Paxlovid (nirmatrelvir tablets co-packaged with ritonavir tablets) continues to be recommended for early stage treatment of mild to moderate COVID-19 among individuals at high risk of progression to severe disease, despite reports of COVID-19 rebound, according to a health advisory issued by the Centers for Disease Control and Prevention (CDC).

The antiviral agent, which was authorized for emergency use by the Food and Drug Administration (FDA) in December 2021, consists of nirmatrelvir, a SARS-CoV-2 main protease inhibitor, and ritonavir, a HIV-1 protease inhibitor and CYP3A inhibitor.

Recent case reports suggest that some patients treated with Paxlovid may have a recurrence of COVID-19 symptoms 2 to 8 days after completing the 5-day course of treatment. In these cases, patients had tested negative for COVID-19 following treatment and then subsequently tested positive. Both the illness and the positive test results resolved on average 3 days later without the need for additional treatment.

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According to the CDC, “a brief return of symptoms may be part of the natural history of SARS-CoV-2 infection in some persons, independent of treatment with Paxlovid and regardless of vaccination status.” Based on information from case reports, the recurrence of COVID-19 was not attributed to SARS-CoV-2 reinfection or the development of resistance to Paxlovid.

Currently, there is no evidence to indicate that additional treatment for COVID-19 is needed for patients who experience COVID-19 rebound after Paxlovid treatment; monitoring continues to be the most appropriate management. Patients should be advised to take precautions to prevent further transmission. In cases where rebound symptoms persist or worsen, clinical evaluation should be considered.

Health care providers are also encouraged to report cases of COVID-19 rebound to Pfizer and to the FDA’s MedWatch. The Paxlovid fact sheet for health care providers can be found here.


COVID-19 rebound after Paxlovid treatment. CDC Health Alert Network. Accessed May 24, 2022.

This article originally appeared on MPR