Association of Nirmatrelvir for Acute SARS-CoV-2 Infection with Subsequent Long COVID Symptoms in an Observational Cohort Study Summary Oral nirmatrelvir/ritonavir is approved as a treatment for acute COVID-19, but the effect of treatment during acute infection on the risk of long COVID is unknown. We hypothesize that treatment with nirmatrelvir during acute SARS-CoV-2 infection reduces the risk of developing long COVID and rebound after treatment is associated with long COVID. We conducted an observational cohort study within the Covid Citizen Science (CCS) study, an online cohort study with over 100,000 participants. We included vaccinated, non-hospitalized, and non-pregnant individuals who reported their first positive SARS-CoV-2 test between March and August 2022. Oral nirmatrelvir/ritonavir treatment was determined during acute SARS-CoV-2 infection. Subsequent surveys asked patients’ reported long COVID symptoms, symptom rebound, and test positivity rebound at least 3 months after SARS-CoV-2 infection. A total of 4,684 people met the eligibility criteria, of whom 988 (21.1%) received treatment and 3,696 (78.9%) did not receive treatment; 353/988 (35.7%) treated and 1258/3696 (34.0%) untreated responded to the Long COVID survey (n = 1611). Among the 1,611 participants, the average age was 55 years and 66% were women. At 5.4±1.3 months post-infection, nirmatrelvir treatment was not associated with subsequent prolonged COVID symptoms (odds ratio [OR]: 1.15, 95% confidence interval [CI]: 0 .80–1.64; p = 0.45). Among the 666 treated who answered rebound questions, rebound symptoms or test positivity were not associated with long COVID symptoms (OR: 1.34; 95% CI: 0.74–2.41; p = 0.33). Within this cohort of vaccinated, non-hospitalized people, treatment with oral nirmatrelvir during acute SARS-CoV-2 infection and rebound after treatment with nirmatrelvir were not associated with long COVID symptoms more than 90 days after infection . |
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University of California San Francisco Medical Center
A team of UC San Francisco researchers found that Paxlovid (Nirmatrelvir-ritonavir) did not reduce the risk of developing long COVID in vaccinated people not hospitalized during their first COVID-19 infection. They also found a higher proportion of people with acute rebound symptoms and positive test results than previously reported.
The study appears in the Journal of Medical Virology .
Paxlovid treatment for acute COVID-19 has been shown to be effective in high-risk unvaccinated people . But the treatment’s effect on the risk of long COVID, 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 2022 and who were not hospitalized. Some of these participants reported receiving oral treatment with Paxlovid during the acute phase of their COVID infection, while others did not. In December 2022, they were invited to take a follow-up survey with questions about long COVID, rebound COVID symptoms, and how long they continued to test positive.
The researchers found that the two groups were similar. About 16% of those treated with Paxlovid had long COVID symptoms compared to 14% of those not treated with the drug. Commonly reported symptoms included fatigue, shortness of breath, confusion, headache, and altered taste and smell .
Those who took Paxlovid and then developed 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 symptoms of severe long COVID as those who did not receive it.
Among people 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 symptoms compared to 8.3% without rebound symptoms.
For participants who repeated the antigen test after testing negative and completing treatment, 25.7% reported rebound test positivity. In total, 26.1% reported rebound symptoms or a positive test result.
"We found a higher proportion of clinical rebound than previously reported, but we did not identify an effect of post-treatment rebound on long COVID symptoms," said the study’s first author, Matthew Durstenfeld, MD, MAS, a cardiologist and assistant professor of UCSF Medicine. "Our finding that Paxlovid treatment during acute infection is not associated with lower odds of long COVID surprised us, but is consistent with two other rigorously conducted studies that found no difference in post-COVID conditions between 4 and 6 months." after infection."
The authors note that the study may have been affected by limitations stemming from its observational nature, as researchers relied on patient reports of treatment and long COVID symptoms.
Conclusions Among vaccinated, non-hospitalized adults in the online COVID Citizen Science cohort, nirmatrelvir treatment during acute SARS-CoV-2 infection was not associated with long COVID symptoms >90 days post-infection. Among those treated, rebound was not associated with long COVID symptoms. |
