Discover what the latest science from RECOVER means for our ability to understand, diagnose, prevent, and treat Long COVID.
This page contains descriptions of findings from RECOVER research studies. These descriptions use plain language and a format that is easy to understand.
If you want to learn more about the scientific discoveries described here, you can also browse and search the complete list of RECOVER Publications.
Sleep problems (such as short sleep time, inability to sleep, or problems with the body’s internal clock) are some of the most common and troubling symptoms people with Long COVID report. In this study, researchers wanted to know if having sleep problems before a SARS-CoV-2 (virus that causes COVID-19) infection would affect the immune system’s ability to regulate inflammation. The researchers looked at three parts of the immune response: T cells (which fight viruses), monocytes (which release inflammatory signals—the body’s “danger messages”), and natural compounds (which help regulate inflammation).
This study analyzed blood samples from 74 adults in the RECOVER adult observational cohort. Participants were included if they (1) had been acutely infected (within 30 days) with a SARS-CoV-2 infection, or (2) were uninfected. Participants were then categorized into groups of Likely Long COVID (LC), Possible LC, and No LC based on the Long COVID Research Index. Slightly more than half of the Likely LC group (53%) reported sleep problems before their SARS-CoV-2 infection, compared with 30% and 23% in the Possible LC and No LC groups, respectively. Overall, the three groups did not show major differences across the immune measures tested. However, researchers found a potentially significant difference in the bodies of people in the Likely LC group who had sleep problems before they got COVID-19. For these people, chemical messengers (hormones) called glucocorticoids were less effective at lowering inflammation.
These findings suggest that the presence of pre-existing sleep disturbance, which has been identified as a risk factor for the development of Long COVID, may compromise the immune system’s ability to regulate inflammation. The authors note important limitations to the study. Sleep problems were measured using a single survey question, so details about the type, severity, or treatment of sleep problems were not available. The study was also small, which limited deeper analyses.
These results, however, point to a promising direction for future research. Understanding which types of sleep disturbance, such as insomnia or excessive sleepiness, affect the body’s inflammatory response could help identify different Long COVID subtypes and guide more targeted treatments. Larger studies with more detailed sleep measurements will be important next steps in turning these early findings into real support for people living with Long COVID.
In this study, researchers used RECOVER data and blood samples to learn more about the biological mechanisms (changes in the body) that can lead to the development of Long COVID symptoms.
The researchers analyzed health information and blood samples collected between 2020 and 2021 from a group (cohort) of 142 people not taking part in RECOVER studies. This cohort included people who did and did not have COVID-19 as well as people experiencing symptoms of Long COVID. To ensure the accuracy (validate) their findings from the study of the 2020-2021 cohort, researchers compared them to findings from a different cohort that also included people without COVID-19, people with COVID-19, and people with Long COVID. The people in this cohort also took part in a RECOVER clinical trial between 2022 and 2024.
Researchers performed multiple tests on blood samples collected from both cohorts and combined those analyses with health data collected from cohort members. The combined test results and health data suggest that Long COVID is associated with changes to the body’s immune system. Among people taking part in the study, the most important of these changes were chronic (long-lasting) inflammation and T cell exhaustion. While inflammation can indicate that the immune system is overreacting and even attacking healthy parts of the body, T cell exhaustion means the immune system has a reduced ability to fight off infections like SARS-CoV-2, the virus that causes COVID-19. Evidence of inflammation and T cell exhaustion appeared in multiple types of blood sample analysis data, including data about how individual immune cells behave and how a person’s body creates the proteins it needs to repair damage. Researchers also found that people who experienced inflammation during an initial (acute) SARS-CoV-2 infection were most likely to develop symptoms of Long COVID like pain, cough, brain fog, and fatigue.
The findings suggest that the immune system may stay activated, and sometimes in a weakened state, for a long time after a person has had COVID. These findings are important because they could inform future studies on diagnosing and treating Long COVID.
