An immunomodulator being investigated by researchers at Vanderbilt University Medical Center holds promise in reversing the effects of long COVID (LC), a condition that impacts about 200 million people globally, 15 million in the U.S. alone.
Vanderbilt researchers are joined by over 40 investigators from five additional sites in conducting this federally-funded phase 3, multicenter, placebo-controlled trial to examine the effect of immunomodulation on long COVID. There are, as yet, no biomarkers identified that conclusively indicate the presence of long COVID and no available treatments.
The subject of the REVERSE-LC trial is baricitinib, a drug FDA-approved for rheumatoid arthritis and alopecia areata. Immunomodulators like baricitinib are considered promising in development of effective treatments for long COVID’s lingering symptoms.
“We’ve already shown that baricitinib saves lives in acute COVID-19, and it became the first immunomodulator with FDA approval for this indication,” said Wes Ely, M.D., M.P.H., co-director of the Vanderbilt Critical Illness, Brain Dysfunction and Survivorship Center and a principal investigator in the study. “Now it’s time to determine if it will help those suffering from long COVID.”
Other principal investigators are Vince Marconi, M.D., an infectious diseases specialist at Emory University in Atlanta, and Priscilla Hsue, M.D., a specialist in cardiovascular diseases at the University of California San Francisco. The study is funded by the NIH’s National Institute on Aging.
Defining Long COVID
Long COVID affects both children and adults across the spectrum of health, disability and socioeconomic status, regardless of age, sex, gender, race, or ethnicity.
Some ways it can manifest include shortness of breath, severe fatigue, post-exertional malaise, difficulty concentrating, memory changes, recurring headaches, dizziness or fast heart rate, sleep disturbances, and problems with taste or smell.
Long COVID can cause new conditions or exacerbate existing ones, including lung disease, cardiovascular disease and arrhythmia, cognitive impairment, myalgic encephalomyelitis/chronic fatigue syndrome, mast cell activation syndrome, diabetes, and other autoimmune disorders such as lupus, rheumatoid arthritis and ankylosing spondylitis.
“In long COVID, the person ends up with a chronic disease state. People look absolutely normal but they’re living in a nightmare and those around them can’t see it.”
The neurocognitive and functional impact of these conditions can include life-altering disability.
“Long COVID has joined the ranks of other acute illnesses caused by infection, where the person ends up with a chronic disease state,” Ely said. “It is a societal disaster. People look absolutely normal but they’re living in a nightmare and those around them don’t see it.”
In early 2024, Ely was an academic member of a committee tasked by the National Academies of Sciences, Engineering, and Medicine to develop an improved definition for long COVID.
The definition would reflect the needs of patients and caregivers, as well as the views and knowledge of public health and health care professionals, researchers, policy and advocacy professionals, payers, and healthcare business professionals.
“Because of long COVID’s far-reaching impact, we wanted to include a broad range of experts,” Ely said.
The resulting 2024 NASEM definition, published in the New England Journal of Medicine, describes long COVID is “an infection-associated chronic condition that occurs after SARS-CoV-2 infection and is present for at least 3 months as a continuous, relapsing and remitting, or progressive disease state that affects one or more organ systems.”
Trial Specifics
The REVERSE-LC trial will test the hypothesis that six months of baricitinib will improve neurocognitive and physical function in patients with long COVID symptoms.
The trial will enroll 550 patients aged 18 and older who have had thinking and memory problems for at least 6 months after a COVID-19 infection. Those enrolled will participate for one year, along with a matched group of control participants who will receive a placebo.
REVERSE-LC will evaluate the effects of baricitinib on motor control, executive function and memory, as well as exercise capacity, cardiorespiratory fitness, post-exertional malaise, mental health and quality of life.
“Long COVID turns on a harmful light switch that alters the immune system in a way that causes immense human suffering, and we need to know if we can safely turn off that switch.”
It will also look at the drug’s effects on autonomic function and biomarkers (blood, cerebrospinal fluid and MRI).
“Long COVID turns on a harmful light switch that alters the immune system in a way that causes immense human suffering, and we need to know if we can safely turn off that switch to help people find a pathway to recovery,” Ely said.
Patients and health care providers interested in participating in REVERSE-LC can learn more at the study’s website.
Update of an article by Nancy Humphrey that appeared in VUMC News.
