Paxlovid is the main oral medicine to prevent 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 about this so-called “COVID-19 rebound.”
In a study published 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 his symptoms was not caused by the development of drug resistance or impaired immunity to the virus. Rather, the rebound of COVID-19 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 became available under an emergency use authorization from the US Food and Drug Administration in December. of 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, chief of infectious diseases and global public health at UC San Diego School of Medicine and an infectious disease specialist at UC San Diego Health, set out to better understand the causes of COVID-19. 19 rebound after Paxlovid treatment.
They first isolated the SARS-CoV-2 BA.2 virus from a rebound COVID-19 patient and tested whether it had developed drug resistance. They found that after Paxlovid treatment, the virus remained sensitive to the drug and had no relevant mutations that could reduce the drug’s efficacy.
“Our main concern was that the coronavirus might be developing resistance to Paxlovid, so finding out that it wasn’t was a huge relief,” said first author Aaron F. Carlin, MD, PhD, an assistant professor in the University of Pennsylvania School of Medicine. UC San Diego. . .
The team then took the patient’s plasma to test their immunity against SARS-CoV-2. The patient’s antibodies were still effective at 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 recurrent symptoms.
The authors said the rebound of COVID-19 symptoms after Paxlovid treatment ended was likely due to insufficient exposure to the drug: not enough drug was reaching infected cells to stop viral replication. They suggested this could be because the drug is metabolized faster in some people or because the drug needs to be given over a longer treatment period.
In the future, Carlin said he hopes doctors will be able to assess whether patients need longer treatment with Paxlovid or might be better treated with a combination drug. In the meantime, Paxlovid users should be aware of the possibility of a rebound in symptoms and be prepared to wear masks and self-quarantine again if symptoms return.
More research is needed to measure the frequency of rebounds, which patient populations are more susceptible, and whether 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’s gotten sick again has needed hospitalization, so it’s still doing its job,” Smith said. . “We just need to understand why some patients rebound and not others. More research is needed to help us adjust treatment plans if necessary. »
Coauthors 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.
Materials provided by University of California-San Diego. Original written by Nicole Mlynaryk. Note: content can be edited for style and length.
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