🕷️ Crawler Inspector

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Raw Queries and Responses

1. Shard Calculation

Query:

Response:

Calculated Shard: 99 (from laksa176)

2. Crawled Status Check

Query:

curl -X POST \
  'http://laksa099.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.wired.com/story/the-secrets-of-covid-brain-fog-are-starting-to-lift/\')), getAhrefsUnparsedNoserviceFromURL(\'https://www.wired.com/story/the-secrets-of-covid-brain-fog-are-starting-to-lift/\'))) FORMAT JSONEachRow'

Response:

{"found_url":"https:\/\/www.wired.com\/story\/the-secrets-of-covid-brain-fog-are-starting-to-lift\/","crawl_time":1776263682,"first_indexed_time":1656673264,"http_code":200,"src_unparsed":"com,wired!www,\/story\/the-secrets-of-covid-brain-fog-are-starting-to-lift\/ s443","src_root_hash":"5736512710119187299","history_drop_reason":null,"meta_title":"The Secrets of Covid ‘Brain Fog’ Are Starting to Lift | WIRED","meta_descriptions":["Scientists are getting closer to understanding the neurology behind the memory problems and cognitive fuzziness that an infection can trigger."],"attrs_boilerpipe_text":"Paige was having\na great start to 2021. Her health was the best it had ever been. She loved her job and the people she worked with as a communications manager for a conservation nonprofit. She could get up early in the mornings to work on creative projects. Things were looking “really, really good,” she says—until she got\nCovid-19\n.\nWhile the initial infection was not fun, what followed was worse. Four weeks later, when Paige (who asked to be identified only by her middle name) had recovered enough to go back to work full-time, she woke up one day with an overwhelming fatigue that just never went away. It was accompanied by a loss of mental sharpness, part of a suite of sometimes hard-to-pin-down symptoms that are often referred to as\nCovid-19 “brain fog,”\na general term for sluggish or fuzzy thinking. “I spent most of 2021 making decisions like: Is this the day where I get a shower, or I go up and microwave myself a frozen dinner?” Paige recalls. The high-level writing required for her job was out of the question. Living with those symptoms was, in her words, “hell on earth.”\nMany of these\nhard-to-define\nCovid-19 symptoms can\npersist over time\n—weeks, months, years. Now, new research in the journal\nCell\nis shedding some light on the biological mechanisms of how Covid-19 affects the brain. Led by researchers Michelle Monje and Akiko Iwasaki, of Stanford and Yale Universities respectively, scientists determined that in mice with mild Covid-19 infections, the virus disrupted the normal activity of several brain cell populations and left behind signs of inflammation. They believe that these findings may help explain some of the cognitive disruption experienced by Covid-19 survivors and provide potential pathways for therapies.\nFor the past 20 years, Monje, a neuro-oncologist, had been trying to understand the neurobiology behind chemotherapy-induced cognitive symptoms—similarly known as “chemo fog.” When Covid-19 emerged as a major immune-activating virus, she worried about the potential for similar disruption. “Very quickly, as reports of cognitive impairment started to come out, it was clear that it was a very similar syndrome,” she says. “The same symptoms of impaired attention, memory, speed of information processing, dis-executive function—it really clinically looks just like the ‘chemo fog’ that people experienced and that we’d been studying.”\nWIRED's Guide to How the Universe Works\nYour weekly roundup of the best stories on health care, the climate crisis, new scientific discoveries, and more.\nIn September 2020, Monje reached out to Iwasaki, an immunologist. Her group had already established a mouse model of Covid-19, thanks to their Biosafety Level 3 clearance to work with the virus. A mouse model is engineered as a close stand-in for a human, and this experiment was meant to mimic the experience of a person with a mild Covid-19 infection. Using a viral vector, Iwasaki’s group introduced the\nhuman ACE2 receptor\ninto cells in the trachea and lungs of the mice. This receptor is the point of entry for the Covid-causing virus, allowing it to bind to the cell. Then they shot a bit of virus up the mice’s noses to cause infection, controlling the amount and delivery so that the virus was limited to the respiratory system. For the mice, this infection cleared up within one week, and they did not lose weight.\nCoupled with biosafety regulations and the challenges of cross-country collaboration, the security precautions required by the pandemic created some interesting work constraints. Because most virus-related work had to be done in Iwasaki’s laboratory, the Yale scientists would take advantage of overnight shipping to fly samples across the country to Monje’s Stanford laboratory where they could be analyzed. Sometimes, they would need to film experiments with a GoPro camera to make sure that everybody could see the same thing. “We made it work,” Monje says.\nMost Popular\nOnce the mice had been infected with the virus, the scientists assessed the levels of cytokines in their blood and cerebrospinal fluid (the liquid surrounding the brain) at seven days and seven weeks after infection. Cytokines are markers secreted by the immune system, and they are critical in regulating inflammation. Not only were certain cytokines elevated in the cerebrospinal fluid at both time periods, but the scientists saw an increase of microglia reactivity in the subcortical white matter of the brain—the squishy white tissue rife with nerve fibers that makes up over half of the brain’s volume. That was another sign of potential trouble.\nMicroglia are sort of like the central nervous system’s hungry scavengers. They are immune cells that clean up the brain by chomping on dead and unwanted neural debris, among other important functions. “There’s a unique subpopulation of microglia in the white matter called axon tract microglia,” Monje says. These have a specific genetic signature, she continues, and “are exquisitely sensitive to a wide range of insults,” like inflammatory or toxic stimuli.\nIn response to these stimuli, microglia can become perpetually reactive. One consequence is that they can begin eating away at needed neurons or other brain cells, which further disrupts the brain’s homeostasis. In the case of Covid-19, the scientists found that this reactivity persisted even at seven weeks after infection. Monje’s team had seen similar elevation in this activity following chemotherapy and in brain samples from human patients who were infected with Covid-19. In the hippocampus (the area of the brain closely associated with memory), this overenthusiastic cleanup effort can deter the creation of new neurons, which are linked to maintaining healthy memory.\nTo figure out what exactly caused the microglia to become reactive, the researchers looked for the cytokines that had reached elevated levels. Specifically, Anthony Fernandez Castaneda, a postdoctoral researcher in Monje’s laboratory and a study coauthor, found CCL11—a factor that can decrease the generation of new neurons and impair learning or memory. “The elevated CCL11 result was very interesting, because it could potentially explain why some Covid survivors experience cognitive symptoms,” he says.\nIn a second phase of the experiment, the researchers gave shots of CCL11 to a separate group of mice. Then they examined tissue from their brains to discover where the microglia had been reactive, and where fewer new neurons had grown. That turned out to be in the hippocampus—indicating that CCL11 acted on very specific cell populations in a memory-related area of the brain.\nNext, the scientists decided to investigate the effects of mild Covid-19 infection on myelinating oligodendrocytes—brain cells that generate the myelin “padding” around neurons to provide insulation for better inter-neuron communication. Previously, work done by Anna Geraghty (another postdoctoral fellow in Monje’s lab and study coauthor) had focused on how chemotherapy affects this process. Myelin loss in the mice treated with chemo was found to be directly linked with deficits in short-term memory and attention. “Even minor adjustments in those myelin can actually impact neuronal communication in quite diverse ways,” she says. “Losing that ability to adaptively respond to neuronal activity led to persistent cognitive impairments in these mice.”\nMost Popular\nGeraghty recalls staying in the lab late at night during the Christmas holiday to finish the analysis of how Covid-19 affected that padding in mouse neurons. The result: The infected mice had lost approximately one-third of their mature oligodendrocytes, and had a statistically significant drop in myelination compared to mice in a control group. The magnitude of myelin loss was almost identical to what the lab had discovered when studying mice and chemo. She excitedly texted the results to Monje. “There was just a big moment in my brain of, ‘Oh my gosh, this data is incredibly interesting,’” Geraghty recalls.\nJoanna Hellmuth, a cognitive neurologist at UC San Francisco who was unaffiliated with the study, notes that the “mouse data is very compelling,” and more studies are needed to see how these results translate into treatments for human patients—like Paige or others struggling with long Covid and cognitive symptoms. Figuring out which drugs to try first, though, could benefit from understanding the biological cause of brain fog symptoms. “‘Brain fog’ is a colloquial term,” says Hellmuth—and it “kind of delegitimizes peoples’ having a neurological disorder.”\nWes Ely, a pulmonary and critical care specialist at Vanderbilt University Medical Center who was unaffiliated with the study, believes that such studies can lead to future therapeutic development. “This work paves the path towards both pharmacological, neuropsychological, and cognitive rehabilitative mechanisms to rebuild brain power,” he says.\nFor example, Monje thinks, some drug candidates that already worked in “chemo fog” animal models might be useful for treating Covid-related cognitive symptoms. She hopes to test these candidates on the Covid-19 mouse model to see if they help.\nThe team would also like to investigate other questions, like whether these neurological effects are different after even longer periods of time, or if they are different following a breakthrough infection after vaccination. They’d also like to compare what they’ve found in Covid-19 mouse models to neurological reactions to another famous virus—H1N1, which causes swine flu. The team had found that in a mouse model of H1N1, the drop in oligodendrocytes and increase in microglial reactivity in the subcortical white matter generally normalized by seven weeks—unlike for the Covid-infected mice. They also found that, in mice infected with either virus, CCL11 was elevated in the cerebrospinal fluid. Monje hopes to study what she calls this “prominent shared mechanism” in further detail.