The US National Institutes of Health is launching four clinical trials to test the safety and effectiveness of potential long Covid treatments, with seven more to begin in the next few months.
The trials follow more than two years of criticism from patient activists and some researchers, who say the nation’s largest sponsor of biomedical research has moved at snail’s pace in trying to find treatments for people facing lingering symptoms after coronavirus infection.
The Washington Post reports that the trials, part of the nearly $1.2bn RECOVER project studying symptoms lasting months after an initial coronavirus infection, will focus on four areas of treatment:
- Reducing viral persistence
- Alleviating brain fog, memory loss and other cognitive problems
- Reducing excessive sleepiness and sleep disturbances
- Treating problems that involve the autonomic nervous system, which includes heart rate, breathing and the digestive system.
A fifth treatment area, expected to focus on exercise intolerance and fatigue, remains under development, with officials awaiting further input from patients and scientific experts.
The first of the trials, which will test a longer regimen of the antiviral medication Paxlovid on people with viral persistence, has already started, and doctors have found in some cases that the virus lasts in patients for as long as 280 days after infection.
The Paxlovid trial will include 900 participants split into three groups: one receiving the full Paxlovid regimen – which includes nirmatrelvir and ritonavir – for 25 days, and two other groups receiving more limited treatments.
The other trials will have 100 to 300 participants each.
The trial focusing on brain fog and other cognitive problems includes several potential treatments. Those include a web-based programme designed to train the brain called BrainHQ, a goal management training programme, and a non-invasive device that provides electrical stimulation of the brain to help cerebral activity and blood flow.
One trial examining excessive sleepiness will compare two wakefulness drugs, potentially modafinil and solriamfetol, with a placebo. A second trial focused on patients who have trouble falling or staying asleep will test treatments designed to improve sleep quality.
NIH acting director Lawrence Tabak called the trials, which will receive funding until they are completed, “a significant milestone”.
“We’re moving a little in the right direction, but I was underwhelmed,” said Ezekiel Emanuel, an oncologist and bioethicist at the University of Pennsylvania, who has previously criticised NIH for not starting the clinical trials sooner.
He said Stanford and Yale universities already have already started Paxlovid trials, and added that the NIH trials should have been less focused on managing symptoms than on treating the disease.
Long covid is a diffuse constellation of more than 200 symptoms that are a ripple effect of the coronavirus.
Researchers “don’t understand whether the symptoms are related to one another”, said Upinder Singh, a professor of infectious disease at Stanford Medicine and co-principal investigator for a Paxlovid clinical trial. “We don’t fully understand why some patients get brain fog and other patients have sleep disturbances.”
While most people who contract Covid recover within days, others have symptoms that can linger for weeks, months or longer, sometimes with debilitating effects.
There is no agreed-upon definition of long covid, and attempts by researchers to assess its prevalence have relied on different lists of symptoms and different time frames after patients came down with acute Covid.
“The answer depends on how you define the problem,” said Walter Koroshetz, director of NIH’s National Institute of Neurological Disorders and Stroke, adding that some studies have suggested 5% to 10% of people in the US infected with the coronavirus go on to have long Covid symptoms, with the frequency higher in earlier versions of the virus than more recent variants.
So far, an estimated 77.5% of Americans have been infected with the coronavirus.
An analysis of nearly 5m US patients who had the coronavirus, based on a collaboration between The Washington Post and electronic health records company Epic, found that about 7% of those patients sought care for long Covid symptoms within six months of their initial infection.
At the time, about 200m people in America were known to have had the coronavirus, so that percentage translated into about 15m with long Covid symptoms. The Post-Epic analysis also found that people with certain other health conditions were more likely to develop these symptoms.
The RECOVER initiative grew out of Congress’s decision to allot more than $1bn to NIH to understand long Covid and to try to find ways to treat it. The initiative began early in 2021.
Tabak said so far, it has involved 24 000 patients who have participated through medical exams or surveys, and analyses of 60m electronic health records.
Emanuel said the 24 000 participants NIH has recruited is well below its established goal of 40 000 by the end of 2022.
Until now, the research sponsored by RECOVER has been observational – meaning it has sought to describe long Covid.
In contrast, clinical trials test possible interventions, finding out whether treatments are safe and effective.
See more from MedicalBrief archives:
Long Covid's impact on life quality worse than some cancers – UK study
UK analysis confirms risk factors for long Covid
Impaired lung function in 25% of long Covid patients – Dutch study
More than half of patients suffer long Covid symptoms – SA study