Researchers Are Studying Whether Paxlovid Can Treat Long COVID

Months after catching COVID-19 in December 2021, Lavanya Visvabharathy was still testing positive on antigen tests and suffering from symptoms including headaches and intense fatigue. So Visvabharathy, a research assistant professor of neurology at the Northwestern University Feinberg School of Medicine who has studied Long COVID since 2020, decided to conduct an experiment on herself.

She asked her doctor to prescribe her Paxlovid, an antiviral therapy that can treat COVID-19 by inhibiting replication of the virus that causes it. Paxlovid is meant to keep high-risk patients with acute COVID-19 from developing severe disease, but Visvabharathy thought it might have another use. Since she was still testing positive months after getting infected, Visvabharathy had a hunch—based on her research—that pieces of that virus were still in her system. She hoped Paxlovid could clear away those remnants of SARS-CoV-2 and ease her Long COVID symptoms.

The results of her experiment, which she published as a case report in Frontiers in Medicine in September, were mixed. A standard five-day course of Paxlovid initially eased her symptoms, and she began testing negative. But about a month after taking the antiviral, she started testing positive again, and her headaches came back. Visvabharathy, who has the autoimmune condition rheumatoid arthritis, temporarily stopped taking her biologic immunosuppressant to see if that would help clear the virus from her system—but when she did, her symptoms worsened and she developed intense brain fog for the first time. When she resumed taking her arthritis drug, the brain fog went away and her other symptoms improved.

Today, after enduring about nine months of Long COVID symptoms, Visvabharathy is finally free of them. But did Paxlovid play a role in her recovery? That’s the million-dollar question.

Read More: You Could Have Long COVID and Not Even Know It

Researchers don’t fully understand why some people develop long-lasting symptoms after a case of COVID-19, but one of the leading theories is that remnants of the virus linger in some people’s bodies, causing lasting issues ranging from extreme fatigue to chronic pain and neurological problems. If that’s the case, it’s logical to think—as Visvabharathy did—that an antiviral like Paxlovid could wipe out those stubborn fragments and clear up symptoms.

There’s already some evidence that people who take Paxlovid shortly after getting infected have lower odds of developing Long COVID. One study posted online in November, which has yet to be peer-reviewed, compared people at risk of severe COVID-19 who took Paxlovid within five days of testing positive with COVID-19 patients of similar risk profiles who did not take the drug. Those who took Paxlovid were about 26% less likely to report Long COVID symptoms 90 days later, the researchers found.

People who survive severe cases of COVID-19 are at increased risk of developing Long COVID, so it makes sense that a drug that lessens the disease’s severity would also shrink the risk of long-term complications. Whether it can reverse lingering symptoms among people who already have them, however, is a separate question—and one to which patients and advocates from the Long COVID community demand an answer.

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Until recently, research on Paxlovid as a treatment for Long COVID was limited to small case studies like Visvabharathy’s. (For the record, Visvabharathy does not recommend that other Long COVID patients follow in her footsteps by DIYing treatment; she recommends consulting a doctor first.) Another case report, published in the journal Pathogens and Immunity in June, found that three patients reported improvements in their post-COVID symptoms after taking Paxlovid anywhere from several weeks to more than two years after their symptoms began. The person who took Paxlovid after two years of Long COVID symptoms did so after getting reinfected and saw “substantial improvement,” according to the report.

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Dr. Upinder Singh, a professor of infectious disease at Stanford Medicine, calls such results “titillating,” but says larger studies are needed to make any firm conclusions about Paxlovid’s role in treating Long COVID. Singh’s research team is recruiting 200 people with moderate or severe Long COVID symptoms, some of whom will receive a placebo and some of whom will be treated with Paxlovid for 15 days—the longest amount of time the drug has been proven to be safe to take. Both groups will then be tracked for four months to measure changes in their symptoms over time, Singh explains. Her group has already begun enrolling patients, but they don’t have results to share yet.

A research team at Duke University will also study Paxlovid’s potential role as a Long COVID therapy through the National Institutes of Health’s RECOVER trial, a wide-ranging initiative to better understand Long COVID. Duke’s research team aims to enroll 1,700 people and compare outcomes among those who take Paxlovid for 15 days versus a placebo.

If large studies show that people’s symptoms improve after taking Paxlovid, it will not only point to a promising treatment option, but also add support to the idea that Long COVID is caused by pieces of the virus lingering in the body, Singh says—a potentially important step on the road to understanding COVID-19’s long-term effects.

“As a physician, I want a solution to give to my patients,” Singh says. “As a scientist, I just want an answer.”