Paxlovid, the five-day antiviral treatment developed by Pfizer for COVID-19, may not effectively reduce the risk of COVID-related hospitalizations and all-cause deaths in vaccinated older adults, according to a recent study. While Paxlovid, which combines nirmatrelvir and ritonavir, has shown success in alleviating symptoms and decreasing hospitalizations and deaths among unvaccinated at-risk patients, its efficacy appears diminished in the vaccinated population.
The study, led by John N. Mafi, an associate professor of medicine at the David Geffen School of Medicine at UCLA, aimed to evaluate the benefits of Paxlovid for older vaccinated adults, particularly given that age is a significant predictor of severe COVID-19 outcomes. Published in JAMA last month, the research analyzed patient data from 2022 and discovered that Paxlovid did not lead to a noteworthy reduction in hospitalizations or overall mortality rates.
“We were surprised and disappointed,” Mafi remarked. “We concluded that it’s because it’s a highly vaccinated group, with 88 percent fully vaccinated.” This finding is crucial for informing patient discussions with healthcare providers about the potential benefits and costs associated with taking Paxlovid.
Mafi emphasized that the cost of Paxlovid, which is approximately $1,650 per treatment course, should be a factor in these conversations. Each treatment typically consists of 30 pills. A spokesperson for Pfizer reiterated the company’s confidence in Paxlovid’s effectiveness, especially in preventing severe outcomes in high-risk patients.
The study revealed that Paxlovid did not significantly lessen the risk of hospitalization or mortality among a cohort of mostly vaccinated adults aged 65 to 74 residing in Ontario in 2022. Mafi noted that, at best, Paxlovid reduced their hospitalization risk by a mere 1.3 percentage points—an effect four times weaker than that observed in Pfizer's clinical trials involving unvaccinated individuals.
Importantly, the researchers employed population-level data, and individual risk factors were not taken into account. Mafi suggested that certain high-risk individuals, such as frail or immunosuppressed patients, may still benefit from Paxlovid.
Researchers from UCLA and the University of Toronto scrutinized health data from over 1.6 million older adults aged 65 to 74 living in Ontario between April and November 2022. At that time, Paxlovid was available only to adults aged 70 and older, as well as to the immunocompromised and others with specific risk factors. This restriction allowed researchers to evaluate the medication’s effects on older adults near the age threshold.
Despite high vaccination rates among participants—almost 88 percent had received at least two doses of a coronavirus vaccine—the findings indicated that Paxlovid was not associated with a significant decrease in COVID-related hospitalizations or deaths.
Peter Wu, an associate professor of medicine at the University of Toronto and co-author of the study, stated, “If you are vaccinated without additional risk factors, I wouldn’t prescribe Paxlovid, and I probably wouldn’t take it if I was a patient.” This highlights the necessity of individualized patient assessments when considering Paxlovid.
Looking ahead, Wu noted the importance of further research to determine whether vaccinated older adults with immunocompromised conditions or other high-risk factors derive any benefits from the antiviral treatment.
While the study provided valuable insights, it relied on aggregate health data, lacking details such as the duration of patients’ symptoms, the timing of Paxlovid administration, and vaccination timelines. Additionally, it did not explore whether Paxlovid could shorten symptom duration or reduce the risk of long COVID. Ongoing trials at Yale School of Medicine and in the UK aim to investigate these aspects, though results are not yet available.
Anupam B. Jena, a professor of health-care policy at Harvard Medical School, described the study as a “good natural experiment.” However, he pointed out that some individuals prescribed Paxlovid may not have required it due to the severity of their symptoms, suggesting that its effectiveness could vary depending on individual health status.
Peter Chin-Hong, an infectious disease specialist at the University of California at San Francisco, who was not involved in the research, cautioned that the study’s findings might not apply to the most vulnerable population—adults aged 75 and older who have not received recent vaccinations.
The recent study raises important questions about the efficacy of Paxlovid in older vaccinated adults. As discussions about treatment options continue, it remains essential for patients and healthcare providers to weigh the potential benefits of Paxlovid against individual health factors and the associated costs.
