Paxlovid rebound patient did not demonstrate drug resistance or compromised immunity

Paxlovid is the primary oral medication used to prevent severe cases of COVID-19 in people at high risk. However, in some patients, symptoms returned after stopping treatment, 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 on June 20, 2022 in Clinical infectious diseases, researchers from the University of California, San Diego School of Medicine studied one such patient and found that the recurrence of their symptoms was not caused by the development of drug resistance or impaired immunity to the virus. Rather, the COVID-19 rebound appears to have been the result of insufficient exposure to the drug.

After a clinical study showed Paxlovid reduced the risk of hospitalization and death from COVID-19 by 89%, 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’s easier to take at home than drugs like remdesivir, which require an intravenous injection. Treatment should be started within five days of symptom onset and taken twice a day for five consecutive days.

The research team, led by lead author Davey M. Smith, MD, director of infectious diseases and global public health at the UC San Diego School of Medicine and infectious disease specialist at UC San Diego Health, set out to understand the causes of COVID-19 Rebound after Paxlovid treatment.

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

“Our main concern was that the coronavirus might be developing resistance to Paxlovid, so it was a great relief to find out that wasn’t the case,” said first author Aaron F. Carlin, MD, PhD, an assistant professor at the UC San Diego School of Medicine . .

The team then took the patient’s plasma to test his immunity to SARS-CoV-2. The patient’s antibodies were still effective in preventing the virus from entering and infecting new cells, suggesting that a lack of antibody-mediated immunity was not the cause of the patient’s recurrent symptoms either.

The authors said that the recurrence of COVID-19 symptoms after stopping treatment with Paxlovid is likely due to insufficient exposure to the drug: not enough drug reached the infected cells to stop virus replication. They suggested that this could be because the drug is metabolized more quickly in some people, or because the drug needs to be given over a longer treatment period.

Carlin said he hopes in the future doctors will be able to test whether patients need longer treatment with Paxlovid or whether they might be better treated with a combination drug. In the meantime, Paxlovid users should be aware of the possibility of symptoms returning and be prepared to go back to wearing masks and self-quarantining if symptoms return.

More research is needed to measure the frequency of rebounds, which patient groups are most vulnerable, and whether symptom recurrence can lead to more severe disease.

“Paxlovid’s goal is to prevent serious illness and death, and so far no one who got sick again has had to be hospitalized, so it’s still doing the job,” Smith said. “We just need to understand why some patients rebound and others don’t. More research is needed to help us adjust treatment plans as needed. »

Co-authors include: Alex E. Clark, Antoine Chaillon, Aaron F. Garretson, William Bray, Magali Porrachia, and Tariq M. Rana, all at UC San Diego, and AsherLev T. Santos at California State University San Marcos .

Source of the story:

Materials provided by University of California – San Diego. Originally written by Nicole Mlynaryk. Note: Content can be edited for style and length.

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