COVID-19 rebound dangers related for Paxlovid and Molnupiravir

In a current article posted to the medRxiv* preprint server, investigators within the United States illustrated that rebound of extreme acute respiratory syndrome coronavirus 2 (SARS-CoV-2) an infection can happen in some sufferers following molnupiravir and Paxlovid SARS-CoV-2 remedy.

Study: COVID-19 rebound after Paxlovid and Molnupiravir during January-June 2022. Image Credit: NIAIDStudy: COVID-19 rebound after Paxlovid and Molnupiravir throughout January-June 2022. ​​​​​​​Image Credit: NIAID


In December 2021, the Food and Drug Administration (FDA) authorised Paxlovid (nirmatrelvir) and Lagevrio (molnupiravir) to deal with mild-to-moderate SARS-CoV-2 an infection in people at excessive danger of growing extreme sickness. However, current case experiences present that two to eight days after ending a five-day therapy of Paxlovid, some sufferers suffered rebound CoV illness 2019 (COVID-19) and disease-related signs.

To inform the general public about the potential for COVID-19 rebound following Paxlovid remedy, the Centers for Disease Control and Prevention (CDC) lately launched a Health Alert Network Health Advisory. Nevertheless, the prevalence of COVID-19 rebound within the normal inhabitants, whether or not Paxlovid is the one medicine that causes the rebound of SARS-CoV-2 an infection, or if some individuals are extra delicate than others, stays unsure.

About the examine

The current work aimed to evaluate the relative dangers and charges of COVID-19 rebound in SARS-CoV-2 sufferers who obtained Paxlovid or molnupiravir remedy and examine the traits of people who did and didn’t undergo the rebound of SARS-CoV-2 an infection. The researchers used the TriNetX Analytics community system, a national, multicenter database within the United States (US), to conduct a retrospective cohort evaluation on the digital well being information (EHRs) of about 92 million people.

The trial inhabitants comprised 13,644 topics aged ≥18 who grew to become COVID-19-positive between 1 January and eight June 2022. Further, inside 5 days after contracting SARS-CoV-2, 11,270 and a pair of,374 of those people obtained Paxlovid and molnupiravir remedy, respectively. COVID-19 sufferers handled with each Paxlovid and molnupiravir have been omitted from the examine. The International Classification of Diseases, tenth revision (ICD-10) prognosis code for COVID-19, i.e., U07.1, or laboratory-confirmed SARS-CoV-2 an infection, was used to find out the standing of COVID-19 among the many members.

The analysis’s main outcomes and metrics have been three sorts of COVID-19 rebound occasions (SARS-CoV-2 infections, COVID-19-linked signs, and SARS-CoV-2-associated hospitalizations) that occurred two days following the final day of molnupiravir or Paxlovid remedy. Additionally, the 95% confidence interval (CI) and hazard ratios (HR) of the seven-day and 30-day probability for COVID-19 rebound amongst sufferers handled with Paxlovid and molnupiravir have been calculated earlier than and following propensity-score matching.


Overall, the examine outcomes depicted that extra COVID-19 sufferers have been handled with Paxlovid relative to molnupiravir, which could be associated to the 2 medicine’ differing effectiveness in stopping SARS-CoV-2-linked hospitalizations or deaths amongst high-risk sufferers in comparison with placebo (88% for Paxlovid versus 30% for molnupiravir). 

Across the 2 teams within the current examine, the sufferers handled with Paxlovid have been significantly completely different from these managed with molnupiravir, regardless of each medicines being authorised to be used in SARS-CoV-2-infected people at excessive danger for extreme COVID-19. The common age of Paxlovid-treated sufferers was 56 in comparison with 62 for molnupiravir-treated sufferers, and the preliminary cohort additionally had fewer co-existing well being situations. Furthermore, the Paxlovid arm comprised extra Hispanics, ladies, Black, and Asian sufferers.

The charges of COVID-19 rebound following seven-day and 30-day Paxlovid therapy have been 3.53% and 5.40%; 2.31% and 5.87%; and 0.44% and 0.77% for SARS-CoV-2 an infection, COVID-19 signs, and SARS-CoV-2-related hospitalizations, respectively. Following molnupiravir remedy, the seven-day and 30-day SARS-CoV-2 rebound charges have been 5.86% and eight.59%; 3.75% and eight.21%; and 0.84% and 1.39% for SARS-CoV-2 an infection, SARS-CoV-2 signs, and COVID-19-linked hospitalizations, respectively. 

There have been no important adjustments within the odds of COVID-19 rebound for SARS-CoV-2 an infection between molnupiravir and Paxlovid following propensity-score matching: SARS-CoV-2 an infection (HR 0.90 and 95% CI: 0.73-1.11), SARS-CoV-2 signs (HR: 1.03 and 95% CI: 0.83-1.27), or COVID-19-linked hospitalizations (HR: 0.92 and 95% CI: 0.56-1.55). Besides, in comparison with these with out, sufferers with SARS-CoV-2 rebound had a statistically larger prevalence of underlying well being points.


The examine findings indicated that SARS-CoV-2 rebound occurred following therapy with each molnupiravir and Paxlovid, notably in sufferers with pre-existing medical situations. This reveals that the COVID-19 rebound was not particular to Paxlovid and that the dangers have been comparable for each Paxlovid and molnupiravir. The workforce means that the rebound may be associated to a continual viral an infection in some people who obtained both antiviral drug. In addition, the charges of SARS-CoV-2 rebound for each medicines heightened over time following therapies.

The present outcomes mandate ongoing monitoring of COVID-19 rebound following molnupiravir and Paxlovid therapies. The authors acknowledged that additional research have been required to determine the mechanisms underpinning SARS-CoV-2 rebounds and assess dosing and length regimens that may cease them in prone sufferers.

*Important discover

medRxiv publishes preliminary scientific experiences that aren’t peer-reviewed and, subsequently, shouldn’t be thought to be conclusive, information scientific apply/health-related conduct, or handled as established data.

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