Use of nirmatrelvir-ritonavir (Paxlovid) in older adults with risk factors for severe disease was associated with a roughly 25% lower risk of a post-COVID condition (PCC), a retrospective study of Veterans Affairs data showed.

In the cohort of over 280,000 patients with a confirmed COVID case, 13% of those prescribed nirmatrelvir-ritonavir went on to develop a PCC over the following 6 months compared with 18% of those who were not prescribed the antiviral (relative risk [RR] 0.74, 95% CI 0.72-0.77), Ziyad Al-Aly, MD, of the VA St. Louis Health Care System in St. Louis, and colleagues reported.

And the nirmatrelvir-ritonavir group experienced a 47% lower risk for post-acute death (0.73% vs 1.38%; HR 0.53, 95% CI 0.46-0.61) and a 24% lower risk of post-acute hospitalization (5.82% vs 7.54%; HR 0.76, 95% CI 0.73-0.80), according to the findings in JAMA Internal Medicine.

“The totality of evidence suggests that improving the uptake and use of nirmatrelvir in the acute phase as a means of not only preventing progression to severe acute disease but also reducing the risk of post-acute adverse health outcomes may be beneficial,” the group wrote, adding that “the magnitude of risk reduction on the absolute scale is also substantial.”

Reductions in PCCs among the nirmatrelvir-ritonavir-treated patients were observed across all subgroups, including the unvaccinated, vaccinated, boosted, and people with a prior infection.

PCC, defined as the “persistence of symptoms beyond 90 days past the acute episode, also known as long COVID, is of great concern because of the large number of persons who become infected with SARS-CoV-2 and the frequency with which PCC occurs,” wrote Mitchell H. Katz, MD, of NYC Health and Hospitals in New York City, in an accompanying editorial, citing estimates ranging anywhere from 8% to 17%.

He noted that the study population was overwhelmingly made up of men, and that outcomes were based on ICD-10 codes, a potential source of confounding, especially if those who didn’t receive treatment with nirmatrelvir were more likely to seek healthcare.

“Also, unresolved is the connection between more serious symptoms with the acute episode and PCC,” said Katz. He pointed out that in a meta-analysis also published in JAMA Internal Medicine, patients who needed hospitalization during their acute COVID-19 infection had a significantly higher risk of PCC (OR 2.48, 95% CI 1.97-3.13), “so it is possible that some of the effect of nirmatrelvir on preventing PCC is by preventing serious sequelae during the initial infection.”

Still, Katz said, “until we have better data, the available evidence suggests that nirmatrelvir may prevent PCC.”

To evaluate the association of nirmatrelvir-ritonavir with PCCs, the researchers compared the health records of 35,717 patients who received the antiviral and 246,076 who did not.

All patients had a positive COVID-19 test between Jan. 3, 2022, and Dec. 31, 2022, and had to have survived at least 30 days from the day of their positive test for inclusion. Participants with liver disease, end-stage kidney disease, and/or a prescription that precluded them from receiving nirmatrelvir-ritonavir were excluded.

Participants were a mean 65.7 years old, 88% were men, three-fourths were white, and 20.5% were Black. Overall, 17% were unvaccinated, 21% had had two doses, and 58% were fully vaccinated with a booster. Prior COVID-19 infection was documented in 17% of the patients.

Limitations of the study included that the data were exclusively from the VA database, the cohort was mostly men, and it relied on filled prescriptions without a guarantee they were used.

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