Abstract: Clinical Infectious Diseases MAJOR ARTICLE Remdesivir for Severe Coronavirus Disease 2019 (COVID19) Versus a Cohort Receiving Standard of Care Susan A. Olender,1 Katherine K. Perez,2 Alan S. Go,3 Bindu Balani,4 Eboni G. Price-Haywood,5 Nirav S. Shah,6 Su Wang,7 Theresa L. Walunas,8 Shobha Swaminathan,9 Jihad Slim,10 BumSik Chin,11 Stéphane De Wit,12 Shamim M. Ali,13 Alex Soriano Viladomiu,14 Philip Robinson,15 Robert L. Gottlieb,16 Tak Yin Owen Tsang,17 I-Heng Lee,18 Hao Hu,19 Richard H. Haubrich,18 Anand P. Chokkalingam,18 Lanjia Lin,18 Lijie Zhong,18 B. Nebiyou Bekele,18 Robertino Mera-Giler,18 Chloé Phulpin,20 Holly Edgar,20 Joel Gallant,18 Helena Diaz-Cuervo,21 Lindsey E. Smith,18 Anu O. Osinusi,18 Diana M. Brainard,18 and Jose I Bernardino22; For the GS-US-540–5773 and GS-US-540–5807 Investigators 1 (See the Editorial Commentary by Gandhi on pages e4175–8.) Background. We compared the efficacy of the antiviral agent, remdesivir, versus standard-of-care treatment in adults with severe coronavirus disease 2019 (COVID-19) using data from a phase 3 remdesivir trial and a retrospective cohort of patients with severe COVID-19 treated with standard of care. Methods. GS-US-540–5773 is an ongoing phase 3, randomized, open-label trial comparing two courses of remdesivir (remdesivircohort). GS-US-540–5807 is an ongoing real-world, retrospective cohort study of clinical outcomes in patients receiving standardof-care treatment (non-remdesivir-cohort). Inclusion criteria were similar between studies: patients had confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, were hospitalized, had oxygen saturation ≤94% on room air or required supplemental oxygen, and had pulmonary infiltrates. Stabilized inverse probability of treatment weighted multivariable logistic regression was used to estimate the treatment effect of remdesivir versus standard of care. The primary endpoint was the proportion of patients with recovery on day 14, dichotomized from a 7-point clinical status ordinal scale. A key secondary endpoint was mortality. Results. After the inverse probability of treatment weighting procedure, 312 and 818 patients were counted in the remdesivirand non-remdesivir-cohorts, respectively. At day 14, 74.4% of patients in the remdesivir-cohort had recovered versus 59.0% in the non-remdesivir-cohort (adjusted odds ratio [aOR] 2.03: 95% confidence interval [CI]: 1.34–3.08, P < .001). At day 14, 7.6% of patients in the remdesivir-cohort had died versus 12.5% in the non-remdesivir-cohort (aOR 0.38, 95% CI: .22–.68, P = .001). Conclusions. In this comparative analysis, by day 14, remdesivir was associated with significantly greater recovery and 62% reduced odds of death versus standard-of-care treatment in patients with severe COVID-19. Clinical Trials Registration. NCT04292899 and EUPAS34303. Keywords. SARS-CoV-2; severe COVID-19; remdesivir; antiviral treatment. Coronavirus disease 2019 (COVID-19) is a major global public health and socioeconomic crisis, with over 18 million cases identified worldwide and more than 700 000 deaths (as of Received 29 May 2020; editorial decision 16 July 2020; accepted 20 July 2020; published online July 24, 2020. Correspondence: R. H. Haubrich, Gilead Sciences, Inc, 333 Lakeside Dr, Foster City, CA USA (Richard.Haubrich@gilead.com). Clinical Infectious Diseases®  2021;73(11):e4166–74 © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America...