Q&A: More Americans could benefit from Paxlovid for COVID infection

One of the best tools for preventing severe complications from COVID infection is the prescription antiviral drug Paxlovid. But not nearly as many people who could benefit from it are being prescribed it, says Amesh Adalja, MD, FIDSA, a senior scholar at the Johns Hopkins Center for Health Security who specializes in infectious diseases and pandemic preparedness.

Adalja says that both patients and providers need to be better informed about the benefits of Paxlovid and other antivirals like it.

Paxlovid is extremely effective when taken within five days of symptom onset. In clinical trials, it reduced the risk of hospitalization and death by almost 90% in unvaccinated people. "It's a tremendous tool that's completely underutilized," says Adalja.

How does Paxlovid work?

"Paxlovid is a class of antiviral drug called a protease inhibitor," explains Adalja. It prevents the SARS-CoV-2 virus, which causes COVID-19 infection, from replicating in the body. At a molecular level, "Paxlovid works by disrupting the protein cutting process of SARS-CoV-2," he explains. "It blocks an essential step in the virus's life cycle."

Who is Paxlovid recommended for?

Paxlovid is designed to benefit people at high risk of severe illness who are at least 12 years old and weigh at least 88 pounds. Its purpose is to prevent hospitalization and death, not to decrease symptoms or to help you recover faster, although patients who take it may experience one or both of those benefits.

Who is considered 'high risk' for severe COVID-19 illness, hospitalization, or death?

According to the CDC, people are more likely to experience severe COVID-19 illness if they are over 50 years old, unvaccinated or not up to date on COVID-19 vaccination, immunocompromised, or have certain medical conditions.

"Any medical condition such as diabetes, hypertension, heart disease, any lung condition like asthma or COPD, would be considered high risk," says Adalja. Other common risk factors include being overweight, obese, or pregnant. "The majority of Americans probably have some high risk factor," he says. "A lot of people would benefit from Paxlovid just based on their weight status."

Is Paxlovid being prescribed as often as it should be?

"Antiviral prescribing is underutilized in the United States," Adalja says. "There are many people with high risk conditions who are not being prescribed Paxlovid [or] an alternative antiviral like molnupiravir."

This may be due to misconceptions, including by physicians, about who should take Paxlovid. "Some might say, 'we're gonna wait, you don't look that bad,' which is a complete misunderstanding of how the drug works," says Adalja. Paxlovid is designed to be given early on to prevent symptoms from becoming more severe. The decision to prescribe someone Paxlovid for a COVID infection should be made based on a patient's risk factors for severe disease, regardless of symptom severity.

The same problem exists with antivirals for influenza. "Many high-risk people do not get prescribed an influenza antiviral despite evidence that they benefit," says Adalja. Doctors may be more comfortable prescribing Tamiflu because they're more familiar with it, but Tamiflu is also underutilized.

How can we improve patient education around Paxlovid?

One reason not enough people know about Paxlovid is that it was under emergency use authorization for quite a while, which prohibited Pfizer from advertising the drug. Instead, they relied on doctors to bring it up. Starting in 2023, Pfizer began promoting Paxlovid to consumers through social media ads and commercials. "People complain about direct-to-patient advertising, but it works," says Adalja. "When patients know a drug by name, they're more likely to ask their doctor about it."

It's important that patients feel empowered to ask their health care providers about any and all treatment options, he says. "Patients should be asking their doctors, 'Would I benefit from Paxlovid?' 'Would I benefit from Tamiflu?' 'Do I really need this antibiotic?'"

Are there alternatives to Paxlovid?

Currently there are two other treatments to prevent hospitalization from COVID: Molnupiravir, which is another oral antiviral taken at home, and remdesivir, which is a three-day daily IV infusion given in a health care facility.

Molnupiravir is a good alternative for individuals taking medications that may interact with Paxlovid, says Adalja.

Are there any downsides to taking Paxlovid if you don't have a risk factor for severe illness?

"It's always a risk-benefit ratio," says Adalja. If you don't have risk factors for severe disease and you take Paxlovid, you may experience the side effects—an altered sense of taste, possible gastrointestinal upset, and possible rebound symptoms—without the benefits the medication is designed to provide.

Can Paxlovid help prevent long COVID?

While some early studies signaled that Paxlovid might reduce a person's chance of developing long COVID, more recent research indicates that it does not. This includes a study published in January 2024 that found no connection between Paxlovid treatment and long COVID symptoms in vaccinated, non-hospitalized individuals.

There are newer antivirals not yet available in the U.S. that have a stronger signal for preventing long COVID, says Adalja.

Do concerns about COVID rebound outweigh the benefits of taking Paxlovid?

No. "[Rebound] doesn't happen to everyone—studies show maybe 1 in 5 people who take Paxlovid experience rebound symptoms," says Adalja. "But even those who do get rebound—with or without taking Paxlovid— don't do badly." For people who take Paxlovid and experience rebound, symptoms are generally mild to moderate and they do not require hospitalization.

"COVID rebound was really made out to be a bigger and more common issue than it is, due to news stories about people like President Biden experiencing it," he explains. The risk of rebound—whether or not it can be definitively linked to Paxlovid—shouldn't preclude someone who's high risk from taking Paxlovid, and it definitely shouldn't preclude doctors from prescribing it.

[COVID rebound is the return of symptoms after someone initially recovers from COVID. The order of events generally looks like this: A person is infected with COVID and feels symptomatic; their symptoms subside over the course of the infection; they may even test negative for COVID on a home antigen test; a few days later, their symptoms return, and they may test positive again on a home antigen test.]

How much does Paxlovid cost?

Through the end of 2023, Paxlovid was free for Americans, with the costs covered by the federal government. An agreement between Pfizer and the U.S. Department of Health and Human Services will ensure Paxlovid remains free through the end of 2024 for patients who are insured through Medicare and Medicaid or uninsured. It will continue to be free through 2028 for individuals who are uninsured and underinsured. Paxlovid is covered by many private insurance plans (costs vary by plan).

How can I get a prescription for Paxlovid?

If you test positive for COVID, talk to your doctor as soon as possible about any factors that put you at greater risk for severe illness and whether you would benefit from taking Paxlovid.

If you don't have a health care provider, the nationwide Test to Treat program helps people access low- or no-cost treatments quickly. Anyone who tests positive for COVID (or flu) can also access free telehealth care and treatment through the Home Test to Treat program.