RECOVER researchers studied how COVID affects people over time. They wanted to know if parts of the SARS-CoV-2 virus (which causes COVID-19), called antigens, stay in people's blood long after a COVID infection. They also wanted to see if these antigens are linked to Long COVID. Long COVID is when a person has 1 or more symptoms that last for at least 3 months after getting COVID. First, the researchers took blood samples from adults who had COVID. These samples were taken a few days after getting sick and up to 14 months later. Then, they looked for 3 types of antigens that are usually in the blood after having COVID: the S1 subunit of the spike protein, the nucleocapsid protein, and the full-length spike protein. The full-length spike protein was the most common antigen found in adults who had COVID, especially in those who had blood taken between 4 and 7 months after getting COVID.
The study also looked at 34 common Long COVID symptoms, like trouble breathing, muscle pain, and brain fog. Many participants said that they had at least 1 Long COVID symptom for 1 month or more after getting sick. In the group with the most common kinds of symptoms, 2 out of 5 people had antigens in their blood. In the group without symptoms, about 1 out of 5 people had antigens in their blood. This study shows that the 3 antigens researchers found might be linked to Long COVID. People with symptoms were twice as likely to have these antigens in their blood for a long time. The results also show that parts of the SARS-CoV-2 virus can stay in the blood for up to 14 months after an infection. This is true for people who have long-term symptoms. But, it is also true in some people who do not have long-term symptoms.
Cognitive issues, such as memory problems and difficulty thinking clearly, may increase the risk of death from COVID-19, especially for people with HIV. Many people with cognitive issues never receive a formal diagnosis. This is particularly true for people with HIV, who face higher rates of HIV-related cognitive issues and age-related thinking problems. Researchers wanted to understand how pre-existing cognitive problems in people with and without HIV affect their risk of death from COVID-19.
The research team studied 64 people with HIV who tested positive for COVID-19 between March 2020 and March 2021. They compared them to 463 people without HIV, matched by age, sex, race, and zip code. First, they checked electronic medical records for dementia diagnoses. Then, they reviewed additional information including HIV characteristics from medical providers and reviewed clinical notes from the year before COVID-19 to identify “cognitive concerns.” These included any documented worries about memory loss, thinking problems, or prescriptions for medications used to treat cognitive symptoms. These data were analyzed to determine the relationship between pre-existing cognitive issues and death after COVID in people with HIV and people without HIV.
In the group of people without cognitive issues, 3.9% of people without HIV and 10% of people with HIV died following COVID infection. However, in the group with cognitive issues, 18% of people without HIV and 40% of people with HIV died after COVID infection. People with HIV who had documented preexisting cognitive issues before infection had roughly a threefold-increased odds of death after COVID infection.
These findings suggest that assessing thinking and memory problems is crucial for COVID-19 care, particularly for people with HIV. Many cognitive issues go undiagnosed, especially in vulnerable populations. Healthcare providers should carefully evaluate cognitive function when determining COVID-19 risk. Better cognitive screening could help identify those at highest risk for severe COVID-19 outcomes.
COVID-19 can damage the heart in ways that doctors are still working to understand. Some people develop heart problems during or after COVID-19 infection, including inflammation of the heart muscle. To better understand how the virus affects the heart, researchers studied heart tissue from people who died with COVID-19. They wanted to learn what happens to the blood vessels in the heart during infection.
The research team examined heart tissue samples from autopsies using advanced techniques. These methods allowed them to see which genes were active in different parts of the tissue. They focused on cells that line the inside of blood vessels in the heart. The researchers compared tissue from 8 people who had COVID-19 to tissue from 4 people who died from other causes. They found that, in people with COVID-19, the blood vessel cells showed signs of stress and inflammation. These cells had turned on genes related to fighting infection and responding to injury. The team also found evidence of the virus itself in some heart tissue samples.
These findings help explain why some people have heart problems after COVID-19. The virus appears to directly affect blood vessels in the heart, causing inflammation and damage. Understanding these changes at the cellular level may lead to new ways to prevent or treat heart problems in Long COVID.
Many people with COVID-19 experience brain-related symptoms like confusion, headaches, and difficulty thinking clearly. These problems can continue for months after infection as part of Long COVID. Scientists are working to understand why the virus affects the brain, even though it mainly attacks the lungs, heart, and intestines.
Researchers studied how SARS-CoV-2 affects the cells that line tiny blood vessels in the brain. These cells form a protective barrier between blood and brain tissue. The team exposed human brain blood vessel cells and African monkey kidney blood vessel cells to live SARS-CoV-2 virus in laboratory experiments. They wanted to see how the virus infects cells and get through the protective barrier into brain tissue. The researchers measured how the cells responded by looking at inflammation markers, changes in the structure of the protective barriers, and changes in the cells’ energy-producing structures called mitochondria, which help maintain the protective brain barrier.
