Long COVID remains an unsolved, complex, and urgent healthcare crisis which, according to the CDC, has affected one in nine adults in the United States who have ever had COVID-19. The condition carries a wide range of symptoms. NIH aims to study and treat Long COVID through the Researching COVID to Enhance Recovery (RECOVER) initiative, which was launched in 2021 with $1.15 billion in Congressional appropriations.

Through the participation of nearly 90,000 adults and children in RECOVER observational studies, initiation of five clinical trials, several with multiple arms, and review of more than 60 million electronic medical records, NIH support has informed critical insights on the disease, as evidenced by the swift pace of RECOVER Publications. Already, researchers have learned so much about: 

• Genetic alterations and changes in activation.
• Comorbidities affecting severity of symptoms. 
• Duration of virus presence in tissues. 
• Immune system function changes. 

NIAID will take a central leadership role in the program’s next phase: RECOVER-Treating Long COVID (TLC). This new initiative is based on the foundational successes and lessons learned from the RECOVER initiative. NIH plans to bolster Long COVID research in the coming years, to include support for RECOVER-TLC, which will develop and launch additional Long COVID clinical studies.  

Starting by Listening 

Building on the progress of the original RECOVER initiative, NIH and the Foundation for National Institutes of Health (FNIH) hosted a 3-day meeting from September 23 to 25, 2024, for researchers, advocacy groups, and other stakeholders to help shape RECOVER-TLC.  

NIH, FNIH, and NIAID leadership asked participants for input to: 

• Ensure RECOVER-TLC applies all the lessons learned over the last 3 years. 
• Discuss the structure and governance of RECOVER-TLC.
• Survey the current research landscape. 
• Help plan future NIH Long COVID clinical trials. 

The international group of presenters, panelists, and audience members filled the 3-day meeting with robust data sharing, discussion, anecdotes, and questioning from multiple points of view. Clinicians, researchers, people living with Long COVID (some of whom are also clinicians or researchers), family, advocates, industry representatives, and government staff all came together to voice their perspectives and discuss how to proceed.  

What We Heard and What We Will Do 

At the close of the conference, NIAID Director Dr. Jeanne Marrazzo summarized the participants’ messages and the initiative’s action plans in her presentation RECOVER-TLC’s Next Steps and How to Proceed. 

Communication, data sharing, and transparency were top priorities among attendees, and they emphasized urgency within the bounds of scientific rigor. Dr. Marrazzo identified multiple strategies such as open forums, meaningful participation for people impacted by Long COVID, monthly progress updates, an annual meeting, and a centralized organizational structure within NIAID’s Office of the Director. 

People living with Long COVID and advocates issued a resounding call for organizers to actively invite their meaningful involvement in the details of RECOVER-TLC plans—they know their conditions best, given the multisystem impacts of the virus that have been poorly characterized and understood to date. They stressed a need to reduce barriers to participation, including limitations around travel, resources, and energy. Dr. Marrazzo acknowledged the importance of having a seat at the table, including participation in working groups, serving on key committees, and linking among community advocacy networks. 

Dr. Marrazzo said the Institute will urgently investigate how the vast collections of specimens and data gathered during the initial RECOVER research can inform next steps in clinical trial prioritization. Multidisciplinary working groups will engage in these efforts to reflect the diversity of inputs. 

Long COVID’s broad and varied effects on diverse populations demand new clinical trial approaches and fewer restrictions to inclusion and access to achieve results. Working groups that invite lived experience and build on RECOVER infrastructure are needed to design protocols that match the true clinical conditions and functional challenges of people with Long COVID. Specifically, RECOVER-TLC must work with the FDA and research teams to define relevant endpoints that can support regulatory decisions, conduct both large and small studies to achieve appropriate regulatory and intervention outcomes, manage portfolios actively to assess the most promising diverse approaches, and involve pediatric and adolescent populations, as well as pregnant and lactating women. 

Among the early outcomes from the meeting is a RECOVER-TLC Intervention Information Request Form where anyone can submit a therapeutic (proposed drugs, devices, or other agents targeted at alleviating symptoms associate with Long COVID) to be considered in future RECOVER-TLC clinical trials.

NIAID also published Request for Information (RFI): Researching COVID to Enhance Recovery – Treating Long COVID (RECOVER-TLC) to invite further input, including from those who could not attend the meeting, on 1) Potential therapeutics for Long COVID, 2) Interest in being involved on working groups, i.e., as patients, caregivers, scientists, or physicians, 3) Biomarkers to be used in future Long COVID clinical trials, and 4) General feedback on RECOVER-TLC. Responses to the RFI are due by January 31, 2025.

Read more about how RECOVER-TLC Will Advance Long COVID Research. Should NIAID announce specific opportunities within the RECOVER-TLC program, we will cover them in this newsletter.