RECOVER Research Update: June 2026

Clinical Trials

Developing a platform protocol for clinical trials evaluating interventions that target proposed mechanisms of Long COVID: RECOVER-VITAL (Clinical Trials, March 2026)

• This publication describes how researchers designed the RECOVER-VITAL clinical trial. It discusses the step-by-step plan that researchers followed to achieve the study’s goals.
• The main goal of the RECOVER-VITAL trial was to determine whether nirmatrelvir–ritonavir (Paxlovid), an antiviral drug used to treat COVID-19, might also be a safe and effective treatment for Long COVID symptoms. 
• Paxlovid works by preventing SARS-CoV-2, the virus that causes COVID-19, from making copies of itself and spreading throughout the body. Researchers think Long COVID symptoms like thinking difficulties, memory problems, dizziness, fast heart rate, fatigue (extreme tiredness), and low energy could be caused by viral persistence. Viral persistence is when copies or pieces of SARS-CoV-2 remain in the body and continue to affect tissues, organs, and the immune system.
• Results from the RECOVER-VITAL trial are posted on ClinicalTrials.gov. A paper describing the full findings and analysis is expected to be published in the coming months.

Visit the RECOVER-VITAL webpage to learn more about this study.

Design and rationale of RECOVER-AUTONOMIC: A randomized platform trial evaluating interventions for Long COVID postural orthostatic tachycardia syndrome (American Heart Journal, February 2026)

• This publication describes how researchers designed the RECOVER-AUTONOMIC clinical trials. It discusses the step-by-step plan that researchers follow to achieve the study’s goals.
• The main goal of the RECOVER-AUTONOMIC trials is to test the safety and effectiveness of possible treatments for Long COVID-related postural orthostatic tachycardia syndrome (POTS).
• POTS affects the autonomic nervous system, which controls automatic body functions like breathing, digesting food, and blood pressure. POTS can cause symptoms such as dizziness, fatigue, and fast heart rate.
• The possible POTS treatments tested in the RECOVER-AUTONOMIC clinical trials include 2 drugs: ivabradine and Gamunex-C, a form of intravenous immunoglobulin. Ivabradine is a common treatment for heart failure that works by reducing a person’s heart rate. Gamunex-C is a treatment developed for autoimmune conditions. In an autoimmune condition, a person’s immune system begins harming healthy cells and tissues instead of fighting off bacteria and viruses.
• RECOVER researchers presented findings from the RECOVER-AUTONOMIC (Ivabradine) trial at the American College of Cardiology Annual Conference on March 28, 2026. A paper describing the full findings and analysis is expected to be published in the coming months.

Visit the RECOVER-AUTONOMIC webpage to learn more about these studies.

Engaging patients and researchers in RECOVER clinical trial protocol development: Key lessons (Journal of Clinical and Translational Science, February 2026)

• This publication discusses lessons learned from working with Patient, Caregiver, and Community Representatives to design the 8 clinical trials included in the RECOVER Clinical Trials (RECOVER-CT) program.
• Responses to a survey created by researchers showed that most Representatives felt their input—including their lived experiences with Long COVID—on study designs was valued. However, these responses also emphasized the importance of open communication and close collaboration between Representatives and researchers.
• Using these findings, the authors offer specific recommendations for partnering with patients and community members to develop future Long COVID clinical trials. These recommendations include: 
  • Well-defined roles and responsibilities.
  • Clearly explained decision-making processes.
  • Training for all partners, including researchers.
  • Development of tools to ensure that people from all backgrounds and walks of life have opportunities to share their input.

Pathobiology Studies

The effect of pre-existing sleep disturbance on T cell responses to SARS-CoV-2 variants, pro-inflammatory and pro-resolving mediators, and glucocorticoid sensitivity in Long COVID (Scientific Reports, April 2026)

