.ncbi.nlm.nih.gov/articles/PMC11156185/#ap1), available with the full text of this letter at NEJM.org). False positive tests were classified as incidental false positives (in participants with at least one negative rapid antigen test during the study period) or persistent false positives (in participants with at least 5 days of positive rapid antigen tests and no negative rapid antigen test during the study period) (Fig. S1 in the [Supplementary Appendix](https://pmc.ncbi.nlm.nih.gov/articles/PMC11156185/#ap1)). Among 11,297 participants who performed 76,610 days of testing, 1.7% had at least one false positive rapid antigen test. Of the 191 participants with false positive results, 13 had persistent false positives ([Table 1](https://pmc.ncbi.nlm.nih.gov/articles/PMC11156185/#t1)). Most of the participants with persistent false positive results were women (12 of 13) and used the Quidel QuickVue rapid antigen test (12 of 13). We found a higher prevalence of participant-reported autoimmune disorders among participants with persistent false positives than among those with incidental false positives (in 6 of 13 vs. 10 of 178; crude odds ratio, 14.4; 95% confidence interval, 3.2 to 59.9). Persistent false positive results were obtained with tests from different lots and were not likely to be related to issues with test quality.[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC11156185/#r4) ## Table 1. Demographic and Testing Characteristics of Participants with Persistently Positive Tests. | Participant No. | Sex | Age | Autoimmune Disorder[\*](https://pmc.ncbi.nlm.nih.gov/articles/PMC11156185/#t1fn1) | Rapid Antigen Test[†](https://pmc.ncbi.nlm.nih.gov/articles/PMC11156185/#t1fn2) | Days of Rapid Antigen Test Positivity[‡](https://pmc.ncbi.nlm.nih.gov/articles/PMC11156185/#t1fn3) | No. of Rapid Antigen Tests Taken | |---|---|---|---|---|---|---| | | | yr | | | | | | 1 | Female | 20 | None | Quidel | 14 | 8 | | 2 | Female | 40 | Rheumatoid arthritis | Quidel | 14 | 8 | | 3 | Female | 58 | None | Quidel | 12 | 7 | | 4 | Female | 19 | None | Abbott | 14 | 8 | | 5 | Female | 33 | None | Quidel | 13 | 7 | | 6 | Female | 50 | None | Quidel | 13 | 4 | | 7 | Female | 68 | Sjögren’s syndrome | Quidel | 53 | 15 | | 8 | Male | 57 | Rheumatoid arthritis | Quidel | 14 | 8 | | 9 | Female | 48 | Lupus and antisynthetase syndrome | Quidel | 16 | 9 | | 10 | Female | 27 | None | Quidel | 12 | 7 | | 11 | Female | 43 | Unidentified disorder | Quidel | 14 | 8 | | 12 | Female | 46 | None | Quidel | 9 | 10 | | 13 | Female | 55 | Unidentified disorder | Quidel | 14 | 7 | [Open in a new tab](https://pmc.ncbi.nlm.nih.gov/articles/PMC11156185/table/t1/) \* Autoimmune disorders were reported by the participants. † Quidel refers to the Quidel QuickVue At-Home OTC COVID-19 Test, and Abbott refers to the Abbott BinaxNOW COVID-19 Antigen Self Test. ‡ Participants were considered to be positive on the days between two positive tests unless the tests were more than 7 days apart. This finding has substantial clinical relevance. The persistent false positivity may be a result of cross-reactivity of test antibodies with rheumatoid factor and could potentially occur in any patient who has a condition characterized by circulating rheumatoid factor.[5](https://pmc.ncbi.nlm.nih.gov/articles/PMC11156185/#r5) Because testing for SARS-CoV-2 is commonly performed among symptomatic patients, false positive results may be unrecognized clinically. However, persons who encounter persistent positive tests after infection or in the absence of symptoms may find reassurance in the recognition of this uncommon but known phenomenon. We suggest that patients with persistent false positive results and a history of autoimmune disease with rheumatoid factor may benefit from repeat testing with a different brand of rapid antigen test. Finally, this report may help public