Paxlovid Found Not to Reduce Long COVID Risk

Drug Topics JournalDrug Topics January/February 2024
Volume 168
Issue 01

A new study found that 16.1% of patients treated with nirmatrelvir-ritonavir (Paxlovid) reported long COVID symptoms, compared to 14% of untreated patients.

Vaccinated patients treated with nirmatrelvir-ritonavir (Paxlovid) who were not hospitalized did not show a lower prevalence of long COVID symptoms 90 days after infection, according to new research published in the Journal of Medical Virology.1

Long COVID occurs in around 10% of patients with a COVID-19 infection, with around 65 million people suffering from the illness globally. More than 200 symptoms have been associated with long COVID, including chest pain, nausea, fatigue, and cognitive impairment.2 Previous studies have shown that vaccination reduces the risk of long COVID, but can’t eliminate the risk entirely.

“Among high-risk, unvaccinated, nonhospitalized individuals with symptomatic COVID-19, nirmatrelvir, a novel orally-administered SARS-CoV-2 main protease inhibitor in combination with ritonavir reduces viral load and progression to severe disease,” the authors wrote. “Anecdotal reports suggest that nirmatrelvir may improve Long COVID symptoms. However, whether treatment with nirmatrelvir during acute infection reduces post-COVID conditions is uncertain…”

Investigators from the University of California San Francisco Medical Center conducted an observational cohort study to examine if treatment with Paxlovid during acute COVID-19 infection is associated with a lower prevalence of patient-reported long COVID symptoms more than 90 days after infection. Data was gathered from the COVID Citizen Science study, an online cohort study that included 100000 participants.

The study cohort included 4684 participants who were vaccinated against COVID-19, were not hospitalized, were not pregnant, and tested positive for SARS-CoV-2 between March and April 2022. Of the participants, 988 were treated with Paxlovid and 3696 were not treated. A long COVID symptom survey was given to the participants, of which 353 treated patients and 1259 untreated patients responded.

Of the participants who responded to the survey, investigators found that 16.1% of patients treated with Paxlovid reported long COVID symptoms. This is compared to 14% of untreated patients. The most commonly reported symptoms included fatigue, shortness of breath, confusion, headache, and altered taste and smell. Results remained similar when demographics, past medical history, and substance use were considered.

Among patients treated with Paxlovid who reported at least 1 long COVID symptom, the median number of symptoms was 1, compared to 2 for untreated patients. Additionally, 6 of the treated patients reported severe or very severe symptoms, compared to 18 untreated patients.

Study limitations include that the cohort was relatively homogenous, that the study relied on self-reports, that the survey did not include all long COVID symptoms, and that it did include objectively measured post-COVID outcomes.

“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,” Matthew Durstenfeld, lead author on the study, said in a release.3 “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.”

1. Durstenfeld MS, Peluso MJ, Lin F, et al. Association of nirmatrelvir for acute SARS-CoV-2 infection with subsequent Long COVID symptoms in an observational cohort study. J Med Virol. 2024; 96:e29333. doi:10.1002/jmv.29333
2. Davis HE, McCorkell L, Vogel JM, et al. Long COVID: major findings, mechanisms and recommendations. Nat Rev Microbiol 21, 133–146 (2023).
3. Krigel M. Study Finds Paxlovid Treatment Does Not Reduce Risk of Long COVID. News Release. UCSF. January 2, 2024. Accessed January 4, 2024.
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