\nWhile Monje and Iwasaki’s work has given researchers a better idea of how Covid might affect the brain, it may take years before there is a working treatment for patients. For Paige, the time cannot come soon enough. In 2022, she got Covid again. “I’m just praying for medicine, praying for treatment,” she says.","attrs_markdown":"[Skip to main content](https:\/\/www.wired.com\/story\/the-secrets-of-covid-brain-fog-are-starting-to-lift\/#main-content)\n\n[SECURITY](https:\/\/www.wired.com\/category\/security\/)\n\n[POLITICS](https:\/\/www.wired.com\/category\/politics\/)\n\n[THE BIG STORY](https:\/\/www.wired.com\/category\/big-story\/)\n\n[BUSINESS](https:\/\/www.wired.com\/category\/business\/)\n\n[SCIENCE](https:\/\/www.wired.com\/category\/science\/)\n\n[CULTURE](https:\/\/www.wired.com\/category\/culture\/)\n\n[REVIEWS](https:\/\/www.wired.com\/category\/gear\/)\n\n[SUBSCRIBE](https:\/\/www.wired.com\/v2\/offers\/wira01035?source=Site_0_JNY_WIR_DESKTOP_NAV_CTA_0_US_ACQ_NLI_QUICK_PAY_GENERIC_ZZ_PANELA)\n\n[Newsletters](https:\/\/www.wired.com\/newsletter?sourceCode=hamburgernav)\n\n[SUBSCRIBE](https:\/\/www.wired.com\/v2\/offers\/wira01035?source=Site_0_JNY_WIR_DESKTOP_NAV_CTA_0_US_ACQ_NLI_QUICK_PAY_GENERIC_ZZ_PANELA)\n\n[Security](https:\/\/www.wired.com\/category\/security\/)\n\n[Politics](https:\/\/www.wired.com\/category\/politics\/)\n\n[The Big Story](https:\/\/www.wired.com\/category\/big-story\/)\n\n[Business](https:\/\/www.wired.com\/category\/business\/)\n\n[Science](https:\/\/www.wired.com\/category\/science\/)\n\n[Culture](https:\/\/www.wired.com\/category\/culture\/)\n\n[Reviews](https:\/\/www.wired.com\/category\/gear\/)\n\nMore\n\n[The Big Interview](https:\/\/www.wired.com\/the-big-interview\/)[Magazine](https:\/\/www.wired.com\/magazine\/)[Events](https:\/\/www.wired.com\/tag\/wired-events\/)[WIRED Insider](https:\/\/www.wired.com\/collection\/wiredinsider\/)[WIRED Consulting](https:\/\/www.wired.com\/tag\/wired-consulting\/)\n\n[Newsletters](https:\/\/www.wired.com\/newsletter?sourceCode=hamburgernav)\n\n[Podcasts](https:\/\/www.wired.com\/podcasts\/)\n\n[Video](https:\/\/www.wired.com\/video\/)\n\n[Livestreams](https:\/\/www.wired.com\/livestreams)\n\n[Merch](https:\/\/shop.wired.com\/)\n\n[Search](https:\/\/www.wired.com\/search\/)\n\n[Sign In](https:\/\/www.wired.com\/auth\/initiate?redirectURL=%2Fstory%2Fthe-secrets-of-covid-brain-fog-are-starting-to-lift%2F&source=VERSO_NAVIGATION)\n\n[START FREE TRIAL](https:\/\/www.wired.com\/v2\/offers\/wira01035?source=Site_0_JNY_WIR_DESKTOP_JNY_WIR_GLOBAL_NAV_DRAWER_0_US_ACQ_NLI_QUICK_PAY_GENERIC_ZZ_PANELA)\n\n[![ZOOM IN \\<br\\> Subscribe today for only \\<del\\>\\$4\\<\/del\\> \\<strong\\>\\$2\/month\\<\/strong\\> and get access to exclusive benefits including \\<strong\\>5 all-new premium newsletters.\\<\/strong\\> CTA:SUBSCRIBE](https:\/\/assets.bonappetit.com\/photos\/686ea38fcb59aaabef7a795d\/original\/pass\/Wired_Zoom_Rollover_300x200_v2a_Shorter.gif?format=original)](https:\/\/www.wired.com\/v2\/offers\/wira01035?source=Site_0_JNY_WIR_DESKTOP_NAV_ROLLOVER_0_US_ACQ_NLI_QUICK_PAY_GENERIC_ZZ_PANELA)\n\n[Sign In](https:\/\/www.wired.com\/auth\/initiate?redirectURL=%2Fstory%2Fthe-secrets-of-covid-brain-fog-are-starting-to-lift%2F&source=VERSO_NAVIGATION)\n\nThe intersection of technology, power, and culture. Start your free trial and get access to **5 all-new premium newsletters.** [START FREE TRIAL](https:\/\/www.wired.com\/v2\/offers\/wira01035?source=Site_0_JNY_WIR_DESKTOP_PAYWALL_THIN_METER_ARTICLE_1_0_US_ACQ_NLI_QUICK_PAY_GENERIC_ZZ_PANELA)\n\n[Maggie Chen](https:\/\/www.wired.com\/author\/maggie-chen\/)\n\n[Science](https:\/\/www.wired.com\/category\/science)\n\nJul 1, 2022 7:00 AM\n# The Secrets of Covid ‘Brain Fog’ Are Starting to Lift\n\nScientists are getting closer to understanding the neurology behind the memory problems and cognitive fuzziness that an infection can trigger.\n\n![Coloured transmission electron micrograph of an oligodendrocyte sending a cell process to a myelinated nerve fiber](https:\/\/media.wired.com\/photos\/62be03837a39cc2124cb2d6f\/3:2\/w_2560%2Cc_limit\/COVID-Brain-Fog-Science-ScienceSource_SS21470210.jpg)\n\nPhotograph: Jose Calvo\/Science Source\n\nSave this story\n\nSave this story\n\nPaige was having a great start to 2021. Her health was the best it had ever been. She loved her job and the people she worked with as a communications manager for a conservation nonprofit. She could get up early in the mornings to work on creative projects. Things were looking “really, really good,” she says—until she got [Covid-19](https:\/\/www.wired.com\/tag\/covid-19).\n\nWhile the initial infection was not fun, what followed was worse. Four weeks later, when Paige (who asked to be identified only by her middle name) had recovered enough to go back to work full-time, she woke up one day with an overwhelming fatigue that just never went away. It was accompanied by a loss of mental sharpness, part of a suite of sometimes hard-to-pin-down symptoms that are often referred to as [Covid-19 “brain fog,”](https:\/\/www.wired.com\/story\/confused-about-covid-brain-fog-doctors-have-questions-too\/) a general term for sluggish or fuzzy thinking. “I spent most of 2021 making decisions like: Is this the day where I get a shower, or I go up and microwave myself a frozen dinner?” Paige recalls. The high-level writing required for her job was out of the question. Living with those symptoms was, in her words, “hell on earth.”\n\n#### Content\nTo honor your privacy preferences, this content can only be viewed on the site it [originates](https:\/\/player.spokenlayer.net\/v1-wired-science?__v=linear&url=http:\/\/www.wired.com\/story\/the-secrets-of-covid-brain-fog-are-starting-to-lift) from.\n\nMany of these [hard-to-define](https:\/\/www.wired.com\/story\/to-help-people-with-long-covid-scientists-need-to-define-it\/) Covid-19 symptoms can [persist over time](https:\/\/www.wired.com\/story\/exactly-how-many-people-long-covid\/)—weeks, months, years. Now, new research in the journal [*Cell*](https:\/\/www.cell.com\/cell\/fulltext\/S0092-8674\$22\$00713-9) is shedding some light on the biological mechanisms of how Covid-19 affects the brain. Led by researchers Michelle Monje and Akiko Iwasaki, of Stanford and Yale Universities respectively, scientists determined that in mice with mild Covid-19 infections, the virus disrupted the normal activity of several brain cell populations and left behind signs of inflammation. They believe that these findings may help explain some of the cognitive disruption experienced by Covid-19 survivors and provide potential pathways for therapies.\n\nFeatured Video\n\n[How Nose Swabs Detect New Covid-19 Strains](https:\/\/www.wired.com\/video\/watch\/wired-news-and-science-how-nose-swabs-detect-new-covid-19-strains)\n\nFor the past 20 years, Monje, a neuro-oncologist, had been trying to understand the neurobiology behind chemotherapy-induced cognitive symptoms—similarly known as “chemo fog.” When Covid-19 emerged as a major immune-activating virus, she worried about the potential for similar disruption. “Very quickly, as reports of cognitive impairment started to come out, it was clear that it was a very similar syndrome,” she says. “The same symptoms of impaired attention, memory, speed of information processing, dis-executive function—it really clinically looks just like the ‘chemo fog’ that people experienced and that we’d been studying.”\n\n### WIRED's Guide to How the Universe Works\nYour weekly roundup of the best stories on health care, the climate crisis, new scientific discoveries, and more.\n\nIn September 2020, Monje reached out to Iwasaki, an immunologist. Her group had already established a mouse model of Covid-19, thanks to their Biosafety Level 3 clearance to work with the virus. A mouse model is engineered as a close stand-in for a human, and this experiment was meant to mimic the experience of a person with a mild Covid-19 infection. Using a viral vector, Iwasaki’s group introduced the [human ACE2 receptor](https:\/\/www.wired.com\/story\/meet-ace2-the-enzyme-at-the-center-of-the-covid-19-mystery\/) into cells in the trachea and lungs of the mice. This receptor is the point of entry for the Covid-causing virus, allowing it to bind to the cell. Then they shot a bit of virus up the mice’s noses to cause infection, controlling the amount and delivery so that the virus was limited to the respiratory system. For the mice, this infection cleared up within one week, and they did not lose weight.\n\nCoupled with biosafety regulations and the challenges of cross-country collaboration, the security precautions required by the pandemic created some interesting work constraints. Because most virus-related work had to be done in Iwasaki’s laboratory, the Yale scientists would take advantage of overnight shipping to fly samples across the country to Monje’s Stanford laboratory where they could be analyzed. Sometimes, they would need to film experiments with a GoPro camera to make sure that everybody could see the same thing. “We made it work,” Monje says.\n\nMost Popular\n\n- [![The Fanfare Around the Band Geese Actually Was a Psyop](https:\/\/media.wired.com\/photos\/69d7c981444a1a70ce52eb20\/1:1\/w_120%2Ch_120%2Cc_limit\/undefined)](https:\/\/www.wired.com\/story\/geese-chaotic-good-marketing-industry-plant\/#intcid=_wired-right-rail_24c22a4b-cb34-4a23-a3aa-f02daaa30eb9_popular4-2)\n  \n  Music\n  \n  [The Fanfare Around the Band Geese Actually Was a Psyop](https:\/\/www.wired.com\/story\/geese-chaotic-good-marketing-industry-plant\/#intcid=_wired-right-rail_24c22a4b-cb34-4a23-a3aa-f02daaa30eb9_popular4-2)\n  \n  By John Semley\n- [![Meta Is Warned That Facial Recognition Glasses Will Arm Sexual Predators](https:\/\/media.wired.com\/photos\/69dd120fd5415cb89341a838\/1:1\/w_120%2Ch_120%2Cc_limit\/undefined)](https:\/\/www.wired.com\/story\/meta-ray-ban-oakley-smart-glasses-no-face-recognition-civil-society\/#intcid=_wired-right-rail_24c22a4b-cb34-4a23-a3aa-f02daaa30eb9_popular4-2)\n  \n  Artificial Intelligence\n  \n  [Meta Is Warned That Facial Recognition Glasses Will Arm Sexual Predators](https:\/\/www.wired.com\/story\/meta-ray-ban-oakley-smart-glasses-no-face-recognition-civil-society\/#intcid=_wired-right-rail_24c22a4b-cb34-4a23-a3aa-f02daaa30eb9_popular4-2)\n  \n  By Dell Cameron\n- [![Government Workers Say They’re Getting Inundated With Religion](https:\/\/media.wired.com\/photos\/69dd3c751720dda876aeb968\/1:1\/w_120%2Ch_120%2Cc_limit\/undefined)](https:\/\/www.wired.com\/story\/government-workers-say-theyre-getting-inundated-with-religion\/#intcid=_wired-right-rail_24c22a4b-cb34-4a23-a3aa-f02daaa30eb9_popular4-2)\n  \n  Politics\n  \n  [Government Workers Say They’re Getting Inundated With Religion](https:\/\/www.wired.com\/story\/government-workers-say-theyre-getting-inundated-with-religion\/#intcid=_wired-right-rail_24c22a4b-cb34-4a23-a3aa-f02daaa30eb9_popular4-2)\n  \n  By Vittoria Elliott\n- [![Staunch Trump Supporters Are Now Asking if He’s the Antichrist](https:\/\/media.wired.com\/photos\/69d83e91a6b1cf7dff37c069\/1:1\/w_120%2Ch_120%2Cc_limit\/undefined)](https:\/\/www.wired.com\/story\/staunch-trump-supporters-are-now-asking-if-hes-the-antichrist\/#intcid=_wired-right-rail_24c22a4b-cb34-4a23-a3aa-f02daaa30eb9_popular4-2)\n  \n  Politics\n  \n  [Staunch Trump Supporters Are Now Asking if He’s the Antichrist](https:\/\/www.wired.com\/story\/staunch-trump-supporters-are-now-asking-if-hes-the-antichrist\/#intcid=_wired-right-rail_24c22a4b-cb34-4a23-a3aa-f02daaa30eb9_popular4-2)\n  \n  By Makena Kelly\n\nOnce the mice had been infected with the virus, the scientists assessed the levels of cytokines in their blood and cerebrospinal fluid (the liquid surrounding the brain) at seven days and seven weeks after infection. Cytokines are markers secreted by the immune system, and they are critical in regulating inflammation. Not only were certain cytokines elevated in the cerebrospinal fluid at both time periods, but the scientists saw an increase of microglia reactivity in the subcortical white matter of the brain—the squishy white tissue rife with nerve fibers that makes up over half of the brain’s volume. That was another sign of potential trouble.\n\nMicroglia are sort of like the central nervous system’s hungry scavengers. They are immune cells that clean up the brain by chomping on dead and unwanted neural debris, among other important functions. “There’s a unique subpopulation of microglia in the white matter called axon tract microglia,” Monje says. These have a specific genetic signature, she continues, and “are exquisitely sensitive to a wide range of insults,” like inflammatory or toxic stimuli.\n\nIn response to these stimuli, microglia can become perpetually reactive. One consequence is that they can begin eating away at needed neurons or other brain cells, which further disrupts the brain’s homeostasis. In the case of Covid-19, the scientists found that this reactivity persisted even at seven weeks after infection. Monje’s team had seen similar elevation in this activity following chemotherapy and in brain samples from human patients who were infected with Covid-19. In the hippocampus (the area of the brain closely associated with memory), this overenthusiastic cleanup effort can deter the creation of new neurons, which are linked to maintaining healthy memory.\n\nTo figure out what exactly caused the microglia to become reactive, the researchers looked for the cytokines that had reached elevated levels. Specifically, Anthony Fernandez Castaneda, a postdoctoral researcher in Monje’s laboratory and a study coauthor, found CCL11—a factor that can decrease the generation of new neurons and impair learning or memory. “The elevated CCL11 result was very interesting, because it could potentially explain why some Covid survivors experience cognitive symptoms,” he says.