COVID-19 Rebounds Due to Insufficient Drug Exposure: Study

Paxlovid rebound patient did not show drug resistance or impaired immunity. But a new study showed insufficient drug exposure as a reason for rebound COVID-19.

Paxlovid is the main oral drug for preventing severe cases of COVID-19 in high-risk individuals. But, symptoms returned in some patients after completion of 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 in Clinical Infectious Diseases, researchers evaluated one patient and found their symptom relapse was not caused by the development of resistance to the drug or impaired immunity against the virus.

‘The rebound of COVID-19 symptoms following Paxlovid treatment could be due to insufficient drug exposure, which means not enough of the drug was getting to infected cells to stop viral replication.’
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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 namely 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. Treatment should be initiated within five days of symptom onset and taken twice daily for five consecutive days.

How COVID-19 Rebounds?

The research team 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.

“Our main concern was that the coronavirus might be developing resistance to Paxlovid, so to find that was not the case was a huge relief,” said first author Aaron F. Carlin.

The team next sampled the patient’s plasma to test their immunity against SARS-CoV-2. The patient’s antibodies were still effective at blocking 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.

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The rebound of COVID-19 symptoms following the end of Paxlovid treatment is likely due to insufficient drug exposure: not enough of the drug was getting to infected cells to stop all viral replication. They suggested this may be due to the drug being metabolized more quickly in some individuals or that the drug needs to be delivered over a longer treatment duration.

Carlin said he hopes physicians will be able to test whether patients require a longer duration of Paxlovid treatment or if they might be best treated by a combination of drugs.

Paxlovid users should be aware of the possibility of symptom rebound, and be prepared to wear masks and quarantine again if symptoms return.

More studies are necessary to measure how often rebound occurs, what patient populations are most susceptible and if returning symptoms can lead to more severe disease.

“The goal of Paxlovid is to prevent serious illness and death, and so far no one who has gotten sick again has needed to be hospitalized, so it’s still doing its job,” said Smith.

“We simply need to understand why the rebound happens in some patients and not others. More research is needed to help us adjust treatment plans as necessary.”

Source-Medindia