New research led by UCLA has challenged the assumption that Paxlovid, a widely used antiviral treatment for COVID-19, significantly reduces hospitalizations and mortality among vaccinated older adults. The study, set to be published in the Journal of the American Medical Association (JAMA), reveals that Paxlovid’s effectiveness in this demographic is far weaker than previously thought.

Pfizer’s 2022 clinical trial initially showed that Paxlovid reduced COVID-19 hospitalizations in unvaccinated middle-aged adults. However, a subsequent 2024 clinical trial found no significant reduction in hospitalizations among vaccinated middle-aged adults. This disparity has left many questions unanswered, particularly for older Americans who have received multiple COVID-19 vaccines.

The recent study analyzed the impact of a natural experiment in Ontario, Canada, where Paxlovid was restricted to symptomatic, COVID-19-positive adults aged 70 and older, unless they were immunocompromised or had other risk factors. The researchers compared outcomes between adults just below and just above the age of 70, who were otherwise similar except for their exposure to Paxlovid. The findings indicate that the policy significantly increased Paxlovid prescriptions by 118% in the 70-year-old age group, but this did not translate into improved COVID-19-related hospitalization, all-cause hospitalization, or mortality outcomes.

“Since the strongest predictor of severe COVID-19 is advanced age, it has been crucial to obtain evidence on whether the results of the Pfizer trials generalized to older and vaccinated populations,” said Dr. John Mafi, a UCLA associate professor-in-residence.

Key Findings and Implications

The study effectively rules out the notion that Paxlovid causes large reductions in COVID-19 hospitalizations in vaccinated older adults. While a small reduction cannot be ruled out, the results suggest that Paxlovid’s potential effect on COVID-19 hospitalization among vaccinated older adults is at best four times weaker than the effect reported in Pfizer’s 2022 clinical trial.

“Our study effectively rules out the notion that Paxlovid causes large reductions in COVID-19 hospitalization in vaccinated older adults.”

The findings, to be published in the peer-reviewed Journal of the American Medical Association (JAMA) are important because Pfizer’s 2022 clinical trial continues to serve as the foundation of evidence supporting Paxlovid’s perceived effectiveness.”

Dr. John Mafi

These findings are particularly important for the U.S. healthcare system, where Pfizer’s 2022 clinical trial has been a cornerstone for Paxlovid’s list price of about $1,650 per treatment course and its widespread use. The study underscores the urgent need for further randomized clinical trials to investigate Paxlovid’s effects in higher-risk populations, such as older subgroups who are frail or immunosuppressed. Experts are now urging the FDA to reconsider its current recommendations for Paxlovid, especially in light of these new findings.

The researchers emphasized that the study’s design, which exploited a natural experiment, avoided the common pitfall of unobserved confounding. This was possible because Paxlovid access was effectively randomized for those close to the age 70 cutoff. “Because access to Paxlovid in this study was in effect randomized for those close to the age 70 cutoff, our results are unlikely to reflect unobserved confounding,” said study co-author Sitaram Vangala.

The importance of these findings is reinforced by the fact that, in Europe and the United Kingdom, similar results with Paxlovid have been found.

Practical Applications and Recommendations

The study has significant implications for healthcare providers and policymakers. Given the limited evidence of Paxlovid’s effectiveness in vaccinated older adults, healthcare providers may need to reconsider their treatment strategies.

Dr. Katherine Kahn, a distinguished professor of medicine in the general internal medicine division and the study’s senior author, highlighted the need for further research:

“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.”

Dr. Katherine Kahn

Speculation in Congress

Two senators have asked HHS officials questions relevant to this issue. This incident underscores the current state of the health community and the Zeitgeist.

Next Steps and Future Research

The study’s limitations, such as the lack of individual patient-level data regarding symptoms, timing of previous COVID-19 vaccinations, receipt of Paxlovid, and medication adherence, highlight the need for more comprehensive research. Future studies should aim to address these limitations and provide a more detailed understanding of Paxlovid’s effectiveness in various populations.

As the COVID-19 pandemic continues to evolve, it is crucial to stay informed about the latest research and scientific guidelines. The findings from this study serve as a reminder that our understanding of COVID-19 treatments is continually evolving, and ongoing research is essential to improve patient outcomes.