Research Summaries

This RECOVER study looked at how a child’s race or ethnicity might affect their chances of developing long-term health problems after getting COVID-19. Researchers studied data from 225,723 children and teens across 13 US hospitals and clinics from March 2020 to October 2022. They compared children who were diagnosed with COVID-19 or had a positive COVID-19 test to those who never tested positive. The study found that children with COVID-19 were more likely to develop many health problems weeks or months after getting COVID-19 than those who never had it. These problems included trouble breathing, feeling very tired (fatigue), and mental health problems.

Researchers also found that the chance of having these problems was different depending on a child's race or ethnicity. For example, Hispanic children with severe COVID-19 were more likely to have hair loss after getting sick than Non-Hispanic White children with severe cases. Non-Hispanic Black children with less severe COVID-19 were more likely to experience cognitive symptoms (related to thinking, memory, or concentration) than Non-Hispanic White children with less severe COVID-19. In children with less severe COVID-19, Asian American/Pacific Islander children were more likely to have more fever, chills, and respiratory symptoms (related to breathing) than Non-Hispanic White children. This study shows that long-term health problems in children and teens after COVID-19 may be different between racial and ethnic groups. This can help doctors better understand and treat Long COVID in people who are more likely to get it.

A RECOVER study looked at whether a person’s sex at birth affects their risk of developing Long COVID. To do this, researchers studied a large group of people enrolled in the RECOVER adult cohort. They found that females were more likely to have Long COVID symptoms than males. Among females, the risk of getting Long COVID changed based on age, pregnancy status while having COVID-19, and if they had gone through menopause. Researchers discovered that the risk of getting Long COVID was higher in females ages 40–54 years and females who had not gone through menopause. On the other hand, females who had already gone through menopause were not at a higher risk compared to males. More research is needed to understand why differences in sex at birth may put someone at higher risk of experiencing the long-term effects of COVID-19. Knowing this and understanding which hormones play a role in Long COVID risk could help researchers develop treatments and ways to prevent Long COVID.

This RECOVER study looked at how well the Pfizer COVID-19 vaccine, called BNT162b2, protected children and teens from long-term health problems after having COVID-19, also known as Long COVID. Researchers studied the electronic health records (EHRs) from more than 385,000 children and adolescents across 13 hospitals and clinics during the Delta and Omicron waves. In the Delta wave, researchers studied the EHRs of 112,590 adolescents ages 12 to 20. Of these, 88,811 adolescents were vaccinated before getting COVID-19. In the Omicron wave, they studied the EHRs of 188,894 children ages 5 to 11 years old, and 84,735 adolescents ages 12 to 20. Of these, 101,277 children, and 37,724 adolescents were vaccinated before getting COVID-19. In the Delta period, the researchers found that vaccinated adolescents were 95% less likely to develop Long COVID. In the Omicron period, the vaccine lowered the risk of Long COVID by 60% in children and 75% in adolescents. The study also showed that the vaccine’s main benefit in preventing Long COVID in children and adolescents came from preventing them from getting COVID-19 in the first place.

This RECOVER study focused on what causes Long COVID and why it affects people in different ways. Researchers created an "omics" task force made up of doctors, scientists, and data experts. For 14 months, they worked together to figure out the best way to study Long COVID. They recommended using "multi-omics," which means studying many layers of health information at the same time, like genes, proteins, and chemicals that show how the body is working. To do this, RECOVER researchers collected blood, urine, and saliva samples from more than 34,000 people including adults, pregnant adults, and children, at least twice since joining the study. Looking at all these layers together gives a clearer picture than studying them one by one. It also avoids differences between laboratories and makes it easier to find patterns that could tell us more about Long COVID. The research and recommendations are important because they can help researchers find out what causes Long COVID, predict who might get it, and find treatments. The data collected in this study will also be shared with other researchers so they can continue to learn more.

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.

This RECOVER study focused on a problem that happens when scientists study rare events. When scientists have very few cases of rare events to study, the usual ways of studying data can give misleading results. One way to fix this is to combine data from many hospitals or clinics so there are more cases to study. But, sharing detailed patient information raises concerns about privacy, so patient privacy must be protected when combining data from multiple healthcare centers.

In this study, RECOVER researchers created a new tool called ODAP-B, which combines information more accurately without sharing patient details. This is because it only needs a summary of patient data, not full health records. By using ODAP-B, researchers can better understand what increases the chance of a rare event happening while protecting patient privacy.

In this paper, RECOVER researchers reviewed existing research to better understand how Long COVID affects older adults. Early research on Long COVID often combined adults ages 18 and older, which makes it difficult to see how Long COVID presents in older adults alone. To learn more, researchers looked at more than 600 studies with keywords like “elderly” and “aged” and focused on adults ages 65 and older. The studies showed that many older adults do not report having Long COVID symptoms. This is because health problems like fatigue, joint pain, or brain fog can be labeled as symptoms of normal aging or other health conditions instead of Long COVID. This research is important because it highlights the need for doctors to identify, track, and provide care for Long COVID symptoms in older adults. It also emphasizes that more research is needed on Long COVID in this population.

This RECOVER literature review paper summarizes what scientists currently know about the relationship between inflammation (the body’s response to an infection or injury) and Long COVID. Researchers reviewed past studies about how different parts of the body work together (biological pathways) and how those pathways can be related to Long COVID. They found that ongoing (chronic) inflammation—inflammation that does not stop when it should—may play an important role in Long COVID. Chronic inflammation can happen for many reasons. One reason is that viruses that were inactive, or “asleep,” in the body may become active again. Another reason is that SARS-CoV-2, the virus that causes COVID-19, may also stay in the body longer than expected. Another reason is that Long COVID may be related to changes in the immune system, which fights against infections. In some cases, the immune system may attack the body’s own healthy tissues by mistake, causing inflammation. Problems with mast cells, which help control allergic reactions and inflammation, may also play a role. Doctors can look for signs of inflammation using common tests, like bloodwork, but these tests by themselves cannot show that a person has Long COVID. The authors found that some early studies suggest that certain treatments for chronic inflammation may lower the risk of developing Long COVID or help manage its symptoms. However, there is no approved or proven treatment for Long COVID yet. This literature review is important because it shows that more research is needed to understand the links between inflammation and Long COVID. Establishing these links could help doctors more easily identify Long COVID and treat its symptoms.

Metformin is a drug that many doctors prescribe as treatment for type 2 diabetes mellitus (T2DM). Past studies have found that taking metformin before and while having COVID-19 helps lower the chances of getting very sick with COVID-19. These studies also found that taking metformin can lower the chance of a person being sick many months after getting COVID-19, which is called Long COVID. In this study, RECOVER researchers were interested in understanding if people with diabetes who were on different medications got Long COVID or died. They looked at electronic health records (EHRs), or computer-based versions of patient health records, for 88,342 adults with T2DM. The study looked at 2 groups. The first group used metformin to control their diabetes, while the second group used other medications to control their diabetes. The researchers found that the chances of getting Long COVID or dying were a little bit lower in the group that took metformin compared to the group taking other medications. Since being on metformin may help only a little bit with Long COVID for adults with T2DM, people taking diabetes medications do not need to change their treatment plans unless told by their doctor.