@article{6d11338d65e845a79636f81bf1b238de,
title = "Clinical severity of, and effectiveness of mRNA vaccines against, covid-19 from omicron, delta, and alpha SARS-CoV-2 variants in the United States: Prospective observational study",
abstract = "Objectives To characterize the clinical severity of covid-19 associated with the alpha, delta, and omicron SARS-CoV-2 variants among adults admitted to hospital and to compare the effectiveness of mRNA vaccines to prevent hospital admissions related to each variant. Design Case-control study. Setting 21 hospitals across the United States. Participants 11 690 adults (≥18 years) admitted to hospital: 5728 with covid-19 (cases) and 5962 without covid-19 (controls). Patients were classified into SARS-CoV-2 variant groups based on viral whole genome sequencing, and, if sequencing did not reveal a lineage, by the predominant circulating variant at the time of hospital admission: Alpha (11 March to 3 July 2021), delta (4 July to 25 December 2021), and omicron (26 December 2021 to 14 January 2022). Main outcome measures Vaccine effectiveness calculated using a test negative design for mRNA vaccines to prevent covid-19 related hospital admissions by each variant (alpha, delta, omicron). Among patients admitted to hospital with covid-19, disease severity on the World Health Organization's clinical progression scale was compared among variants using proportional odds regression. Results Effectiveness of the mRNA vaccines to prevent covid-19 associated hospital admissions was 85% (95% confidence interval 82% to 88%) for two vaccine doses against the alpha variant, 85% (83% to 87%) for two doses against the delta variant, 94% (92% to 95%) for three doses against the delta variant, 65% (51% to 75%) for two doses against the omicron variant; and 86% (77% to 91%) for three doses against the omicron variant. In-hospital mortality was 7.6% (81/1060) for alpha, 12.2% (461/3788) for delta, and 7.1% (40/565) for omicron. Among unvaccinated patients with covid-19 admitted to hospital, severity on the WHO clinical progression scale was higher for the delta versus alpha variant (adjusted proportional odds ratio 1.28, 95% confidence interval 1.11 to 1.46), and lower for the omicron versus delta variant (0.61, 0.49 to 0.77). Compared with unvaccinated patients, severity was lower for vaccinated patients for each variant, including alpha (adjusted proportional odds ratio 0.33, 0.23 to 0.49), delta (0.44, 0.37 to 0.51), and omicron (0.61, 0.44 to 0.85). Conclusions mRNA vaccines were found to be highly effective in preventing covid-19 associated hospital admissions related to the alpha, delta, and omicron variants, but three vaccine doses were required to achieve protection against omicron similar to the protection that two doses provided against the delta and alpha variants. Among adults admitted to hospital with covid-19, the omicron variant was associated with less severe disease than the delta variant but still resulted in substantial morbidity and mortality. Vaccinated patients admitted to hospital with covid-19 had significantly lower disease severity than unvaccinated patients for all the variants.",
author = "Lauring, {Adam S.} and Tenforde, {Mark W.} and Chappell, {James D.} and Manjusha Gaglani and Ginde, {Adit A.} and Tresa Mcneal and Shekhar Ghamande and Douin, {David J.} and Talbot, {H. Keipp} and Casey, {Jonathan D.} and Mohr, {Nicholas M.} and Anne Zepeski and Shapiro, {Nathan I.} and Gibbs, {Kevin W.} and Files, {D. Clark} and Hager, {David N.} and Arber Shehu and Prekker, {Matthew E.} and Erickson, {Heidi L.} and Exline, {Matthew C.} and Gong, {Michelle N.} and Amira Mohamed and Johnson, {Nicholas J.} and Vasisht Srinivasan and Steingrub, {Jay S.} and Peltan, {Ithan D.} and Brown, {Samuel M.} and Martin, {Emily T.} and Monto, {Arnold S.} and Akram Khan and Hough, {Catherine L.} and Busse, {Laurence W.} and {Ten Lohuis}, {Caitlin C.} and Abhijit Duggal and Wilson, {Jennifer G.} and Gordon, {Alexandra June} and Nida Qadir and Chang, {Steven Y.} and Christopher Mallow and Carolina Rivas and Babcock, {Hilary M.} and Kwon, {Jennie H.} and Natasha Halasa and Grijalva, {Carlos G.} and Rice, {Todd W.} and Stubblefield, {William B.} and Adrienne Baughman and Womack, {Kelsey N.} and Rhoads, {Jillian P.} and Lindsell, {Christopher J.} and Hart, {Kimberly W.} and Yuwei Zhu and Katherine Adams and Schrag, {Stephanie J.} and Olson, {Samantha M.} and Miwako Kobayashi and Verani, {Jennifer R.} and Patel, {Manish M.} and Self, {Wesley H.}",
note = "Funding Information: 26Department of Emergency Medicine, Stanford University School of Medicine, Stanford, CA, USA 27Department of Medicine, University of California‑Los Angeles, Los Angeles, CA, USA 28Department of Medicine, University of Miami, Miami, FL, USA 29Department of Medicine, Washington University, St Louis, MI, USA 30Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville, TN, USA 31Vanderbilt Institute for Clinical and Translational Research, Vanderbilt University Medical Center, Nashville, TN, USA 32Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA See supplementary appendix A for full list of investigators and collaborators in the Influenza and other Viruses in the Acutely Ill (IVY) Network. Contributors: ASL, MWT, and JDC contributed equally to this work as lead authors. WHS (protocol and data integrity and participant enrollment), MWT (statistical