December 27, 2023
2 min read
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Key takeaways:
- Paxlovid and other antiviral treatments do not increase risk for COVID-19 rebound.
- Studies show rebound risk is linked to the same risk factors for severe COVID-19.
SARS-CoV-2 rebound risk is more likely related to the individual person, rather than reinfection or resistance to treatment such as Paxlovid, according to two studies.
The studies — one an analysis of SARS-CoV-2 rebound studies among patients who did and did not receive Paxlovid or another antiviral and experienced a rebound, and the other an analysis of two clinical trials of Paxlovid — suggest that the risk for rebound is linked to the same risk factors for severe COVID-19.
Analyses of several studies and trials suggests that COVID-19 rebound is not linked to Paxlovid or other antiviral drugs. Image: NIAID
Paxlovid was approved by the FDA in May for treatment of adults at risk for severe COVID-19 if infected by the SARS-CoV-2 virus nearly 2 years after it was granted an emergency use authorization for people age years and older.
The antiviral has been shown in studies to reduce the risk for hospitalization and death from COVID-19, but studies have been inconsistent as to the risk for rebound in people receiving the drug — some studies have suggested that up to 20% of people treated with Paxlovid experience a rebound.
“Rebound is typically described as a recurrence of symptoms after recovery or a new positive viral test after testing negative,” Pragna Patel, MD, MPH, DRM&H, chief medical officer in the Coronavirus and Other Respiratory Viruses division of the CDC’s National Center for Immunization and Respiratory Diseases, told Healio.
“We found that there was no consistent association between treatment for COVID-19 and COVID-19 rebound. Also, we found that COVID-19 rebound can happen among patients whether they received antiviral treatments or not,” Patel said.
Patel and colleagues analyzed 23 SARS-CoV-2 rebound studies published between Feb. 1, 2020, and Nov. 29, 2023, for inclusion in the analysis, with seven meeting criteria — one randomized trial and six observational studies.
Although some observational studies showed a higher frequency of rebound among people treated with Paxlovid or molnupiravir (10% to 14%), the randomized controlled trial and other observational studies found no consistent association between treatment and rebound, according to the study.
The other study is an analysis of two phase 2/3 randomized, double-blind, placebo-controlled clinical trials of Paxlovid that collectively enrolled roughly 3,000 participants in 2021 and 2022, with some receiving treatment and others a placebo. The trials were analyzed both for rebound of SARS-CoV-2 viral shedding and for signs and symptoms of COVID-19 rebound after treatment.
Overall, the rate of rebound between participants receiving Paxlovid and participants receiving placebo was similar, according to the study, whereas 6.4% to 8.4% of Paxlovid recipients and 5.9% to 6.5% of placebo recipients in the two trials experienced viral RNA rebound.
The results of the analyses, Patel said, show that further studies are needed to understand the health characteristics or underlying medical conditions that increase risk for a person to experience COVID-19 rebound.
But with no increased risk of hospitalization or death among participants in any of the studies and trials who experienced COVID-19 rebound, he said Paxlovid and other antivirals should still be used.
“Clinicians should continue to prescribe antiviral treatments for eligible patients, given the substantial benefit of reducing the risk of severe illness, hospitalization and death,” Patel said.
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