BETHESDA, Md. – The National Institutes of Health announced Monday that it is launching four clinical trials to test the safety and effectiveness of potential long covid treatments, with seven more to begin in coming months – efforts to alleviate the suffering of millions of patients that critics say are long overdue.
The launch of these clinical trials comes after more than two years of criticism by long covid patient activists and some researchers, who have contended that the nation’s largest sponsor of biomedical research has moved sluggishly in trying to find treatments for those facing lingering symptoms after coronavirus infection. The critics also expressed frustration that early parts of NIH’s special funding to study long covid have not yielded the expected fruits or recruited enough patients.
The trials, part of the nearly $1.2 billion RECOVER project studying symptoms that endure 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, which is expected to focus on exercise intolerance and fatigue, remains under development, and officials said they are waiting for more input from patients and scientific experts.
The first of the clinical trials, which will test a longer regimen of the antiviral medication Paxlovid on people with viral persistence, is underway. Doctors have found in some cases that the virus persists 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 are slated to 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 program designed to train the brain called BrainHQ, a goal management training program and a noninvasive 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 A. Tabak called the trials, which will receive funding until they are completed, “a significant milestone” and said they will be carried out at institutions with a record of attracting diverse participants.
“We’re moving a little in the right direction, but I was underwhelmed,” said Ezekiel J. Emanuel, an oncologist and bioethicist at the University of Pennsylvania, who has previously criticized NIH for not starting the clinical trials sooner. He said Stanford and Yale universities already have already gotten Paxlovid trials up and running, and added that the NIH trials should have been less focused on managing symptoms than on treating the disease.
“I don’t know that it’s going to cost lives,” Emanuel said, referring to what he described as the slow pace of NIH research into long covid. “It’s going to cost suffering.”
Hannah Davis, co-founder of the Patient-Led Collaborative, a group of patients also involved with research, said more than 50 medications are waiting to enter clinical trials, and “the patient community is concerned that [NIH] is only trying one or two” in the trials announced Monday.
Long covid is a diffuse constellation of more than 200 symptoms that are a ripple effect of the coronavirus, the worst public health crisis in a century.
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 suffer from 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 kind of depends on how you define the problem,” Walter Koroshetz, director of NIH’s National Institute of Neurological Disorders and Stroke, said during a news conference Monday.
Koroshetz said some studies have suggested that 5 percent to 10 percent of people in the United States 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 percent of Americans have been infected with the coronavirus.
An analysis of nearly 5 million U.S. patients who had the coronavirus, based on a collaboration between The Washington Post and electronic health records company Epic, found that about 7 percent of those patients sought care for long covid symptoms within six months of their initial infection. At the time, about 200 million people in the United States were known to have had the coronavirus, so that percentage translated into about 15 million with long covid symptoms. The Post-Epic analysis also found that people with certain other health conditions were more likely to develop long covid symptoms.
The RECOVER initiative grew out of Congress’s decision to allot more than $1 billion to NIH to understand the mysterious phenomenon of long covid and to try to find ways to treat it. The initiative began early in 2021. Tabak said during Monday’s briefing that, so far, it has involved 24,000 patients who have participated through medical exams or surveys and analyses of 60 million electronic health records.
“Long covid is preventing people from living their normal lives,” Tabak said, “and solutions can’t come quickly enough.”
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.
Patient advocates and some researchers have been impatient for NIH to begin the clinical trials, arguing they should have begun long before now.
“It’s been close to three years,” since RECOVER began, “and it really shouldn’t take that long,” said Ziyad Al-Aly, director of the Clinical Epidemiology Center at Washington University School of Medicine in St. Louis and a major long covid researcher.
“They don’t have the sense of urgency they needed to have,” said Al-Aly, whose own research uses Department of Veterans Affairs data and does not rely on NIH funding. “There is a lot of time lost. I want RECOVER to succeed, but I also want them to have a sense of urgency around it.”
In the meantime, he said that researchers at a few universities have found other sources of support to study potential treatments for long covid, including from Pfizer, a major pharmaceutical manufacturer.
NIH released no details about the seven additional trials that are expected to start within a few months.
(c) 2023, The Washington Post · Mark Johnson, Amy Goldstein