A study aims to determine whether longer-term Paxlovid can mitigate long COVID

For several years now, Gabriel San Emeterio has been living with HIV as well as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)―a condition marked by chronic and debilitating pain and both mental and physical fatigue. I’ve watched up close how San Emeterio has had to carefully pace out their work to avoid overexerting themself. But even when they’ve thoughtfully planned their day, they often experience “post-exertional malaise,” or PEM.

After being diagnosed with COVID last June, San Emeterio determined that they were experiencing long COVID, which has no real test, after realizing that their symptoms—chronic cognitive impairment called “brain fog,” exhaustion, pain, and irregular heartbeat or palpitations—overlapped with ME/CFS.

Patients and doctors alike think the same mechanism may underlie both long COVID and ME/CFS, such as persistent virus of some sort in the body that either directly causes symptoms or keeps the immune system in a state of chronic overaction (inflammation).

Because of this symptom similarity and because long COVID has been so widespread, it has brought attention to poorly understood and research-underfunded ME/CFS―whose patients have long complained that doctors don’t believe them and tell them it’s “all in their head.” For example, many people with ME/CFS are often told that they are depressed and need to be in therapy and/or go on antidepressants to alleviate their condition.

Now, in addition to their pre-existing ME/CFS symptoms, San Emeterio says that long COVID has added more intense energy crashes, nausea, daily headaches, and gastrointestinal discomfort. Back when they first tested positive for COVID, they took the common five-day course of Paxlovid―an antiviral drug that is supposed to keep COVID sufferers from progressing to severe illness, hospitalization, and death. It may well have done that for them, but the short course didn’t seem to do anything to prevent San Emeterio from developing long COVID.

“I had my pacing techniques down to deal with my ME/CFS, but long COVID has definitely worsened those symptoms and made them more unpredictable,” they say.

San Emeterio, who with fellow ME/CFS and long COVID survivor JD Davids runs the advocacy group Network for Long COVID Justice, is definitely not alone. Last year, the Centers for Disease Control and Prevention (CDC) reported that nearly one in five Americans who have had COVID still have long COVID—that’s 19% of all American adults who’ve had COVID! (Also, at least one study suggests that folks living with HIV face higher chances of developing long COVID.)

In late 2020, Congress responded to the wide emergence of long COVID by apportioning $1.15 billion to its study, mitigation, and possible cures. Exactly how that money is being used is a source of tension among long COVID patient advocates because the government is considering putting some of it toward studies that they and ME/CFS advocates say are counterproductive―such as studies on cognitive behavior therapy (CBT) or encouraging phased-in exercising, even though most patients of both conditions say that exercise exacerbates rather than mitigates their fatigue and other symptoms.

Advocates say that talk therapy may help patients cope with symptoms but also runs the risk of falling into the old, “You have a psychological problem,” line of thinking. Recently, almost 1,300 people signed a petition to the National Institutes of Health asking them not to use the $1.15 billion for those purposes―especially because Congress did not increase funding last year.

However, there is a study being funded by the NIH’s RECOVER initiative for long COVID that advocates support and are hopeful about. Though not yet open, the study aims to enroll 1,700 participants at sites nationwide this year to determine whether a 15-day course of Paxlovid―which is three times longer than the usual course taken for acute COVID―can mitigate or clear long COVID symptoms.

During the study, participants will be randomly assigned to two groups―with half given the 15-day course, while the other half will be placed on a placebo. The study will look for changes in three self-reported features of long COVID: brain fog, ME/CFS-like chronic fatigue and pain, and cardiovascular palpitations.

Steven Deeks, M.D.―who is not affiliated with this study―tells TheBody, “It’s possible that each of these features could have different mechanisms behind them, with the virus causing one feature and immune inflammation causing a different one.”

Deeks is a longtime University of California San Francisco HIV researcher who is also the co-director of LIINC, which is following a cohort of long COVID patients long term. (He was among the researchers on the study finding that people with HIV had a higher risk for long COVID.)

A similar though separate study at Stanford University in California―which is currently enrolling―is also researching treatment with Paxlovid for 15 days to reduce severe symptoms of long COVID.

Deeks acknowledges that exactly what drives long COVID remains unclear. “The top theory is that COVID virus persists indefinitely” in people with long COVID, he says, “replicating in tissues and causing local damage—either directly or, more likely, because it’s causing immune inflammation, which causes the tissue damage.” This is believed, he says, because pieces of COVID have been found in the bodies of people suffering from long COVID, especially those who were previously immunocompromised—and also, to a lesser extent, because some people with long COVID who’ve gone on an antiviral end up feeling better after.

Deeks says that LIINC also wants to set up a study to see if an injection of a monoclonal antibody can mitigate or cure long COVID; those who are interested can keep an eye out for that on the LIINC website.

Davids says he’s eager to see if both studies yield results. If they don’t, he explained, “Long COVID may need longer-term treatment—or even continuous treatment. We just don’t know yet.”

Regardless, it is important that the NIH spend its $1.15 billion budget wisely, he says. “We need to save resources for the most potentially pivotal studies leading to treatment breakthroughs on core [elements of long COVID] like viral persistence”—not, he says, into investigations of the efficacy of exercise and talk therapy, both of which have generally failed patients with the similar ME/CFS.

Deeks points out that existing research on long COVID was sparked from the same source as the research that eventually led to HIV breakthroughs: “a powerful group of community advocates pushing for change—including longtime HIV activists like JD Davids who understand how this game is played. That’s why we currently have the funding for long COVID that we do.”

By Tim Murphy