health officials and health care providers to distinguish between cross-reactive false positivity and SARS-CoV-2 rebound. ## Supplementary Appendix [NEJMc2313517\_appendix.pdf](https://pmc.ncbi.nlm.nih.gov/articles/instance/11156185/bin/NEJMc2313517_appendix.pdf) (149.2KB, pdf) ## Disclosure Forms [NEJMc2313517\_disclosures.pdf](https://pmc.ncbi.nlm.nih.gov/articles/instance/11156185/bin/NEJMc2313517_disclosures.pdf) (314.1KB, pdf) The views expressed in this letter are those of the authors and do not necessarily represent the views of the National Institute of Biomedical Imaging and Bioengineering; the National Heart, Lung, and Blood Institute; the National Institutes of Health (NIH); or the U.S. Department of Health and Human Services. ## Footnotes Supported by a grant (3U54HL143541-02S2) from the *NIH RADx Tech Initiative* and by an *NIH Clinical and Translational Science Award* (UL1TR001453). [Disclosure forms](https://pmc.ncbi.nlm.nih.gov/articles/PMC11156185/#ap2) provided by the authors are available with the full text of this letter at NEJM.org. ## References - 1\. Soni A, Herbert C, Lin H, et al. Performance of rapid antigen tests to detect symptomatic and asymptomatic SARS-CoV-2 infection: a prospective cohort study. Ann Intern Med 2023;176:975-982. \[[DOI](https://doi.org/10.7326/M23-0385)\] \[[PMC free article](https://pmc.ncbi.nlm.nih.gov/articles/PMC10321467/)\] \[[PubMed](https://pubmed.ncbi.nlm.nih.gov/37399548/)\] \[[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Ann%20Intern%20Med&title=Performance%20of%20rapid%20antigen%20tests%20to%20detect%20symptomatic%20and%20asymptomatic%20SARS-CoV-2%20infection:%20a%20prospective%20cohort%20study.&author=A%20Soni&author=C%20Herbert&author=H%20Lin&volume=176&publication_year=2023&pages=975-982&pmid=37399548&doi=10.7326/M23-0385&)\] - 2\. Gans JS, Goldfarb A, Agrawal AK, Sennik S, Stein J, Rosella L. False-positive results in rapid antigen tests for SARS-CoV-2. JAMA 2022;327:485-486. \[[DOI](https://doi.org/10.1001/jama.2021.24355)\] \[[PMC free article](https://pmc.ncbi.nlm.nih.gov/articles/PMC8742218/)\] \[[PubMed](https://pubmed.ncbi.nlm.nih.gov/34994775/)\] \[[Google Scholar](https://scholar.google.com/scholar_lookup?journal=JAMA&title=False-positive%20results%20in%20rapid%20antigen%20tests%20for%20SARS-CoV-2.&author=JS%20Gans&author=A%20Goldfarb&author=AK%20Agrawal&author=S%20Sennik&author=J%20Stein&volume=327&publication_year=2022&pages=485-486&pmid=34994775&doi=10.1001/jama.2021.24355&)\] - 3\. Herbert C, Kheterpal V, Suvarna T, et al. Design and preliminary findings of adherence to the Self-Testing for Our Protection from COVID-19 (STOP COVID-19) risk-based testing protocol: prospective digital study. JMIR Form Res 2022;6(6):e38113-e38113. \[[DOI](https://doi.org/10.2196/38113)\] \[[PMC free article](https://pmc.ncbi.nlm.nih.gov/articles/PMC9205422/)\] \[[PubMed](https://pubmed.ncbi.nlm.nih.gov/35649180/)\] \[[Google Scholar](https://scholar.google.com/scholar_lookup?journal=JMIR%20Form%20Res&title=Design%20and%20preliminary%20findings%20of%20adherence%20to%20the%20Self-Testing%20for%20Our%20Protection%20from%20COVID-19%20\(STOP%20COVID-19\)%20risk-based%20testing%20protocol:%20prospective%20digital%20study.&author=C%20Herbert&author=V%20Kheterpal&author=T%20Suvarna&volume=6&issue=6&publication_year=2022&pages=e38113-e38113&pmid=35649180&doi=10.2196/38113&)\] - 4\. Carter AM, Viloria Winnett A, Romano AE, Akana R, Shelby N, Ismagilov RF. Laboratory evaluation links some false-positive COVID-19 antigen test results observed in a field study to a specific lot of test strips. Open Forum Infect Dis 2023;10(1):ofac701-ofac701. \[[DOI](https://doi.org/10.1093/ofid/ofac701)\] \[[PMC free article](https://pmc.ncbi.nlm.nih.gov/articles/PMC9887260/)\] \[[PubMed](https://pubmed.ncbi.nlm.nih.gov/36726541/)\] \[[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Open%20Forum%20Infect%20Dis&title=Laboratory%20evaluation%20links%20some%20false-positive%20COVID-19%20antigen%20test%20results%20observed%20in%20a%20field%20study%20to%20a%20specific%20lot%20of%20test%20strips.