In a study of nearly 13,000 hospitalized adults in Hong Kong, COVID-19 rebound was uncommon after use of the oral antivirals Paxlovid and molnupiravir to lower the risk of severe outcomes.
Viral rebound is a return of infection and symptoms after apparent recovery and was defined in this study as a polymerase chain reaction (PCR) cycle threshold (Ct) value greater than 40 (negative for COVID-19) that falls to 40 or less (positive). Ct is a proxy for SARS-CoV-2 viral load, with higher values indicating a lower load.
Early reports suggested a link between nirmatrelvir-ritonavir (Paxlovid) and viral rebound, but more recent studies have concluded that rebound may be simply part of the natural course of some COVID-19 cases.
1% or less affected
In the study, published today in JAMA Network Open, Chinese University of Hong Kong researchers assessed data from 12,629 COVID-19 patients who were hospitalized from Jan 1 to Mar 31, 2022, and had at least three Ct measurements. The Omicron variant was predominant during the study period.
Patients received Paxlovid (195 patients), molnupiravir (746), or no antiviral (11,688) and were followed until Jul 31, death, or 30-day follow-up, whichever occurred first. Average patient age was 65.4 years, and 52.5% were men.
Antiviral users were older and had more underlying medical conditions and lower rates of complete COVID-19 vaccination than nonusers. Average baseline Ct value was marginally higher in Paxlovid users (22.2) than nonusers (21.0) and molnupiravir recipients (20.9).
Viral rebound occurred in 68 nonusers (0.6%), 2 Paxlovid recipients (1.0%), and 6 molnupiravir users (0.8%). Most rebounds occurred 2 to 5 days after completion of the last antiviral dose. In an analysis using a lower cutoff of Ct values (greater than 36) that declined to 36 or less, viral fluctuation occurred in 34 molnupiravir users (4.6%), 9 Paxlovid recipients (4.6%), and 509 nonusers (4.4%).
'Antivirals should be prescribed to more patients'
Of the 76 patients who experienced viral rebound, 17.6% of nonusers died of COVID-19, as did 17.1% of molnupiravir recipients. No Paxlovid users died of their infections.
Antiviral nonusers who experienced rebound had a higher case-fatality rate (CFR; 17.6%) than those with no rebound (9.8%), while antiviral recipients with rebound (12.5%) didn't have a higher CFR than those with no rebound (12.6%).
"The marginal increase in CFR among antiviral nonusers might be associated with the small sample size of patients with viral rebound," the study authors wrote.
Of 552 patients with viral fluctuation, 48 of 509 nonusers (5.4%) and 5 of 34 molnupiravir recipients (14.7%) died of COVID-19; 1 of 9 Paxlovid users (11.1%) died of pancreatic cancer.
The marginal increase in CFR among antiviral nonusers might be associated with the small sample size
The findings, the researchers said, show that treatment of COVID-19 rebound is unnecessary. "In this study, viral rebound was uncommon in adults with COVID-19 after treatment with nirmatrelvir-ritonavir and molnupiravir, suggesting that these novel oral antivirals should be prescribed to more patients with COVID-19 in the early phase of the infection," they wrote.