COVID-19 rebound after taking Paxlovid likely due to insufficient drug exposure, study finds: Paxlovid rebound patient did not show drug resistance or impaired immunity

Paxlovid is the leading oral medication for preventing severe cases of COVID-19 in high-risk individuals. However, symptoms returned in some patients after treatment was completed, prompting the Centers for Disease Control and Prevention (CDC) to issue a health advisory on this so-called “COVID-19 rebound.”

In a study published June 20, 2022 in Clinical Infectious Diseases, researchers at University of California San Diego School of Medicine evaluated one such patient and found their symptom relapse was not caused by the development of resistance to the drug or impaired immunity against the virus. Rather, the COVID-19 rebound appears to have been the result of insufficient exposure to the drug.

After a clinical trial showed that Paxlovid could reduce the risk of hospitalization and death from COVID-19 by 89 percent, the drug was made available under an emergency use authorization from the U.S. Food and Drug Administration in December 2021.

The treatment consists of two drugs — nirmatrelvir and ritonavir — which work together to suppress SARS-CoV-2 by blocking an enzyme that allows the virus to replicate in the body. It is easier to take at home compared to drugs like Remdesivir, which require intravenous injection. Treatment should be initiated within five days of symptom onset and taken twice daily for five consecutive days.

The research team, led by senior author Davey M. Smith, MD, chief of Infectious Diseases and Global Public Health at UC San Diego School of Medicine and infectious disease specialist at UC San Diego Health, set out to better understand the causes of COVID-19 rebound following Paxlovid treatment.

They first isolated the SARS-CoV-2 BA.2 virus from a COVID-19 rebound patient and tested whether it had developed any drug resistance. They found that after Paxlovid treatment, the virus was still sensitive to the drug and showed no relevant mutations that would reduce the drug’s effectiveness.

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