&author=AM%20Carter&author=A%20Viloria%20Winnett&author=AE%20Romano&author=R%20Akana&author=N%20Shelby&volume=10&issue=1&publication_year=2023&pages=ofac701-ofac701&pmid=36726541&doi=10.1093/ofid/ofac701&)\] - 5\. Vinyé Bausà M, Bausà Peris R, Corominas H. Cross-reactions between rheumatoid factor and IgM SARS-CoV-2. Med Clin (Engl Ed) 2020;155:417-418. \[[DOI](https://doi.org/10.1016/j.medcle.2020.07.006)\] \[[PMC free article](https://pmc.ncbi.nlm.nih.gov/articles/PMC7546231/)\] \[[PubMed](https://pubmed.ncbi.nlm.nih.gov/33072868/)\] \[[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Med%20Clin%20\(Engl%20Ed\)&title=Cross-reactions%20between%20rheumatoid%20factor%20and%20IgM%20SARS-CoV-2.&author=M%20Viny%C3%A9%20Baus%C3%A0&author=R%20Baus%C3%A0%20Peris&author=H%20Corominas&volume=155&publication_year=2020&pages=417-418&pmid=33072868&doi=10.1016/j.medcle.2020.07.006&)\] ## Associated Data *This section collects any data citations, data availability statements, or supplementary materials included in this article.* ### Supplementary Materials [NEJMc2313517\_appendix.pdf](https://pmc.ncbi.nlm.nih.gov/articles/instance/11156185/bin/NEJMc2313517_appendix.pdf) (149.2KB, pdf) [NEJMc2313517\_disclosures.pdf](https://pmc.ncbi.nlm.nih.gov/articles/instance/11156185/bin/NEJMc2313517_disclosures.pdf) (314.1KB, pdf) *** Articles from The New England Journal of Medicine are provided here courtesy of **Massachusetts Medical Society** ![Close](https://cdn.ncbi.nlm.nih.gov/pmc/pd-medc-pmc-cloudpmc-viewer/production/8a2a0396/var/data/static/img/usa-icons/close.svg) ## ACTIONS - [![View on publisher site icon](https://cdn.ncbi.nlm.nih.gov/pmc/pd-medc-pmc-cloudpmc-viewer/production/8a2a0396/var/data/static/img/launch.svg) View on publisher site](https://doi.org/10.1056/NEJMc2313517) - [![Download PDF icon](https://cdn.ncbi.nlm.nih.gov/pmc/pd-medc-pmc-cloudpmc-viewer/production/8a2a0396/var/data/static/img/file_download.svg) PDF (338.3 KB)](https://pmc.ncbi.nlm.nih.gov/articles/PMC11156185/pdf/NEJMc2313517.pdf) - ![Cite icon](https://cdn.ncbi.nlm.nih.gov/pmc/pd-medc-pmc-cloudpmc-viewer/production/8a2a0396/var/data/static/img/format_quote.svg) Cite - ![Collections icon](https://cdn.ncbi.nlm.nih.gov/pmc/pd-medc-pmc-cloudpmc-viewer/production/8a2a0396/var/data/static/img/action-bookmark-full.svg) ![Collections icon](https://cdn.ncbi.nlm.nih.gov/pmc/pd-medc-pmc-cloudpmc-viewer/production/8a2a0396/var/data/static/img/action-bookmark-empty.svg) Collections - ![Permalink icon](https://cdn.ncbi.nlm.nih.gov/pmc/pd-medc-pmc-cloudpmc-viewer/production/8a2a0396/var/data/static/img/share.svg) Permalink ## PERMALINK ![Copy icon](https://cdn.ncbi.nlm.nih.gov/pmc/pd-medc-pmc-cloudpmc-viewer/production/8a2a0396/var/data/static/img/content_copy.svg) Copy ## RESOURCES ### Similar articles ### Cited by other articles ### Links to NCBI Databases ## Cite ![Close icon](https://cdn.ncbi.nlm.nih.gov/pmc/pd-medc-pmc-cloudpmc-viewer/production/8a2a0396/var/data/static/img/close.svg) - ![Copy icon](https://cdn.ncbi.nlm.nih.gov/pmc/pd-medc-pmc-cloudpmc-viewer/production/8a2a0396/var/data/static/img/content_copy.svg) Copy - [![Download icon](https://cdn.ncbi.nlm.nih.gov/pmc/pd-medc-pmc-cloudpmc-viewer/production/8a2a0396/var/data/static/img/file_download.svg) Download .nbib .nbib](https://pmc.ncbi.nlm.nih.gov/articles/PMC11156185/ "Download a file for external citation management software") - Format: ## Add to Collections Follow NCBI [NCBI on X (formerly known as Twitter)](https://twitter.com/ncbi) [NCBI on Facebook](https://www.facebook.com/ncbi.nlm) [NCBI on LinkedIn](https://www.linkedin.com/company/ncbinlm) [NCBI on GitHub](https://github.com/ncbi) [NCBI RSS feed](https://ncbiinsights.ncbi.nlm.nih.gov/) Connect with NLM [NLM on X (formerly known as Twitter)](https://twitter.com/nlm_nih) [NLM on Facebook](https://www.facebook.com/nationallibraryofmedicine) [NLM on YouTube](https://www.youtube.com/user/NLMNIH) [National Library of Medicine 8600 Rockville Pike Bethesda, MD 20894](https://www.google.com/maps/place/8600+Rockville+Pike,+Bethesda,+MD+20894/%4038.9959508,%0A%20%20%20%20%20%20%20%20%20%20%20%20-77.101021,17z/data%3D!3m1!4b1!4m5!3m4!1s0x89b7c95e25765ddb%3A0x19156f88b27635b8!8m2!3d38.9959508!