The study has limitations due to its design, which compiled data from a large Israeli health system rather than enrolling patients in a randomised study with a control group - the gold standard for medical research.
The findings reflect the changing nature of the pandemic, in which the vast majority of people already have some protection against the virus due to vaccination or prior infection. For younger adults, in particular, that greatly reduces their risks of severe Covid-19 complications. The Centers for Disease Control and Prevention recently estimated that 95 per cent of Americans 16 and older have acquired some level of immunity against the virus.
"Paxlovid will remain important for people at the highest risk of severe Covid-19, such as seniors and those with compromised immune systems," said Dr David Boulware, a University of Minnesota researcher and physician, who was not involved in the study. "But for the vast majority of Americans who are now eligible, this really doesn't have a lot of benefit."
A spokesman for Pfizer declined to comment on the results, which were published in the New England Journal of Medicine.
The US Food and Drug Administration authorised Paxlovid late last year for adults and children 12 and older who are considered high risk due to conditions like obesity, diabetes and heart disease. More than 42 per cent of US adults are considered obese, representing 138 million Americans, according to the CDC.
At the time of the FDA decision, there were no options for treating Covid-19 at home, and Paxlovid was considered critical to curbing hospitalizations and deaths during the pandemic's second winter surge. The drug's results were also far stronger than a competing pill from Merck.
The FDA made its decision based on a Pfizer study on high-risk patients who hadn't been vaccinated or treated for prior Covid-19 infection.
"Those people do exist but they're relatively rare because most people now have either gotten vaccinated or they've gotten infected," Boulware said.
Pfizer reported earlier this summer that a separate study of Paxlovid in healthy adults - vaccinated and unvaccinated - failed to show a significant benefit. Those results have not yet been published in a medical journal.
More than 3.9 million prescriptions for Paxlovid have been filled since the drug was authorised, according to federal records. A treatment course is three pills twice a day for five days.