Two new studies find limited evidence of the usefulness of Paxlovid (nirmatrelvir-ritonavir) to prevent the development of long COVID—but with a small reduction for older COVID-19 patients.
Paxlovid is an antiviral drug approved for use in US patients 12 years an older who are at risk of developing severe complications from COVID-19 infections.
Several observation studies have shown a small protective effect of Paxlovid on long COVID, but the two new studies look at the protective factor in the wake of Omicron and subvariants in the United States.
Small effect seen on oldest patients
In the first study, published yesterday in PLOS Medicine, an analysis of a large cohort of people in the RECOVER trial who had COVID-19 since April 1, 2022, found that Paxlovid had no protective effect overall on the development of long COVID.
Data on 445,738 patients from the US National COVID Cohort Collaborative’s electronic health record database was used for this study. Of those patients, 151,180 (33.92%) had a Paxlovid prescription within the treatment period, and 18,663 (4.20%) had been diagnosed as having long COVID.
The adjusted cumulative incidence of long-COVID estimates were 4.53% (95% confidence interval [CI], 4.40 to 4.66) for treated patients and 4.60% (95% CI, 4.51 to 4.68) for untreated patients.
There was a small protective effects among patients aged 65 years or more, the authors said. There was no effect for other ages, and no effect seen between unvaccinated and fully vaccinated patients.
Although it may have a small protective effect among higher-risk patients and on certain symptoms, the effect sizes are negligible.
“Although it may have a small protective effect among higher-risk patients and on certain symptoms, the effect sizes are negligible,” the authors said. “For example, an absolute risk reduction of 0.43% among patients aged 65 years or more means that 233 people would need to be treated with Paxlovid to prevent one case of PASC [postacute sequelae of COVID-19].”
They concluded, “Although some prior observational studies suggested that Paxlovid held promise as a PASC preventive, this study—with a large, nationally sampled cohort; a contemporary study period; and causal inference methodology—found that Paxlovid treatment during acute COVID-19 had no effect on subsequent PASC incidence.”
Small risk reduction in adults
In the second study, published today in Open Forum Infectious Diseases, researchers from the Centers for Disease Control and Prevention (CDC) found that Paxlovid offered some protection against long COVID in a retrospective cohort study where 291,433 treated patients were matched to 582,866 untreated patients.
The effect was only seen, however, in older adults. A minimal effect was noted in adults ages 18 to 49, but no effect was found in adolescents.
Study participants were diagnosed with COVID-19 in the spring and summer of 2022 (April 1 to August 31) and had a higher risk of severe COVID-19 based on age (50 years and older) or underlying risk factors. Of 291,433 treated patients, 98,084 (33.7%) had one or more long-COVID symptoms and 40,147 (13.8%) had two or more symptoms.
Among participants 65 and older, Paxlovid was associated with a 12% reduced risk of at least one long-COVID symptom (adjusted hazard ratio (aHR), 0.88; 95% CI, 0.87 to 0.90).
Younger adults aged 18 to 49 years had a smaller 7% reduction in overall risk of long COVID (aHR, 0.93; 95% CI, 0.92 to 0.95) and a reduced risk of some but not all individual conditions, the authors said.
“Recent studies have found that nirmatrelvir-ritonavir is underutilized among older patients who are at risk of severe disease, despite the evidence of its benefits,” the authors concluded. “Clinicians may consider treatment of persons with mild to moderate acute COVID-19 who are at high risk of severe disease, particularly those aged ≥50 years, not only to prevent hospitalization and death but also to mitigate possible long-term consequences.”
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