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
T2 - 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.
N1 - Publisher Copyright:
© Author(s) (or their employer(s)) 2019.
PY - 2022/3/9
Y1 - 2022/3/9
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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85126080206&partnerID=8YFLogxK
U2 - 10.1136/bmj-2021-069761
DO - 10.1136/bmj-2021-069761
M3 - Article
C2 - 35264324
AN - SCOPUS:85126080206
SN - 0959-8146
VL - 376
JO - The BMJ
JF - The BMJ
M1 - e069761
ER -