Research Summaries

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.

In this RECOVER study, researchers looked at how well COVID-19 vaccines protected children and adolescents who’d already had COVID-19 from getting it again. Researchers reviewed the electronic health records (EHRs) of nearly 600,000 children ages 5–11 and adolescents ages 12–17. These young people received health care at 37 children’s hospitals located across the US. Researchers compared young people who received at least one COVID-19 vaccine with those who had not. Researchers found that vaccine protection changed as new versions (variants) of SARS-CoV-2, the virus that causes COVID-19, appeared. Early in the Omicron variant period, vaccines lowered the chance of getting COVID-19 again by about 62% in children and 65% in adolescents. In the mid-Omicron variant period, the vaccines lowered the chance of getting COVID-19 again by 57% in children but did not work as well for adolescents. During the later Omicron variant period, the vaccines did not stop children or adolescents from getting COVID-19 again. These findings are important because they show that vaccines offered protection against getting COVID-19 again at first, but that protection became weaker as SARS-CoV-2 changed over time.   

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.

In this RECOVER study, researchers looked at the relationship between a young person’s weight and their health after getting COVID-19. Researchers reviewed the electronic health records (EHRs) of over 139,000 children and young adults, ages 5–20 years, across the US. They grouped participants based on their body mass index (BMI). BMI is a number that helps show whether someone is at a healthy weight, is overweight, has obesity, or has severe obesity based on their height and weight. The researchers checked if any new health problems were added to participants’ EHRs between 1 and 6 months after getting COVID-19. The study found that children and young adults with severe obesity were much more likely to develop health problems after getting COVID-19. These included problems related to the heart, like high blood pressure, and stomach problems, like diarrhea and heartburn. The researchers also checked whether participants had mental health issues after getting COVID-19. Those results were less clear and may have been due to other factors. This study is important because it shows that doctors should be thinking about the weight of children and young adults affected by COVID-19. If a child is overweight or has obesity and gets COVID-19, doctors should monitor their heart and stomach health to make sure they receive the care they need. 

In this study, RECOVER researchers looked at whether getting COVID-19 during pregnancy affects a baby’s brain development. Researchers followed over 1,000 families across the US and compared babies up to 18 months in age who were exposed to COVID-19 during their mother’s pregnancy to those who were not. Researchers tracked the babies’ development at 12 and 18 months, looking at how they moved, talked, solved problems, and interacted with others. Researchers found that babies exposed to COVID-19, mostly during the Omicron wave of the pandemic, scored just as well as babies who were not exposed. Researchers also found no big differences in babies’ social skills or risk of delays in their brain development during their first 18 months of life. These findings are important because they can reassure mothers who get COVID-19 during pregnancy about the brain development of their child. However, doctors should continue to check children who were exposed to COVID-19 during their mother’s pregnancy as they grow to ensure their development stays on track.

This RECOVER study looked at whether COVID-19 was linked to a higher risk for dyslipidemia (unusual levels of fats or cholesterol in the blood) or a high body mass index (BMI) in children and young adults. BMI is a number that helps show if someone's weight is in the healthy range for their height. A higher BMI can be a sign that a person may be overweight or have obesity. Researchers looked at the electronic health records (EHRs) of over one million children and young adults, from birth to age 21, across 25 different children’s hospitals in the US. Researchers followed the health of children and young adults for up to 6 months after they got COVID-19 for the first time and compared them to a group of children and young adults who did not get COVID-19. Researchers found that children and young adults who got COVID-19 were about 24% more likely to develop dyslipidemia and 15% more likely to develop a high or unhealthy BMI than those who never had COVID-19. These findings are important because they show that COVID-19 may be linked to a higher risk of health problems related to blood fats and weight. These findings also highlight the need for closer follow-up of children and young adults during their recovery from COVID-19.