\n\nIn a second phase of the experiment, the researchers gave shots of CCL11 to a separate group of mice. Then they examined tissue from their brains to discover where the microglia had been reactive, and where fewer new neurons had grown. That turned out to be in the hippocampus—indicating that CCL11 acted on very specific cell populations in a memory-related area of the brain.\n\nNext, the scientists decided to investigate the effects of mild Covid-19 infection on myelinating oligodendrocytes—brain cells that generate the myelin “padding” around neurons to provide insulation for better inter-neuron communication. Previously, work done by Anna Geraghty (another postdoctoral fellow in Monje’s lab and study coauthor) had focused on how chemotherapy affects this process. Myelin loss in the mice treated with chemo was found to be directly linked with deficits in short-term memory and attention. “Even minor adjustments in those myelin can actually impact neuronal communication in quite diverse ways,” she says. “Losing that ability to adaptively respond to neuronal activity led to persistent cognitive impairments in these mice.”\n\nMost Popular\n\n- [![The Fanfare Around the Band Geese Actually Was a Psyop](https:\/\/media.wired.com\/photos\/69d7c981444a1a70ce52eb20\/1:1\/w_120%2Ch_120%2Cc_limit\/undefined)](https:\/\/www.wired.com\/story\/geese-chaotic-good-marketing-industry-plant\/#intcid=_wired-right-rail_24c22a4b-cb34-4a23-a3aa-f02daaa30eb9_popular4-2)\n  \n  Music\n  \n  [The Fanfare Around the Band Geese Actually Was a Psyop](https:\/\/www.wired.com\/story\/geese-chaotic-good-marketing-industry-plant\/#intcid=_wired-right-rail_24c22a4b-cb34-4a23-a3aa-f02daaa30eb9_popular4-2)\n  \n  By John Semley\n- [![Meta Is Warned That Facial Recognition Glasses Will Arm Sexual Predators](https:\/\/media.wired.com\/photos\/69dd120fd5415cb89341a838\/1:1\/w_120%2Ch_120%2Cc_limit\/undefined)](https:\/\/www.wired.com\/story\/meta-ray-ban-oakley-smart-glasses-no-face-recognition-civil-society\/#intcid=_wired-right-rail_24c22a4b-cb34-4a23-a3aa-f02daaa30eb9_popular4-2)\n  \n  Artificial Intelligence\n  \n  [Meta Is Warned That Facial Recognition Glasses Will Arm Sexual Predators](https:\/\/www.wired.com\/story\/meta-ray-ban-oakley-smart-glasses-no-face-recognition-civil-society\/#intcid=_wired-right-rail_24c22a4b-cb34-4a23-a3aa-f02daaa30eb9_popular4-2)\n  \n  By Dell Cameron\n- [![Government Workers Say They’re Getting Inundated With Religion](https:\/\/media.wired.com\/photos\/69dd3c751720dda876aeb968\/1:1\/w_120%2Ch_120%2Cc_limit\/undefined)](https:\/\/www.wired.com\/story\/government-workers-say-theyre-getting-inundated-with-religion\/#intcid=_wired-right-rail_24c22a4b-cb34-4a23-a3aa-f02daaa30eb9_popular4-2)\n  \n  Politics\n  \n  [Government Workers Say They’re Getting Inundated With Religion](https:\/\/www.wired.com\/story\/government-workers-say-theyre-getting-inundated-with-religion\/#intcid=_wired-right-rail_24c22a4b-cb34-4a23-a3aa-f02daaa30eb9_popular4-2)\n  \n  By Vittoria Elliott\n- [![Staunch Trump Supporters Are Now Asking if He’s the Antichrist](https:\/\/media.wired.com\/photos\/69d83e91a6b1cf7dff37c069\/1:1\/w_120%2Ch_120%2Cc_limit\/undefined)](https:\/\/www.wired.com\/story\/staunch-trump-supporters-are-now-asking-if-hes-the-antichrist\/#intcid=_wired-right-rail_24c22a4b-cb34-4a23-a3aa-f02daaa30eb9_popular4-2)\n  \n  Politics\n  \n  [Staunch Trump Supporters Are Now Asking if He’s the Antichrist](https:\/\/www.wired.com\/story\/staunch-trump-supporters-are-now-asking-if-hes-the-antichrist\/#intcid=_wired-right-rail_24c22a4b-cb34-4a23-a3aa-f02daaa30eb9_popular4-2)\n  \n  By Makena Kelly\n\nGeraghty recalls staying in the lab late at night during the Christmas holiday to finish the analysis of how Covid-19 affected that padding in mouse neurons. The result: The infected mice had lost approximately one-third of their mature oligodendrocytes, and had a statistically significant drop in myelination compared to mice in a control group. The magnitude of myelin loss was almost identical to what the lab had discovered when studying mice and chemo. She excitedly texted the results to Monje. “There was just a big moment in my brain of, ‘Oh my gosh, this data is incredibly interesting,’” Geraghty recalls.\n\nJoanna Hellmuth, a cognitive neurologist at UC San Francisco who was unaffiliated with the study, notes that the “mouse data is very compelling,” and more studies are needed to see how these results translate into treatments for human patients—like Paige or others struggling with long Covid and cognitive symptoms. Figuring out which drugs to try first, though, could benefit from understanding the biological cause of brain fog symptoms. “‘Brain fog’ is a colloquial term,” says Hellmuth—and it “kind of delegitimizes peoples’ having a neurological disorder.”\n\nWes Ely, a pulmonary and critical care specialist at Vanderbilt University Medical Center who was unaffiliated with the study, believes that such studies can lead to future therapeutic development. “This work paves the path towards both pharmacological, neuropsychological, and cognitive rehabilitative mechanisms to rebuild brain power,” he says.\n\nFor example, Monje thinks, some drug candidates that already worked in “chemo fog” animal models might be useful for treating Covid-related cognitive symptoms. She hopes to test these candidates on the Covid-19 mouse model to see if they help.\n\nThe team would also like to investigate other questions, like whether these neurological effects are different after even longer periods of time, or if they are different following a breakthrough infection after vaccination. They’d also like to compare what they’ve found in Covid-19 mouse models to neurological reactions to another famous virus—H1N1, which causes swine flu. The team had found that in a mouse model of H1N1, the drop in oligodendrocytes and increase in microglial reactivity in the subcortical white matter generally normalized by seven weeks—unlike for the Covid-infected mice. They also found that, in mice infected with either virus, CCL11 was elevated in the cerebrospinal fluid. Monje hopes to study what she calls this “prominent shared mechanism” in further detail.\n\nWhile Monje and Iwasaki’s work has given researchers a better idea of how Covid might affect the brain, it may take years before there is a working treatment for patients. For Paige, the time cannot come soon enough. In 2022, she got Covid again. “I’m just praying for medicine, praying for treatment,” she says.\n\n## More From WIRED on Covid-19\n- 📩 The latest on tech, science, and more: [Get our newsletters](https:\/\/www.wired.com\/newsletter?sourceCode=BottomStories)\\!\n- The Covid virus keeps evolving. [Why haven't vaccines](https:\/\/www.wired.com\/story\/the-covid-virus-keeps-evolving-why-havent-vaccines\/?itm_campaign=BottomRelatedStories_Coronavirus&itm_content=footer-recirc)?\n- Can medicine recover from the [pandemic’s superbug surge](https:\/\/www.wired.com\/story\/the-pandemic-fueled-a-superbug-surge-can-medicine-recover\/?itm_campaign=BottomRelatedStories_Coronavirus&itm_content=footer-recirc)?\n- [The secrets of Covid “brain fog”](https:\/\/www.wired.com\/story\/the-secrets-of-covid-brain-fog-are-starting-to-lift\/?itm_campaign=BottomRelatedStories_Coronavirus&itm_content=footer-recirc) are starting to lift\n- [Rapid at-home Covid tests](https:\/\/www.wired.com\/story\/best-rapid-at-home-covid-19-test-kits\/?itm_campaign=BottomRelatedStories_Coronavirus&itm_content=footer-recirc)—and where to find them\n- [Need a face mask](https:\/\/www.wired.com\/gallery\/best-face-masks\/?itm_campaign=BottomRelatedStories_Coronavirus&itm_content=footer-recirc)? Here are ones we like to wear\n- Read all of [our coronavirus coverage here](https:\/\/www.wired.com\/tag\/coronavirus\/?itm_campaign=BottomRelatedStories_Coronavirus&itm_content=footer-recirc)\n\n[Maggie Chen](https:\/\/www.wired.com\/author\/maggie-chen\/) is a scientist and science journalist who enjoys watching heart cells beat under a microscope or writing about health, biotech, and history. ... [Read More](https:\/\/www.wired.com\/author\/maggie-chen)\n\nContributor\n\nTopics[COVID-19](https:\/\/www.wired.com\/tag\/covid-19\/)[viruses](https:\/\/www.wired.com\/tag\/viruses\/)[Neuroscience](https:\/\/www.wired.com\/tag\/neuroscience\/)[diseases](https:\/\/www.wired.com\/tag\/diseases\/)[medicine](https:\/\/www.wired.com\/tag\/medicine\/)[coronavirus](https:\/\/www.wired.com\/tag\/coronavirus\/)\n\n### WIRED's Guide to How the Universe Works\nYour weekly roundup of the best stories on health care, the climate crisis, new scientific discoveries, and more.\n\nRead More\n\n[![A Billionaire-Backed Startup Wants to Grow 'Organ Sacks' to Replace Animal Testing](https:\/\/media.wired.com\/photos\/69bd923f33c22df804229607\/16:9\/w_640%2Cc_limit\/undefined)](https:\/\/www.wired.com\/story\/a-billionaire-backed-startup-wants-to-grow-organ-sacks-to-replace-animal-testing\/#intcid=_wired-article-bottom-recirc_2f28f1a6-80da-43d1-b4e8-8d05a3d518c4_roberta-similarity1)\n\n[A Billionaire-Backed Startup Wants to Grow 'Organ Sacks' to Replace Animal Testing](https:\/\/www.wired.com\/story\/a-billionaire-backed-startup-wants-to-grow-organ-sacks-to-replace-animal-testing\/#intcid=_wired-article-bottom-recirc_2f28f1a6-80da-43d1-b4e8-8d05a3d518c4_roberta-similarity1)\n\nR3 Bio has a bold idea for replacing lab animals: genetically-engineered whole organ systems that lack a brain. The long-term goal, says a cofounder, is to make human versions.\n\nEmily Mullin\n\n[![Snake Bros Keep Getting Bitten by Their Lethal Pets. Only Zoos Can Save Them](https:\/\/media.wired.com\/photos\/69cffdb3640c23d3efe3532c\/16:9\/w_640%2Cc_limit\/undefined)](https:\/\/www.wired.com\/snake-bros-antivenom-index-zoos-influencers-chris-gifford\/#intcid=_wired-article-bottom-recirc_2f28f1a6-80da-43d1-b4e8-8d05a3d518c4_roberta-similarity1)\n\n[Snake Bros Keep Getting Bitten by Their Lethal Pets. Only Zoos Can Save Them](https:\/\/www.wired.com\/snake-bros-antivenom-index-zoos-influencers-chris-gifford\/#intcid=_wired-article-bottom-recirc_2f28f1a6-80da-43d1-b4e8-8d05a3d518c4_roberta-similarity1)\n\nYour venomous serpent bites you, and the clock is ticking. America’s zookeepers—and a cooler full of rare antivenom—are your best chance of survival.\n\nClaire McNear\n\n[![Marine Animals in the Strait of Hormuz Don’t Get a Ceasefire](https:\/\/media.wired.com\/photos\/69dd05f668f51d0b7f425afa\/16:9\/w_640%2Cc_limit\/undefined)](https:\/\/www.wired.com\/story\/marine-animals-in-the-strait-of-hormuz-dont-get-a-ceasefire\/#intcid=_wired-article-bottom-recirc_2f28f1a6-80da-43d1-b4e8-8d05a3d518c4_roberta-similarity1)\n\n[Marine Animals in the Strait of Hormuz Don’t Get a Ceasefire](https:\/\/www.wired.com\/story\/marine-animals-in-the-strait-of-hormuz-dont-get-a-ceasefire\/#intcid=_wired-article-bottom-recirc_2f28f1a6-80da-43d1-b4e8-8d05a3d518c4_roberta-similarity1)\n\nAs ships return to the Strait of Hormuz, mines, sonar, and congestion continue to reshape the Gulf beneath the surface.\n\nEvangeline Elsa\n\n[![No One Knows Where US Vaccine Policy Goes Next](https:\/\/media.wired.com\/photos\/69d808d3ce1f65d162ddb258\/16:9\/w_640%2Cc_limit\/undefined)](https:\/\/www.wired.com\/story\/no-one-knows-where-us-vaccine-policy-goes-next\/#intcid=_wired-article-bottom-recirc_2f28f1a6-80da-43d1-b4e8-8d05a3d518c4_roberta-similarity1)\n\n[No One Knows Where US Vaccine Policy Goes Next](https:\/\/www.wired.com\/story\/no-one-knows-where-us-vaccine-policy-goes-next\/#intcid=_wired-article-bottom-recirc_2f28f1a6-80da-43d1-b4e8-8d05a3d518c4_roberta-similarity1)\n\nRobert F. Kennedy Jr.’s sweeping changes to federal vaccine guidance are paused for now. But even if they’re reversed, lasting damage has already been done.\n\nEmily Mullin\n\n[![Hassan Took a Bike Ride. Now He’s One of the Thousands Missing in Gaza](https:\/\/media.wired.com\/photos\/69bb3e4c52ccb057f936398b\/16:9\/w_640%2Cc_limit\/undefined)](https:\/\/www.wired.com\/story\/hassan-took-a-bike-ride-now-hes-one-of-the-thousands-missing-in-gaza\/#intcid=_wired-article-bottom-recirc_2f28f1a6-80da-43d1-b4e8-8d05a3d518c4_roberta-similarity1)\n\n[Hassan Took a Bike Ride. Now He’s One of the Thousands Missing in Gaza](https:\/\/www.wired.com\/story\/hassan-took-a-bike-ride-now-hes-one-of-the-thousands-missing-in-gaza\/#intcid=_wired-article-bottom-recirc_2f28f1a6-80da-43d1-b4e8-8d05a3d518c4_roberta-similarity1)\n\nIn a place denied access to basic forensic technology—and where people disappear into Israeli detention—the fate of thousands remains unknown. One of them is an autistic teenager.