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

被引：461

作者：

Lauring, Adam S. ^{[1
,2
,3
]}

Tenforde, Mark W. ^{[4
]}

Chappell, James D. ^{[5
]}

Gaglani, Manjusha ^{[6
]}

Ginde, Adit A. ^{[7
]}

McNeal, Tresa ^{[6
]}

Ghamande, Shekhar ^{[6
]}

Douin, David J. ^{[8
]}

Talbot, H. Keipp ^{[9
,10
]}

Casey, Jonathan D. ^{[10
]}

Mohr, Nicholas M. ^{[11
]}

Zepeski, Anne ^{[11
]}

Shapiro, Nathan, I ^{[12
]}

Gibbs, Kevin W. ^{[13
]}

Files, D. Clark ^{[13
]}

Hager, David N. ^{[14
]}

Shehu, Arber ^{[14
]}

Prekker, Matthew E. ^{[15
,16
]}

Erickson, Heidi L. ^{[16
]}

Exline, Matthew C. ^{[17
]}

Gong, Michelle N. ^{[18
]}

Mohamed, Amira ^{[18
]}

Johnson, Nicholas J. ^{[19
,20
]}

Srinivasan, Vasisht ^{[20
]}

Steingrub, Jay S. ^{[21
]}

Peltan, Ithan D. ^{[22
,23
]}

Brown, Samuel M. ^{[22
,23
]}

Martin, Emily T. ^{[24
]}

Monto, Arnold S. ^{[24
]}

Khan, Akram ^{[25
]}

Hough, Catherine L. ^{[25
]}

Busse, Laurence W. ^{[26
]}

ten Lohuis, Caitlin C. ^{[27
]}

Duggal, Abhijit ^{[28
]}

Wilson, Jennifer G. ^{[29
]}

Gordon, Alexandra June ^{[29
]}

Qadir, Nida ^{[30
]}

Chang, Steven Y. ^{[30
]}

Mallow, Christopher ^{[31
]}

Rivas, Carolina ^{[31
]}

Babcock, Hilary M. ^{[32
]}

Kwon, Jennie H. ^{[32
]}

Halasa, Natasha ^{[5
]}

Grijalva, Carlos G. ^{[9
]}

Rice, Todd W. ^{[10
]}

Stubblefield, William B. ^{[33
]}

Baughman, Adrienne ^{[33
]}

Womack, Kelsey N. ^{[34
]}

Rhoads, Jillian P. ^{[34
]}

Lindsell, Christopher J. ^{[35
]}

机构：

[1] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA

[2] Univ Michigan, Dept Microbiol, Ann Arbor, MI 48109 USA

[3] Univ Michigan, Dept Immunol, Ann Arbor, MI 48109 USA

[4] CDC COVID 19 Response Team, Atlanta, GA USA

[5] Vanderbilt Univ, Med Ctr, Dept Pediat, Nashville, TN 37232 USA

[6] Texas A&M Univ, Coll Med, Baylor Scott & White Hlth, Temple, TX 76508 USA

[7] Univ Colorado, Sch Med, Dept Emergency Med, Aurora, CO USA

[8] Univ Colorado, Sch Med, Dept Anesthesiol, Aurora, CO USA

[9] Vanderbilt Univ, Med Ctr, Dept Hlth Policy, Nashville, TN USA

[10] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA

[11] Univ Iowa, Dept Emergency Med, Iowa City, IA USA

[12] Beth Israel Deaconess Med Ctr, Dept Emergency Med, Boston, MA 02215 USA

[13] Wake Forest Sch Med, Dept Med, Winston Salem, NC 27101 USA

[14] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA

[15] Hennepin Cty Med Ctr, Dept Emergency Med, Minneapolis, MN 55415 USA

[16] Hennepin Cty Med Ctr, Dept Med, Minneapolis, MN 55415 USA

[17] Ohio State Univ, Dept Med, Columbus, OH 43210 USA

[18] Albert Einstein Coll Med, Dept Med, Montefiore Hlth Syst, Bronx, NY USA

[19] Univ Washington, Div Pulm Crit Care & Sleep Med, Seattle, WA 98195 USA

[20] Univ Washington, Dept Emergency Med, Seattle, WA 98195 USA

[21] Baystate Med Ctr, Dept Med, Springfield, MA 01199 USA

[22] Intermt Med Ctr, Dept Med, Murray, UT USA

[23] Univ Utah, Salt Lake City, UT USA

[24] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA

[25] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA

[26] Emory Univ, Dept Med, Atlanta, GA 30322 USA

[27] Emory Healthcare, Emory Crit Care Ctr, Atlanta, GA USA

[28] Cleveland Clin, Dept Med, Cleveland, OH USA

[29] Stanford Univ, Sch Med, Dept Emergency Med, Stanford, CA 94305 USA

[30] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA

[31] Univ Miami, Dept Med, Miami, FL USA

[32] Washington Univ, Dept Med, St Louis, MI USA

[33] Vanderbilt Univ, Dept Emergency Med, Med Ctr, Nashville, TN 37235 USA

[34] Vanderbilt Univ, Vanderbilt Inst Clin & Translat Res, Med Ctr, Nashville, TN 37235 USA

[35] Vanderbilt Univ, Dept Biostat, Med Ctr, Nashville, TN USA

来源：

BMJ-BRITISH MEDICAL JOURNAL | 2022年 / 376卷

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1136/bmj-2021-069761

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页数：12

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