RECOVER-SLEEP Trial Investigates Lingering Effects of Long COVID

Innovations in Pulmonology, Critical Care & Sleep Medicine | Spring 2025

University Hospitals Cleveland Medical Center is Northeast Ohio’s only site participating in the national RECOVER-SLEEP clinical trial, sponsored by Duke University. The study of the range and prevalence of sleep disturbances following COVID infection is an arm of the RECOVER initiative established by the National Institutes of Health (NIH) that is bringing together experts and community members to better understand how to identify and treat people struggling with long-haul symptoms.

Kingman Strohl, MD

“RECOVER-SLEEP focuses on identifying and entering those with long COVID into randomized controlled trials to treat symptomatic waketime sleepiness and/or insomnia,” says Kingman Strohl, MD, sleep medicine specialist and Director of the Sleep Medicine Fellowship at University Hospitals Cleveland Medical Center. “It complements the program we have with James Reynolds, PhD, in respiratory and anesthesia, to discover relevant markers or other alternative therapies to help patients with this stubborn condition.”

Researchers are investigating potential treatments for sleep disturbances related to long COVID, including difficulty falling and staying asleep, daytime sleepiness or irregular sleep-wake schedules. Study interventions include:

• Wakefulness-promoting the use of the investigational drug Modafinil/Solriamfetol for the potential treatment of hypersomnia
• Melatonin + light therapy for the potential treatment of complex sleep disturbance

Building on University Hospitals Long COVID Clinic

Before the selection as a RECOVER-SLEEP site, experts at University Hospitals (UH) were already working to address the sequelae of long COVID under the leadership of UH pulmonologist David Rosenberg, MD.

The clinic was funded through a UH Department of Medicine TEAMS grant prompted by the UH Primary Care Institute. “Providers were seeing patients who were reporting symptoms of long COVID not usually encountered by primary care,” Dr. Strohl says. “There wasn’t a wealth of medical literature on how to treat patients experiencing new fatigue, anosmia, orthostatic hypotension and cognitive difficulties long after the acute COVID infection, and the long COVID clinic provided a central hub to focus our attention.”

Dr. Strohl explains that the clinic has helped connect patients to resources throughout the health system. “Patients with long-haul symptoms have a stubborn condition, but this broader interest in the post-COVID experience has helped us guide individuals to the appropriate subspecialties, including endocrinology, rheumatology, cardiology and pulmonology, to receive additional help,” he says. “Although long-term effects of viral infection are not completely new to medicine, past outbreaks were not as common as with acute COVID, where 10 percent or more of people experience lingering — even disabling — symptoms.”

Continued Surveillance

Researchers at UH continue to track 287 primary care patients referred to its Long COVID Clinic. Their work has produced abstracts and an upcoming publication suggesting problems like preexisting anxiety and major depression — and not sleep disorders — as potential predisposing factors. “Data show that brain fog, sleep apnea or other sleep disorders are not strongly associated with the presence or severity of fatigue,” Dr. Strohl says. “There is a group of patients [~20 percent] who meet all of the 2015 Centers for Disease Control and Prevention criteria for myalgic encephalitis/chronic fatigue syndrome, a condition found with other viral infections.” These findings suggest that there are patients with a spectrum of sub-types of fatigue. Whether post-COVID fatigue has a unique signature remains to be seen. 

Working Toward a Solution

Standardized questionnaires have been helpful tools in identifying patients with long COVID. “Fatigue has always been the predominant symptom, accompanied by difficulty with memory, finding words, forgetfulness, dizziness and brain fog,” Dr. Strohl says. “These and other persisting complaints have left individuals experiencing significant social and professional impairment.”

The mission of the NIH RECOVER program and its participating physician-scientists is to employ a large-scale, multidisciplinary approach to define the risk factors of long COVID, understand how symptoms change over time and identify possible treatments in a concentrated effort to bring relief to patients. 

For more information, contact Dr. Strohl at Kingman.Strohl@UHhospitals.org.

Contributing Expert:
Kingman Strohl, MD
Director, Sleep Medicine Fellowship
University Hospitals Cleveland Medical Center
Professor of Medicine and Physiology & Biophysics
Case Western Reserve University School of Medicine