\n\nMahmoud Mushtaha\n\n[![The Ghosts of Al-Shifa Hospital](https:\/\/media.wired.com\/photos\/69c552e4fa7ad3cd5ef140f8\/16:9\/w_640%2Cc_limit\/undefined)](https:\/\/www.wired.com\/story\/gaza-war-al-shifa-hospital-ghosts\/#intcid=_wired-article-bottom-recirc_2f28f1a6-80da-43d1-b4e8-8d05a3d518c4_roberta-similarity1)\n\n[The Ghosts of Al-Shifa Hospital](https:\/\/www.wired.com\/story\/gaza-war-al-shifa-hospital-ghosts\/#intcid=_wired-article-bottom-recirc_2f28f1a6-80da-43d1-b4e8-8d05a3d518c4_roberta-similarity1)\n\nMonths into a supposed ceasefire in Gaza, doctors still have to smuggle in basic medical supplies—and treat new casualties of war.\n\nSpencer Ackerman\n\n[![Anduril Wants to Own the Future of War Tech. Mishaps, Delays, and Challenges Abound](https:\/\/media.wired.com\/photos\/69c2bfbc5854d831d24bbc07\/16:9\/w_640%2Cc_limit\/undefined)](https:\/\/www.wired.com\/story\/andurils-real-war-is-with-itself\/#intcid=_wired-article-bottom-recirc_2f28f1a6-80da-43d1-b4e8-8d05a3d518c4_roberta-similarity1)\n\n[Anduril Wants to Own the Future of War Tech. Mishaps, Delays, and Challenges Abound](https:\/\/www.wired.com\/story\/andurils-real-war-is-with-itself\/#intcid=_wired-article-bottom-recirc_2f28f1a6-80da-43d1-b4e8-8d05a3d518c4_roberta-similarity1)\n\nFrom drones to missiles to submarines, the \\$30.5 billion defense startup wants to transform how the tools of war are made. It’s not all going as planned.\n\nParesh Dave\n\n[![Your Body Is Betraying Your Right to Privacy](https:\/\/media.wired.com\/photos\/69c1aa958d470e1446eb5d44\/16:9\/w_640%2Cc_limit\/undefined)](https:\/\/www.wired.com\/story\/book-excerpt-your-data-will-be-used-against-you-andrew-guthrie-ferguson\/#intcid=_wired-article-bottom-recirc_2f28f1a6-80da-43d1-b4e8-8d05a3d518c4_roberta-similarity1)\n\n[Your Body Is Betraying Your Right to Privacy](https:\/\/www.wired.com\/story\/book-excerpt-your-data-will-be-used-against-you-andrew-guthrie-ferguson\/#intcid=_wired-article-bottom-recirc_2f28f1a6-80da-43d1-b4e8-8d05a3d518c4_roberta-similarity1)\n\nAttachment to smart devices and biometric surveillance leaves Americans more vulnerable to police searches than ever. Left unchecked it will only get worse.\n\nAndrew Guthrie Ferguson\n\n[![Get Ready for a Year of Chaotic Weather in the US](https:\/\/media.wired.com\/photos\/69b967163d7bc629bb6ef27c\/16:9\/w_640%2Cc_limit\/undefined)](https:\/\/www.wired.com\/story\/get-ready-for-a-year-of-chaotic-weather-in-the-us\/#intcid=_wired-article-bottom-recirc_2f28f1a6-80da-43d1-b4e8-8d05a3d518c4_roberta-similarity1)\n\n[Get Ready for a Year of Chaotic Weather in the US](https:\/\/www.wired.com\/story\/get-ready-for-a-year-of-chaotic-weather-in-the-us\/#intcid=_wired-article-bottom-recirc_2f28f1a6-80da-43d1-b4e8-8d05a3d518c4_roberta-similarity1)\n\nA massive Western heat wave and a potential El Niño event raise concerns about a long stretch of unpredictable and extreme weather.\n\nMolly Taft\n\n[![A Single Strike Won’t Shut Off the Gulf’s Desalination System](https:\/\/media.wired.com\/photos\/69d3cedfd1ed3fbe37496db8\/16:9\/w_640%2Cc_limit\/undefined)](https:\/\/www.wired.com\/story\/a-single-strike-wont-shut-off-the-gulfs-desalination-system\/#intcid=_wired-article-bottom-recirc_2f28f1a6-80da-43d1-b4e8-8d05a3d518c4_roberta-similarity1)\n\n[A Single Strike Won’t Shut Off the Gulf’s Desalination System](https:\/\/www.wired.com\/story\/a-single-strike-wont-shut-off-the-gulfs-desalination-system\/#intcid=_wired-article-bottom-recirc_2f28f1a6-80da-43d1-b4e8-8d05a3d518c4_roberta-similarity1)\n\nThe Gulf’s water system is built with layers of backup, but it relies on continuous operation to hold.\n\nDana Alomar\n\n[![What Happens When You Can’t Get a Death Certificate in Gaza](https:\/\/media.wired.com\/photos\/69bc9d53d27f8b362a665d48\/16:9\/w_640%2Cc_limit\/undefined)](https:\/\/www.wired.com\/story\/what-happens-when-you-cant-get-a-death-certificate-in-gaza\/#intcid=_wired-article-bottom-recirc_2f28f1a6-80da-43d1-b4e8-8d05a3d518c4_roberta-similarity1)\n\n[What Happens When You Can’t Get a Death Certificate in Gaza](https:\/\/www.wired.com\/story\/what-happens-when-you-cant-get-a-death-certificate-in-gaza\/#intcid=_wired-article-bottom-recirc_2f28f1a6-80da-43d1-b4e8-8d05a3d518c4_roberta-similarity1)\n\nFor families of the missing, systemic obstacles to identifying remains and locating people in Israeli detention has created a kind of social and legal purgatory.\n\nMahmoud Mushtaha\n\n[![A New Implant Aims to Rewire the Brain to Help Stroke Patients](https:\/\/media.wired.com\/photos\/69cd4de4db42d7e554e1433d\/16:9\/w_640%2Cc_limit\/undefined)](https:\/\/www.wired.com\/story\/a-new-implant-aims-to-rewire-the-brain-to-help-stroke-patients\/#intcid=_wired-article-bottom-recirc_2f28f1a6-80da-43d1-b4e8-8d05a3d518c4_roberta-similarity1)\n\n[A New Implant Aims to Rewire the Brain to Help Stroke Patients](https:\/\/www.wired.com\/story\/a-new-implant-aims-to-rewire-the-brain-to-help-stroke-patients\/#intcid=_wired-article-bottom-recirc_2f28f1a6-80da-43d1-b4e8-8d05a3d518c4_roberta-similarity1)\n\nEpia Neuro’s brain-computer interface will include a motorized glove to help stroke patients recover movement in their hand.\n\nEmily Mullin\n\n[![ZOOM IN \\<br\\> Insights at the intersection of technology, power, and culture \\<br\\> Subscribe today for only \\<del\\>\\$4\\<\/del\\> \\<strong\\>\\$2\/month\\<\/strong\\> and get access to exclusive benefits including \\<strong\\>5 all-new premium newsletters.\\<\/strong\\> \\<br\\> CTA:SUBSCRIBE](https:\/\/assets.bonappetit.com\/photos\/686ea46a1d57bf34560db527\/original\/pass\/Wired_Zoom_Footer_Desktop_940x140_v2e.gif?format=original)](https:\/\/www.wired.com\/v2\/offers\/wira01035?source=Site_0_JNY_WIR_DESKTOP_FOOTER_0_US_ACQ_NLI_QUICK_PAY_GENERIC_ZZ_PANELA)\n\n[![WIRED](https:\/\/www.wired.com\/verso\/static\/wired-us\/assets\/logo-reverse.svg)](https:\/\/www.wired.com\/)\n\nWIRED is obsessed with what comes next. 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WIRED: For Future Reference.\n\nMore From WIRED\n\n- [Subscribe](https:\/\/www.wired.com\/subscribe\/)\n- [Newsletters](https:\/\/www.wired.com\/newsletter?sourceCode=HeaderAndFooter)\n- [Livestreams](https:\/\/www.wired.com\/livestreams)\n- [Travel](https:\/\/www.wired.com\/tag\/travel\/)\n- [FAQ](https:\/\/www.wired.com\/about\/faq\/)\n- [WIRED Staff](https:\/\/www.wired.com\/about\/wired-staff\/)\n- [WIRED Education](https:\/\/www.wirededucation.com\/)\n- [Editorial Standards](https:\/\/www.wired.com\/about\/wired-on-background-policy\/)\n- [Archive](https:\/\/archive.wired.com\/t\/storefront\/storefront)\n- [RSS](https:\/\/www.wired.com\/about\/rss-feeds\/)\n- [Site Map](https:\/\/www.wired.com\/sitemap\/)\n- [Accessibility Help](https:\/\/www.wired.com\/about\/accessibility-help\/)\n\nReviews and Guides\n\n- [Reviews](https:\/\/www.wired.com\/category\/gear\/)\n- [Buying Guides](https:\/\/www.wired.com\/category\/gear\/buying-guides\/)\n- [Streaming Guides](https:\/\/www.wired.com\/tag\/culture-guides\/)\n- [Wearables](https:\/\/www.wired.com\/tag\/wearables\/)\n- [Coupons](https:\/\/www.wired.com\/tag\/coupons\/)\n- [Gift Guides](https:\/\/www.wired.com\/tag\/gift-guides\/)\n\n- [Advertise](https:\/\/www.condenast.com\/brands\/wired)\n- [Contact Us](https:\/\/www.wired.com\/about\/feedback\/)\n- [Manage Account](https:\/\/www.wired.com\/account\/profile)\n- [Jobs](https:\/\/www.wired.com\/about\/wired-jobs\/)\n- [Press Center](https:\/\/www.wired.com\/about\/press\/)\n- [Condé Nast Store](https:\/\/condenaststore.com\/)\n- [User Agreement](https:\/\/www.condenast.com\/user-agreement\/)\n- [Privacy Policy](http:\/\/www.condenast.com\/privacy-policy#privacypolicy)\n- [Your California Privacy Rights](http:\/\/www.condenast.com\/privacy-policy#privacypolicy-california)\n\n© 2026 Condé Nast. All rights reserved. *WIRED* may earn a portion of sales from products that are purchased through our site as part of our Affiliate Partnerships with retailers. The material on this site may not be reproduced, distributed, transmitted, cached or otherwise used, except with the prior written permission of Condé Nast. [Ad Choices](http:\/\/www.aboutads.info\/)\n\n###### Select international site\nUnited States\n\n- [Italia](https:\/\/www.wired.it\/)\n- [Japón](https:\/\/wired.jp\/)\n- [Czech Republic & Slovakia](https:\/\/www.wired.cz\/)\n\nYour Privacy Choices","attrs_readable_markdown":"Paige was having a great start to 2021. Her health was the best it had ever been. She loved her job and the people she worked with as a communications manager for a conservation nonprofit. She could get up early in the mornings to work on creative projects. Things were looking “really, really good,” she says—until she got [Covid-19](https:\/\/www.wired.com\/tag\/covid-19).\n\nWhile the initial infection was not fun, what followed was worse. Four weeks later, when Paige (who asked to be identified only by her middle name) had recovered enough to go back to work full-time, she woke up one day with an overwhelming fatigue that just never went away. It was accompanied by a loss of mental sharpness, part of a suite of sometimes hard-to-pin-down symptoms that are often referred to as [Covid-19 “brain fog,”](https:\/\/www.wired.com\/story\/confused-about-covid-brain-fog-doctors-have-questions-too\/) a general term for sluggish or fuzzy thinking. “I spent most of 2021 making decisions like: Is this the day where I get a shower, or I go up and microwave myself a frozen dinner?” Paige recalls. The high-level writing required for her job was out of the question. Living with those symptoms was, in her words, “hell on earth.”\n\nMany of these [hard-to-define](https:\/\/www.wired.com\/story\/to-help-people-with-long-covid-scientists-need-to-define-it\/) Covid-19 symptoms can [persist over time](https:\/\/www.wired.com\/story\/exactly-how-many-people-long-covid\/)—weeks, months, years. Now, new research in the journal [*Cell*](https:\/\/www.cell.com\/cell\/fulltext\/S0092-8674\$22\$00713-9) is shedding some light on the biological mechanisms of how Covid-19 affects the brain. Led by researchers Michelle Monje and Akiko Iwasaki, of Stanford and Yale Universities respectively, scientists determined that in mice with mild Covid-19 infections, the virus disrupted the normal activity of several brain cell populations and left behind signs of inflammation. They believe that these findings may help explain some of the cognitive disruption experienced by Covid-19 survivors and provide potential pathways for therapies.\n\nFor the past 20 years, Monje, a neuro-oncologist, had been trying to understand the neurobiology behind chemotherapy-induced cognitive symptoms—similarly known as “chemo fog.” When Covid-19 emerged as a major immune-activating virus, she worried about the potential for similar disruption. “Very quickly, as reports of cognitive impairment started to come out, it was clear that it was a very similar syndrome,” she says. “The same symptoms of impaired attention, memory, speed of information processing, dis-executive function—it really clinically looks just like the ‘chemo fog’ that people experienced and that we’d been studying.”\n\n### WIRED's Guide to How the Universe Works\nYour weekly roundup of the best stories on health care, the climate crisis, new scientific discoveries, and more.\n\nIn September 2020, Monje reached out to Iwasaki, an immunologist. Her group had already established a mouse model of Covid-19, thanks to their Biosafety Level 3 clearance to work with the virus. A mouse model is engineered as a close stand-in for a human, and this experiment was meant to mimic the experience of a person with a mild Covid-19 infection. Using a viral vector, Iwasaki’s group introduced the [human ACE2 receptor](https:\/\/www.wired.com\/story\/meet-ace2-the-enzyme-at-the-center-of-the-covid-19-mystery\/) into cells in the trachea and lungs of the mice. This receptor is the point of entry for the Covid-causing virus, allowing it to bind to the cell. Then they shot a bit of virus up the mice’s noses to cause infection, controlling the amount and delivery so that the virus was limited to the respiratory system. For the mice, this infection cleared up within one week, and they did not lose weight.