Insufficient drug exposure likely behind COVID-19 rebound symptoms after Paxlovid: Study

Drug resistance or impaired immunity against the coronavirus are likely not the cause of rebound symptoms some patients experience after taking Pfizer's antiviral Paxlovid, according to a new study from University of California San Diego researchers. 

To better understand the cause behind rebound symptoms after completing a course of the antiviral, a team of researchers from UC San Diego School of Medicine isolated the virus from a patient infected with BA.2 to test whether it had developed resistance to the drug. They also sampled the patient's plasma to test their immunity against the virus, according to the study published June 20 in Clinical Infectious Diseases.

After a course of treatment, researchers found the virus was still responsive to the drug and saw no evidence of mutations that would reduce Paxlovid's effectiveness. The patient's antibodies were also effective at blocking the virus from infecting new cells, indicating impaired immunity wasn't the cause of their recurring symptoms. 

"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 Aaron Carlin, MD, PhD, study author and assistant professor at UC San Diego School of Medicine.

Instead, researchers believe insufficient drug exposure is the reason behind the symptom rebound — meaning not enough of the medication was reaching infected cells to bring all viral replication to a halt — and called for additional studies to determine whether certain patients are more vulnerable to recurring symptoms and whether treatment adjustments are necessary. 

The CDC in May issued a health advisory warning that symptom rebound can occur after a course of Paxlovid. The agency said there is currently no evidence that additional treatment with Paxlovid or other therapies is needed in cases where rebound is suspected.


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