RECOVER program takes first steps in advancing toward clinical trials to better understand Long COVID

The NIH RECOVER initiative is preparing several clinical trials to evaluate treatments to improve symptoms related to post-acute sequelae of SARS-CoV-2 infection (PASC) or Long COVID. A trial protocol recently posted to ClinicalTrials.gov is in the final stages of development and approvals, and is expected to begin enrolling participants in early 2023.

This trial is one of several that will test a variety of treatments for Long COVID. The causes of Long COVID are not well understood, and there are many different symptoms of Long COVID. Each trial will examine a treatment that targets one of five specific clusters of symptoms and their potential causes. The identification of the symptom clusters of focus began with patients. Through RECOVER study questionnaires, surveys, and discussions with people who have Long COVID, these were considered most burdensome, most important to address, and the priorities for trial protocols under development. The symptom clusters include:

• Viral persistence: When the COVID-19 virus stays in some people’s bodies.
• Autonomic dysfunction: Changes in ability to regulate heart rate, body temperature, breathing, digestion, and sensation.
• Sleep disturbances: Changes to sleep patterns or ability to sleep.
• Cognitive Dysfunction: Trouble thinking clearly or brain fog.
• Exercise intolerance/fatigue: Changes in a person’s activity and/or energy level.

The goal of these trials is to reduce the patient burden of illness due to Long COVID. The protocols for each trial were developed with patients and experts in these symptom areas. RECOVER researchers will also continue to engage patients, caregivers, and community representatives to better understand the impact of Long COVID on different groups.

As an important complement to the therapeutic trials, RECOVER continues to conduct several longitudinal observational cohort studies and related sub-studies, more than 40 pathobiology studies, evaluation of potential PASC biomarkers, and analyses of more than 60 million electronic health records. The understanding of symptoms that patients are experiencing and their underlying biologic causes – as emerging from these studies – is informing the selection of clinical endpoints and other aspects of clinical trial design.

More information about the clinical trials will be posted on recoverCOVID.org as it becomes available.