NIH adds funds to long COVID-19 research, advances work on new clinical trials

NIH recently received approval to reallocate $147 million to support ongoing efforts of the Researching COVID to Enhance Recovery (RECOVER) Initiative. This allocation is in addition to the $515 million that NIH announced earlier this year, bringing total new funding to $662 million.

These funds add to the $1.15 billion that Congress appropriated in 2021 to support the establishment of the RECOVER nationwide research program. To date, the program is conducting large, multi-site observational studies with more than 40,000 participants. The adult cohort has donated more than 822,000 biospecimens, and the pediatric cohort has donated more than 85,000 biospecimens – all accessible through the RECOVER biorepository for further studies within and beyond RECOVER.  In addition, RECOVER supports 40 existing pathobiology studies to understand the biological mechanism of disease, ongoing studies evaluating 60 million electronic health records, and eight existing phase 2 clinical trials testing the safety and efficacy of 13 treatments that include drugs, biologics, medical devices, and other therapies.

In July, NIH began planning for the next phase of long COVID clinical trials through a newly launched program called RECOVER-Treating Long COVID (RECOVER-TLC). NIH’s National Institute of Allergy and Infectious Diseases is leading the program in partnership with the Foundation for the National Institutes of Health and in collaboration with NIH’s National Heart, Lung, and Blood Institute and National Institute of Neurological Disorders and Stroke. 

The $662 million in funds will be allocated over Fiscal Years 2025-2029 to support the following research areas:

• RECOVER-TLC clinical trials
• Completion of adult and pediatric observational studies
• Additional pathobiology studies to examine how long COVID affects different parts of the body which will help to inform clinical trials
• Preservation and broader access to data and biospecimens and maintaining RECOVER-supported research infrastructure over the next five years

Update on Progress

RECOVER-TLC

RECOVER will allocate approximately $300 million to RECOVER-TLC clinical trials. In September 2024, NIH convened more than 1400 patients, advocates, health care providers, and scientists from academia and pharmaceutical and biotech industries to discuss research priorities and plans for clinical trials that are most needed. During the three-day workshop, participants discussed a variety of topics, including pathobiology, biomarkers, epidemiology and cohort studies, clinical trial designs, interventional prioritization strategies, and endpoint selection. Importantly, participants at the workshop emphasized the importance of meaningful engagement and collaboration with people affected by Long COVID. NIH plans to convene another workshop and a series of webinars in 2025.

In October, NIH issued a Request For Information to gather ideas on candidate pharmacologic and non-pharmacologic interventions for this next phase of trials, which will remain open until Feb. 1, 2025. Additionally, NIH opened a portal for idea submission for therapeutics and biologics and established a review process for vetting these ideas.

RECOVER-TLC will design nimble clinical trials with direct and transparent engagement with scientific, industry, and patient communities. RECOVER-TLC will continue to provide access and sharing of deidentified data with public and scientific communities.

New pathobiology awards

RECOVER will award nearly $18 million from the initial $1.15 billion for an additional 20 pathobiology research projects. Pathobiology studies look at biological mechanisms—processes that take place inside the body and its cells—of long COVID. This research is advancing our understanding of the changes in tissues and organs that are caused by SARS-CoV-2 infection and identifying biological markers for therapeutic target based on individuals’ risk factors.

By examining biospecimens such as blood, saliva and other samples and data collected from RECOVER cohorts and clinical trial participants, the new pathobiology studies will help us better understand the 200 conditions associated with long COVID, including:

• The effects of COVID-19 on the respiratory, vascular, and other body systems
• How long COVID compares with other infection-associated chronic conditions
• The remaining gaps in knowledge of tissue-specific manifestations, including molecular mechanisms such as dysregulation or disruption of normal physiologic pathways

These sub-awards build on the more than 40 pathobiology research projects awarded in 2022 that are yielding important results.  For example, one study found that severe COVID-19 may cause long-lasting alterations to the innate immune system, the first line of defense against pathogens, making some people susceptible to other infections. Another study found that symptoms for some long COVID sufferers appear to be caused by persistent infection and may respond to antiviral medications.

Long COVID is a complex and debilitating chronic condition affecting people’s ability to work, attend school, and participate in their regular activities. Alleviating the suffering of so many individuals, their families, and their caregivers is a priority of NIH. We look forward to further advancing our understanding of long COVID and advancing prevention and treatment.

Monica M. Bertagnolli, M.D.
Director, National Institutes of Health