Hong Kong—Viral rebound sometimes occurs after treatment with Paxlovid (nirmatrelvir; ritonavir) for the treatment of COVID-19. Apparently, viral rebound also occurs with molnupiravir but not very commonly, according to a new study.

Researchers from the Chinese University of Hong Kong sought to examine the incidence of viral rebound in patients with COVID-19 who were treated with those oral antiviral agents. To do that, the study team conducted a cohort study of patients with COVID-19 in Hong Kong who were hospitalized from January 1, 2022, to March 31, 2022. This study assessed 12,629 patients with serial cycle threshold (Ct) values that were measured. Follow-up of the patients continued until the occurrence of the clinical end point of interest, death, date of data retrieval (July 31, 2022), or up to 30 days of follow-up, whichever came first.

For purposes of the study, viral rebound was defined as a Ct value greater than 40 that decreased to 40 or less. The results were reported in Journal of the American Medical Associate Network Open.

Of the patients with a median age of 65.4 years, 52.5% were male, 92.5% were oral antiviral nonusers, 5.9% were molnupiravir users, and 1.5% were nirmatrelvir-ritonavir users. “Compared with nonusers, oral antiviral users were older, had more comorbidities, and had lower complete vaccination rates,” according to the authors. “The mean (SD) baseline Ct value was slightly higher in nirmatrelvir-ritonavir users (22.2 [6.0]) than nonusers (21.0 [5.4]) and molnupiravir users (20.9 [5.4]) (P = .04).”

The researchers reported that viral rebound occurred in 68 nonusers (0.6%), two nirmatrelvir-ritonavir users (1.0%), and six molnupiravir users (0.8%). “Among 76 patients with viral rebound, 12 of 68 nonusers, 1 of 6 molnupiravir users, and neither of the nirmatrelvir-ritonavir users died of COVID-19,” the researchers advise.

The cohort study concluded that viral rebound was uncommon in patients taking molnupiravir or nirmatrelvir-ritonavir and was not associated with increased risk of mortality. “Given these findings, novel oral antivirals should be considered as a treatment for more patients with COVID-19 in the early phase of the infection,” the authors suggested.

The background information in the study pointed out that since the two oral antiviral agents, molnupiravir and nirmatrelvir-ritonavir became available in late 2021, millions of patients with COVID-19 have received them in an effort to reduce hospitalization rates or adverse clinical outcomes.

While it is well known that patients treated with Paxlovid can experience rebound of COVID-19 infections and symptoms after completing the 5-day course—a health alert from the CDC addressed that issue in May 2022—data have remained scarce on whether viral rebound would also occur in molnupiravir-treated or even untreated patients with COVID-19.

“In this territory-wide study in Hong Kong, we aimed to examine the incidence rates of viral rebound in patients with COVID-19 receiving molnupiravir, nirmatrelvir-ritonavir, or neither in a community setting and whether viral rebound is associated with clinical outcomes,” the authors wrote.

They pointed out that their cohort study is one of the first to describe the incidence and clinical outcomes of patients hospitalized for viral rebound of COVID-19 in a community setting. “Viral rebound occurred not only in a few nirmatrelvir-ritonavir users but also in molnupiravir users and nonusers,” the researchers explained. “Fortunately, viral rebound did not increase the CFR in molnupiravir users and nirmatrelvir-ritonavir users. The marginal increase in CFR among antiviral nonusers might be associated with the small sample size of patients with viral rebound.”

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