The efficacy of convalescent plasma for coronavirus disease 2019 (COVID-19) is unclear. Although most randomized controlled trials have shown negative results, uncontrolled studies have suggested that the antibody content could influence patient outcomes. We conducted an open-label, randomized controlled trial of convalescent plasma for adults with COVID-19 receiving oxygen within 12 d of respiratory symptom onset (NCT04348656). Patients were allocated 2:1 to 500 ml of convalescent plasma or standard of care. The composite primary outcome was intubation or death by 30 d. Exploratory analyses of the effect of convalescent plasma antibodies on the primary outcome was assessed by logistic regression. The trial was terminated at 78% of planned enrollment after meeting stopping criteria for futility. In total, 940 patients were randomized, and 921 patients were included in the intention-to-treat analysis. Intubation or death occurred in 199/614 (32.4%) patients in the convalescent plasma arm and 86/307 (28.0%) patients in the standard of care arm—relative risk (RR) = 1.16 (95% confidence interval (CI) 0.94–1.43, P = 0.18). Patients in the convalescent plasma arm had more serious adverse events (33.4% versus 26.4%; RR = 1.27, 95% CI 1.02–1.57, P = 0.034). The antibody content significantly modulated the therapeutic effect of convalescent plasma. In multivariate analysis, each standardized log increase in neutralization or antibody-dependent cellular cytotoxicity independently reduced the potential harmful effect of plasma (odds ratio (OR) = 0.74, 95% CI 0.57–0.95 and OR = 0.66, 95% CI 0.50–0.87, respectively), whereas IgG against the full transmembrane spike protein increased it (OR = 1.53, 95% CI 1.14–2.05). Convalescent plasma did not reduce the risk of intubation or death at 30 d in hospitalized patients with COVID-19. Transfusion of convalescent plasma with unfavorable antibody profiles could be associated with worse clinical outcomes compared to standard care.

Background: The role of remdesivir inThe primary outcome was in-hospital 24.8% and 28.2%, respectively (95% CI the treatment of patients in hospital mortality. Secondary outcomes 0.72 to 1.07). For patients not mechanwith COVID-19 remains ill defined in a included changes in clinical severity, ically ventilated at baseline, the need for global context. The World Health Organ-oxygen-and ventilator-free days (at mechanical ventilation was 8.0% in those ization Solidarity randomized controlled 28 d), incidence of new oxygen or assigned remdesivir, and 15.0% in those trial (RCT) evaluated remdesivir in mechanical ventilation use, duration of receiving standard of care (RR 0.53, 95% CI patients across many countries, with hospital stay, and adverse event rates. 0.38 to 0.75). Mean oxygen-free and Canada enrolling patients using anWe performed a priori subgroup analy-ventilator-free days at day 28 were 15.9 expanded data collection format in the ses according to duration of symptoms (± standard deviation [SD] 10.5) and 21.4 Canadian Treatments for COVID-19 before enrolment, age, sex and severity (± SD 11.3) in those receiving remdesivir (CATCO) trial. We report on the Canad-of symptoms on presentation. and 14.2 (± SD 11) and 19.5 (± SD 12.3) in ian findings, with additional demo-those receiving standard of care (p = 0.006 graphics, characteristics and clinical Results: Across 52 Canadian hospitals, and 0.007, respectively). There was no difoutcomes, to explore the potential for we randomized 1282 patients between ference in safety events of new dialysis, differential effects across different Aug. 14, 2020, and Apr. 1, 2021, to remde-change in creatinine, or new hepatic dyshealth care systems.sivir (n = 634) or standard of care (n = function between the 2 groups. 648). Of these, 15 withdrew consent or Methods: We performed an open-label, were still in hospital, for a total sample of Interpretation: Remdesivir, when compragmatic RCT in Canadian hospitals, in 1267 patients. Among patients assigned pared with standard of care, has a modest conjunction with the Solidarity trial. We to receive remdesivir, in-hospital mortal-but significant efect on outcomes imporrandomized patients to 10 days of rem-ity was 18.7%, compared with 22.6% in tant to patients and health systems, such desivir (200 mg intravenously [IV] on day the standard-of-care arm (relative risk as the need for mechanical ventilation. 0, followed by 100 mg IV daily), plus[RR] 0.83 (95% confidence interval [CI] Trial registration: ClinicalTrials.gov, no. standard care, or standard care alone. 0.67 to 1.03), and 60-day mortality was NCT04330690.