• Hana M El Sahly, Lindsey R Baden, Brandon Essink, Susanne Doblecki-Lewis, Judith M Martin, Evan J Anderson, Thomas B Campbell, Jesse Clark, Lisa A Jackson, Carl J Fichtenbaum, Marcus Zervos, Bruce Rankin, Frank Eder, Gregory Feldman, Christina Kennelly, Laurie Han-Conrad, Michael Levin, Kathleen M Neuzil, Lawrence Corey, Peter Gilbert, Holly Janes, Dean Follmann, Mary Marovich, Laura Polakowski, John R Mascola, Julie E Ledgerwood, Barney S Graham, Allison August, Heather Clouting, Weiping Deng, Shu Han, Brett Leav, Deb Manzo, Rolando Pajon, Florian Schödel, Joanne E Tomassini, Honghong Zhou, Jacqueline Miller, and COVE Study Group.
• From Baylor College of Medicine, Houston (H.M.E.S.), and Javara, The Woodlands (C.K.) - both in Texas; Brigham and Women's Hospital, Boston (L.R.B.), and Moderna, Cambridge (A.A., H.C., W.D., S.H., B.L., D.M., R.P., F.S., J.E.T., H.Z., J.M.) - both in Massachusetts; Meridian Clinical Research, Baton Rouge, LA (B.E., F.E.); University of Miami, Miami (S.D.-L.), and DeLand Clinical Research Unit, DeLand (B.R.) - both in Florida; University of Pittsburgh School of Medicine, Pittsburgh (J.M.M.); Emory University School of Medicine, Atlanta (E.J.A.); University of Colorado School of Medicine, Aurora (T.B.C.); University of California, Los Angeles (J.C.), and Wake Research-Medical Center for Clinical Research, San Diego (L.H.-C.) - both in California; Kaiser Permanente Washington Health Research Institute (L.A.J.), and Fred Hutchinson Cancer Research Center (L.C., P.G., H.J.) - both in Seattle; University of Cincinnati, Cincinnati (C.J.F.); Henry Ford Health System, Detroit (M.Z.); Vitalink Research, Greenville, SC (G.F.); Clinical Research Center of Nevada, Wake Research, Las Vegas (M.L.); and the University of Maryland, College Park (K.M.N.), and the Vaccine Research Center (J.R.M., J.E.L., B.S.G.), National Institute of Allergy and Infectious Diseases (D.F., M.M., L.P.), National Institutes of Health, Bethesda - both in Maryland.
• N. Engl. J. Med. 2021 Nov 4; 385 (19): 177417851774-1785.

BackgroundAt interim analysis in a phase 3, observer-blinded, placebo-controlled clinical trial, the mRNA-1273 vaccine showed 94.1% efficacy in preventing coronavirus disease 2019 (Covid-19). After emergency use of the vaccine was authorized, the protocol was amended to include an open-label phase. Final analyses of efficacy and safety data from the blinded phase of the trial are reported.MethodsWe enrolled volunteers who were at high risk for Covid-19 or its complications; participants were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 μg) or placebo, 28 days apart, at 99 centers across the United States. The primary end point was prevention of Covid-19 illness with onset at least 14 days after the second injection in participants who had not previously been infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The data cutoff date was March 26, 2021.ResultsThe trial enrolled 30,415 participants; 15,209 were assigned to receive the mRNA-1273 vaccine, and 15,206 to receive placebo. More than 96% of participants received both injections, 2.3% had evidence of SARS-CoV-2 infection at baseline, and the median follow-up was 5.3 months in the blinded phase. Vaccine efficacy in preventing Covid-19 illness was 93.2% (95% confidence interval [CI], 91.0 to 94.8), with 55 confirmed cases in the mRNA-1273 group (9.6 per 1000 person-years; 95% CI, 7.2 to 12.5) and 744 in the placebo group (136.6 per 1000 person-years; 95% CI, 127.0 to 146.8). The efficacy in preventing severe disease was 98.2% (95% CI, 92.8 to 99.6), with 2 cases in the mRNA-1273 group and 106 in the placebo group, and the efficacy in preventing asymptomatic infection starting 14 days after the second injection was 63.0% (95% CI, 56.6 to 68.5), with 214 cases in the mRNA-1273 group and 498 in the placebo group. Vaccine efficacy was consistent across ethnic and racial groups, age groups, and participants with coexisting conditions. No safety concerns were identified.ConclusionsThe mRNA-1273 vaccine continued to be efficacious in preventing Covid-19 illness and severe disease at more than 5 months, with an acceptable safety profile, and protection against asymptomatic infection was observed. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; COVE ClinicalTrials.gov number, NCT04470427.).Copyright © 2021 Massachusetts Medical Society.

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