ABSTRACT
Background: Sotrovimab is a pan-sarbecovirus monoclonal antibody clinically evaluated for prevention of progression of COVID-19 in high-risk patients early in the course of infection. We investigated the rate of prevention of hospitalization or death by baseline anti-SARS-CoV-2 serostatus. Methods: COMET-ICE (NCT04545060) was a multicenter, double-blind, Phase III trial in nonhospitalized adults with symptomatic COVID-19 and ≥1 risk factor for disease progression. Participants were randomized 1:1 to an IV infusion of sotrovimab 500 mg or placebo. The primary efficacy endpoint was all-cause hospitalization >24 hours or death due to any cause within 29 days. Anti-nucleocapsid SARS-CoV-2 antibody was measured by the Abbott SARS-CoV-2 IgG assay run on the Architect i2000SR immunoassay analyzer. Results: In the final dataset (N=1057), the adjusted relative risk (RR) reduction in all-cause hospitalization or death due to any cause in the sotrovimab group compared to the placebo group was 79% (p<0.001) at Day 29. 70% and 19% of participants were seronegative and seropositive for anti-nucleocapsid protein at baseline, respectively. 11% of participants had unknown antibody status and were excluded. In the seronegative subgroup, 4/365 (1%) participants in the sotrovimab group met the primary endpoint compared to 26/375 (7%) in the placebo group (84% reduction in risk [RR: 0.16;95% CI: 0.06, 0.45]). Of the 4 seronegative participants who received sotrovimab and met the primary endpoint, 1 participant was hospitalized for small intestinal obstruction that was likely unrelated to COVID-19. Two of the 26 seronegative participants in the placebo arm who met the primary endpoint died compared to no deaths in the sotrovimab group. In the seropositive subgroup, conclusions are limited by small numbers. Numerically fewer participants in the sotrovimab group (2/105, 2%) were hospitalized compared to the placebo group (4/97, 4%). Importantly, both hospitalized seropositive participants in the sotrovimab group had an alternative reason for their hospitalization that was likely unrelated to COVID-19 (diabetic foot ulcer, non-small cell lung cancer). Progression rates in the sotrovimab arm were low and similar regardless of serostatus (1% seronegative, 2% seropositive). Safety profile by serostatus was consistent with that reported in the overall population. Conclusion: Sotrovimab appeared to consistently reduce the likelihood of a COVID-19-related hospitalization or death regardless of baseline serostatus.