Research Summaries

In this RECOVER study, researchers looked at how people with Long COVID, caregivers, and community members were included as partners in research. These partners are called Representatives. Researchers studied how Representatives joined RECOVER, how they took part in meetings and decisions, and how well this process worked. Researchers used surveys to learn about Representatives’ roles and experiences. The study found that most Representatives understood their roles and responsibilities. About 3 out of 4 said they felt comfortable sharing their ideas and taking part in decisions. The study found challenges, including words used in meetings that were hard to understand and not having enough time to share opinions. It also highlighted a need for clearer communication and more participation from rural and tribal communities. In addition to sharing their lived experiences, RECOVER Representatives work with researchers to help decide how studies should be conducted and how study results should be shared. Representatives' input keeps the research focused on what matters most to people affected by Long COVID. Representatives' input also makes it easier for everyone to understand what RECOVER researchers have done and what they've learned about Long COVID. This study is important because it shows that working with Representatives can help build trust between researchers and the community. Researchers also recommend ways that future studies can successfully partner with patients and community members.

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 RECOVER study, researchers looked at the link between Long COVID and school difficulties in school-age children (ages 6 –11 years old) and adolescents (ages 12–17 years old). Researchers studied 1,976 children across the US, including 406 school-age children and 1,570 adolescents, both with and without Long COVID. Based on information about school performance reported by their caregivers, children with Long COVID were about twice as likely to have worsened grades after the COVID-19 pandemic compared to those without Long COVID. About 1 in 5 school-age children and nearly 3 in 10 adolescents with Long COVID had worse grades. Those who experienced Long COVID were also more likely to have trouble paying attention in school and had a harder time having fun with their friends. Children and adolescents with Long COVID were also more likely to have an Individualized Education Program (IEP) or be in the process of getting one. An IEP is a special plan that schools use to help students with special needs. These findings show that Long COVID can make school harder for children and adolescents. The study also highlights the continued need for schools to offer support to students with Long COVID.

The researchers leading the RECOVER-VITAL clinical trial published a paper describing the study’s design in the journal Clinical Trials. RECOVER-VITAL tested 2 different treatment durations of nirmatrelvir/ritonavir, an antiviral medication commonly used to treat mild to moderate COVID-19. The trial evaluated whether the antiviral could improve Long COVID symptoms including brain fog, dizziness, fast heart rate, fatigue, and low energy. Researchers believe these symptoms may be caused by viral persistence, which occurs when the virus that causes COVID-19 remains in the body and disrupts organs or the immune system.

The design paper outlines how the trial was organized and conducted to produce accurate results. The authors describe how the protocol was developed, as well as the development of the primary and secondary outcomes. The authors also describe the study’s broader goals: advancing understanding of Long COVID symptoms, strengthening clinical trial design, and evaluating potential treatments at a time when limited evidence was available.

The researchers leading the RECOVER-AUTONOMIC clinical trials recently published a paper describing the study’s design. The trial was a multicenter, randomized, double-blinded, placebo-controlled, platform trial employing a flexible, adaptive design. The trial tested 3 possible interventions, or study treatments, for postural orthostatic tachycardia syndrome (POTS), an autonomic nervous system disorder that can develop in some people with Long COVID. These study treatments included intravenous immunoglobulin (IVIG), ivabradine, and coordinated non-drug care.

The design paper includes details on the development of the study protocol and determination of the outcomes studied. Results from RECOVER-AUTONOMIC will be shared in the coming months.

This RECOVER study looked at whether social determinants of health (SDOH) affect the risk of children developing Long COVID after having COVID-19. SDOH are the conditions in the places where people live, learn, work, and play that can affect health, such as safety or access to food, education, and healthcare. Researchers looked at survey data from more than 4,500 children. The surveys included questions about family income, access to food, school life, and how children are treated by others. The study found that children whose families struggled to pay for basic needs, like housing and food, were much more likely to have Long COVID. However, children in families who always had access to food, even if they struggled to pay for other things, were less likely to have Long COVID. This study also found that children who felt they were treated worse than others or parents who did not have enough support from friends and family had a higher chance of Long COVID. This RECOVER study is important because it shows that access to food and a supportive community may play a key role in protecting children from developing Long COVID.

This RECOVER paper combined research findings, patient experiences, and possible explanations about how the body works to understand how different germs and health factors might play a role in Long COVID. Researchers looked at how having a viral, bacterial, or fungal infection before, during, or after COVID-19 might make someone more likely to develop Long COVID. The combined information suggests that these infections can confuse the immune system, making it attack healthy cells or cause problems to the body’s organs. For example, the stress of fighting SARS-CoV-2, the virus that causes COVID-19, might “wake up” old viruses that were dormant (asleep or inactive) in the body, which can make a person sicker or more likely to develop Long COVID. This paper is important because it shows that Long COVID is complex and may involve different germs that change the body’s responses to infection. By learning more about these connections, researchers hope to find better ways to test for and treat Long COVID in everyone.

In this RECOVER study, researchers wanted to find out how Long COVID symptoms change over 15 months. To do this, researchers studied 3,659 adults who had COVID-19 before joining the RECOVER study or while they were enrolled. Researchers found that Long COVID does not look the same in everyone. Instead, people’s Long COVID symptoms usually fell into 1 of 8 different patterns over time. While most people felt better after recovering from COVID-19, about 1 in 20 participants had symptoms of Long COVID that lasted throughout the entire study. About 3 in 25 participants with Long COVID had symptoms that came and went. Other participants did not have Long COVID symptoms early on but started having health problems many months after having COVID-19. These findings show that doctors should continue monitoring patients for a long time after they have COVID-19 because their symptoms can stay, come and go, or start several months after getting sick. Understanding these patterns will help researchers find better ways to prevent and treat Long COVID in different groups of people.