Researchers Are Testing Paxlovid as a Treatment for Long COVID

Several clinical trials around the country are enrolling people with long COVID to see if a multi-week course of the antiviral drug Paxlovid might be effective against the condition. 

Paxlovid, made by Pfizer, was authorized to treat COVID-19 in December 2021, and has since proven quite effective. A study published in the journal Clinical Infectious Diseases in February, for example, found that compared with COVID vaccination alone, Paxlovid was more effective in preventing severe disease and death in older adults, immunocompromised individuals, and people with underlying cardiac and neurologic conditions. 

Now, researchers want to see if the drug has any benefit for long COVID.

“One theory behind what is causing long COVID is that in some people, the virus has never left their body,” Harlan Krumholz, MD, a professor of medicine at the Yale School of Medicine and co-lead investigator on a Paxlovid trial at Yale, told Verywell. “The hope is that giving Paxlovid for longer than the five days—the amount of time the drug is typically given to treat COVID-19—can deactivate the virus.”

One in 13 U.S. adults have long COVID, according to the Centers for Disease Control and Prevention (CDC). While many people get COVID-19 and then recover fully, others develop lingering symptoms—some for a year or longer—which can include fatigue, cognitive and memory issues, shortness of breath, and tremors. 

There is no current cure nor very effective treatments for the condition, which is why clinical trials are so important.

“Clinical trials to test effective treatments and interventions are a core component of the whole-of-government response to long COVID,” said Admiral Rachel L. Levine, MD, Assistant Secretary for Health, Department of Health and Human Services in a statement about clinical trials funded by NIH. “Coupled with adequate supports and services, access to clinical care and up-to-date information on what we know about long COVID, we can work toward relief for individuals and families impacted most.”

How Paxlovid Long COVID Trials Will Work

Researchers from the Yale clinical trial will administer a 15-day regimen of Paxlovid to participants with long COVID. Other long COVID clinical trials provide Paxlovid for as long as 25 days. By collecting blood and saliva samples before and after the trial, researchers will be able to examine immune system responses to the medication.

Krumholz said there may only be a small subset of people who benefit, but the study is important to potentially determine exactly those people may be.

Because the known side effects of Paxlovid are fairly mild—including a metallic taste and upset stomach—it’s considered a safe candidate to test for long COVID.

“I’m not minimizing those effects, but we know what to expect when people take Paxlovid,” Krumholz said.

Because Paxlovid can interact with many medications, including statins and blood thinners, the Yale study is excluding anyone with a potential for a drug interaction.

While some COVID patients may be able to avoid or manage interactions by temporarily forgoing one of their medications over the course of the standard 5-day treatment, that may not be possible for the 15- or 25-day courses being explored for long COVID treatment.

Jason Gallagher, PharmD, a professor of pharmacology at the Temple University School of Pharmacy, told Verywell other antivirals are in development now that may have even fewer interactions with medications. If Paxlovid is shown to have benefit against long COVID, those antivirals could be tested as long COVID treatment options for those who can’t take Paxlovid. 

Other Long COVID Trials Underway

Yale, Duke, and Stanford, along with NIH-sponsored centers like UTHealth Houston, are among the academic centers offering Paxlovid trials for long COVID.

In addition to the Paxlovid trials, current NIH-sponsored long COVID trials include: 

1. RECOVER-NEURO: This will look at interventions for cognitive dysfunction related to long COVID (brain fog, memory problems, difficulty thinking clearly, etc.). Interventions include a web-based brain training program to improve cognitive function, a web-based goal management training program to improve executive function, and a device used for home-based current stimulation. The latter may help brain activity and blood flow.
2. RECOVER-SLEEP: This will test interventions for altered sleep patterns after having COVID-19. Two drugs will be compared to a placebo in a trial for excessive daytime sleepiness (hypersomnia).
3. RECOVER-AUTONOMIC: This will examine ways to treat symptoms associated with problems in the autonomic nervous system, which is responsible for functions like breathing, digestion, and heart rate. Trials will focus on people with postural orthostatic tachycardia syndrome (POTS) and increased heart rate.

While it’s still too early to know how well any of the treatments now being tested will work against long COVID, clinical trials are the best way to try out options that are not yet available.

The information in this article is current as of the date listed, which means newer information may be available when you read this. For the most recent updates on COVID-19, visit our coronavirus news page.