Comparative severity of COVID-19 cases caused by Alpha, Delta or Omicron SARS-CoV-2 variants and its association with vaccination

BACKGROUND: This study compares the severity of SARS-CoV-2 infections caused by Alpha, Delta or Omicron variants in periods of co-circulation in Spain, and estimates the variant-specific association of vaccination with severe disease. METHODS: SARS-CoV-2 infections notified to the national epidemiological surveillance network with information on genetic variant and vaccination status were considered cases if they required hospitalisation or controls otherwise. Alpha and Delta were compared during June–July 2021; and Delta and Omicron during December 2021–January 2022. Adjusted odds ratios (aOR) were estimated using logistic regression, comparing variant and vaccination status between cases and controls. RESULTS: We included 5,345 Alpha and 11,974 Delta infections in June–July and 5,272 Delta and 10,578 Omicron in December–January. Unvaccinated cases of Alpha (aOR: 0.57; 95% CI: 0.46–0.69) or Omicron (0.28; 0.21–0.36) had lower probability of hospitalisation vs. Delta. Complete vaccination reduced hospitalisation, similarly for Alpha (0.16; 0.13–0.21) and Delta (June–July: 0.16; 0.14–0.19; December–January: 0.36; 0.30–0.44) but lower from Omicron (0.63; 0.53–0.75) and individuals aged 65+ years. CONCLUSION: Results indicate higher intrinsic severity of the Delta variant, compared with Alpha or Omicron, with smaller differences among vaccinated individuals. Nevertheless, vaccination was associated to reduced hospitalisation in all groups.