In this study, use of casirivimab and imdevimab (monoclonal antibodies) in combination in patients hospitalized for COVID-19 led to decrease in 28-day mortality in those who were seronegative (and thus had not mounted their own humoral immune response) at baseline but not in those who were seropositive at baseline.

• In this randomized, controlled, open-label platform trial (RECOVERY), patients aged at least 12 years admitted to hospital with clinically suspected or laboratory-confirmed SARS-CoV-2 infection were included.

• A total of 4,839 patients were randomized to casirivimab and imdevimab plus usual care and 4946 to usual care alone.

• In the primary efficacy population of seronegative patients, death within 28 days occurred of 24% of patients who received casirivimab and imdevimab vs 30% of patients allocated to usual care (rate ratio [RR] 0·79).

• In an analysis of all randomly assigned patients (regardless of baseline antibody status), 19% of patients treated with casirivimab and imdevimab vs 21% of patients allocated to usual care died within 28 days (RR 0·94).

• The proportional impact of casirivimab and imdevimab on death varied significantly between seropositive and seronegative patients.

• No treatment related deaths occurred, and no meaningful between-group differences existed in the pre-specified safety outcomes of cause-specific mortality, cardiac arrhythmia, thrombosis, or major bleeding events.