RESUMO
BackgroundHospitalized patients with COVID-19 experience high mortality rates, ranging from 10% to 30%. Combined casirivimab and imdevimab (CAS+IMD) is authorized for use in outpatients with COVID-19 and in post-exposure prophylaxis. The UK-based platform RECOVERY study reported improved survival in hospitalized seronegative patients treated with CAS+IMD; however, in most of the world, anti-spike monoclonal antibody therapy is currently not approved for hospitalized patients. MethodsIn this phase I/II/III double-blind placebo-controlled trial, patients hospitalized with COVID-19 were randomized (1:1:1) to 2.4 g or 8.0 g of CAS+IMD or placebo, and characterized at baseline for viral load and SARS-CoV-2 endogenous immune response. Results1336 patients on low-flow or no supplemental oxygen were treated. The primary endpoint was met: in seronegative patients, the least squares mean difference (CAS+IMD vs placebo) for time-weighted average change from baseline viral load was -0.28 log10 copies/mL (95% confidence interval [CI] -0.51 to -0.05; P = .0172). The primary clinical analysis of death or mechanical ventilation from day 6 to 29 in patients with high viral load had a strong positive trend but did not reach significance. CAS+IMD numerically reduced all-cause mortality in seronegative patients through day 29 (relative risk reduction, 55.6%; 95% CI 24.2-74.0; nominal P = .0032). No safety concerns were noted. ConclusionsIn hospitalized patients with COVID-19 on low-flow or no oxygen, CAS+IMD treatment reduced viral load and the risk of death or mechanical ventilation as well as all-cause mortality in the overall population, with the benefit driven by seronegative patients and no harm observed in seropositive patients.