%0A%20%20%20%20%20%20%20%20%20%20%20%204d-77.0988323) - [Web Policies](https://www.nlm.nih.gov/web_policies.html) - [FOIA](https://www.nih.gov/institutes-nih/nih-office-director/office-communications-public-liaison/freedom-information-act-office) - [HHS Vulnerability Disclosure](https://www.hhs.gov/vulnerability-disclosure-policy/index.html) - [Help](https://support.nlm.nih.gov/) - [Accessibility](https://www.nlm.nih.gov/accessibility.html) - [Careers](https://www.nlm.nih.gov/careers/careers.html) - [NLM](https://www.nlm.nih.gov/) - [NIH](https://www.nih.gov/) - [HHS](https://www.hhs.gov/) - [USA.gov](https://www.usa.gov/) Back to Top ![back to top icon](https://cdn.ncbi.nlm.nih.gov/pmc/pd-medc-pmc-cloudpmc-viewer/production/8a2a0396/var/data/static/img/arrow_upward.svg)
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*** *To the Editor:* Rapid antigen tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are effective tools for the diagnosis of acute infection, particularly when used serially.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC11156185/#r1) The percentage of rapid antigen tests with false positive results is reported to be less than 1%.[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC11156185/#r2) However, we have observed persons who repeatedly test positive with rapid antigen tests despite concurrent negative molecular tests; this infrequent phenomenon occurs predominantly among women and persons with autoimmune disorders. Our report is based on two longitudinal cohort studies in which participants underwent serial, paired rapid antigen testing and reverse-transcriptase–polymerase-chain-reaction (RT-PCR) testing for SARS-CoV-2.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC11156185/#r1),[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC11156185/#r3) Participants were considered to have a false positive result if they reported a positive rapid antigen test with a corresponding negative RT-PCR test of samples obtained within 48 hours of each other. All tests were performed with anterior nasal samples, and RT-PCR tests were performed with the Roche Cobas 6800 SARS-CoV-2 assay (see the Methods section in the [Supplementary Appendix](https://pmc.ncbi.nlm.nih.gov/articles/PMC11156185/#ap1), available with the full text of this letter at NEJM.org). False positive tests were classified as incidental false positives (in participants with at least one negative rapid antigen test during the study period) or persistent false positives (in participants with at least 5 days of positive rapid antigen tests and no negative rapid antigen test during the study period) (Fig. S1 in the [Supplementary Appendix](https://pmc.ncbi.nlm.nih.gov/articles/PMC11156185/#ap1)). Among 11,297 participants who performed 76,610 days of testing, 1.7% had at least one false positive rapid antigen test. Of the 191 participants with false positive results, 13 had persistent false positives ([Table 1](https://pmc.ncbi.nlm.nih.gov/articles/PMC11156185/#t1)). Most of the participants with persistent false positive results were women (12 of 13) and used the Quidel QuickVue rapid antigen test (12 of 13). We found a higher prevalence of participant-reported autoimmune disorders among participants with persistent false positives than among those with incidental false positives (in 6 of 13 vs. 10 of 178; crude odds ratio, 14.4; 95% confidence interval, 3.2 to 59.9). Persistent false positive results were obtained with tests from different lots and were not likely to be related to issues with test quality.