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Paxlovid rebound raises questions, but studies have answers

Analysis  |  By Robin Robinson  
   August 08, 2022

Biden's rebound is far from the first, although they are reportedly "rare."

Nothing like President Joe Biden having a rebound case of COVID-19 after taking the anti-viral Paxlovid by Pfizer to shine a light on the drug's effectiveness.

The President tested positive for COVID-19 for a second time right after being treated with Paxlovid for his first bout, the Associated Press reported. While the effectiveness of Paxlovid has come into question, some experts are saying that Biden's relapse is just a reminder that sometimes that's what happens when one sole anti-viral is chasing an ever-evolving virus.

Biden's rebound is far from the first, although they are reportedly "rare." Since the anti-viral got EU approval late in December, occurrences of rebound have been cited. Some medical experts are saying they may be more common than previously thought, The Washington Post reported.

A report in Science describes how easily a virus can learn to work around a single drug, and researchers expect Paxlovid will eventually lose its effectiveness as the virus mutates to thwart it.  So far, no mutations have seemed to interfere with Paxlovid’s effectiveness, the Science report says, and scientists are still trying to determine why these rebounds are happening. But, they warned, "recent studies suggest the virus is poised to develop resistance—a fate that befalls many antiviral drugs."

Likewise, a University of California San Diego School of Medicine study published June 20, 2022 in Clinical Infectious Diseases suggests insufficient drug exposure is most likely the cause for a Paxlovid rebound, at least that was the case in one patient studied, as the patient did not show drug resistance or impaired immunity. The authors said the rebound of COVID-19 symptoms following treatment is likely due to not enough of the drug getting to infected cells to stop all viral replication. This leaves it up to the prescribing physician to determine the adequate drug protocol beyond the standard five days.

Also, Paxlovid is not meant for every patient with COVID-19  – only those at increased risk due to age, disease such as cancer, diabetes, hypertension, obesity, or being a former or current smoker, for example. In other words, according to Pfizer's own report, Paxlovid is not recommended for people who are unlikely to get seriously ill from COVID-19. To that point, the June, Pfizer discontinued a clinical trial for standard-risk people because Paxlovid didn’t significantly reduce hospitalization and death in that group.

In many patients, Paxlovid has shown positive results, not only keeping them from becoming very ill, but consequently, keeping them out of the hospital.

A new study by Epic Research calls Paxlovid a "game changer," as it found that patients prescribed Paxlovid are roughly five times less likely to be hospitalized and 10 times less likely to die than patients with COVID-19 who are not prescribed. Paxlovid prescriptions have increased throughout 2022, with a notable increase following the federal Test to Treat announcement in March 2022, Epic Research reports. The nationwide initiative was launched in March, giving individuals “One-Stop Test to Treat” sites at thousands of locations nationwide. In May, the program was expanded to include federally supported Test to Treat sites. According to Epic Research, the prescription rate peaked in May 2022 when 23% of patients with COVID-19 were prescribed Paxlovid.

According to study author Jeff Trinkl, MD, director of clinical informatics at Epic, one of the most surprising findings from the study is how drastic the difference in death rate is between those who were prescribed Paxlovid and those who were not. "While we expected a lower rate of hospitalization and death, the numbers were even greater than expected," he says. There were over 97,000 Paxlovid prescriptions during the study period in the Epic data set. This study evaluated any patient with a COVID diagnosis and/or positive test during the study period, December 1, 2021 – June 30, 2022. "We did not exclude patients who may be deemed to be at lower risk, but currently, Paxlovid has emergency use authorization for those at risk for severe COVID-19 illness, so it is likely the group prescribed Paxlovid is at greater risk for hospitalization and death than the general population," Finkl adds.

The anti-viral appears to be working well for Pfizer, as its second-quarter revenue and profit was largely driven by sales of its COVID-19 vaccine and Paxlovid. Pfizer booked $27.7 billion in revenue, a 47% increase over the same period last year and its largest quarterly sales on record. The pharmaceutical company reported $9.9 billion in net income, a 78% increase over the second quarter of 2021.

Robin Robinson is a contributing writer for HealthLeaders. 


COVID-19 rebounds, like President Biden's, are considered rare, but can happen.

Paxlovid is only for high-risk patients.

Pfizer reorted largest quarterly sales on record, partly due to Paxlovid.

Epic Research: Patients prescribed Paxlovid are five times less likely to be hospitalized and 10 times less likely to die.

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