In this ongoing, double-blind, phase 1–3 trial involving nonhospitalized patients with Covid-19, two fully human, neutralizing monoclonal antibodies against SARS-CoV-2 spike protein, used in a combined cocktail (REGN-COV2) to reduce the risk of the emergence of treatment-resistant mutant virus. Patients were randomly assigned (1:1:1) to receive placebo, 2.4 g of REGN-COV2, or 8.0 g of REGN-COV2 and were prospectively characterized at baseline for endogenous immune response against SARS-CoV-2. Data from 275 patients are reported. The least-squares mean difference (combined REGN-COV2 dose groups vs. placebo group) in the time-weighted average change in viral load from day 1 through day 7 was −0.56 log10 copies per milliliter (95% confidence interval [CI], −1.02 to −0.11) among patients who were serum antibody– negative at baseline and −0.41 log10 copies per milliliter (95% CI, −0.71 to −0.10) in the overall trial population. In this interim analysis, the REGN-COV2 antibody cocktail reduced viral load, with a greater effect in patients whose immune response had not yet been initiated or who had a high viral load at baseline. Safety outcomes were similar in the combined REGN-COV2 dose groups and the placebo group.

Patients hospitalized with Covid-19 pneumonia who were not receiving mechanical ventilation were randomly assigned (in a 2:1 ratio) to receive standard care plus one or two doses of either tocilizumab (8 mg per kilogram of body weight intravenously) or placebo. A total of 389 patients underwent randomization, and the modified intention-to-treat population included 249 patients in the tocilizumab group and 128 patients in the placebo group. The cumulative percentage of patients who had received mechanical ventilation or who had died by day 28 was 12.0% (95% confidence interval [CI], 8.5 to 16.9) in the tocilizumab group and 19.3% (95% CI, 13.3 to 27.4) in the placebo group (hazard ratio for mechanical ventilation or death, 0.56; 95% CI, 0.33 to 0.97; P=0.04 by the log-rank test). Clinical failure as assessed in a time-to-event analysis favored tocilizumab over placebo (hazard ratio, 0.55; 95% CI, 0.33 to 0.93). Death from any cause by day 28 occurred in 10.4% of the patients in the tocilizumab group and 8.6% of those in the placebo group (weighted difference, 2.0 percentage points; 95% CI, –5.2 to 7.8). In the safety population, serious adverse events occurred in 38 of 250 patients (15.2%) in the tocilizumab group and 25 of 127 patients (19.7%) in the placebo group. In hospitalized patients with Covid-19 pneumonia who were not receiving mechanical ventilation, tocilizumab reduced the likelihood of progression to the composite outcome of mechanical ventilation or death, but it did not improve survival. No new safety signals were identified.