rewrite this title Paxlovid May Not Significantly Benefit Vaccinated Seniors, Study Says

Most of us are pretty adept by now at managing COVID-19, with an armor of past infections, vaccinations, self-tests, and antiviral medications like Paxlovid.

In the latest study, however, researchers report that taking Paxlovid may not provide as much benefit as doctors originally thought—particularly for older people who are vaccinated.

In a research letter published in JAMA on Feb. 20, Dr. John Mafi, associate professor of medicine at the David Geffen School of Medicine at UCLA, and his colleagues used Canadian data to explore what happened when people took Paxlovid. A Canadian health policy in 2022 allowed prescriptions for Paxlovid only for symptomatic people around age 70 in order to reserve the medication for those who needed it most. Older people are at higher risk of developing complications from COVID-19. The policy allowed the scientists to compare people in this age group who took Paxlovid to those who didn’t.

Among the nearly 1.5 million people they studied, those who received prescriptions for the drug did not have significantly different rates of being hospitalized or dying from COVID-19 than those who didn’t get the drug. Most of the people studied were vaccinated.

“Our main finding was that among vaccinated older adults, Paxlovid showed no statistically significant reduction in COVID-19 hospitalizations or on mortality,” says Mafi, the study’s lead author.

That’s very different from the results that Paxlovid’s maker, Pfizer, first reported in 2022. In that study, Pfizer found that the drug reduced hospitalizations and deaths from COVID-19 by 89% compared to people receiving placebo. But the group they studied was mostly middle-aged and unvaccinated, which is a much different population than exists today. “Yet that 2022 Pfizer study was and continues to be used to support the assumption that the benefits of Paxlovid in unvaccinated adults also apply to vaccinated adults,” says Mafi. “That’s what is being used to justify its perceived effectiveness—and its list price at $1,650 per treatment course.”

In a statement, Pfizer said it could not comment on a study in which it did not participate, but that the company “remain[s] confident in Paxlovid’s clinical effectiveness at preventing severe outcomes, including hospitalization and death, from COVID-19 in patients at high risk of severe illness.”

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Paxlovid is meant to help those at high risk of developing complications from COVID-19, including the elderly, people with compromised immune systems, and those with multiple underlying health conditions. That remains a primary criterion for prescribing the medication, which is now available for anyone age 12 or older and who is at high risk of severe disease.

Still, Mafi says there aren’t strong data on how Paxlovid affects the disease course in people who are vaccinated. His findings suggest that the benefits are about four times smaller than those reported by Pfizer.

“We are not saying that Paxlovid is useless,” says Mafi. “What this research is saying is that its effectiveness in older groups who are most vulnerable to COVID-19, but who are vaccinated, is far lower than what the earlier evidence from unvaccinated groups showed.”

More research is needed, but doctors can consider this new information when deciding whether to recommend a patient take Paxlovid. Other important factors include a person’s medical history, the medication’s risk of relatively mild side effects, and Paxlovid rebound, in which people taking Paxlovid may test positive again after testing negative.

Dr. Katherine Kahn, distinguished professor of medicine at UCLA and the study’s senior author, says that she will discuss the latest results with her patients, and “for generally health people, I’m not encouraging or discouraging [Paxlovid] if they meet the criteria for taking it,” she says. “But for people with higher risk of morbidity or mortality, we’re more likely to say we might consider [Paxlovid] at this time, even though we don’t know 100% if you will benefit.”

The new study raises questions for future research. It doesn’t take into account, for instance, how past infections might cause the body to respond to Paxlovid. Mafi and Kahn say that they were also not able to delve more deeply into participants’ vaccination history—how many and which doses they received—or confirm whether they took Paxlovid within five days of their first symptoms, when the drug is most effective. But they are planning to access the individual-level data and do a more in-depth analysis of other factors that may impact how effective the drug is at reducing hospitalizations and deaths.

“One of the conclusions of this study is the recommendation for more studies, of both older individuals and those who are vaccinated, of the effectiveness of Paxlovid,” says Kahn.