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Multiple Trials of Long COVID Treatments Advancing, NIH Says

Editor’s note: Find the latest long COVID news and guidance in Medscape’s Long COVID Resource Center.

Enrollment is opening for four clinical trials that will evaluate new treatments for long COVID, the National Institutes of Health (NIH) announced at a media briefing today. Additional clinical trials to test at least seven more treatments are expected to launch in the coming months, officials said.

The trials are part of the NIH’s research effort known as the Researching COVID to Enhance Recovery (RECOVER) Initiative. In December 2020, Congress approved $1.15 billion for the NIH to research and test treatments for long COVID. The new clinical trials are in phase 2 and will test safety and effectiveness.

“The condition affects nearly all body systems and presents with more than 200 symptoms,” said Walter J. Koroshetz, MD, director of the NIH National Institute of Neurological Disorders and Stroke and co-lead of the RECOVER Initiative. How many people have long COVID is uncertain, he told attendees at the briefing. “The answer kind of depends on how you define the problem and also what variant caused it. The incidence was higher in Delta.” Some estimates suggest that 5% to 10% of those infected develop long COVID. “I don’t think we have solid numbers, as it’s a moving target,” Koroshetz said.

Patients with long COVID have grown increasingly frustrated at the lack of effective treatments. Some doctors have turned to off-label use of some drugs to treat them.

The four trials include the following:

  • RECOVER-VITAL will focus on a treatment for viral persistence, which can occur if the virus lingers and causes the immune system to not work properly. One treatment will test a longer dose regimen of the antiviral Paxlovid (nirmatrelvir and ritonavir), which is currently used to treat mild to moderate COVID to halt progression to severe COVID.

  • RECOVER-NEURO will target treatments for symptoms such as brain fog, memory problems, and attention challenges. Among the potential treatments are a program called BrainHQ, which provides web-based training, and PASC-Cognitive Recovery (post-acute sequelae of COVID), a web-based program developed by Mount Sinaia Health System in New York. Also being tested is a direct current stimulation program to improve brain activity.

  • RECOVER-SLEEP will evaluate treatments for sleep problems, which can include daytime sleepiness and other problems. According to Koroshetz, melatonin, light therapy, and an educational coaching system are among the treatments that will be studied.

  • RECOVER-AUTONOMIC will evaluate treatments to address symptoms linked with problems of the autonomic nervous system. The first trial will target postural orthostatic tachycardia syndrome (POTS), which can include irregular heartbeat, fatigue, and dizziness. A treatment for immune disease and a drug currently used to treat chronic heart failure will be tested.


The first trial, on viral persistence, has launched, said Kanecia Zimmerman, MD, a principal investigator at the Duke Clinical Research Institute, the clinical trials data coordinating center for the trials. “We are actively working to launch the second on cognitive dysfunction.” The sleep and autonomic trials will launch in the coming months, she said. Also planned is a trial to study exercise intolerance, which is reported by many with long COVID.

Information on how to join long COVID trials is available here.

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