Clinical Severity and mRNA Vaccine Effectiveness for Omicron, Delta, and Alpha SARS-CoV-2 Variants in the United States: A Prospective Observational Study

Abstract

ObjectivesTo characterize the clinical severity of COVID-19 caused by Omicron, Delta, and Alpha SARS-CoV-2 variants among hospitalized adults and to compare the effectiveness of mRNA COVID-19 vaccines to prevent hospitalizations caused by each variant.DesignA case-control study of 11,690 hospitalized adults.SettingTwenty-one hospitals across the United States.ParticipantsThis study included 5728 cases hospitalized with COVID-19 and 5962 controls hospitalized without COVID-19. Cases 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 (March 11 to July 3, 2021), Delta (July 4 to December 25, 2021), and Omicron (December 26, 2021 to January 14, 2022).Main Outcome MeasuresVaccine effectiveness was calculated using a test-negative design for COVID-19 mRNA vaccines to prevent COVID-19 hospitalizations by each variant (Alpha, Delta, Omicron). Among hospitalized patients with COVID-19, disease severity on the WHO Clinical Progression Ordinal Scale was compared among variants using proportional odds regression.ResultsVaccine effectiveness of the mRNA vaccines to prevent COVID-19-associated hospitalizations included: 85% (95% CI: 82 to 88%) for 2 vaccine doses against Alpha; 85% (95% CI: 83 to 87%) for 2 doses against Delta; 94% (95% CI: 92 to 95%) for 3 doses against Delta; 65% (95% CI: 51 to 75%) for 2 doses against Omicron; and 86% (95% CI: 77 to 91%) for 3 doses against Omicron. Among hospitalized unvaccinated COVID-19 patients, severity on the WHO Clinical Progression Scale was higher for Delta than Alpha (adjusted proportional odds ratio [aPOR] 1.28, 95% CI: 1.11 to 1.46), and lower for Omicron than Delta (aPOR 0.61, 95% CI: 0.49 to 0.77). Compared to unvaccinated cases, severity was lower for vaccinated cases for each variant, including Alpha (aPOR 0.33, 95% CI: 0.23 to 0.49), Delta (aPOR 0.44, 95% CI: 0.37 to 0.51), and Omicron (aPOR 0.61, 95% CI: 0.44 to 0.85).ConclusionsmRNA vaccines were highly effective in preventing COVID-19-associated hospitalizations from 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 Delta and Alpha. Among adults hospitalized with COVID-19, Omicron caused less severe disease than Delta, but still resulted in substantial morbidity and mortality. Vaccinated patients hospitalized with COVID-19 had significantly lower disease severity than unvaccinated patients for all the variants.

Effectiveness of Covid-19 vaccines against SARS-CoV-2 Omicron variant (B.1.1.529): A systematic review with meta-analysis and meta-regression

“…Full dose vaccination represents 2 doses of BNT162b2, ChAdOx1 nCov-19 and mRNA-1273 vaccines, or 1 dose of Ad26.COV2.S vaccines, whereas booster dose vaccination was defined as the administration of an extra dose of Covid-19 vaccine on top of the full dose vaccination. Two studies 31,37 did not specify the type of vaccines being used; therefore, in this study, we defined it as a mixture. However, it does not necessarily mean that the vaccines are heterologous or mix-and-matched.…”

Identification of a SARS-CoV-2 host metalloproteinase-dependent entry pathway differentially used by SARS-CoV-2 and variants of concern Alpha, Delta, and Omicron

“…Omicron S has two mutations near the furin cleavage site, N679K and P681H, however the mechanism by which these or other mutations alter S processing remains to be determined. In addition, whether the inefficient use of the metalloproteinase pathway for activation of S to mediate viral entry and cell-cell fusion plays a role in the apparent distinct clinical manifestations and tropism of Omicron is unclear [11,[70][71][72][73]. Nonetheless, our findings of an additional entry pathway suggest a potential for increased tropism in the presence of MMPs during inflammation to cells that do not express serine proteases and could play important roles in dissemination and disease severity.…”

Real-World Effectiveness of the mRNA COVID-19 Vaccines in Japan: A Case–Control Study

“…Some recent studies reported a diminished VE against omicron (B1.1.529) variant COVID-19 infection [ 30 , 31 ] due to the potential for immune evasion, which was supported by in vitro neutralization assays [ 8 , 32 , 33 , 34 ]. In contrast to the VE against the delta variant, the VE against the omicron variant in terms of hospitalization was reportedly lower, at 65% (95% CI: 51–75%), although it remained above 50% [ 35 ]. However, it was reported that the VE against hospitalization improved to 86% (95% CI: 77–91%) after three doses of the vaccine [ 8 , 35 ].…”