Clinical and experimental evidence suggest omicron variant of SARS-CoV-2 is inherently less pathogenic than delta variant independent of previous immunity

To study clinical disease outcomes in both human and animal models to understand the pathogenicity of omicron compared to the delta variant. In this cross-sectional observational study, clinical outcomes of adults who tested positive at 2 testing centres in Delhi National Capital Region between January 2022 and March 2022 (omicron-infected; N = 2998) were compared to a similar geographical cohort (delta-infected; N = 3292). In addition, disease course and outcomes were studied in SARS-CoV-2-infected golden Syrian hamsters and K-18 humanized ACE2 transgenic mice. Omicron variant infection was associated with a milder clinical course [83% (95% CI 61, 94) reduced risk of severity compared against delta] adjusting for vaccination, age, sex, prior infection and occupational risk. This correlated with lower disease index and vir comparing omicron with other variants in animal models. Infections caused by the omicron variant were milder compared to those caused by the delta variant independent of previous immunity.