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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.
BMJ. 2022 03 09; 376:e069761.BMJ

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.

Authors+Show Affiliations

Departments of Internal Medicine and Microbiology and Immunology, University of Michigan, Ann Arbor, MI, USA.CDC COVID-19 Response Team, Atlanta, GA, USA.Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA.Baylor Scott and White Health, Texas A&M University College of Medicine, Temple, TX, USA.Department of Emergency Medicine, University of Colorado School of Medicine, Aurora, CO, USA.Baylor Scott and White Health, Texas A&M University College of Medicine, Temple, TX, USA.Baylor Scott and White Health, Texas A&M University College of Medicine, Temple, TX, USA.Department of Anesthesiology, University of Colorado School of Medicine, Aurora, CO, USA.Department of Health Policy, Vanderbilt University Medical Center, Nashville, TN, USA. Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.Department of Emergency Medicine, University of Iowa, Iowa City, IA, USA.Department of Emergency Medicine, University of Iowa, Iowa City, IA, USA.Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.Department of Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA.Department of Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA.Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.Department of Emergency Medicine, Hennepin County Medical Center, Minneapolis, MN, USA. Department of Medicine, Hennepin County Medical Center, Minneapolis, MN, USA.Department of Medicine, Hennepin County Medical Center, Minneapolis, MN, USA.Department of Medicine, The Ohio State University, Columbus, OH, USA.Department of Medicine, Montefiore Health System, Albert Einstein College of Medicine, Bronx, New York, NY, USA.Department of Medicine, Montefiore Health System, Albert Einstein College of Medicine, Bronx, New York, NY, USA.Division of Pulmonary, Critical Care and Sleep Medicine, University of Washington, Seattle, WA, USA. Department of Emergency Medicine, University of Washington, Seattle, WA, USA.Department of Emergency Medicine, University of Washington, Seattle, WA, USA.Department of Medicine, Baystate Medical Center, Springfield, MA, USA.Department of Medicine, Intermountain Medical Center, Murray, Utah and University of Utah, Salt Lake City, UT, USA.Department of Medicine, Intermountain Medical Center, Murray, Utah and University of Utah, Salt Lake City, UT, USA.School of Public Health, University of Michigan, Ann Arbor, MI, USA.School of Public Health, University of Michigan, Ann Arbor, MI, USA.Department of Medicine, Oregon Health and Sciences University, Portland, OR, USA.Department of Medicine, Oregon Health and Sciences University, Portland, OR, USA.Department of Medicine, Emory University, Atlanta, GA, USA.Emory Critical Care Center, Emory Healthcare, Atlanta, GA, USA.Department of Medicine, Cleveland Clinic, Cleveland, OH, USA.Department of Emergency Medicine, Stanford University School of Medicine, Stanford, CA, USA.Department of Emergency Medicine, Stanford University School of Medicine, Stanford, CA, USA.Department of Medicine, University of California-Los Angeles, Los Angeles, CA, USA.Department of Medicine, University of California-Los Angeles, Los Angeles, CA, USA.Department of Medicine, University of Miami, Miami, FL, USA.Department of Medicine, University of Miami, Miami, FL, USA.Department of Medicine, Washington University, St Louis, MI, USA.Department of Medicine, Washington University, St Louis, MI, USA.Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA.Department of Health Policy, Vanderbilt University Medical Center, Nashville, TN, USA.Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.Vanderbilt Institute for Clinical and Translational Research, Vanderbilt University Medical Center, Nashville, TN, USA.Vanderbilt Institute for Clinical and Translational Research, Vanderbilt University Medical Center, Nashville, TN, USA.Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA.Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA.Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA.CDC COVID-19 Response Team, Atlanta, GA, USA.CDC COVID-19 Response Team, Atlanta, GA, USA.CDC COVID-19 Response Team, Atlanta, GA, USA.CDC COVID-19 Response Team, Atlanta, GA, USA.CDC COVID-19 Response Team, Atlanta, GA, USA.CDC COVID-19 Response Team, Atlanta, GA, USA.Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville, TN, USA wesley.self@vumc.org. Vanderbilt Institute for Clinical and Translational Research, Vanderbilt University Medical Center, Nashville, TN, USA.No affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Observational Study
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

35264324

Citation

Lauring, Adam S., et al. "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." BMJ (Clinical Research Ed.), vol. 376, 2022, pp. e069761.
Lauring AS, Tenforde MW, Chappell JD, et al. 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. BMJ. 2022;376:e069761.
Lauring, A. S., Tenforde, M. W., Chappell, J. D., Gaglani, M., Ginde, A. A., McNeal, T., Ghamande, S., Douin, D. J., Talbot, H. K., Casey, J. D., Mohr, N. M., Zepeski, A., Shapiro, N. I., Gibbs, K. W., Files, D. C., Hager, D. N., Shehu, A., Prekker, M. E., Erickson, H. L., ... Self, W. H. (2022). 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. BMJ (Clinical Research Ed.), 376, e069761. https://doi.org/10.1136/bmj-2021-069761
Lauring AS, et al. 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. BMJ. 2022 03 9;376:e069761. PubMed PMID: 35264324.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Lauring,Adam S, AU - Tenforde,Mark W, AU - Chappell,James D, AU - Gaglani,Manjusha, AU - Ginde,Adit A, AU - McNeal,Tresa, AU - Ghamande,Shekhar, AU - Douin,David J, AU - Talbot,H Keipp, AU - Casey,Jonathan D, AU - Mohr,Nicholas M, AU - Zepeski,Anne, AU - Shapiro,Nathan I, AU - Gibbs,Kevin W, AU - Files,D Clark, AU - Hager,David N, AU - Shehu,Arber, AU - Prekker,Matthew E, AU - Erickson,Heidi L, AU - Exline,Matthew C, AU - Gong,Michelle N, AU - Mohamed,Amira, AU - Johnson,Nicholas J, AU - Srinivasan,Vasisht, AU - Steingrub,Jay S, AU - Peltan,Ithan D, AU - Brown,Samuel M, AU - Martin,Emily T, AU - Monto,Arnold S, AU - Khan,Akram, AU - Hough,Catherine L, AU - Busse,Laurence W, AU - Ten Lohuis,Caitlin C, AU - Duggal,Abhijit, AU - Wilson,Jennifer G, AU - Gordon,Alexandra June, AU - Qadir,Nida, AU - Chang,Steven Y, AU - Mallow,Christopher, AU - Rivas,Carolina, AU - Babcock,Hilary M, AU - Kwon,Jennie H, AU - Halasa,Natasha, AU - Grijalva,Carlos G, AU - Rice,Todd W, AU - Stubblefield,William B, AU - Baughman,Adrienne, AU - Womack,Kelsey N, AU - Rhoads,Jillian P, AU - Lindsell,Christopher J, AU - Hart,Kimberly W, AU - Zhu,Yuwei, AU - Adams,Katherine, AU - Schrag,Stephanie J, AU - Olson,Samantha M, AU - Kobayashi,Miwako, AU - Verani,Jennifer R, AU - Patel,Manish M, AU - Self,Wesley H, AU - ,, Y1 - 2022/03/09/ PY - 2022/3/10/entrez PY - 2022/3/11/pubmed PY - 2022/3/15/medline SP - e069761 EP - e069761 JF - BMJ (Clinical research ed.) JO - BMJ VL - 376 N2 - 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. SN - 1756-1833 UR - https://www.unboundmedicine.com/medline/citation/35264324/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_ DB - PRIME DP - Unbound Medicine ER -