\n\nCoupled with biosafety regulations and the challenges of cross-country collaboration, the security precautions required by the pandemic created some interesting work constraints. Because most virus-related work had to be done in Iwasaki’s laboratory, the Yale scientists would take advantage of overnight shipping to fly samples across the country to Monje’s Stanford laboratory where they could be analyzed. Sometimes, they would need to film experiments with a GoPro camera to make sure that everybody could see the same thing. “We made it work,” Monje says.\n\nMost Popular\n\nOnce the mice had been infected with the virus, the scientists assessed the levels of cytokines in their blood and cerebrospinal fluid (the liquid surrounding the brain) at seven days and seven weeks after infection. Cytokines are markers secreted by the immune system, and they are critical in regulating inflammation. Not only were certain cytokines elevated in the cerebrospinal fluid at both time periods, but the scientists saw an increase of microglia reactivity in the subcortical white matter of the brain—the squishy white tissue rife with nerve fibers that makes up over half of the brain’s volume. That was another sign of potential trouble.\n\nMicroglia are sort of like the central nervous system’s hungry scavengers. They are immune cells that clean up the brain by chomping on dead and unwanted neural debris, among other important functions. “There’s a unique subpopulation of microglia in the white matter called axon tract microglia,” Monje says. These have a specific genetic signature, she continues, and “are exquisitely sensitive to a wide range of insults,” like inflammatory or toxic stimuli.\n\nIn response to these stimuli, microglia can become perpetually reactive. One consequence is that they can begin eating away at needed neurons or other brain cells, which further disrupts the brain’s homeostasis. In the case of Covid-19, the scientists found that this reactivity persisted even at seven weeks after infection. Monje’s team had seen similar elevation in this activity following chemotherapy and in brain samples from human patients who were infected with Covid-19. In the hippocampus (the area of the brain closely associated with memory), this overenthusiastic cleanup effort can deter the creation of new neurons, which are linked to maintaining healthy memory.\n\nTo figure out what exactly caused the microglia to become reactive, the researchers looked for the cytokines that had reached elevated levels. Specifically, Anthony Fernandez Castaneda, a postdoctoral researcher in Monje’s laboratory and a study coauthor, found CCL11—a factor that can decrease the generation of new neurons and impair learning or memory. “The elevated CCL11 result was very interesting, because it could potentially explain why some Covid survivors experience cognitive symptoms,” he says.\n\nIn a second phase of the experiment, the researchers gave shots of CCL11 to a separate group of mice. Then they examined tissue from their brains to discover where the microglia had been reactive, and where fewer new neurons had grown. That turned out to be in the hippocampus—indicating that CCL11 acted on very specific cell populations in a memory-related area of the brain.\n\nNext, the scientists decided to investigate the effects of mild Covid-19 infection on myelinating oligodendrocytes—brain cells that generate the myelin “padding” around neurons to provide insulation for better inter-neuron communication. Previously, work done by Anna Geraghty (another postdoctoral fellow in Monje’s lab and study coauthor) had focused on how chemotherapy affects this process. Myelin loss in the mice treated with chemo was found to be directly linked with deficits in short-term memory and attention. “Even minor adjustments in those myelin can actually impact neuronal communication in quite diverse ways,” she says. “Losing that ability to adaptively respond to neuronal activity led to persistent cognitive impairments in these mice.”\n\nMost Popular\n\nGeraghty recalls staying in the lab late at night during the Christmas holiday to finish the analysis of how Covid-19 affected that padding in mouse neurons. The result: The infected mice had lost approximately one-third of their mature oligodendrocytes, and had a statistically significant drop in myelination compared to mice in a control group. The magnitude of myelin loss was almost identical to what the lab had discovered when studying mice and chemo. She excitedly texted the results to Monje. “There was just a big moment in my brain of, ‘Oh my gosh, this data is incredibly interesting,’” Geraghty recalls.\n\nJoanna Hellmuth, a cognitive neurologist at UC San Francisco who was unaffiliated with the study, notes that the “mouse data is very compelling,” and more studies are needed to see how these results translate into treatments for human patients—like Paige or others struggling with long Covid and cognitive symptoms. Figuring out which drugs to try first, though, could benefit from understanding the biological cause of brain fog symptoms. “‘Brain fog’ is a colloquial term,” says Hellmuth—and it “kind of delegitimizes peoples’ having a neurological disorder.”\n\nWes Ely, a pulmonary and critical care specialist at Vanderbilt University Medical Center who was unaffiliated with the study, believes that such studies can lead to future therapeutic development. “This work paves the path towards both pharmacological, neuropsychological, and cognitive rehabilitative mechanisms to rebuild brain power,” he says.\n\nFor example, Monje thinks, some drug candidates that already worked in “chemo fog” animal models might be useful for treating Covid-related cognitive symptoms. She hopes to test these candidates on the Covid-19 mouse model to see if they help.\n\nThe team would also like to investigate other questions, like whether these neurological effects are different after even longer periods of time, or if they are different following a breakthrough infection after vaccination. They’d also like to compare what they’ve found in Covid-19 mouse models to neurological reactions to another famous virus—H1N1, which causes swine flu. The team had found that in a mouse model of H1N1, the drop in oligodendrocytes and increase in microglial reactivity in the subcortical white matter generally normalized by seven weeks—unlike for the Covid-infected mice. They also found that, in mice infected with either virus, CCL11 was elevated in the cerebrospinal fluid. Monje hopes to study what she calls this “prominent shared mechanism” in further detail.\n\nWhile Monje and Iwasaki’s work has given researchers a better idea of how Covid might affect the brain, it may take years before there is a working treatment for patients. For Paige, the time cannot come soon enough. In 2022, she got Covid again. “I’m just praying for medicine, praying for treatment,” she says.","meta_canonical":null}

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Boilerpipe Text	Paige was having a great start to 2021. Her health was the best it had ever been. She loved her job and the people she worked with as a communications manager for a conservation nonprofit. She could get up early in the mornings to work on creative projects. Things were looking “really, really good,” she says—until she got Covid-19 . While the initial infection was not fun, what followed was worse. Four weeks later, when Paige (who asked to be identified only by her middle name) had recovered enough to go back to work full-time, she woke up one day with an overwhelming fatigue that just never went away. It was accompanied by a loss of mental sharpness, part of a suite of sometimes hard-to-pin-down symptoms that are often referred to as Covid-19 “brain fog,” a general term for sluggish or fuzzy thinking. “I spent most of 2021 making decisions like: Is this the day where I get a shower, or I go up and microwave myself a frozen dinner?” Paige recalls. The high-level writing required for her job was out of the question. Living with those symptoms was, in her words, “hell on earth.” Many of these hard-to-define Covid-19 symptoms can persist over time —weeks, months, years. Now, new research in the journal Cell is shedding some light on the biological mechanisms of how Covid-19 affects the brain. Led by researchers Michelle Monje and Akiko Iwasaki, of Stanford and Yale Universities respectively, scientists determined that in mice with mild Covid-19 infections, the virus disrupted the normal activity of several brain cell populations and left behind signs of inflammation. They believe that these findings may help explain some of the cognitive disruption experienced by Covid-19 survivors and provide potential pathways for therapies. For the past 20 years, Monje, a neuro-oncologist, had been trying to understand the neurobiology behind chemotherapy-induced cognitive symptoms—similarly known as “chemo fog.” When Covid-19 emerged as a major immune-activating virus, she worried about the potential for similar disruption. “Very quickly, as reports of cognitive impairment started to come out, it was clear that it was a very similar syndrome,” she says. “The same symptoms of impaired attention, memory, speed of information processing, dis-executive function—it really clinically looks just like the ‘chemo fog’ that people experienced and that we’d been studying.” WIRED's Guide to How the Universe Works Your weekly roundup of the best stories on health care, the climate crisis, new scientific discoveries, and more. In September 2020, Monje reached out to Iwasaki, an immunologist. Her group had already established a mouse model of Covid-19, thanks to their Biosafety Level 3 clearance to work with the virus. A mouse model is engineered as a close stand-in for a human, and this experiment was meant to mimic the experience of a person with a mild Covid-19 infection. Using a viral vector, Iwasaki’s group introduced the human ACE2 receptor into cells in the trachea and lungs of the mice. This receptor is the point of entry for the Covid-causing virus, allowing it to bind to the cell. Then they shot a bit of virus up the mice’s noses to cause infection, controlling the amount and delivery so that the virus was limited to the respiratory system. For the mice, this infection cleared up within one week, and they did not lose weight. Coupled with biosafety regulations and the challenges of cross-country collaboration, the security precautions required by the pandemic created some interesting work constraints. Because most virus-related work had to be done in Iwasaki’s laboratory, the Yale scientists would take advantage of overnight shipping to fly samples across the country to Monje’s Stanford laboratory where they could be analyzed. Sometimes, they would need to film experiments with a GoPro camera to make sure that everybody could see the same thing. “We made it work,” Monje says. Most Popular Once the mice had been infected with the virus, the scientists assessed the levels of cytokines in their blood and cerebrospinal fluid (the liquid surrounding the brain) at seven days and seven weeks after infection. Cytokines are markers secreted by the immune system, and they are critical in regulating inflammation. Not only were certain cytokines elevated in the cerebrospinal fluid at both time periods, but the scientists saw an increase of microglia reactivity in the subcortical white matter of the brain—the squishy white tissue rife with nerve fibers that makes up over half of the brain’s volume. That was another sign of potential trouble. Microglia are sort of like the central nervous system’s hungry scavengers. They are immune cells that clean up the brain by chomping on dead and unwanted neural debris, among other important functions. “There’s a unique subpopulation of microglia in the white matter called axon tract microglia,” Monje says. These have a specific genetic signature, she continues, and “are exquisitely sensitive to a wide range of insults,” like inflammatory or toxic stimuli. In response to these stimuli, microglia can become perpetually reactive. One consequence is that they can begin eating away at needed neurons