Paxlovid Improved Long Covid Symptoms in Some Patients, Researchers Report

Can Paxlovid treat long Covid? A new report suggests it might help some patients, but which patients might benefit remains unclear.

The report, published Monday in the journal Communications Medicine, describes the cases of 13 long Covid patients who took extended courses of the antiviral drug. Results were decidedly mixed: Nine patients reported some improvement, but only five said it lasted. Four reported no improvement at all.

Perhaps more than anything, the report underscores that nearly five years after the pandemic began, there is still little known about what can help the millions of people with long Covid. While some people improve on their own or with various therapies and medications, no treatment has yet been shown to be widely successful.

“People with long Covid are eager for treatments that can help,” said Alison Cohen, an epidemiologist at the University of California, San Francisco, who is an author of the new report and has long Covid herself. “There’s been a lot of research, but it continues to be slow going.”

Paxlovid, made by Pfizer, is considered a tantalizing prospect because it can prevent severe illness during active Covid infections and because patients who take the five-day course during the infection have been less likely to develop long Covid later.

In addition, a theory that some long Covid cases may be caused by remnants of virus in the body suggests that an antiviral like Paxlovid might vanquish those symptoms by extinguishing lingering virus.

Last year, the first randomized trial of Paxlovid for long Covid showed no benefit. Conducted at Stanford, it involved 155 patients who took the drug or a placebo for 15 days. While taking Paxlovid for that long was found to be safe, it didn’t help patients much: Ten weeks later, the placebo and Paxlovid groups showed no significant difference in severity of long Covid symptoms.

Dr. Upinder Singh, an infectious disease specialist and a leader of that trial, said its results and the new report primarily generated “more questions to answer”: Could Paxlovid help if taken for longer than 15 days or paired with other medications? Does its effect vary by types of symptoms or by when symptoms started?

“It’s very possible that within long Covid, there’s different disease types,” said Dr. Singh, now head of internal medicine at the University of Iowa. Maybe Paxlovid or other antivirals would help patients who could be clearly determined to have lingering virus in their bodies, she said.

Akiko Iwasaki, an immunologist at Yale University, said scientists shouldn’t “throw in the towel” on the possibility of antivirals for long Covid.

“If you look in the aggregate, you don’t see a difference between the placebo group, but these case reports demonstrate there are people who truly benefit, so we need to home in on those people,” said Dr. Iwasaki, who is leading another randomized trial of Paxlovid, the results of which have yet to be published.

She said important next steps would be identifying biological markers in people whose long Covid symptoms improved with Paxlovid and seeing whether other antivirals help different patients.

The new report was not a clinical trial, but a collection of self-reports from 13 long Covid patients around the country who had tried extended courses of Paxlovid. It is the first published case series of such patients, according to the authors, who include Dr. Michael Peluso, an infectious disease physician at U.C.S.F., and members of the Patient-Led Research Collaborative, a group of researchers who also have long Covid.

The experiences of the patients were too varied to yield a consistent trajectory, but the variety may provide clues for larger studies, the authors said.

The patients, ranging in age from 25 to 55, were infected between March 2020 and December 2022. They experienced one or more of a range of symptoms, including fatigue; gastrointestinal problems; cognitive problems like brain fog; muscle pain; irregular heart rate; and a condition called post-exertional malaise, in which physical or mental exertion causes setbacks.

As with the Stanford trial, most patients in the new report had been vaccinated by the time they took Paxlovid. Their Paxlovid courses ranged from 7.5 days to 30 days. Most tried it to find relief from their persistent long-Covid symptoms; two patients with long Covid received extended courses of Paxlovid when they were reinfected with the virus.

Most patients were also taking other medications or supplements, making it difficult to determine the drug’s specific effect, Dr. Cohen said. Still, some said Paxlovid helped them significantly.

Kate Leslie, 46, a social worker in Boulder, Colo., said she was healthy and athletic before her coronavirus infection in March 2022. Six weeks later, she said, she felt as if she’d had a concussion, struggling to think clearly and find words.

She developed postural orthostatic tachycardia syndrome, with symptoms including erratic heart rate and blood pressure and occasional fainting. A longtime Ultimate Frisbee player and coach, she began experiencing profound fatigue and could barely lift her arms.

“It was like concrete blocks are on your body,” she said. “I couldn’t get out of bed. My husband had to wash my hair and dry it and dress me.”

After an antiviral she was prescribed for a flu infection, Tamiflu, ended up easing some of her long Covid symptoms, Ms. Leslie wondered whether Covid-related antivirals might help even more, she said. In February 2023, she found a doctor to prescribe a 15-day course of Paxlovid.

Afterward, “I could feel my body getting restabilized,” she said, adding, “I started to get my energy back.”

About six months later, she obtained another 15-day course, which helped again, she said. She estimates she can now function at about 85 percent of her pre-Covid level.

Ms. Leslie said, however, that a couple of her medical issues worsened after Paxlovid, including an immune system condition that has caused allergies. Three other patients also reported bothersome issues after taking Paxlovid, including tingling and gastrointestinal discomfort.

Among those who didn’t perceive any benefit from the drug was Julia Moore Vogel. Dr. Vogel, 39, a senior program director at Scripps Research, was a long-distance runner before being infected with the coronavirus in July 2020. Now she uses a wheelchair and is largely housebound, she said.

She and her daughter recently moved across the country, from California, to live with her parents in Schaghticoke, N.Y. “I got to the point where we were like, I either need to stop working or we need more help at home,” she said.

Dr. Vogel, whose symptoms include fatigue, post-exertional malaise and migraines, took a 10-day course of Paxlovid in April 2023. “It just had no impact for me at all,” she said.

These days, she manages by carefully budgeting her energy, trying to leave the house no more than once a week. Migraine medications provided some relief, she said, but other than that, “I’ve tried many things, and basically nothing has really helped me improve.”

Dr. Cohen said the report strengthens the theory that long Covid has many different causes and treatments.

“A really important question is who may benefit from taking an extended course of Paxlovid and why,” she said, “and if it benefits some symptoms, which symptoms does it benefit?”