Discussion
death, cancer, Nucleocapsid, infection, infectious SARS-CoV-2
ADVERSE EVENTS, INFECTION, VIRUS, CANCER
Immunocompromised participants in phase 3 of the MOVe-OUT trial who received molnupiravir had a lower incidence of all-cause hospitalization or death without any concerning adverse events through Day 29 compared to placebo (8.3% [2/24] versus 22.6% [7/31]). Reductions in viral RNA in both treatment groups were generally consistent in immunocompromised participants, but no infectious virus was detected after baseline in any immunocompromised molnupiravir-treated participants, while infectious virus was detected post-baseline in the placebo group. Consistent with its mechanism of action, an increased viral error rate was observed in molnupiravir-treated participants, regardless of immunocompromised status. Immunocompromised participants receiving molnupiravir were not more likely to develop novel treatment-emergent amino acid substitutions in this study. Nucleocapsid antibody positivity was generally similar in both treatment groups irrespective of immunocompromised status, while a smaller mean increase from baseline in neutralizing antibody titers in molnupiravir-treated immunocompromised participants was observed at Day 29.Delayed clearance of infectious virus in immunocompromised individuals is concerning from an infection control standpoint because of increased potential for transmission and emergence of new SARS-CoV-2 variants. Case reports have noted persistent infectious SARS-CoV-2 shedding in immunocompromised individuals [The proportion of immunocompromised participants positive for spike protein neutralizing antibody at baseline was about 10% lower than the proportion positive in non-immunocompromised participants. In general, antibody responses were comparable in both treatment groups regardless of immunocompromised status. The smaller mean change from baseline in neutralizing antibody titers observed in immunocompromised participants in the molnupiravir group compared with the placebo group at Day 29 may have resulted from less antigenic stimulation due to earlier clearance of the virus with molnupiravir therapy.Real-world evidence on the use of molnupiravir in immunocompromised patients is beginning to emerge in published literature [A strength of this analysis is the scope of virologic data that were evaluated in this cohort of immunocompromised participants, with analyses performed on nasopharyngeal samples that were prospectively collected at multiple timepoints in phase 3 of the MOVe-OUT trial. These data add to the very limited literature on outcomes in immunocompromised individuals treated for COVID-19 since they are usually excluded from clinical trials. Our analysis was limited by the small sample of non-hospitalized immunocompromised participants, most of whom had active cancer or well-controlled HIV; therefore, this cohort is not representative of all immunocompromised individuals, for example, patients with depleted T-cells due to uncontrolled HIV or recipients of T-cell depleting agents (i.e., antithymocyte globulin, alemtuzumab) [