analysis), ASL (viral sequencing laboratory methods), and JDC (reverse‑transcription polymerase chain reaction laboratory methods) are the guarantors for this work. WHS was responsible for the decision to submit the manuscript and takes responsibility for the work overall. ASL, MWT, JDC, MMP, and WHS wrote the initial manuscript draft (the authors alone wrote the manuscript without outside assistance). ASL, MWT, JDC, HKT, CJL, CGG, SJS, MK, JRV, MMP, and WHS conceptualized the study methods. ASL, JDC, MG, AAG, TMcN, SG, DJD, HKT, JDC, NMM, AZ, NIS, KWG, DCF, DNH, AS, MEP, HLE, MCE, MNG, AM, NJJ, VS, JSS, IDP, SMB, ETM, ASM, AK, CLH, LWB, CCtL, AD, JGW, AJG, NQ, SYC, CM, CR, HMB, JHK, NH, CGG, TWR, WBS, AB, KNW, JPR, and WHS collected the data. MWT, CJL, KWH, YZ, KA, and SMO were responsible for statistical analysis and data management. WHS acquired the funding. ASL, MWT, JDC, MG, AAG, TMcN, SG, DJD, HKT, JDC, NMM, AZ, NIS, KWG, DCF, DNH, AS, MEP, HLE, MCE, MNG, AM, NJJ, VS, JSS, IDP, SMB, ETM, ASM, AK, CLH, LWB, CCtL, AD, JGW, AJG, NQ, SYC, CM, CR, HMB, JHK, NH, CGG, TWR, WBS, AB, KNW, JPR, ASL, KWH, YZ, KA, SJS, SMO, MK, JRV, MMP, and WHS critically reviewed the manuscript for important intellectual content. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. Funding: This study was funded by the US Centers for Disease Control and Prevention (CDC, award 75D30121F00002 to WHS). Scientists from CDC participated in all aspects of this study, including its design, analysis, interpretation of data, writing of the report, and the decision to submit the article for publication. The REDCap data tool used in this study was supported by a Clinical and Translational Science Award (UL1 TR002243) from the National Center for Advancing Translational Sciences, National Institutes of Health. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of CDC or the Agency for Toxic Substances and Disease Registry. Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare the following. This study was funded by the US Centers for Disease Control and Prevention (CDC). ASL reports consultant fees from Sanofi and fees from Roche for membership on a trial steering committee. JDC reports grant support from CDC and National Institutes of Health (NIH). MG reports grant support from CDC. AAG reports grant support from CDC, NIH, Department of Defense (DoD), and an investigator initiated grant support from AbbVie and Faron Pharmaceuticals. HKT reports a grant from CDC. JDC reports a grant from the NIH (K23HL153584). DCF reports consultant fees from Cytovale and membership on a Medpace data safety monitoring board (DSMB). DNH reports a contract from CDC (via subcontract with Vanderbilt University Medical Center) and salary support from Incyte, EMPACT Precision Medicine, and the Marcus Foundation. MCE reports talks on nutrition in covid‑19 pneumonia at the Nutritional Science and Practice Conference sponsored by Abbott Laboratories. MNG reports grant support from CDC, funding from the National Heart, Lung, and Blood Institute, and fees for participating on a DSMB for Regeneron. IDP reports grants from CDC, NIH, Intermountain Research and Medical Foundation, and Janssen Pharmaceuticals, institutional fees from Asahi Kasei Pharma and from Regeneron. SMB reports grants from CDC, Sedana, Janssen, NIH, and DoD; fees from Hamilton for chairing a DSMB; institutional fees from Faron; book royalties from Oxford University and Brigham Young University; and personal fees from New York University for service on a DSMB. ETM reports a grant from Merck for unrelated work. AK reports grants from Gilead, Ely Lily, United Therapeutics, Johnson and Johnson (Actelion), Liquidia Pharmaceuticals, and 4D Medical. SYC was a speaker for La Jolla Pharmaceuticals and a consultant for PureTech Health. JHK reports grant support from NIH/National Institute of Allergy and Infectious Diseases (1K23 AI137321‑01A1). NH reports grants from CDC, Sanofi, and Quidel. CGG reports consultant fees from Pfizer, Merck, and Sanofi‑Pasteur and grants from Campbell Alliance/Syneos Health, CDC, NIH, Food and Drug Administration, Agency for Healthcare Research and Quality, and Sanofi. TR reports grant support from CDC. CJL reports grants from CDC, NIH, DoD, and the Marcus Foundation; organizational contract fees from bioMerieux, Endpoint, and Entegrion; and a patent issued to Cincinnati Children{\textquoteright}s Hospital Medical Center for risk stratification in sepsis and septic shock. WHS reports grant funding from CDC for this work, grants and consultant fees from Merck outside this work, and consultant fees from Aerpio Pharmaceuticals outside this work. Ethical approval: This programme was approved as a public health surveillance activity with waiver of informed consent by institutional review boards at the US Centers for Disease Control and Prevention, the programme{\textquoteright}s coordinating center at Vanderbilt University Medical Center, and each participating site. Data sharing: No additional data available. The study guarantors (WHS, MWT, ASL, and JDC) affirm that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned have been explained. Publisher Copyright: {\textcopyright} Author(s) (or their employer(s)) 2019.",
year = "2022",
month = mar,
day = "9",
doi = "10.1136/bmj-2021-069761",
language = "English (US)",
volume = "376",
journal = "BMJ (Online)",
issn = "0267-0623",
publisher = "BMJ Publishing Group",
}