[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC11156185/#r4) ## Table 1. Demographic and Testing Characteristics of Participants with Persistently Positive Tests. | Participant No. | Sex | Age | Autoimmune Disorder[\*](https://pmc.ncbi.nlm.nih.gov/articles/PMC11156185/#t1fn1) | Rapid Antigen Test[†](https://pmc.ncbi.nlm.nih.gov/articles/PMC11156185/#t1fn2) | Days of Rapid Antigen Test Positivity[‡](https://pmc.ncbi.nlm.nih.gov/articles/PMC11156185/#t1fn3) | No. of Rapid Antigen Tests Taken | |---|---|---|---|---|---|---| | | | yr | | | | | | 1 | Female | 20 | None | Quidel | 14 | 8 | | 2 | Female | 40 | Rheumatoid arthritis | Quidel | 14 | 8 | | 3 | Female | 58 | None | Quidel | 12 | 7 | | 4 | Female | 19 | None | Abbott | 14 | 8 | | 5 | Female | 33 | None | Quidel | 13 | 7 | | 6 | Female | 50 | None | Quidel | 13 | 4 | | 7 | Female | 68 | Sjögren’s syndrome | Quidel | 53 | 15 | | 8 | Male | 57 | Rheumatoid arthritis | Quidel | 14 | 8 | | 9 | Female | 48 | Lupus and antisynthetase syndrome | Quidel | 16 | 9 | | 10 | Female | 27 | None | Quidel | 12 | 7 | | 11 | Female | 43 | Unidentified disorder | Quidel | 14 | 8 | | 12 | Female | 46 | None | Quidel | 9 | 10 | | 13 | Female | 55 | Unidentified disorder | Quidel | 14 | 7 | \* Autoimmune disorders were reported by the participants. † Quidel refers to the Quidel QuickVue At-Home OTC COVID-19 Test, and Abbott refers to the Abbott BinaxNOW COVID-19 Antigen Self Test. ‡ Participants were considered to be positive on the days between two positive tests unless the tests were more than 7 days apart. This finding has substantial clinical relevance. The persistent false positivity may be a result of cross-reactivity of test antibodies with rheumatoid factor and could potentially occur in any patient who has a condition characterized by circulating rheumatoid factor.[5](https://pmc.ncbi.nlm.nih.gov/articles/PMC11156185/#r5) Because testing for SARS-CoV-2 is commonly performed among symptomatic patients, false positive results may be unrecognized clinically. However, persons who encounter persistent positive tests after infection or in the absence of symptoms may find reassurance in the recognition of this uncommon but known phenomenon. We suggest that patients with persistent false positive results and a history of autoimmune disease with rheumatoid factor may benefit from repeat testing with a different brand of rapid antigen test. Finally, this report may help public health officials and health care providers to distinguish between cross-reactive false positivity and SARS-CoV-2 rebound. ## Supplementary Appendix ## Disclosure Forms The views expressed in this letter are those of the authors and do not necessarily represent the views of the National Institute of Biomedical Imaging and Bioengineering; the National Heart, Lung, and Blood Institute; the National Institutes of Health (NIH); or the U.S. Department of Health and Human Services. ## Footnotes Supported by a grant (3U54HL143541-02S2) from the *NIH RADx Tech Initiative* and by an *NIH Clinical and Translational Science Award* (UL1TR001453). [Disclosure forms](https://pmc.ncbi.nlm.nih.gov/articles/PMC11156185/#ap2) provided by the authors are available with the full text of this letter at NEJM.org. ## References - 1\. Soni A, Herbert C, Lin H, et al. Performance of rapid antigen tests to detect symptomatic and asymptomatic SARS-CoV-2 infection: a prospective cohort study. Ann Intern Med 2023;176:975-982. \[[DOI](https://doi.org/10.7326/M23-0385)\] \[[PMC free article](https://pmc.ncbi.nlm.nih.gov/articles/PMC10321467/)\] \[[PubMed](https://pubmed.ncbi.nlm.nih.gov/37399548/)\] \[[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Ann%20Intern%20Med&title=Performance%20of%20rapid%20antigen%20tests%20to%20detect%20symptomatic%20and%20asymptomatic%20SARS-CoV-2%20infection:%20a%20prospective%20cohort%20study.