COVID-19 rebound after Paxlovid treatment likely due to insufficient exposure to the drug

“COVID-19 rebound,” the relapse of symptoms that occurred in some patients treated with Paxlovid, may actually be caused by insufficient drug exposure, according to a recent study published in Clinical Infectious Diseases. 

Recently, the Centers for Disease Control and Prevention (CDC) had issued a health advisory warning individuals about “COVID-19 rebound” where symptoms of COVID infection returned in some patients after a course of treatment with the medication Paxlovid. Paxlovid is currently the leading oral medication used to prevent severe cases of COVID-19 in high-risk patients, according to the researchers. 

“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,” senior 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, said in a news release.  

The investigators from the University Of California San Diego School Of Medicine evaluated one patient who suffered a “Covid-19 rebound” after being treated with Paxlovid. They discovered that the patient’s relapse in COVID symptoms after taking Paxlovid, was not caused by a developed resistance to the drug or impaired immunity against the coronavirus, but was due to having insufficient amounts or exposure to the drug, according to the study authors.  

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“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,” first author Aaron F. Carlin, MD, PhD, an assistant professor at UC San Diego School of Medicine said in the release.  

The researchers isolated the SARS-CoV-2 BA.2 virus from a COVID-19 rebound patient and tested to see if it developed any drug resistance. The team, led by Smith, found that after treatment with the medication, the virus was still sensitive to Paxlovid and did not show any type of mutations that would reduce the effectiveness of the drug.  

The investigators also took a sample of the patient’s plasma and noted that the patient’s antibodies were still effective in preventing the virus from entering and infecting new cells. They said this suggested that an impaired immune system could be ruled out as a contributing factor to the individual’s relapse.  

The California researchers concluded that the COVID-19 rebound following a course of Paxlovid treatment is likely due to insufficient drug exposure. The authors further explained this means that infected cells were not getting enough of the drug to stop all viral replication either because the medication was being metabolized too quickly in some patients or that the drug needs to be given for a longer duration.  

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Carlin said in the release that he hopes physicians will be able to test to see if patients need a longer course of treatment of Paxlovid or receive a combination of medications.  

The authors said in the release that Paxlovid users should be mindful of the risk of rebound of symptoms and follow precautions such as wearing masks and quarantining if symptoms return. 

The investigators also noted that further research is needed to see how common this type of rebound occurs and which patients are most vulnerable.   

“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,” Smith said in the release.