Paxlovid does not significantly reduce COVID-19 hospitalization or mortality among vaccinated older adults, according to new research led by UCLA. This study challenges the assumption that Paxlovid’s effectiveness in reducing hospitalizations and deaths in unvaccinated adults also applies to those who are fully immunized.
Pfizer’s 2022 clinical trial showed reduced COVID-19 hospitalization rates among unvaccinated middle-aged adults. However, a subsequent 2024 clinical trial found no significant reduction in vaccinated middle-aged adults. Given that most older Americans have received two or more doses of the vaccine, Paxlovid’s effectiveness on this demographic has remained an important unanswered question.
Dr. John Mafi, an associate professor-in-residence of medicine at UCLA and lead author of the study, explained why their research is crucial: “Since advanced age is one of the strongest predictors for severe COVID-19 outcomes, it’s vital to understand if Pfizer’s findings apply to older vaccinated individuals.” He added that their study effectively refutes the notion that Paxlovid significantly reduces hospitalization rates in fully immunized seniors. While they cannot rule out a small reduction, Mafi pointed out that any potential effect is at least four times weaker than originally reported by Pfizer.
These findings are significant because they impact decisions about Paxlovid’s use and pricing. Dr. Katherine Kahn, the senior author of the study, emphasized: “Since our research found no meaningful reductions in hospitalization or death rates among vaccinated older adults, there is an urgent need for further randomized clinical trials to examine Paxlovid’s effectiveness in higher-risk populations.” These subgroups might include frail individuals or those with compromised immune systems.
To evaluate the impact of Paxlovid on health outcomes, researchers took advantage of a natural experiment in Ontario, Canada. Starting April 1 and ending November 30, 2022, Ontario implemented an age-restrictive policy to access Paxlovid for symptomatic COVID-19 patients aged 70 or older unless they were immunocompromised or had other risks factors.
Data from several linked health databases in Ontario allowed researchers to compare outcomes of individuals just below and above the age threshold, ensuring their similarity except for exposure to Paxlovid. Their analysis involved 1.6 million highly vaccinated seniors aged around 70 years old.
Surprisingly, restricting access based on age increased prescription rates by about 118% at the cutoff point without significantly impacting hospitalization or mortality outcomes among these individuals.
This policy-driven restriction created a rare natural experiment that researchers could analyze to assess Paxlovid’s impact effectively avoiding unobserved confounding. Study co-author Sitaram Vangala explained: “In observational studies, factors influencing the use of treatments can also influence health risks, leading to incorrect conclusions about treatment efficacy.” However, by making access somewhat randomized around age 70 due to policy restrictions, this study mitigates these biases.
Nevertheless, researchers noted limitations. They lacked individual patient-level data such as symptoms, timing of previous vaccinations, receipt of Paxlovid medication adherence. Additional authors include Manying Cui and Artem Romanov from UCLA and Drs. Moira Kapral and Peter Wu from the University of Toronto with whom Dr. Wu is also affiliated with ICES.
This study was funded by the Commonwealth Fund and a National Institute on Aging award (K76AG064392-01A1). It was supported by ICES, which receives an annual grant from both the Ontario Ministry of Health (MOH) and the Ministry of Long-Term Care (MLTC).
