Study Finds Paxlovid Treatment Does Not Reduce Risk of Long COVID

A team of researchers from UC San Francisco has found that Paxlovid did not reduce the risk of developing long COVID for vaccinated, non-hospitalized individuals during their first COVID-19 infection. They also found that a higher proportion of individuals than previously reported experience rebounds after taking Paxlovid. 

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. 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, 10.8% reported one or more long COVID symptoms. For those who did not rebound, 8.3% reported at least one long COVID symptom. 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,” said study first author Matthew Durstenfeld, MD, MAS, a cardiologist and UCSF assistant professor of Medicine. “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.”

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.

Authors: Other UCSF authors include Michael J. Peluso, Feng Lin, Noah D. Peyser, Carmen Isasi, Thomas W. Carton, Timothy J. Henrich, Steven G. Deeks, Jeffrey E. Olgin, Mark J. Pletcher, Alexis L. Beatty, Gregory M. Marcus, Priscilla Y. Hsue

Funding: This work (Eureka Research Platform) was supported by NIH/NIBIB 3U2CEB021881-05S1. The COVID-19 Citizen Science Study is supported by Patient-Centered Outcomes Research Institute (PCORI) contract COVID-2020C2-10761 and Bill and Melinda Gates Foundation contract INV-017206. Dr. Durstenfeld is supported by NIH/NHLBI grant K12HL143961.

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