• This pathobiology study found a potentially important change in the bodies of people who had sleep problems (disturbances) before they developed Long COVID.
• Sleep problems can affect the immune system, meaning people who experience poor sleep may have less natural protection against viral infections like SARS-CoV-2 (the virus that causes COVID).
• The researchers cite multiple studies that show that nearly 3 in 10 people with Long COVID experience sleep disturbances. Moreover, Long COVID can make these disturbances worse for people who experienced sleep problems before they got COVID.
• Researchers examined data and blood samples collected from adults taking part in RECOVER’s observational study to explore the links between sleep disturbances, the immune system, and possible causes of Long COVID.
  • Using a special tool developed by other RECOVER scientists called a research index, researchers identified a group of study participants who, based on their symptoms, most likely had Long COVID.
  • Researchers tested blood samples for the presence of several substances produced by or associated with the immune system. These substances included chemical messengers. Chemical messengers play an important role in activating the immune system and telling it which germs, like viruses and bacteria, to attack.
• Researchers found that chemical messengers called glucocorticoids worked differently in the bodies of people who experienced sleep disturbances before they got COVID and who were later classified as having likely Long COVID.
• For these people, glucocorticoids were less effective at lowering inflammation. Chronic inflammation, or inflammation that lasts a long time, can harm healthy cells and tissues.
• These findings are important because they supply more evidence that pre-existing sleep disturbances can be a risk factor for developing Long COVID. 
• The researchers also recommend that future studies investigate which specific sleep disturbances are most associated with inflammation caused by ineffective glucocorticoids. Findings from those studies could help identify specific types of Long COVID and inform more targeted treatments.

Macrophage activation syndrome-associated proteins and enhanced interferon-γ responsiveness in the plasma proteome of patients with multisystem inflammatory syndrome in children in a pretreatment replication single-center cohort (ACR Open Rheumatology, February 2026)

• In this pathobiology study, researchers confirmed the findings of an earlier study that identified a way to diagnose multisystem inflammatory syndrome in children (MIS-C). Some children who get COVID-19 can develop MIS-C.
• MIS-C causes a fever that lasts more than 24 hours and inflammation in different parts of the body, such as the heart, lungs, brain, gut (intestines), and kidneys. In addition to swelling and fever, this inflammation can cause symptoms like upset stomach, difficulty breathing, and chest pain. In some cases, a child’s MIS-C symptoms can be so serious that they require hospitalization.
• MIS-C can be hard to diagnose because its symptoms are similar to those of other health conditions that affect children and cause fevers, including toxic shock syndrome, Kawasaki disease, macrophage activation syndrome (MAS), and infection-associated chronic conditions other than Long COVID.
• Researchers examined blood samples from children diagnosed with MIS-C and compared them with samples from children who had other viral infections. 
• After analyzing these samples, researchers found higher levels of 3 proteins in the blood of children with MIS-C. 
• Together, these proteins could be used as biomarkers (measurable signs) that someone has or could develop MIS-C.
• Researchers also confirmed that intravenous immunoglobulin (IVIG), a drug often used to treat MIS-C, can change the mix of proteins in a person’s blood. This change can make it harder to find biomarkers for MIS-C.
• These findings are important because they can help ensure that children with MIS-C receive the right diagnosis, treatment, and care.

Observational Cohort Studies

School difficulties and Long COVID in children and adolescents (Academic Pediatrics, April 2026)

• Researchers found that young people living with Long COVID can be more likely to face challenges at school and with friends than those without Long COVID.
• Almost 2,000 young people enrolled in the RECOVER pediatric observational cohort took part in this study. This study group included more than 400 children aged 6 to 11 (school-aged children) and more than 1,570 children aged 12 to 17 (adolescents). 
• First, researchers identified which school-aged children and adolescents likely had Long COVID. To do this, they used a research index created by other RECOVER scientists studying how Long COVID affects young people. Next, researchers examined information about these young people’s school performance as provided by their caregivers. 
• The data that caregivers provided showed that young people with likely Long COVID were more than twice as likely to have worsening grades than young people without Long COVID. More of those school-aged children and adolescents with worsening grades had also begun participating in Individualized Education Programs (IEPs). IEPs are designed for students with special needs.
• Additionally, almost 40% of young people with likely Long COVID had trouble paying attention in class—more than twice the rate seen in young people without Long COVID.
• The study also shows that Long COVID may affect more than just physical health. Caregivers said that 28% of school-aged children and 43% of adolescents with likely Long COVID had difficulty having fun with their friends. By comparison, caregivers said that 9% of school-aged children and 21% of adolescents without Long COVID had difficulty having fun with their friends.
• These results are important because they add to our understanding of the broad and long-lasting impacts Long COVID can have beyond the symptoms it causes.
• These findings could also inform future efforts to strengthen school-based support for young people living with Long COVID. This support is critical for helping these young people meet daily life challenges and thrive into adulthood.