or other brain cells, which further disrupts the brain’s homeostasis. In the case of Covid-19, the scientists found that this reactivity persisted even at seven weeks after infection. Monje’s team had seen similar elevation in this activity following chemotherapy and in brain samples from human patients who were infected with Covid-19. In the hippocampus (the area of the brain closely associated with memory), this overenthusiastic cleanup effort can deter the creation of new neurons, which are linked to maintaining healthy memory. To figure out what exactly caused the microglia to become reactive, the researchers looked for the cytokines that had reached elevated levels. Specifically, Anthony Fernandez Castaneda, a postdoctoral researcher in Monje’s laboratory and a study coauthor, found CCL11—a factor that can decrease the generation of new neurons and impair learning or memory. “The elevated CCL11 result was very interesting, because it could potentially explain why some Covid survivors experience cognitive symptoms,” he says. In a second phase of the experiment, the researchers gave shots of CCL11 to a separate group of mice. Then they examined tissue from their brains to discover where the microglia had been reactive, and where fewer new neurons had grown. That turned out to be in the hippocampus—indicating that CCL11 acted on very specific cell populations in a memory-related area of the brain. Next, the scientists decided to investigate the effects of mild Covid-19 infection on myelinating oligodendrocytes—brain cells that generate the myelin “padding” around neurons to provide insulation for better inter-neuron communication. Previously, work done by Anna Geraghty (another postdoctoral fellow in Monje’s lab and study coauthor) had focused on how chemotherapy affects this process. Myelin loss in the mice treated with chemo was found to be directly linked with deficits in short-term memory and attention. “Even minor adjustments in those myelin can actually impact neuronal communication in quite diverse ways,” she says. “Losing that ability to adaptively respond to neuronal activity led to persistent cognitive impairments in these mice.” Most Popular Geraghty recalls staying in the lab late at night during the Christmas holiday to finish the analysis of how Covid-19 affected that padding in mouse neurons. The result: The infected mice had lost approximately one-third of their mature oligodendrocytes, and had a statistically significant drop in myelination compared to mice in a control group. The magnitude of myelin loss was almost identical to what the lab had discovered when studying mice and chemo. She excitedly texted the results to Monje. “There was just a big moment in my brain of, ‘Oh my gosh, this data is incredibly interesting,’” Geraghty recalls. Joanna Hellmuth, a cognitive neurologist at UC San Francisco who was unaffiliated with the study, notes that the “mouse data is very compelling,” and more studies are needed to see how these results translate into treatments for human patients—like Paige or others struggling with long Covid and cognitive symptoms. Figuring out which drugs to try first, though, could benefit from understanding the biological cause of brain fog symptoms. “‘Brain fog’ is a colloquial term,” says Hellmuth—and it “kind of delegitimizes peoples’ having a neurological disorder.” Wes Ely, a pulmonary and critical care specialist at Vanderbilt University Medical Center who was unaffiliated with the study, believes that such studies can lead to future therapeutic development. “This work paves the path towards both pharmacological, neuropsychological, and cognitive rehabilitative mechanisms to rebuild brain power,” he says. For example, Monje thinks, some drug candidates that already worked in “chemo fog” animal models might be useful for treating Covid-related cognitive symptoms. She hopes to test these candidates on the Covid-19 mouse model to see if they help. The team would also like to investigate other questions, like whether these neurological effects are different after even longer periods of time, or if they are different following a breakthrough infection after vaccination. They’d also like to compare what they’ve found in Covid-19 mouse models to neurological reactions to another famous virus—H1N1, which causes swine flu. The team had found that in a mouse model of H1N1, the drop in oligodendrocytes and increase in microglial reactivity in the subcortical white matter generally normalized by seven weeks—unlike for the Covid-infected mice. They also found that, in mice infected with either virus, CCL11 was elevated in the cerebrospinal fluid. Monje hopes to study what she calls this “prominent shared mechanism” in further detail. While Monje and Iwasaki’s work has given researchers a better idea of how Covid might affect the brain, it may take years before there is a working treatment for patients. For Paige, the time cannot come soon enough. In 2022, she got Covid again. “I’m just praying for medicine, praying for treatment,” she says.
Markdown	[Skip to main content](https://www.wired.com/story/the-secrets-of-covid-brain-fog-are-starting-to-lift/#main-content) [SECURITY](https://www.wired.com/category/security/) [POLITICS](https://www.wired.com/category/politics/) [THE BIG STORY](https://www.wired.com/category/big-story/) [BUSINESS](https://www.wired.com/category/business/) [SCIENCE](https://www.wired.com/category/science/) [CULTURE](https://www.wired.com/category/culture/) [REVIEWS](https://www.wired.com/category/gear/) [SUBSCRIBE](https://www.wired.com/v2/offers/wira01035?source=Site_0_JNY_WIR_DESKTOP_NAV_CTA_0_US_ACQ_NLI_QUICK_PAY_GENERIC_ZZ_PANELA) [Newsletters](https://www.wired.com/newsletter?sourceCode=hamburgernav) [SUBSCRIBE](https://www.wired.com/v2/offers/wira01035?source=Site_0_JNY_WIR_DESKTOP_NAV_CTA_0_US_ACQ_NLI_QUICK_PAY_GENERIC_ZZ_PANELA) [Security](https://www.wired.com/category/security/) [Politics](https://www.wired.com/category/politics/) [The Big Story](https://www.wired.com/category/big-story/) [Business](https://www.wired.com/category/business/) [Science](https://www.wired.com/category/science/) [Culture](https://www.wired.com/category/culture/) [Reviews](https://www.wired.com/category/gear/) More [The Big Interview](https://www.wired.com/the-big-interview/)[Magazine](https://www.wired.com/magazine/)[Events](https://www.wired.com/tag/wired-events/)[WIRED Insider](https://www.wired.com/collection/wiredinsider/)[WIRED Consulting](https://www.wired.com/tag/wired-consulting/) [Newsletters](https://www.wired.com/newsletter?sourceCode=hamburgernav) [Podcasts](https://www.wired.com/podcasts/) [Video](https://www.wired.com/video/) [Livestreams](https://www.wired.com/livestreams) [Merch](https://shop.wired.com/) [Search](https://www.wired.com/search/) [Sign In](https://www.wired.com/auth/initiate?redirectURL=%2Fstory%2Fthe-secrets-of-covid-brain-fog-are-starting-to-lift%2F&source=VERSO_NAVIGATION) [START FREE TRIAL](https://www.wired.com/v2/offers/wira01035?source=Site_0_JNY_WIR_DESKTOP_JNY_WIR_GLOBAL_NAV_DRAWER_0_US_ACQ_NLI_QUICK_PAY_GENERIC_ZZ_PANELA) [![ZOOM IN \<br\> Subscribe today for only \<del\>\$4\</del\> \<strong\>\$2/month\</strong\> and get access to exclusive benefits including \<strong\>5 all-new premium newsletters.\</strong\> CTA:SUBSCRIBE](https://assets.bonappetit.com/photos/686ea38fcb59aaabef7a795d/original/pass/Wired_Zoom_Rollover_300x200_v2a_Shorter.gif?format=original)](https://www.wired.com/v2/offers/wira01035?source=Site_0_JNY_WIR_DESKTOP_NAV_ROLLOVER_0_US_ACQ_NLI_QUICK_PAY_GENERIC_ZZ_PANELA) [Sign In](https://www.wired.com/auth/initiate?redirectURL=%2Fstory%2Fthe-secrets-of-covid-brain-fog-are-starting-to-lift%2F&source=VERSO_NAVIGATION) The intersection of technology, power, and culture. Start your free trial and get access to 5 all-new premium newsletters. [START FREE TRIAL](https://www.wired.com/v2/offers/wira01035?source=Site_0_JNY_WIR_DESKTOP_PAYWALL_THIN_METER_ARTICLE_1_0_US_ACQ_NLI_QUICK_PAY_GENERIC_ZZ_PANELA) [Maggie Chen](https://www.wired.com/author/maggie-chen/) [Science](https://www.wired.com/category/science) Jul 1, 2022 7:00 AM # The Secrets of Covid ‘Brain Fog’ Are Starting to Lift Scientists are getting closer to understanding the neurology behind the memory problems and cognitive fuzziness that an infection can trigger. ![Coloured transmission electron micrograph of an oligodendrocyte sending a cell process to a myelinated nerve fiber](https://media.wired.com/photos/62be03837a39cc2124cb2d6f/3:2/w_2560%2Cc_limit/COVID-Brain-Fog-Science-ScienceSource_SS21470210.jpg) Photograph: Jose Calvo/Science Source Save this story Save this story Paige was having a great start to 2021. Her health was the best it had ever been. She loved her job and the people she worked with as a communications manager for a conservation nonprofit. She could get up early in the mornings to work on creative projects. Things were looking “really, really good,” she says—until she got [Covid-19](https://www.wired.com/tag/covid-19). While the initial infection was not fun, what followed was worse. Four weeks later, when Paige (who asked to be identified only by her middle name) had recovered enough to go back to work full-time, she woke up one day with an overwhelming fatigue that just never went away. It was accompanied by a loss of mental sharpness, part of a suite of sometimes hard-to-pin-down symptoms that are often referred to as [Covid-19 “brain fog,”](https://www.wired.com/story/confused-about-covid-brain-fog-doctors-have-questions-too/) a general term for sluggish or fuzzy thinking. “I spent most of 2021 making decisions like: Is this the day where I get a shower, or I go up and microwave myself a frozen dinner?” Paige recalls. The high-level writing required for her job was out of the question. Living with those symptoms was, in her words, “hell on earth.” #### Content To honor your privacy preferences, this content can only be viewed on the site it [originates](https://player.spokenlayer.net/v1-wired-science?__v=linear&url=http://www.wired.com/story/the-secrets-of-covid-brain-fog-are-starting-to-lift) from. Many of these [hard-to-define](https://www.wired.com/story/to-help-people-with-long-covid-scientists-need-to-define-it/) Covid-19 symptoms can [persist over time](https://www.wired.com/story/exactly-how-many-people-long-covid/)—weeks, months, years. Now, new research in the journal [Cell](https://www.cell.com/cell/fulltext/S0092-8674$22$00713-9) is shedding some light on the biological mechanisms of how Covid-19 affects the brain. Led by researchers Michelle Monje and Akiko Iwasaki, of Stanford and Yale Universities respectively, scientists determined that in mice with mild Covid-19 infections, the virus disrupted the normal activity of several brain cell populations and left behind signs of inflammation. They believe that these findings may help explain some of the cognitive disruption experienced by Covid-19 survivors and provide potential pathways for therapies. Featured Video [How Nose Swabs Detect New Covid-19 Strains](https://www.wired.com/video/watch/wired-news-and-science-how-nose-swabs-detect-new-covid-19-strains) For the past 20 years, Monje, a neuro-oncologist, had been trying to understand the neurobiology behind chemotherapy-induced cognitive symptoms—similarly known as “chemo fog.” When Covid-19 emerged as a major immune-activating virus, she worried about the potential for similar disruption. “Very quickly, as reports of cognitive impairment started to come out, it was clear that it was a very similar syndrome,” she says. “The same symptoms of impaired attention, memory, speed of information processing, dis-executive function—it really clinically looks just like the ‘chemo fog’ that people experienced and that we’d been studying.” ### WIRED's Guide to How the Universe Works Your weekly roundup of the best stories on health care, the climate crisis, new scientific discoveries, and more. In September 2020, Monje reached out to Iwasaki, an immunologist. Her group had already established a mouse model of Covid-19, thanks to their Biosafety Level 3 clearance to work with the virus. A mouse model is engineered as a close stand-in for a human, and this experiment was meant to mimic the experience of a person with a mild Covid-19 infection. Using a viral vector, Iwasaki’s group introduced the [human ACE2 