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Rebound of COVID-19 Omicron infection after Nirmatrelvir–Ritonavir


September 7, 2022

BOSTON , MA — In a case series of 13 fully vaccinated, boosted patients, rebound occurred a median of nine days following initial diagnosis of COVID-19 due to the SARS-CoV-2 Omicron variant, according to an article published in the New England Journal of Medicine today.

Clinicians and researchers at the VA Boston Healthcare System, VA Connecticut HCS, National Basketball Association, and the Columbia University Vagelos College of Physicians and Surgeons found that rebound symptoms occurred after patients had been asymptomatic or improving for a median of six days and lasted a median of four days.   The most frequent rebound symptoms were cold-like symptoms and fatigue. 

“Rebound symptoms were typically milder than initial symptoms,” said Dr. Michael Charness, chief medical officer for VA Boston HCS, and professor of neurology and associate dean at Harvard Medical School and Boston University School of Medicine, co-author of the article. “None of the patients required hospitalization, but during viral rebound, people may be contagious and should restart their isolation.”

Viral sequencing indicated that rebound was due to increased replication of the original SARS-CoV-2 virus, rather than infection with a different subvariant or virus. Viral load during rebound returned to the same high levels observed during the initial infection. After a period of undetectable or greatly reduced viral load following Paxlovid treatment, rapid antigen tests became positive a median of 10 days after the initial infection and remained positive for a median of six days.

“We should emphasize that National Institutes of Health guidelines continue to recommend Paxlovid for outpatients with mild to moderate COVID-19 who are at high risk of progression to severe illness,” added Dr. Kalpana Gupta, associate chief of staff and chief of infectious diseases for the VA Boston HCS, and professor of medicine at Boston University School of Medicine, co-author of the article. “Preventing hospitalization or death is more important than avoiding non-life-threatening rebound and some additional isolation.”

The article is available at

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