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As Covid cases rise, what to know about Paxlovid

The antiviral pills can reduce risk of hospitalization or death.
Mary Ann Neilsen holds her last Paxlovid pills while recovering from Covid-19 in Santa Barbara, Calif.
Mary Ann Neilsen holds her last Paxlovid pills while recovering from Covid-19 in Santa Barbara, Calif., on Jan. 6.Alex Welsh / The New York Times/Redux file

Covid cases and hospitalizations have risen again. Some Americans are anxious about possibly getting very sick from the infection. Paxlovid antiviral pills remain an option for mitigating the risk. But what do we know about how well the treatment works, and who stands to benefit?

Paxlovid lowers the amount of virus in the body. Research has shown that it is associated with a reduced risk of hospitalization or death — but only for those who are already at higher risk of severe illness from Covid because they are older or have underlying health conditions. Plus, there are potential downsides: Paxlovid can clash with many medications and it can cause some side effects, including a particularly weird one. 

If you are thinking about taking Paxlovid, here are things to consider:

How Paxlovid works

The prescription medication must be started within five days of the onset of Covid symptoms. By lowering the amount of coronavirus in the blood early in the course of infection, it is meant to keep symptoms from getting worse.

Three pills are taken twice a day for five days. The doses include:

  • Two pills of nirmatrelvir, an antiviral that blocks coronavirus replication.
  • One pill of ritonavir, a drug that impedes the liver’s effort to metabolize nirmatrelvir. This leaves more of the drug in the body.

Who would benefit from Paxlovid?

“Anyone who is high risk for developing complications should consider taking Paxlovid,” said Dr. Sarju Ganatra, a cardiologist at Lahey Hospital and Medical Center in Burlington, Massachusetts. “That is what is consistent with clinical trials and all the other studies as well.”

The strongest evidence backing Paxlovid’s effectiveness concerns an increasingly small group: unvaccinated adults at high risk of progressing to severe Covid. This includes people who are age 60 or older or have health conditions such as cancer, heart disease, diabetes or obesity. 

A 2022 trial found that among these higher-risk adults, Paxlovid significantly lowered their rate of hospitalization or death by nearly 90%. 

A new study from researchers at the Cleveland Clinic looked at high-risk people who took Paxlovid between April 2022 and February 2023. The research, published Thursday in JAMA Network Open, found that the antiviral was associated with a 37% lower likelihood of hospitalization or death within 90 days and an 84% lower chance when looking only at death within 90 days. 

It’s unclear what, if any, substantial benefit Paxlovid has for people who aren’t at substantial risk of getting very sick from Covid.

Retired Toronto residents Bruce Woodrow, 71, and Marianne Moershel, 76, are at higher risk of Covid hospitalization because of their age. But they’re both vaccinated and don’t have any high-risk medical conditions.

When the married couple tested positive one day after the other in the spring of 2022, Woodrow took Paxlovid, but Moershel decided she didn’t feel well enough to go to the doctor for a prescription.

“Her symptoms and my symptoms, other than being a day apart, pretty much ran the same course,” said Woodrow. “Neither one of us can look back and say that I had any obvious benefit from taking it, but no downside.”

Paxlovid and long Covid 

A spring 2022 study of veterans with at least one risk factor for severe Covid found that three months after taking Paxlovid, they had a 26% lower rate of various symptoms that are considered signs of long Covid compared with untreated vets. According to the study, which was published in March 2023, for every 1,000 people treated with Paxlovid, there were 23 fewer who had evidence of long Covid.

The treatment was tied to a lower risk of these long-term symptoms, regardless of whether the vets were vaccinated or had had Covid before. 

Dr. Lao-Tzu Allan-Blitz, a resident internist at Brigham and Women’s Hospital in Boston, said, “There’s a lot more research that needs to be done” regarding long Covid prevention. The condition remains “an enigma,” he said.

