Summary
This prospective observational case-control study of 11,690 US adults assessed mRNA vaccine effectiveness and clinical severity of COVID-19 across three SARS-CoV-2 variants. Two doses of mRNA vaccine provided 85% protection against alpha and delta variants, but only 65% against omicron; three doses restored protection to 86% against omicron. Disease severity varied by variant, with delta associated with higher mortality (12.2%) than omicron (7.1%), and vaccinated patients consistently experiencing lower severity than unvaccinated patients across all variants.
UK applicability
The findings are broadly applicable to the United Kingdom, where the same mRNA vaccines were deployed during the same variant waves. UK vaccination policy and clinical management decisions for COVID-19 would have benefited from these data on dose requirements for omicron protection and variant-specific severity profiles.
Key measures
Vaccine effectiveness (percentage with 95% confidence intervals); in-hospital mortality rates by variant; WHO clinical progression scale severity scores; proportional odds ratios for disease severity comparisons
Outcomes reported
The study measured mRNA vaccine effectiveness in preventing COVID-19 hospital admissions for alpha, delta, and omicron variants, and compared clinical disease severity among hospitalised patients across variants using the WHO clinical progression scale.
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