A roadmap for development of community engagement: Early lessons learned from the RECOVER Initiative (Progress in Community Health Partnerships: Research, Education, and Action, April 2026)

• In this publication, researchers share 3 recommendations for conducting patient- and community-centered medical research on a large scale. Researchers developed these recommendations after surveying RECOVER Representatives and analyzing their responses.
• These survey questions covered the following topics:
  • Representatives’ roles and responsibilities within the RECOVER Initiative.
  • Representatives’ experiences working on RECOVER, including how they felt about their specific contributions.
  • What Representatives believed worked well.
  • What Representatives thought could be improved.
• Most of the 35 Representatives who completed the survey shared that they understood their roles and responsibilities, felt comfortable offering feedback, and felt included in the decision-making process. These Representatives particularly valued having opportunities to help inform study plans.
• However, less than half of the Representatives who completed the survey felt that RECOVER meetings gave them enough time to share feedback or that they knew whom to contact if they had questions or concerns. Less than 20% of the Representatives who completed the survey felt they understood why RECOVER did not act on ideas they shared.
• Researchers also reviewed RECOVER’s organizational structure, overall engagement strategy, and history of working with Representatives.
• Using these findings and survey results, researchers recommend that future studies seeking to engage patients and community members take 3 steps:
  • Make sure patient and community partners have a voice in making important decisions about research and how it is conducted.
  • Clearly communicate the engagement plan is to everyone involved, including researchers and study staff.
  • Include patient and community partners from a wide range of backgrounds and walks of life, especially people who live in rural and tribal communities.

Electronic Health Record (EHR) Studies

Target trial emulation of vaccine effectiveness in 5- to 17-years-olds with prior SARS-CoV-2 infection (Nature Communications, April 2026)

• This study investigated whether vaccines help protect young people from getting COVID-19 more than once (reinfection).
• This study focused on the Omicron strain (variant) of SARS-CoV-2, the virus that causes COVID-19. Researchers chose Omicron because it caused the most confirmed cases of COVID during the study period (January 2022 through August 2023).
• Few previous studies had investigated how well COVID vaccines protected young people from reinfection. Young people’s immune systems are different from adults’, and COVID can affect young people differently.
• Omicron has changed over time, creating subvariants. Although these subvariants are all related, they can behave differently enough to become more (or less) contagious and more (or less) likely to cause serious illness.
• Researchers collected data from the EHRs of more than 600,000 children (aged 5 to 11) and adolescents (aged 12 to 17).
• All children and adolescents in this group had COVID at least once before joining the study. More than 80% of these young people had not received at least one dose of a COVID vaccine before the study began. A small portion of these young people (less than 10%) received at least one dose of a COVID vaccine sometime during the study period. The rest of the young people in the study remained unvaccinated during the study period.
• Using the EHR data they collected, researchers created a target trial emulation (TTE). Like clinical trials, TTEs explore the effectiveness of treatments like drugs or medical devices. Unlike clinical trials, which give people treatments and study how those treatments change people’s health, TTEs analyze EHR data to learn how treatments people are already taking might be affecting their health.
• The TTE showed that COVID vaccines were much more effective at preventing reinfections caused by Omicron subvariants that emerged in 2022 (subvariants named BA.1/BA.2 and BA.4/BA.5) than Omicron subvariants that emerged in late 2022 and 2023 (subvariants named XBB and later). 
• These findings are important because they suggest that, even if a young person has already had COVID, they can still benefit from vaccination. Additionally, these findings highlight the importance of updating vaccines so they can offer protection against new variants and subvariants of SARS-CoV-2.

Pre-COVID-19 body mass index and postacute cardiovascular, gastrointestinal, and neuropsychiatric outcomes among children and young adults with SARS-CoV-2 infection: An EHR-based cohort study from the RECOVER Initiative (Journal of Infection, February 2026)

• Researchers found that children diagnosed as being overweight or obese before they got COVID-19 were more likely to develop Long COVID.
• Researchers analyzed EHR data from more than 139,000 children (aged 5 to 11), adolescents (aged 12 to 17), and young adults (aged 18 to 20). 
• Using these EHR data, researchers used a health measurement called body mass index (BMI) to determine whether a young person was overweight or obese.
• Researchers found that young people who were overweight or obese experienced a greater risk of developing long-term heart and stomach problems after getting COVID-19 than children who were not overweight or obese.
• The most common heart problems linked to young people being overweight or obese were high blood pressure and irregular heartbeat.
• The most common stomach problems overweight or obese young people experienced were diarrhea and heartburn caused by gastroesophageal reflux disease (GERD).
• Researchers also reviewed the EHR data for information about young people’s mental health. They found no clear link between obesity and the risk of young people developing conditions like anxiety or depression after having COVID-19. They also note that mental health problems may be underdiagnosed in young people due to weight-related bias in healthcare settings.
• These findings could help healthcare providers identify and provide appropriate care for young people who may be at greater risk of developing Long COVID.