Michael Vagnini is a 38-year-old chemist living in Midland, Michigan. He’s vaccinated against Covid, healthy and physically active, with a particular zeal for rock climbing. A number of Vagnini’s friends have suffered from ongoing symptoms after Covid infection. So he took Paxlovid when he got Covid in November 2022, hoping the treatment might protect him from long Covid. 

“I wasn’t super concerned about severe disease,” Vagnini said. “But I was concerned about a long recovery or lingering symptoms.” After grappling with fatigue and an occasional racing heart beat for a couple of months, he recovered fully. 

Woodrow wonders if his decision to take Paxlovid might still be benefiting his health. “It’s possible that had I not taken it, maybe I would have some long Covid issues,” he said. “But there’s no way of knowing that.”

Researchers, meanwhile, are conducting studies of Paxlovid in children and immunocompromised people, and in those who follow the regimen for up to 25 days as a treatment for long Covid.

What are side effects from taking Paxlovid? 

Most notably, Paxlovid can produce a rather strange, bitter, metallic taste in the mouth. It can also cause diarrhea. The metallic taste goes away after finishing the five-day regimen.

After taking three courses of Paxlovid — twice while receiving platinum-based chemotherapy for cancer, which is itself notorious for producing a dreadful metallic taste in the mouth — this reporter found the best way to mitigate the gross taste was to suck on sour candies, especially Green Apple Blow Pops. Peppermint tea also helps.

How Paxlovid interacts with other medications

The drug ritonavir, included in Paxlovid, can affect not just the nirmatrelvir component but also the drug levels of many other medications. This includes some statins, blood thinners, immunosuppressants and antidepressants. It’s very important that people who are considering taking Paxlovid alert both their doctor and pharmacist to all the other medications and supplements they are taking. It might be possible to adjust the dose of a medication or temporarily stop taking it to allow the safe use of Paxlovid.

Peter Anderson, a professor of pharmaceutical sciences at the University of Colorado Anschutz Medical Campus, noted that since Paxlovid was approved, experts have developed a revised list of notable drugs that may clash with ritonavir and published it on the National Institutes of Health website.

Who shouldn’t take Paxlovid

Paxlovid is not recommended for people with severe kidney disease. Caution is advised for people with liver disease or abnormal liver enzyme levels. The prescribing doctor may ask to see results of routine blood tests in your recent medical records to determine if you have any kidney or liver health issues.

The fast-mutating coronavirus doesn’t seem to have reduced Paxlovid’s effectiveness. Nevertheless, Dr. Jeremy Faust, an instructor at Harvard Medical School, warned that doctors should still avoid overprescribing a treatment that only offers a clear, substantial benefit to a small segment of the population.

“Anytime you have a treatment that has no benefit or very, very low benefit, all that remains are risks, known and unknown,” Faust said. He said that whenever doctors prescribe an antibiotic or an antiviral like Paxlovid, there’s always the chance of prompting the emergence of drug-resistant strains of the infection.

Can symptoms rebound?

Covid symptoms are known to sometimes rebound a number of days after people finish taking Paxlovid. Researchers have found that the Covid rebound rate is comparable in people who took Paxlovid and those who didn’t. It could be that people who take Paxlovid are more likely to report rebounding symptoms, giving the impression that it’s more common among them.

The good news is that Covid rebounds typically resolve themselves well on their own and aren’t apparently tied to a higher risk of severe illness.

What does Paxlovid cost?

Out of a stockpile of 24 million Paxlovid treatment packs the federal government purchased to distribute for free, there are still about 8 million courses left. 

Once that supply runs out, insurers will determine coverage and may require that people pay out-of-pocket costs. They also might require doctors to submit prior authorization requests for prescriptions for certain patients or deny some people coverage outright. 

Medicaid must cover Paxlovid through September 2024. People with Medicare, including Medicare Advantage plans, should expect coverage of the treatment but may be subjected to cost sharing.

CORRECTION (Sept. 25, 2:00 p.m. ET): An earlier version of this article misstated whether a spring 2022 study of veterans had been peer reviewed. It was published in a peer-reviewed journal in March.