Should You Take an Antiviral to Prevent Long COVID?

The only guaranteed way to prevent Long COVID is to avoid getting infected by SARS-CoV-2, the virus that causes COVID-19. Recently, however, researchers have found promising signs that certain drugs may reduce the risk of developing Long COVID if they’re taken shortly after infection.

Those studies are preliminary, but they raise an intriguing question: Should everyone who gets COVID-19 take medication in hopes of avoiding Long COVID?

Here’s what experts say.

Which drugs might prevent Long COVID?

Studies have recently highlighted two promising drugs: Paxlovid and metformin.

Paxlovid is an antiviral authorized to treat COVID-19 among people at high risk of severe disease, including elderly adults and people with underlying health conditions. Last year, researchers found that high-risk people who took Paxlovid within five days of testing positive for COVID-19 were 26% less likely to have Long COVID symptoms after 90 days, compared to people who weren’t treated. On Mar. 23, the same researchers published updated data in JAMA Internal Medicine. Among a larger group of high-risk people who were tracked for six months—more than 35,000 of whom took Paxlovid—the drug showed the same reduction in risk.

Metformin, meanwhile, is not a classic antiviral; it’s long been approved as a Type 2 diabetes treatment. But studies suggest that it may have antiviral properties, potentially limiting SARS-CoV-2’s ability to copy itself. In one recent study (which has not yet been peer-reviewed), metformin cut the risk of Long COVID by more than 40% among overweight or obese adults who took it when they had COVID-19, compared to those who didn’t take the drug.

I have COVID-19. Should I take an antiviral to prevent Long COVID?

It’s too soon to recommend that for the general population. Dr. Harlan Krumholz, a professor at the Yale School of Medicine who is studying Paxlovid as a potential treatment for Long COVID, says even the most promising study results need to be confirmed before they influence medical decisions.

“We zig and we zag on evidence all the time. To simply start telling everybody to start taking a medication” before there’s solid data is overzealous, he says.

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There’s still debate about what causes Long COVID, adds Stefan Sarafianos, a professor at Emory University who studies antivirals. Some experts think remnants of the virus linger in the body and cause long-lasting symptoms. If that’s true, it’s “intuitive” that an antiviral drug could help prevent that outcome—but, Sarafianos says, it’s not clear if that hypothesis is the right one. “Long COVID is a big mystery,” he says.

Despite the unknowns, certain patients may want to pursue Paxlovid prescriptions, says Dr. Ziyad Al-Aly, a clinical epidemiologist at the Washington University School of Medicine in St. Louis and co-author of the JAMA study on Paxlovid. For people at high risk of severe COVID-19, who already stand to benefit from Paxlovid, the possibility of preventing Long COVID is an added bonus, Al-Aly says.

But “in people who don’t have risk factors,” Al-Aly says, it’s basically “an evidence-free zone.”

Studies have shown that Paxlovid has minimal effect among lower-risk people up to 28 days after their illnesses began. Krumholz says it’s worth tracking the drug’s effects over a longer period of time, but as of now, there’s no strong data to suggest younger, healthy people should be taking it.

Metformin may be useful for a larger group of people, argues Dr. David Boulware, a professor at the University of Minnesota Medical School and co-author of the study on the drug’s potential ability to prevent Long COVID. Boulware and his colleagues studied adults ages 30 to 85 who were either overweight or obese. More than 70% of U.S. adults are either overweight or obese, so that includes a large swath of the population.

Boulware personally decided to take metformin when he caught the virus last summer. But, he says, it’s one thing for a physician to make a personal choice, or to recommend a drug for a specific patient based on their health profile, and another to make a sweeping recommendation for the whole population.

Dr. Anand Viswanathan, a clinical assistant professor at the NYU Grossman School of Medicine, agrees that it’s too soon to recommend metformin to the general public. The research “represents a good early signal,” he says. But “we need more studies to corroborate that data before I would vouch for mass use.”

That’s especially true, Krumholz says, because metformin isn’t a classic antiviral. He’d like more information on how it may work against SARS-CoV-2 before recommending it to patients for the prevention of Long COVID.

Is it risky to take Paxlovid or metformin to prevent Long COVID?

Both Paxlovid and metformin are safe, but they come with possible side effects including gastrointestinal issues, muscle pain, and unpleasant aftertastes, as well as rarer but more serious issues.

Plus, Paxlovid interacts with a number of common medications, Viswanathan says, meaning patients may have to pause their other treatments while they take it. That may be worthwhile for someone who could get seriously ill from untreated COVID-19, but it’s a harder sell for someone who may not even benefit from taking Paxlovid.

Widespread Paxlovid use could also theoretically raise the risk of antiviral resistance, Sarafianos says. Drug resistance happens when pathogens mutate enough to stop responding to the medications meant to tame them. Overuse or misuse of drugs (such as by missing doses or stopping treatment early) increases the chances of that happening.

Although resistance to Paxlovid is not currently a major concern, Sarafianos says it is possible—potentially more so if the drug is widely used, since some patients might not take Paxlovid properly because of its unpleasant aftertaste and side effects.

It’s “a numbers game,” Sarafianos says. “As more people take [a drug], the more possibilities there are to come up with a resistant strain.”

Viswanathan adds that there could be shortages if everyone with COVID-19 starts clamoring for these drugs, regardless of whether they really work. “These medications are a limited resource, they have side effects, and we should be prioritizing their use for the intended patient populations that would actually get the [proven] benefit,” Viswanathan says.

The situation may change in the future, as more research comes together. But for now, experts say, it’s best to use Paxlovid and metformin in the ways regulators have authorized them.