receptor](https://www.wired.com/story/meet-ace2-the-enzyme-at-the-center-of-the-covid-19-mystery/) into cells in the trachea and lungs of the mice. This receptor is the point of entry for the Covid-causing virus, allowing it to bind to the cell. Then they shot a bit of virus up the mice’s noses to cause infection, controlling the amount and delivery so that the virus was limited to the respiratory system. For the mice, this infection cleared up within one week, and they did not lose weight. Coupled with biosafety regulations and the challenges of cross-country collaboration, the security precautions required by the pandemic created some interesting work constraints. Because most virus-related work had to be done in Iwasaki’s laboratory, the Yale scientists would take advantage of overnight shipping to fly samples across the country to Monje’s Stanford laboratory where they could be analyzed. Sometimes, they would need to film experiments with a GoPro camera to make sure that everybody could see the same thing. “We made it work,” Monje says. Most Popular - [![The Fanfare Around the Band Geese Actually Was a Psyop](https://media.wired.com/photos/69d7c981444a1a70ce52eb20/1:1/w_120%2Ch_120%2Cc_limit/undefined)](https://www.wired.com/story/geese-chaotic-good-marketing-industry-plant/#intcid=_wired-right-rail_24c22a4b-cb34-4a23-a3aa-f02daaa30eb9_popular4-2) Music [The Fanfare Around the Band Geese Actually Was a Psyop](https://www.wired.com/story/geese-chaotic-good-marketing-industry-plant/#intcid=_wired-right-rail_24c22a4b-cb34-4a23-a3aa-f02daaa30eb9_popular4-2) By John Semley - [![Meta Is Warned That Facial Recognition Glasses Will Arm Sexual Predators](https://media.wired.com/photos/69dd120fd5415cb89341a838/1:1/w_120%2Ch_120%2Cc_limit/undefined)](https://www.wired.com/story/meta-ray-ban-oakley-smart-glasses-no-face-recognition-civil-society/#intcid=_wired-right-rail_24c22a4b-cb34-4a23-a3aa-f02daaa30eb9_popular4-2) Artificial Intelligence [Meta Is Warned That Facial Recognition Glasses Will Arm Sexual Predators](https://www.wired.com/story/meta-ray-ban-oakley-smart-glasses-no-face-recognition-civil-society/#intcid=_wired-right-rail_24c22a4b-cb34-4a23-a3aa-f02daaa30eb9_popular4-2) By Dell Cameron - [![Government Workers Say They’re Getting Inundated With Religion](https://media.wired.com/photos/69dd3c751720dda876aeb968/1:1/w_120%2Ch_120%2Cc_limit/undefined)](https://www.wired.com/story/government-workers-say-theyre-getting-inundated-with-religion/#intcid=_wired-right-rail_24c22a4b-cb34-4a23-a3aa-f02daaa30eb9_popular4-2) Politics [Government Workers Say They’re Getting Inundated With Religion](https://www.wired.com/story/government-workers-say-theyre-getting-inundated-with-religion/#intcid=_wired-right-rail_24c22a4b-cb34-4a23-a3aa-f02daaa30eb9_popular4-2) By Vittoria Elliott - [![Staunch Trump Supporters Are Now Asking if He’s the Antichrist](https://media.wired.com/photos/69d83e91a6b1cf7dff37c069/1:1/w_120%2Ch_120%2Cc_limit/undefined)](https://www.wired.com/story/staunch-trump-supporters-are-now-asking-if-hes-the-antichrist/#intcid=_wired-right-rail_24c22a4b-cb34-4a23-a3aa-f02daaa30eb9_popular4-2) Politics [Staunch Trump Supporters Are Now Asking if He’s the Antichrist](https://www.wired.com/story/staunch-trump-supporters-are-now-asking-if-hes-the-antichrist/#intcid=_wired-right-rail_24c22a4b-cb34-4a23-a3aa-f02daaa30eb9_popular4-2) By Makena Kelly Once the mice had been infected with the virus, the scientists assessed the levels of cytokines in their blood and cerebrospinal fluid (the liquid surrounding the brain) at seven days and seven weeks after infection. Cytokines are markers secreted by the immune system, and they are critical in regulating inflammation. Not only were certain cytokines elevated in the cerebrospinal fluid at both time periods, but the scientists saw an increase of microglia reactivity in the subcortical white matter of the brain—the squishy white tissue rife with nerve fibers that makes up over half of the brain’s volume. That was another sign of potential trouble. Microglia are sort of like the central nervous system’s hungry scavengers. They are immune cells that clean up the brain by chomping on dead and unwanted neural debris, among other important functions. “There’s a unique subpopulation of microglia in the white matter called axon tract microglia,” Monje says. These have a specific genetic signature, she continues, and “are exquisitely sensitive to a wide range of insults,” like inflammatory or toxic stimuli. In response to these stimuli, microglia can become perpetually reactive. One consequence is that they can begin eating away at needed neurons or other brain cells, which further disrupts the brain’s homeostasis. In the case of Covid-19, the scientists found that this reactivity persisted even at seven weeks after infection. Monje’s team had seen similar elevation in this activity following chemotherapy and in brain samples from human patients who were infected with Covid-19. In the hippocampus (the area of the brain closely associated with memory), this overenthusiastic cleanup effort can deter the creation of new neurons, which are linked to maintaining healthy memory. To figure out what exactly caused the microglia to become reactive, the researchers looked for the cytokines that had reached elevated levels. Specifically, Anthony Fernandez Castaneda, a postdoctoral researcher in Monje’s laboratory and a study coauthor, found CCL11—a factor that can decrease the generation of new neurons and impair learning or memory. “The elevated CCL11 result was very interesting, because it could potentially explain why some Covid survivors experience cognitive symptoms,” he says. In a second phase of the experiment, the researchers gave shots of CCL11 to a separate group of mice. Then they examined tissue from their brains to discover where the microglia had been reactive, and where fewer new neurons had grown. That turned out to be in the hippocampus—indicating that CCL11 acted on very specific cell populations in a memory-related area of the brain. Next, the scientists decided to investigate the effects of mild Covid-19 infection on myelinating oligodendrocytes—brain cells that generate the myelin “padding” around neurons to provide insulation for better inter-neuron communication. Previously, work done by Anna Geraghty (another postdoctoral fellow in Monje’s lab and study coauthor) had focused on how chemotherapy affects this process. Myelin loss in the mice treated with chemo was found to be directly linked with deficits in short-term memory and attention. “Even minor adjustments in those myelin can actually impact neuronal communication in quite diverse ways,” she says. “Losing that ability to adaptively respond to neuronal activity led to persistent cognitive impairments in these mice.” Most Popular - [![The Fanfare Around the Band Geese Actually Was a Psyop](https://media.wired.com/photos/69d7c981444a1a70ce52eb20/1:1/w_120%2Ch_120%2Cc_limit/undefined)](https://www.wired.com/story/geese-chaotic-good-marketing-industry-plant/#intcid=_wired-right-rail_24c22a4b-cb34-4a23-a3aa-f02daaa30eb9_popular4-2) Music [The Fanfare Around the Band Geese Actually Was a Psyop](https://www.wired.com/story/geese-chaotic-good-marketing-industry-plant/#intcid=_wired-right-rail_24c22a4b-cb34-4a23-a3aa-f02daaa30eb9_popular4-2) By John Semley - [![Meta Is Warned That Facial Recognition Glasses Will Arm Sexual Predators](https://media.wired.com/photos/69dd120fd5415cb89341a838/1:1/w_120%2Ch_120%2Cc_limit/undefined)](https://www.wired.com/story/meta-ray-ban-oakley-smart-glasses-no-face-recognition-civil-society/#intcid=_wired-right-rail_24c22a4b-cb34-4a23-a3aa-f02daaa30eb9_popular4-2) Artificial Intelligence [Meta Is Warned That Facial Recognition Glasses Will Arm Sexual Predators](https://www.wired.com/story/meta-ray-ban-oakley-smart-glasses-no-face-recognition-civil-society/#intcid=_wired-right-rail_24c22a4b-cb34-4a23-a3aa-f02daaa30eb9_popular4-2) By Dell Cameron - [![Government Workers Say They’re Getting Inundated With Religion](https://media.wired.com/photos/69dd3c751720dda876aeb968/1:1/w_120%2Ch_120%2Cc_limit/undefined)](https://www.wired.com/story/government-workers-say-theyre-getting-inundated-with-religion/#intcid=_wired-right-rail_24c22a4b-cb34-4a23-a3aa-f02daaa30eb9_popular4-2) Politics [Government Workers Say They’re Getting Inundated With Religion](https://www.wired.com/story/government-workers-say-theyre-getting-inundated-with-religion/#intcid=_wired-right-rail_24c22a4b-cb34-4a23-a3aa-f02daaa30eb9_popular4-2) By Vittoria Elliott - [![Staunch Trump Supporters Are Now Asking if He’s the Antichrist](https://media.wired.com/photos/69d83e91a6b1cf7dff37c069/1:1/w_120%2Ch_120%2Cc_limit/undefined)](https://www.wired.com/story/staunch-trump-supporters-are-now-asking-if-hes-the-antichrist/#intcid=_wired-right-rail_24c22a4b-cb34-4a23-a3aa-f02daaa30eb9_popular4-2) Politics [Staunch Trump Supporters Are Now Asking if He’s the Antichrist](https://www.wired.com/story/staunch-trump-supporters-are-now-asking-if-hes-the-antichrist/#intcid=_wired-right-rail_24c22a4b-cb34-4a23-a3aa-f02daaa30eb9_popular4-2) By Makena Kelly Geraghty recalls staying in the lab late at night during the Christmas holiday to finish the analysis of how Covid-19 affected that padding in mouse neurons. The result: The infected mice had lost approximately one-third of their mature oligodendrocytes, and had a statistically significant drop in myelination compared to mice in a control group. The magnitude of myelin loss was almost identical to what the lab had discovered when studying mice and chemo. She excitedly texted the results to Monje. “There was just a big moment in my brain of, ‘Oh my gosh, this data is incredibly interesting,’” Geraghty recalls. Joanna Hellmuth, a cognitive neurologist at UC San Francisco who was unaffiliated with the study, notes that the “mouse data is very compelling,” and more studies are needed to see how these results translate into treatments for human patients—like Paige or others struggling with long Covid and cognitive symptoms. Figuring out which drugs to try first, though, could benefit from understanding the biological cause of brain fog symptoms. “‘Brain fog’ is a colloquial term,” says Hellmuth—and it “kind of delegitimizes peoples’ having a neurological disorder.” Wes Ely, a pulmonary and critical care specialist at Vanderbilt University Medical Center who was unaffiliated with the study, believes that such studies can lead to future therapeutic development. “This work paves the path towards both pharmacological, neuropsychological, and cognitive rehabilitative mechanisms to rebuild brain power,” he says. For example, Monje thinks, some drug candidates that already worked in “chemo fog” animal models might be useful for treating Covid-related cognitive symptoms. She hopes to test these candidates on the Covid-19 mouse model to see if they help. The team would also like to investigate other questions, like whether these neurological effects are different after even longer periods of time, or if they are different following a breakthrough infection after vaccination. They’d also like to compare what they’ve found in Covid-19 mouse models to neurological reactions to another famous virus—H1N1, which causes swine flu. The team had found that in a mouse model of H1N1, the drop in oligodendrocytes and increase in microglial reactivity in the subcortical white matter generally normalized by seven weeks—unlike for the Covid-infected mice. They also found that, in mice infected with either virus, CCL11 was elevated in the cerebrospinal fluid. Monje hopes to study what she calls this “prominent shared mechanism” in further detail. While Monje and Iwasaki’s work has given researchers a better idea of how Covid might affect the brain, it may take years before there is a working treatment for patients. For Paige, the time cannot come soon enough. In 2022, she got Covid again. “I’m just praying for medicine, praying for treatment,” she says. ## More From WIRED on Covid-19 - 📩 The latest on tech, science, and more: [Get our newsletters](https://www.wired.com/newsletter?sourceCode=BottomStories)\! - The Covid virus keeps evolving. [Why haven't vaccines](https://www.wired.com/story/the-covid-virus-keeps-evolving-why-havent-vaccines/?itm_campaign=BottomRelatedStories_Coronavirus&itm_content=footer-recirc)? - Can medicine recover from the [pandemic’s superbug surge](https://www.wired.com/story/the-pandemic-fueled-a-superbug-surge-can-medicine-recover/?itm_campaign=BottomRelatedStories_Coronavirus&itm_content=footer-recirc)? - [The secrets of Covid “brain fog”](https://www.wired.com/story/the-secrets-of-covid-brain-fog-are-starting-to-lift/?itm_campaign=BottomRelatedStories_Coronavirus&itm_content=footer-recirc) are starting to lift - [Rapid at-home Covid tests](https://www.wired.com/story/best-rapid-at-home-covid-19-test-kits/?itm_campaign=BottomRelatedStories_Coronavirus&itm_content=footer-recirc)—and where to find them - [Need a face mask](https://www.wired.com/gallery/best-face-masks/?itm_campaign=BottomRelatedStories_Coronavirus&itm_content=footer-recirc)? Here are ones we like to wear - Read all of [our coronavirus coverage here](https://www.wired.com/tag/coronavirus/?itm_campaign=BottomRelatedStories_Coronavirus&itm_content=footer-recirc) [Maggie Chen](https://www.wired.com/author/maggie-chen/) is a scientist and science journalist who enjoys watching heart cells beat under a microscope or writing about health, biotech, and history. ... [Read More](https://www.wired.com/author/maggie-chen) Contributor Topics[COVID-19](https://www.wired.com/tag/covid-19/)[viruses](https://www.wired.com/tag/viruses/)[Neuroscience](https://www.wired.com/tag/neuroscience/)[diseases](https://www.wired.com/tag/diseases/)[medicine](https://www.wired.com/tag/medicine/)[coronavirus](https://www.wired.com/tag/coronavirus/) ### WIRED's Guide to How the Universe Works Your weekly roundup of the best stories on health care, the climate crisis, new scientific discoveries, and more. 