&author=A%20Soni&author=C%20Herbert&author=H%20Lin&volume=176&publication_year=2023&pages=975-982&pmid=37399548&doi=10.7326/M23-0385&)\] - 2\. Gans JS, Goldfarb A, Agrawal AK, Sennik S, Stein J, Rosella L. False-positive results in rapid antigen tests for SARS-CoV-2. JAMA 2022;327:485-486. \[[DOI](https://doi.org/10.1001/jama.2021.24355)\] \[[PMC free article](https://pmc.ncbi.nlm.nih.gov/articles/PMC8742218/)\] \[[PubMed](https://pubmed.ncbi.nlm.nih.gov/34994775/)\] \[[Google Scholar](https://scholar.google.com/scholar_lookup?journal=JAMA&title=False-positive%20results%20in%20rapid%20antigen%20tests%20for%20SARS-CoV-2.&author=JS%20Gans&author=A%20Goldfarb&author=AK%20Agrawal&author=S%20Sennik&author=J%20Stein&volume=327&publication_year=2022&pages=485-486&pmid=34994775&doi=10.1001/jama.2021.24355&)\] - 3\. Herbert C, Kheterpal V, Suvarna T, et al. Design and preliminary findings of adherence to the Self-Testing for Our Protection from COVID-19 (STOP COVID-19) risk-based testing protocol: prospective digital study. JMIR Form Res 2022;6(6):e38113-e38113. \[[DOI](https://doi.org/10.2196/38113)\] \[[PMC free article](https://pmc.ncbi.nlm.nih.gov/articles/PMC9205422/)\] \[[PubMed](https://pubmed.ncbi.nlm.nih.gov/35649180/)\] \[[Google Scholar](https://scholar.google.com/scholar_lookup?journal=JMIR%20Form%20Res&title=Design%20and%20preliminary%20findings%20of%20adherence%20to%20the%20Self-Testing%20for%20Our%20Protection%20from%20COVID-19%20\(STOP%20COVID-19\)%20risk-based%20testing%20protocol:%20prospective%20digital%20study.&author=C%20Herbert&author=V%20Kheterpal&author=T%20Suvarna&volume=6&issue=6&publication_year=2022&pages=e38113-e38113&pmid=35649180&doi=10.2196/38113&)\] - 4\. Carter AM, Viloria Winnett A, Romano AE, Akana R, Shelby N, Ismagilov RF. Laboratory evaluation links some false-positive COVID-19 antigen test results observed in a field study to a specific lot of test strips. Open Forum Infect Dis 2023;10(1):ofac701-ofac701. \[[DOI](https://doi.org/10.1093/ofid/ofac701)\] \[[PMC free article](https://pmc.ncbi.nlm.nih.gov/articles/PMC9887260/)\] \[[PubMed](https://pubmed.ncbi.nlm.nih.gov/36726541/)\] \[[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Open%20Forum%20Infect%20Dis&title=Laboratory%20evaluation%20links%20some%20false-positive%20COVID-19%20antigen%20test%20results%20observed%20in%20a%20field%20study%20to%20a%20specific%20lot%20of%20test%20strips.&author=AM%20Carter&author=A%20Viloria%20Winnett&author=AE%20Romano&author=R%20Akana&author=N%20Shelby&volume=10&issue=1&publication_year=2023&pages=ofac701-ofac701&pmid=36726541&doi=10.1093/ofid/ofac701&)\] - 5\. Vinyé Bausà M, Bausà Peris R, Corominas H. Cross-reactions between rheumatoid factor and IgM SARS-CoV-2. Med Clin (Engl Ed) 2020;155:417-418. \[[DOI](https://doi.org/10.1016/j.medcle.2020.07.006)\] \[[PMC free article](https://pmc.ncbi.nlm.nih.gov/articles/PMC7546231/)\] \[[PubMed](https://pubmed.ncbi.nlm.nih.gov/33072868/)\] \[[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Med%20Clin%20\(Engl%20Ed\)&title=Cross-reactions%20between%20rheumatoid%20factor%20and%20IgM%20SARS-CoV-2.&author=M%20Viny%C3%A9%20Baus%C3%A0&author=R%20Baus%C3%A0%20Peris&author=H%20Corominas&volume=155&publication_year=2020&pages=417-418&pmid=33072868&doi=10.1016/j.medcle.2020.07.006&)\] ## Associated Data *This section collects any data citations, data availability statements, or supplementary materials included in this article.* ### Supplementary Materials *** Articles from The New England Journal of Medicine are provided here courtesy of **Massachusetts Medical Society**
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