Hospitalisation and mortality risk of SARS-COV-2 variant omicron sub-lineage BA.2 compared to BA.1 in England

Abstract

The Omicron variant of SARS-CoV-2 became the globally dominant variant in early 2022. A sub-lineage of the Omicron variant (BA.2) was identified in England in January 2022. Here, we investigated hospitalisation and mortality risks of COVID-19 cases with the Omicron sub-lineage BA.2 (n = 258,875) compared to BA.1 (n = 984,337) in a large cohort study in England. We estimated the risk of hospital attendance, hospital admission or death using multivariable stratified proportional hazards regression models. After adjustment for confounders, BA.2 cases had lower or similar risks of death (HR = 0.80, 95% CI 0.71-0.90), hospital admission (HR = 0.88, 95% CI 0.83-0.94) and any hospital attendance (HR = 0.98, 95% CI 0.95-1.01). These findings that the risk of severe outcomes following infection with BA.2 SARS-CoV-2 was slightly lower or equivalent to the BA.1 sub-lineage can inform public health strategies in countries where BA.2 is spreading.

Fig. 1. Time series of BA.1 and BA.2 cases in England, 01 December 2021 to 25 March 2022.

Descriptive frequencies of the earliest specimen date of COVID-19 cases with Omicron lineages BA.1 (top panel) and BA.2 (bottom panel), in England between 01 December 2021 and 25 March 2022 (n = 1,243,212). COVID-19: coronavirus disease 2019. Shading indicates the method of case identification: validated whole genome sequencing, or genotyping in combination with available S-gene status (SGTF or SGTP) for the episode, or from 24th January onwards S-gene status was used in absence of sequencing or genotyping for the episode.

Fig. 2. Relative risk of attendance, admission or death, BA.2 versus BA.1 by age group.

Risk of hospitalisation and mortality, overall and by age group, for COVID-19 cases with Omicron lineage BA.2 compared to BA.1 in England, 01 December 2021–2025 March 2022. The central measures are adjusted hazard ratios and the errors bars are the corresponding 95% confidence intervals from Cox regression models stratified for exact specimen date, area of residence, age group and vaccination status, and additionally using regression adjustments for within-age-group residual differences in exact age, sex, ethnicity, index of multiple deprivation (IMD) quintile and within-IMD-quintile residual differences in exact IMD rank, and reinfection status. A shows risk of any hospital attendance, including admissions, within 14 days of the earliest specimen date in the COVID-19 episode following infection with SARS-CoV-2 lineage BA.2, compared to BA.1. B shows the risk of hospital admission within 14 days. C shows the risk of death within 28 days. For the death outcome, hazard ratios were not estimated for cases aged <20 years due to small numbers. Likelihood ratio test (LRT) P values from two-sided tests for interaction between age group and variant status for attendance, admission, and death are 0.010, 0.0003958, and 0.003 respectively. These explorative tests were not adjusted for multiple comparisons. The adjusted hazard ratio estimates and 95% confidence intervals that the figure is based on are included in Table S3.

Fig. 3. Relative risk of hospital attendance, admission or death, by vaccination status and reinfection status.

Risk of hospitalisation and mortality by vaccination status and reinfection status, for COVID-19 cases with Omicron lineage BA.2 compared to BA.1 in England, 01 December 2021–2025 March 2022. The central measures are adjusted hazard ratios and the error bars are the corresponding 95% confidence intervals (CI) from Cox regression models with an interaction term between variant (BA.2 vs BA.1), and vaccination (A total n = 1,243,212; unvaccinated or ≤28 days after vaccination = 247,748; ≥28 days after first dose = 64,694; ≥14 days after second dose = 294,071; ≥14 days after third dose = 537,822) or reinfection (B total n = 1,243,212; reinfection = 125,239; first infection = 1,117,973) status. The models were stratified for exact specimen date, area of residence, age group and vaccination status, and additionally using regression adjustments for within-age-group residual differences in exact age, sex, ethnicity, index of multiple deprivation (IMD) quintile and within-IMD-quintile residual differences in exact IMD rank, and reinfection status. LRT P values from two-sided tests for interaction between vaccination status and variant status for attendance, admission, and death are 0.65, 0.87, and 0.11 respectively. LRT P values from two-sided tests for interaction between reinfection status and variant status for attendance, admission, and death are 0.34, 0.70, and 0.16, respectively. These explorative tests were not adjusted for multiple comparisons. The adjusted hazard ratio estimates and 95% confidence intervals that the figure is based on are included in Table S4.