Paxlovid rebound patient did not show drug resistance or impaired immunity

Paxlovid is the primary oral medication for preventing severe cases of COVID-19 in people at high risk. However, symptoms returned in some patients after treatment ended, 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 at the University of California, San Diego School of Medicine evaluated one such patient and found that the relapse 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 trial showed that Paxlovid could reduce the risk of hospitalization and death from COVID-19 by 89%, the drug was made available under an emergency use authorization from the United States 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 initiated within five days of the onset of symptoms and taken twice daily for five consecutive days.

The research team, led by lead 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 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 effectiveness of the drug.

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

The team then took the patient’s plasma to test his immunity against 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 also not the cause of the patient’s recurring symptoms.

The authors said that the rebound of COVID-19 symptoms after Paxlovid treatment ended is likely due to insufficient exposure to the drug: not enough drug was reaching infected cells to stop any viral replication. They suggested this could be because the drug is metabolized faster in some people or the drug needs to be given over a longer treatment period.

Going forward, Carlin said he hopes doctors will be able to test whether patients need longer treatment with Paxlovid or if they might be better treated with a combination drug. In the meantime, Paxlovid users should be aware of the possibility of symptom rebound and be prepared to wear masks and self-quarantine again if symptoms return.

Further research is needed to measure the frequency of rebounds, which patient populations are most susceptible, and whether the return of symptoms can lead to more severe disease.

“Paxlovid’s goal is to prevent serious illness and death, and so far no one who has gotten sick again has needed hospitalization, so it’s still doing its job,” Smith said. . “We just need to understand why rebound occurs in some patients and not in others. Further research is needed to help us adjust treatment plans if necessary. »

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. Original written by Nicole Mlynaryk. Note: Content may be edited for style and length.



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