The study found that exposure to SARS-CoV-2 triggered strong inflammation in brain blood vessel cells. The virus activated a specific inflammation pathway called NF-κB that isn't usually turned on in these cells. This led to increased production of inflammatory substances that could alter brain tissue. The researchers also discovered that the virus changed how mitochondria work in these cells. Mitochondria became longer and more connected to each other, which can happen when cells are under stress. These changes occurred even though the virus didn't directly infect or kill the brain blood vessel cells.
These findings help explain how COVID-19 might cause brain symptoms without the virus directly infecting brain cells. The inflammation and changes in mitochondria could disrupt the cellular structure of the protective barrier between blood and brain. This disruption might allow harmful substances to enter brain tissue and cause thinking and memory problems seen in people with COVID. Understanding these mechanisms is an important step toward developing treatments for the neurological symptoms of COVID.
Many people who have had COVID-19 continue to experience symptoms for months or even years afterward. This condition, known as Long COVID, shares many similarities with another chronic illness called ME/CFS (myalgic encephalomyelitis/chronic fatigue syndrome). ME/CFS causes post-exertional malaise (PEM), which is extreme exhaustion that gets worse after physical or mental activity, along with problems sleeping, thinking clearly, and managing pain. Researchers wanted to understand how many people with Long COVID might also have ME/CFS and PEM to help doctors better identify and treat these conditions.
The study included 465 adults with Long COVID who completed online questionnaires about their symptoms. Participants had been experiencing COVID symptoms for an average of about 70 weeks. They answered questions about how often and how severely they experienced 38 different symptoms common to COVID and Long COVID. They also completed validated questionnaires specifically designed to identify ME/CFS and measure PEM. Most participants were white women living in North America.
The researchers found that 58% of people with Long COVID met the criteria for ME/CFS. Many people were unsure about their own condition. Among those who said they had ME/CFS, only 71% actually met the diagnostic criteria. Meanwhile, 40% of people who said they didn't have ME/CFS actually did meet the criteria. People who met ME/CFS criteria experienced more severe PEM symptoms overall, especially extreme tiredness, feeling worse after activity, and difficulty thinking or concentrating. They also reported greater disability in their daily activities compared to those without ME/CFS.
This research shows that ME/CFS is common among people with Long COVID. The findings suggest that many people may not realize they have ME/CFS, highlighting the need for better screening tools in medical settings. Understanding this connection could help doctors provide more targeted care and support for people experiencing persistent symptoms after COVID-19.
Loss of smell is one of the most common symptoms of COVID-19, and, for some people, it can last months or even years after infection. While most people recover their sense of smell within weeks, researchers don’t fully understand why some people experience persistent smell loss as part of Long COVID. This study aimed to uncover what happens in the nose tissue of people with long-lasting smell loss after COVID-19.
Researchers examined nose tissue samples from 24 people, including 9 individuals with Long COVID who had objectively confirmed smell loss lasting at least 4 months after their initial COVID-19 infection. They compared these samples to tissue samples from 13 people who never had COVID-19 and 2 people who recovered their smell after COVID-19. The team used advanced techniques to look at individual cells and analyze which genes were turned on or off in the tissue responsible for smell.
The study found that people with persistent smell loss had immune cells called T-cells in their smell tissue, indicating ongoing inflammation. Surprisingly, the nerve cells responsible for detecting smells appeared mostly intact, suggesting the problem wasn’t permanent damage to these cells. However, these smell nerve cells showed reduced activity by the genes needed for detecting smells. The researchers also found changes in genes related to inflammation and immune responses. These findings suggest that lingering inflammation in the nose, rather than damaged cells, may explain why some people can’t smell properly long after having COVID-19.
This research provides important clues about Long COVID smell loss and suggests it might be treatable. Since the nerve cells responsible for detecting smells remain largely intact, treatments that reduce inflammation could potentially help restore smell function. Understanding the biological basis of persistent smell loss brings us closer to helping the many people living with this challenging Long COVID symptom regain their sense of smell.