Respiratory virus coinfections during the COVID-19 pandemic: epidemiologic analysis and clinical outcomes from the Phase 2/3 molnupiravir trial (MOVe-OUT).

This exploratory post hoc analysis assessed the incidence of respiratory viral coinfections and their impact on clinical outcomes in non-hospitalized adults with mild-to-moderate coronavirus disease-2019 (COVID-19) treated with molnupiravir versus placebo for 5 days in the Phase 2/3 MOVe-OUT trial (NCT04575597), which took place in October 2020 to January 2021 (Phase 2, n = 302) and May 2021 to October 2021 (Phase 3, n = 1,433). Among 1,735 total randomized participants, 1,674 had a baseline respiratory pathogen panel (NxTAG Respiratory Pathogen Panel for the Luminex MAGPIX instrument) performed and 69 (4.1%) were coinfected with at least one additional respiratory viral pathogen. Human rhinovirus/enterovirus (39/69, 56.5%) was the most common coinfection detected at baseline. In the modified intention-to-treat population, two participants with coinfecting respiratory RNA viruses were hospitalized and received respiratory interventions through Day 29, and none died; one participant in the molnupiravir group was coinfected with human rhinovirus/enterovirus, and one participant in the placebo group was coinfected with human metapneumovirus. Hospitalization or death occurred in 6.2% and 9.0% of non-coinfected participants in the molnupiravir versus placebo group, respectively, and over 90% did not require respiratory interventions. Most coinfecting respiratory RNA viruses detected at baseline were not detected at the end of therapy in both the molnupiravir and placebo groups. In summary, participants coinfected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and another respiratory RNA virus were not more likely to be hospitalized or die, or require respiratory interventions, compared to participants who were not coinfected with another respiratory RNA virus at baseline in both groups. IMPORTANCE: Respiratory viral coinfections are known to occur with coronavirus disease-2019 (COVID-19). In a cohort of non-hospitalized adults with mild-to-moderate COVID-19 treated with molnupiravir versus placebo in the MOVe-OUT trial during October 2020 to October 2021, 4.1% of participants had a documented viral coinfection; human rhinovirus/enterovirus was the most common pathogen detected with the NxTAG Respiratory Pathogen Panel assay. Participants who had a coinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and another respiratory RNA virus were not more likely to have worse clinical outcomes compared to those participants without a viral coinfection, and many coinfecting respiratory RNA viruses were no longer detected at the end of the 5-day treatment period in both groups.

Randomized Trial of Molnupiravir or Placebo in Patients Hospitalized with Covid-19.

BACKGROUND: Molnupiravir is an oral prodrug of ß-D-N4-hydroxycytidine, active against SARS-CoV-2 in vitro and in animal models. We report data from the phase 2 component of MOVe-IN, a clinical trial evaluating molnupiravir in patients hospitalized with Covid-19. METHODS: We conducted a randomized, placebo-controlled, double-blind phase 2/3 trial in patients 18 years old and older requiring in-hospital treatment for laboratory-confirmed Covid-19 with symptom onset 10 or fewer days before randomization. Participants were randomly assigned to placebo or molnupiravir 200 mg, 400 mg, or 800 mg (1:1:1:1 ratio), twice daily for 5 days. Primary end points were safety and sustained recovery (participant alive and either not hospitalized or medically ready for discharge) through day 29. RESULTS: Of 304 randomly assigned participants, 218 received at least one dose of molnupiravir and 75 of placebo. At baseline, 74.0% had at least one risk factor for severe Covid-19. Adverse events were reported in 121 of 218 (55.5%) molnupiravir-treated and 46 of 75 (61.3%) placebo-treated participants, with no apparent dose effect on adverse event rates and no evidence of hematologic toxicity based on prespecified adverse events. Of 16 confirmed deaths, most were in participants with severe Covid-19 (75.0%), with underlying comorbidities (87.5%), older than 60 years of age (81.3%), and/or symptom duration longer than 5 days (75.0%) at randomization. Median time to sustained recovery was 9 days in all groups, with similar day 29 recovery rates ranging from 81.5% to 85.2%. CONCLUSIONS: In this phase 2 trial of patients hospitalized with Covid-19, a 5-day course of molnupiravir up to 800 mg twice daily was not associated with dose-limiting side effects or adverse events, but did not demonstrate clinical benefit. (Funded by Merck Sharp & Dohme; ClinicalTrials.gov NCT04575584.)