Paxlovid does not reduce long COVID risk in vaccinated individuals, study finds

A team of researchers from UC San Francisco has found that Paxlovid (Nirmatrelvir-ritonavir) did not reduce the risk of developing long COVID for vaccinated, non-hospitalized individuals during their first COVID-19 infection. They also found a higher proportion of individuals with acute symptoms rebound and test-positivity than previously reported.

The study appears Jan. 4, 2024, in the Journal of Medical Virology.

Paxlovid treatment for acute COVID-19 has been shown to be effective for high-risk unvaccinated individuals. But the effect of the treatment on long COVID risk, including whether it protects vaccinated people from getting long COVID, has been less clear.

The research team selected a group of vaccinated people from the UCSF Covid-19 Citizen Science study who had reported their first positive test for COVID-19 between March and August of 2022 and who were not hospitalized. Some of these participants reported taking oral Paxlovid treatment during the acute phase of their COVID infection, while others did not. In December of 2022, they were invited to answer a follow-up survey with questions about long COVID, COVID rebound symptoms and how long they continued to test positive.

Researchers found the two groups were similar. About 16% of those treated with Paxlovid had long COVID symptoms compared to 14% of those who were not treated with the medication. Commonly reported symptoms included fatigue, shortness of breath, confusion, headache, and altered taste and smell. Those who took Paxlovid and then went on to develop long COVID reported as many long COVID symptoms as those who were not treated with Paxlovid. A small percentage of people developed severe long COVID, and those who had received Paxlovid were just as likely to have severe Long COVID symptoms as those who did not.

Among individuals who experienced symptomatic improvement during Paxlovid treatment, 21% reported rebound symptoms. And among those with rebound symptoms, 10.8% reported one or more Long COVID symptom compared to 8.3% without rebound symptoms. For participants who repeated antigen testing after testing negative and completing treatment, 25.7% reported rebound test positivity. In total, 26.1% reported rebound symptoms or test positivity.

We found a higher proportion with clinical rebound than previously reported but did not identify an effect of post-treatment rebound on long COVID symptoms. Our finding that Paxlovid treatment during acute infection is not associated with lower odds of long COVID surprised us, but it is consistent with two other rigorously conducted studies finding no difference in post-COVID conditions between 4 and 6 months after infection."

Matthew Durstenfeld, MD, MAS, cardiologist and UCSF assistant professor of Medicine

The authors note that the study may have been impacted by limitations arising from its observational nature with researchers relying on patient self-reporting of treatment and Long COVID symptoms.