We just published an article in the JAMA Network Open (link to open access publication), in which we developed a comprehensive digital surveillance system, using a robust statistical framework, to measure SARS-CoV-2’s intrinsic severity over time.


The SARS-CoV-2 Omicron subvariant, BA.2, may be less severe than previous variants; however, confounding factors make interpreting the intrinsic severity challenging. The objective of this study was to compare the adjusted risks of mortality, hospitalization, intensive care unit admission, and invasive ventilation between the BA.2 subvariant and the Omicron and Delta variants, after accounting for multiple confounders. This was a retrospective cohort study that applied an entropy balancing approach. Patients in a multicenter inpatient and outpatient system in New England with COVID-19 between March 3, 2020, and June 20, 2022, were identified. Cases were assigned as being exposed to the Delta (B.1.617.2) variant, the Omicron (B.1.1.529) variant, or the Omicron BA.2 lineage subvariants. The primary study outcome planned before analysis was risk of 30-day mortality. Secondary outcomes included the risks of hospitalization, invasive ventilation, and intensive care unit admissions.Of 102,315 confirmed COVID-19 cases (mean [SD] age, 44.2 [21.6] years; 63,482 women [62.0%]), 20,770 were labeled as Delta variants, 52,605 were labeled as the Omicron B.1.1.529 variant, and 28,940 were labeled as Omicron BA.2 subvariants. Patient cases were excluded if they occurred outside the prespecified temporal windows associated with the variants or had minimal longitudinal data in the Mass General Brigham system before COVID-19. Mortality rates were 0.7% for Delta (B.1.617.2), 0.4% for Omicron (B.1.1.529), and 0.3% for Omicron (BA.2). The adjusted odds ratio of mortality from the Delta variant compared with the Omicron BA.2 subvariants was 2.07 (95% CI, 1.04-4.10) and that of the original Omicron variant compared with the Omicron BA.2 subvariant was 2.20 (95% CI, 1.56-3.11). For all outcomes, the Omicron BA.2 subvariants were significantly less severe than that of the Omicron and Delta variants.