Research Summaries

We need good ways to measure how adults with Long COVID are feeling and functioning so that we can test new therapies that may be able to help them feel better. Since very few surveys have been specifically designed for Long COVID, we wanted to see how well 4 existing surveys worked by asking adults with Long COVID to give us feedback. 30 English-speaking adults with Long COVID reviewed the surveys during an interview. Evidence from the interviews indicated that adults with Long COVID could understand the questions within the surveys and most of the items were relevant to their experience with Long COVID. Our findings support use of the 4 surveys in the Long COVID clinical trial they were chosen for, and we also identified future ways to make these surveys even better for this population.

In this RECOVER study, researchers wanted to learn how Long COVID affects the everyday functioning of children, teenagers, and young adults. Researchers examined the electronic health records (EHRs) of 686 children and young adults under 21 years old, including 651 who got COVID-19 and received care in 21 hospitals in the US. Researchers compared young people who had Long COVID to those who had COVID-19 but did not have Long COVID. Researchers found that young people with Long COVID were more likely to have trouble in school, need extra help in school, and develop new or worsening behavioral or mental health issues like anxiety and depression. This study is important because it highlights that doctors should ask about school, daily activities, and emotional well-being when caring for young people who've had COVID-19. Long COVID can affect these parts of everyday life and some children and young adults may need support in these areas.

This RECOVER study looked at whether taking selective serotonin reuptake inhibitors (SSRIs) and serotonin–norepinephrine reuptake inhibitors (SNRIs) around the time of having COVID-19 was linked to Long COVID in children, teenagers, and young adults. SSRIs and SNRIs are medicines used to manage mood and mental health symptoms. Researchers reviewed the electronic health records (EHRs) of more than 110,000 young people ages 5 to 20 who had neuropsychiatric conditions and COVID-19. Neuropsychiatric conditions affect how the brain works and how a person thinks, feels, or acts. Researchers compared young people who took SSRIs or SNRIs to those who did not. The study found that taking SSRIs or SNRIs was not linked to a higher or lower chance of receiving a Long COVID diagnosis. However, young people taking these medicines were less likely to have fever, chills, or hair loss documented after COVID-19. They were more likely to have extreme tiredness (fatigue), memory problems, and postural orthostatic tachycardia syndrome (POTS), which is a condition that can cause a fast heart rate when standing up. These findings are important because they suggest that children, teens, and young adults taking SSRIs or SNRIs may experience different long-term symptoms after getting COVID-19, which doctors should monitor.

In this RECOVER study, researchers looked at whether children who received steroids soon after getting COVID-19 were less likely to develop Long COVID. Steroids are medicines that help with inflammation (swelling and irritation) in the body. Researchers reviewed the electronic health records (EHRs) of more than 850,000 children under 19 years old who had a positive COVID-19 test, a COVID-19 diagnosis, or received antiviral medicines for COVID-19 between March 2020 and April 2024. Researchers then compared children who received steroids within 12 days of getting COVID-19 to those who did not. They also looked at children who were hospitalized and children who were treated at home. Researchers found that steroid use was not linked to a lower risk of developing Long COVID. However, children who were not hospitalized with COVID-19 and took steroids had a lower risk of experiencing stomach problems associated with Long COVID. This study is important because it shows that early steroid use was not linked to a lower risk of Long COVID in children. More research is needed to understand which treatments may help prevent long-term symptoms from developing in children who get COVID-19.

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.