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Readable Markdown	Paige was having a great start to 2021. Her health was the best it had ever been. She loved her job and the people she worked with as a communications manager for a conservation nonprofit. She could get up early in the mornings to work on creative projects. Things were looking “really, really good,” she says—until she got [Covid-19](https://www.wired.com/tag/covid-19). While the initial infection was not fun, what followed was worse. Four weeks later, when Paige (who asked to be identified only by her middle name) had recovered enough to go back to work full-time, she woke up one day with an overwhelming fatigue that just never went away. It was accompanied by a loss of mental sharpness, part of a suite of sometimes hard-to-pin-down symptoms that are often referred to as [Covid-19 “brain fog,”](https://www.wired.com/story/confused-about-covid-brain-fog-doctors-have-questions-too/) a general term for sluggish or fuzzy thinking. “I spent most of 2021 making decisions like: Is this the day where I get a shower, or I go up and microwave myself a frozen dinner?” Paige recalls. The high-level writing required for her job was out of the question. Living with those symptoms was, in her words, “hell on earth.” Many of these [hard-to-define](https://www.wired.com/story/to-help-people-with-long-covid-scientists-need-to-define-it/) Covid-19 symptoms can [persist over time](https://www.wired.com/story/exactly-how-many-people-long-covid/)—weeks, months, years. Now, new research in the journal [Cell](https://www.cell.com/cell/fulltext/S0092-8674$22$00713-9) is shedding some light on the biological mechanisms of how Covid-19 affects the brain. Led by researchers Michelle Monje and Akiko Iwasaki, of Stanford and Yale Universities respectively, scientists determined that in mice with mild Covid-19 infections, the virus disrupted the normal activity of several brain cell populations and left behind signs of inflammation. They believe that these findings may help explain some of the cognitive disruption experienced by Covid-19 survivors and provide potential pathways for therapies. For the past 20 years, Monje, a neuro-oncologist, had been trying to understand the neurobiology behind chemotherapy-induced cognitive symptoms—similarly known as “chemo fog.” When Covid-19 emerged as a major immune-activating virus, she worried about the potential for similar disruption. “Very quickly, as reports of cognitive impairment started to come out, it was clear that it was a very similar syndrome,” she says. “The same symptoms of impaired attention, memory, speed of information processing, dis-executive function—it really clinically looks just like the ‘chemo fog’ that people experienced and that we’d been studying.” ### WIRED's Guide to How the Universe Works Your weekly roundup of the best stories on health care, the climate crisis, new scientific discoveries, and more. In September 2020, Monje reached out to Iwasaki, an immunologist. Her group had already established a mouse model of Covid-19, thanks to their Biosafety Level 3 clearance to work with the virus. A mouse model is engineered as a close stand-in for a human, and this experiment was meant to mimic the experience of a person with a mild Covid-19 infection. Using a viral vector, Iwasaki’s group introduced the [human ACE2 receptor](https://www.wired.com/story/meet-ace2-the-enzyme-at-the-center-of-the-covid-19-mystery/) into cells in the trachea and lungs of the mice. This receptor is the point of entry for the Covid-causing virus, allowing it to bind to the cell. Then they shot a bit of virus up the mice’s noses to cause infection, controlling the amount and delivery so that the virus was limited to the respiratory system. For the mice, this infection cleared up within one week, and they did not lose weight. Coupled with biosafety regulations and the challenges of cross-country collaboration, the security precautions required by the pandemic created some interesting work constraints. Because most virus-related work had to be done in Iwasaki’s laboratory, the Yale scientists would take advantage of overnight shipping to fly samples across the country to Monje’s Stanford laboratory where they could be analyzed. Sometimes, they would need to film experiments with a GoPro camera to make sure that everybody could see the same thing. “We made it work,” Monje says. Most Popular Once the mice had been infected with the virus, the scientists assessed the levels of cytokines in their blood and cerebrospinal fluid (the liquid surrounding the brain) at seven days and seven weeks after infection. Cytokines are markers secreted by the immune system, and they are critical in regulating inflammation. Not only were certain cytokines elevated in the cerebrospinal fluid at both time periods, but the scientists saw an increase of microglia reactivity in the subcortical white matter of the brain—the squishy white tissue rife with nerve fibers that makes up over half of the brain’s volume. That was another sign of potential trouble. Microglia are sort of like the central nervous system’s hungry scavengers. They are immune cells that clean up the brain by chomping on dead and unwanted neural debris, among other important functions. “There’s a unique subpopulation of microglia in the white matter called axon tract microglia,” Monje says. These have a specific genetic signature, she continues, and “are exquisitely sensitive to a wide range of insults,” like inflammatory or toxic stimuli. In response to these stimuli, microglia can become perpetually reactive. One consequence is that they can begin eating away at needed neurons or other brain cells, which further disrupts the brain’s homeostasis. In the case of Covid-19, the scientists found that this reactivity persisted even at seven weeks after infection. Monje’s team had seen similar elevation in this activity following chemotherapy and in brain samples from human patients who were infected with Covid-19. In the hippocampus (the area of the brain closely associated with memory), this overenthusiastic cleanup effort can deter the creation of new neurons, which are linked to maintaining healthy memory. To figure out what exactly caused the microglia to become reactive, the researchers looked for the cytokines that had reached elevated levels. Specifically, Anthony Fernandez Castaneda, a postdoctoral researcher in Monje’s laboratory and a study coauthor, found CCL11—a factor that can decrease the generation of new neurons and impair learning or memory. “The elevated CCL11 result was very interesting, because it could potentially explain why some Covid survivors experience cognitive symptoms,” he says. In a second phase of the experiment, the researchers gave shots of CCL11 to a separate group of mice. Then they examined tissue from their brains to discover where the microglia had been reactive, and where fewer new neurons had grown. That turned out to be in the hippocampus—indicating that CCL11 acted on very specific cell populations in a memory-related area of the brain. Next, the scientists decided to investigate the effects of mild Covid-19 infection on myelinating oligodendrocytes—brain cells that generate the myelin “padding” around neurons to provide insulation for better inter-neuron communication. Previously, work done by Anna Geraghty (another postdoctoral fellow in Monje’s lab and study coauthor) had focused on how chemotherapy affects this process. Myelin loss in the mice treated with chemo was found to be directly linked with deficits in short-term memory and attention. “Even minor adjustments in those myelin can actually impact neuronal communication in quite diverse ways,” she says. “Losing that ability to adaptively respond to neuronal activity led to persistent cognitive impairments in these mice.” Most Popular Geraghty recalls staying in the lab late at night during the Christmas holiday to finish the analysis of how Covid-19 affected that padding in mouse neurons. The result: The infected mice had lost approximately one-third of their mature oligodendrocytes, and had a statistically significant drop in myelination compared to mice in a control group. The magnitude of myelin loss was almost identical to what the lab had discovered when studying mice and chemo. She excitedly texted the results to Monje. “There was just a big moment in my brain of, ‘Oh my gosh, this data is incredibly interesting,’” Geraghty recalls. Joanna Hellmuth, a cognitive neurologist at UC San Francisco who was unaffiliated with the study, notes that the “mouse data is very compelling,” and more studies are needed to see how these results translate into treatments for human patients—like Paige or others struggling with long Covid and cognitive symptoms. Figuring out which drugs to try first, though, could benefit from understanding the biological cause of brain fog symptoms. “‘Brain fog’ is a colloquial term,” says Hellmuth—and it “kind of delegitimizes peoples’ having a neurological disorder.” Wes Ely, a pulmonary and critical care specialist at Vanderbilt University Medical Center who was unaffiliated with the study, believes that such studies can lead to future therapeutic development. “This work paves the path towards both pharmacological, neuropsychological, and cognitive rehabilitative mechanisms to rebuild brain power,” he says. For example, Monje thinks, some drug candidates that already worked in “chemo fog” animal models might be useful for treating Covid-related cognitive symptoms. She hopes to test these candidates on the Covid-19 mouse model to see if they help. The team would also like to investigate other questions, like whether these neurological effects are different after even longer periods of time, or if they are different following a breakthrough infection after vaccination. They’d also like to compare what they’ve found in Covid-19 mouse models to neurological reactions to another famous virus—H1N1, which causes swine flu. The team had found that in a mouse model of H1N1, the drop in oligodendrocytes and increase in microglial reactivity in the subcortical white matter generally normalized by seven weeks—unlike for the Covid-infected mice. They also found that, in mice infected with either virus, CCL11 was elevated in the cerebrospinal fluid. Monje hopes to study what she calls this “prominent shared mechanism” in further detail. While Monje and Iwasaki’s work has given researchers a better idea of how Covid might affect the brain, it may take years before there is a working treatment for patients. For Paige, the time cannot come soon enough. In 2022, she got Covid again. “I’m just praying for medicine, praying for treatment,” she says.
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