Limitations
death, subvariants
While the randomized placebo-controlled design, standardized outcome measures, and diverse population are strengths of our study, there are limitations. Foremost, phase 2 studies within ACTIV-2 were powered for the primary virologic end point and were not designed to detect differences in rates of hospitalization or death. As age is a major risk factor for COVID-19 progression, the younger age of participants in this study could have contributed to lower hospitalization rates, further limiting evaluation of this end point. Although only higher-risk participants were eligible for the IV group, and the effect of the study agent on COVID-19 progression appeared stronger in that group, which was older than the IM group, the hospitalization rate across the IM and IV placebo arms was similar. Enrollment into the IV group was truncated, which reduced statistical power and our ability to detect signals in the primary analyses.Enrollment into ACTIV-2 occurred prior to the widespread circulation of the Delta variant, and this mAb combination has reduced neutralization against Omicron subvariants.