COVID Antiviral Paxlovid Provides “No Significant Benefit” to Vaccinated Seniors

Paxlovid, the antiviral drug that became the go-to treatment for SARS-CoV-2 infections during the pandemic, did not reduce hospitalizations or death in older adults who had gotten COVID-19 shots, according to a new study published in the Journal of the American Medical Association (JAMA) last month. Researchers who tested the COVID treatment Paxlovid (nirmatrelvir-ritonavir) on vaccinated and unvaccinated people, found that the widely-used antiviral drug helped prevent hospitalizations in people who had not been vaccinated against COVID; but for people who had already been vaccinated, it offered no significant benefit.^{1 2}

A 2022 Canadian health policy restricted Paxlovid prescriptions to symptomatic adults around age 70, prioritizing those at higher risk of severe COVID complications. This policy enabled researchers to compare outcomes between older adults who took the antiviral and those who did not. Analyzing this Canadian data from approximately 1.5 million people, the study found no significant difference in hospitalization or death rates between the two groups. “Our main finding was that among vaccinated older adults, Paxlovid showed no statistically significant reduction in COVID hospitalizations or on mortality,” says John Mafi, MD, MPH, the study’s lead author.³

Paxlovid’s High Cost vs. Low Impact: What the Data Shows for the Vaccinated

These findings stand in stark contrast to Pfizer’s 2022 clinical trial results, which claimed Paxlovid reduced COVID hospitalizations and deaths by 89 percent compared to a placebo. However, Pfizer’s study primarily included unvaccinated, high-risk, middle-aged adults. The landscape of COVID risk has since shifted, raising questions about Paxlovid’s real-world effectiveness in vaccinated older adults, the group most likely to be prescribed the drug now.³

“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,” Mafi said in an interview. “That’s what is being used to justify its perceived effectiveness—and its list price at $1,650 per treatment course.” Mafi’s findings indicate that Paxlovid’s benefits are approximately four times less than what Pfizer originally reported. ³

Study author Katherine Kahn, MD said:

Since the study found no significant effect on COVID-19 hospitalizations and deaths among vaccinated older adults, our findings underscore the urgent need for further randomized-clinical trials investigating Paxlovid’s effects in higher-risk populations, such as older subgroups who are frail or immunosuppressed.¹

Pfizer, who said they could not comment on a study in which they did not participate, said they “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.” ³

Pfizer’s Warns Paxlovid Risks Can Be ‘Severe, Life-Threatening, or Fatal’

There is little information about risks of giving Paxlovid to at-risk seniors who have already gotten COVID shots. The risks of taking Paxlovid are higher for older adults due to its potential to interact with many common medications seniors take, including those for blood pressure, cholesterol, blood thinners, and certain antidepressants. These interactions can increase the risk of severe and potentially fatal side effects, making the risk-to-benefit profile more questionable, especially since the drug does not provide meaningful protection against severe COVID, hospitalization, or death in vaccinated individuals.

On Pfizer’s Paxlovid website, the manufacturer warns that drug interactions can be severe, life-threatening, or fatal, and urges providers to “Consider the benefit of treatment in reducing hospitalization and death, and whether the risk of potential drug-drug interactions for an individual patient can be appropriately managed.”⁴

“We are not saying that Paxlovid is useless,” Dr. Mafi said. “What this research is saying is that its effectiveness in older groups who are most vulnerable to COVID, but who are vaccinated, is far lower than what the earlier evidence from unvaccinated groups showed.”³

1 in 5 Paxlovid Users Experience COVID Rebound Infections: 2023 Study

Even before the latest concerns about Paxlovid’s efficacy in vaccinated individuals, the drug faced scrutiny over a 2023 study that found users were significantly more likely to experience COVID reinfections compared to those who never took the drug. Published in the Annals of Internal Medicine, the study reported that 1 in 5 Paxlovid users experienced rebound infections, raising further questions about its long-term effectiveness. Pfizer’s response was a copy-paste of its usual defense: “We remain very confident in Paxlovid’s clinical effectiveness at preventing severe outcomes from COVID-19 in patients at increased risk.”^{5 6}

Paxlovid received full approval from the U.S. Food and Drug Administration (FDA) in May 2022 for the treatment of mild-to-moderate COVID in adults at high risk of severe illness, hospitalization, or death. The U.S. Centers for Disease Control and Prevention (CDC) still recommends the drug for individuals over age 12 who are at higher risk for COVID complications. To date, many Paxlovid users reported incomplete recovery or testing positive again after initially testing negative following the five-day treatment course.⁷

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