Paxlovid Is Beneficial for High-Risk Acute COVID-19 Patients, Study Suggests

[Originally published: July 8, 2024. Updated: July 9, 2024]

A study published in The New England Journal of Medicine offers evidence supporting the benefits of Paxlovid in COVID-19 patients who are at high risk for severe or prolonged disease, particularly older adults and those who are immunocompromised. Paxlovid, the brand name for a combination of nirmatrelvir (a drug that inhibits viral replication) and ritonavir (a similar drug that is also used to treat HIV and can serve as a booster for nirmatrelvir), has been one of the primary weapons in the battle against COVID-19. The drug works by inhibiting a key COVID replication protein known as a protease, which in turn disrupts the ability of SARS-CoV-2 to replicate.

However, there has been limited data highlighting the efficacy of Paxlovid in treating COVID-19 in non-high risk individuals and, as one would expect, this lack of utility holds true in studies conducted on Paxlovid’s effect on Long COVID (discussed later in this post). While there may be some benefit to taking Paxlovid for patients who are at high risk of hospitalization and death from COVID-19 (including those who are immunocompromised and older adults), that may not be true for patients who are not considered high risk, a new study suggests.

“We believe COVID-19 will be with us for some time, if not indefinitely,” says Jennifer Hammond, PhD, head of infectious disease development at Pfizer and one of the study’s lead authors. “We intend to provide significant medical contributions across the COVID-19 disease spectrum, from prevention with vaccines to therapeutics that help patients avoid or address severe outcomes of disease.”

Does Paxlovid affect COVID-19 recovery time?

The latest study, conducted by researchers at Pfizer (the pharmaceutical company that developed Paxlovid), involved 1,288 participants. One group received the drug and another took a placebo.

The experimental group took about 12 days, on average, to recover from COVID-19 symptoms. The placebo group recovered in approximately 13 days. However, there was no statistical difference between the groups. In other words, the study found that Paxlovid does not definitively reduce recovery time in people with acute cases of COVID-19.

“This was a well-done study, but results were somewhat surprising in that Paxlovid did not show great benefit for low-risk patients,” says Scott Roberts, MD, assistant professor of infectious diseases at Yale School of Medicine, who was not involved in the research.

Does Paxlovid reduce hospitalizations?

The research also compared hospitalizations and death across both groups. Only 0.8% of those who took Paxlovid (regardless of vaccination status) were hospitalized or died compared to 1.6% of patients who received the placebo.

Among the small number who were hospitalized, none of the patients who received Paxlovid were admitted to the ICU. Meanwhile 30% of hospitalized patients who took a placebo ended up in the ICU.

When researchers looked only at high-risk individuals, 0.9% of the group taking Paxlovid were hospitalized, while 2.2% of the patients in the placebo group were hospitalized. Finally, patients taking Paxlovid recorded a lower number of medical visits compared to the placebo group.

These findings seem to indicate that Paxlovid, while not necessarily effective at reducing the duration of COVID-19 symptoms, may lessen the number of hospitalizations related to COVID-19 in high-risk patients. Furthermore, the reduced number of visits for medical attention in the treatment groups suggests that the illness itself may have been less severe.

Meanwhile, the researchers did not observe any difference in the number of adverse events, such as diarrhea, in patients taking the drug versus patients who were in the placebo group. However, of the minority of participants (12.7%) who had adverse events linked to Paxlovid treatment, a metallic taste was most frequently cited.

Future studies will explore Paxlovid as a treatment for Long COVID

When it comes to Long COVID, there are questions whether Paxlovid is effective. One study, the STOP-PASC Trial, showed that Paxlovid did not improve symptoms. Another study of Paxlovid for Long COVID, led by Yale School of Medicine’s Harlan Krumholz, MD, Harold H. Hines, Jr. Professor of Medicine (Cardiology), and Akiko Iwasaki, PhD, Sterling Professor of Immunobiology, will report results soon.

Long COVID likely has multiple drivers, and there may be a subset of patients whose symptoms are indeed caused by SARS-CoV-2 persistence. The Yale study, which employed a groundbreaking decentralized design, will test the effect of Paxlovid overall and study in more detail who is most likely to benefit from antiviral treatment. To do so, the team collected biospecimens from the participants before, during, and after receiving a 15-day course of Paxlovid or placebo. They will measure many biological markers to assess predictors of response and identify possible targets for future diagnostic and therapeutic strategies.

“This study is exceptionally novel—from its decentralized design to the application of deep immune phenotyping, a method to discover how immune function relates to disease and recovery,” said Krumholz.

“While at this time Paxlovid has not been licensed or approved for use as a treatment or prophylactic for Long COVID, we are collaborating on multiple investigator-sponsored studies, including with Yale, to evaluate Paxlovid for potential use in patients with Long COVID,” says Hammond. “By investing in this collaborative approach, we aim to help accelerate and streamline research efforts that can advance our collective knowledge about Long COVID.”

Fabrizio Darby is an MD candidate at Yale School of Medicine.

The last word by Lisa Sanders, MD

This is an important study on the use of Paxlovid to reduce symptoms in adults at risk for some of the complications of acute COVID-19. Turns out that for these patients, whose increased risk is primarily due to smoking, obesity, or hypertension, Paxlovid may reduce the severity of the illness but not the duration. However, a thoughtful editorial, published in the same issue of The New England Journal of Medicine, suggests that the study “enrolled only a small percentage of persons at the highest risk for progression—older persons, those who are immunocompromised, and those with serious coexisting conditions (e.g., heart or lung disease)—who constitute most of the patients hospitalized with COVID-19.”

This segment of patients deserve a closer look at how Paxlovid may alter their COVID-19 infection. However, before those outside these highest risk groups give up on Paxlovid, one issue not touched on by this study was whether the drug changes an individual’s risk of developing Long COVID—for infection survivors the greatest complication of acute COVID-19. There are studies that suggest that it can reduce that risk. One study published last year reviewed the charts of nearly 300,000 veterans with at least one risk factor for progression to severe disease and found that treatment with Paxlovid reduced the likelihood of their developing Long COVID.

I would encourage those who are concerned about Long COVID to continue to consider using Paxlovid when infected with SARS-Co-V2 until we have good evidence that it doesn’t change outcomes beyond death and hospitalizations—important but thankfully less common these days—and that includes Long COVID patients.

Read other installments of Long COVID Dispatches here.

If you’d like to share your experience with Long COVID for possible use in a future post (under a pseudonym), write to us at: LongCovidDispatches@yale.edu

Information provided in Yale Medicine content is for general informational purposes only. It should never be used as a substitute for medical advice from your doctor or other qualified clinician. Always seek the individual advice of your health care provider for any questions you have regarding a medical condition.