In a recent article published on the medRxiv * prepress server, U.S. researchers illustrated that the rebound of severe acute respiratory syndrome by coronavirus 2 (SARS-CoV-2) infection can occur in some patients after of therapy with molnupiravir and Paxlovid SARS-CoV-2. .
Study: Rise of COVID-19 after Paxlovid and Molnupiravir during January-June 2022. Image Credit: NIAID
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In December 2021, the Food and Drug Administration (FDA) approved Paxlovid (nirmatrelvir) and Lagevrio (molnupiravir) to treat mild to moderate SARS-CoV-2 infection in people at high risk of developing a serious illness. . However, recent case reports show that two to eight days after finishing a five-day treatment with Paxlovid, some patients suffered from 2019 CoV rebound disease (COVID-19) and disease-related symptoms.
To inform the public about the possibility of a rise in COVID-19 after Paxlovid therapy, the Centers for Disease Control and Prevention (CDC) recently issued a Health Alert to the Health Alert Network. However, the prevalence of the rise in COVID-19 in the general population, if Paxlovid is the only drug that causes the rebound of SARS-CoV-2 infection, or if some people are more sensitive than others, continues feeling uncertain.
About the study
The present study aimed to assess the relative risks and rebound rates of COVID-19 in patients with SARS-CoV-2 who received therapy with Paxlovid or molnupiravir and to compare the traits of individuals who suffered and not the rebound. of SARS-CoV-2 infection. . The researchers used the TriNetX Analytics network system, a nationwide multicenter database in the United States, to conduct a retrospective cohort analysis of electronic health records (EHRs) of about 92 million of individuals.
The trial population consisted of 13,644 subjects ≥18 years of age who became positive for COVID-19 between January 1 and June 8, 2022. In addition, within five days after the SARS-CoV-2 recruitment, 11,270 and 2,374 of these individuals received treatment with Paxlovid and molnupiravir, respectively. . Patients with COVID-19 treated with both Paxlovid and molnupiravir were omitted from the study. The diagnostic code of the International Classification of Diseases, 10th revision (ICD-10) for COVID-19, i.e. U07.1, or laboratory-confirmed SARS-CoV-2 infection, was used to determine the status of COVID-19 among participants. .
The main results and metrics of the research were three types of COVID-19 bounce events (SARS-CoV-2 infections, COVID-19-related symptoms, and SARS-CoV-2-associated hospitalizations) that occurred. two days after the last day of molnupiravir. or Paxlovid therapy. In addition, the 95% confidence interval (CI) and the hazard ratios (HR) of the seven-day, 30-day probability of rebound of COVID-19 between patients treated with Paxlovid and molnupiravir before and after were calculated. after the propensity score match.
Results
Overall, the results of the study showed that more patients with COVID-19 were treated with Paxlovid relative to molnupiravir, which may be related to the different efficacy of the two drugs to prevent hospitalizations or SARS-related deaths. CoV-2 among high-risk patients compared with placebo (88% for Paxlovid versus 30% for molnupiravir).
In both groups of the present study, patients treated with Paxlovid were significantly different from those treated with molnupiravir, although both drugs were approved for use in people infected with SARS-CoV-2 with a high risk of severe COVID-19. . The mean age of Paxlovid-treated patients was 56 years compared with 62 of molnupiravir-treated patients, and the initial cohort also had fewer coexisting health conditions. In addition, the Paxlovid arm comprised more Hispanic, female, black, and Asian patients.
Bounce rates of COVID-19 after seven- and 30-day Paxlovid treatment were 3.53% and 5.40%; 2.31% and 5.87%; and 0.44% and 0.77% for SARS-CoV-2 infection, COVID-19 symptoms, and SARS-CoV-2-related hospitalizations, respectively. After molnupiravir therapy, the seven- and 30-day SARS-CoV-2 rebound rates were 5.86% and 8.59%, respectively; 3.75% and 8.21%; and 0.84% and 1.39% for SARS-CoV-2 infection, SARS-CoV-2 symptoms, and COVID-19-related hospitalizations, respectively.
There were no significant changes in the probability of rebound of COVID-19 for SARS-CoV-2 infection between molnupiravir and Paxlovid after the coincidence of the propensity score: SARS-CoV-2 infection (HR 0, 90 and 95% CI: 0.73-1.11), SARS -CoV-2 symptoms (HR: 1.03 and 95% CI: 0.83-1.27), or hospitalizations related to COVID- 19 (HR: 0.92 and 95% CI: 0.56–1.55). In addition, compared with those who did not, patients with SARS-CoV-2 rebound had a statistically higher prevalence of underlying health problems.
Conclusions
The results of the study indicated that the rebound of SARS-CoV-2 occurred after treatment with both molnupiravir and Paxlovid, especially in patients with pre-existing medical conditions. This shows that the rebound of COVID-19 was not Paxlovid specific and that the risks were comparable for both Paxlovid and molnupiravir. The team suggests that the rebound could be related to a chronic viral infection in some individuals who received any antiviral drug. In addition, SARS-CoV-2 rebound rates for both drugs increased over time after treatments.
Current results require continuous monitoring of COVID-19 rebound after treatments with molnupiravir and Paxlovid. The authors stated that more studies were needed to identify the mechanisms underlying SARS-CoV-2 bounces and to evaluate dosage and duration regimens that could stop them in susceptible patients.
* Important news
medRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered conclusive, guided by clinical practice or health-related behavior, or treated as established information.