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Clinical severity of COVID-19 patients admitted to hospitals during the Omicron wave in South Africa

Background: Clinical severity of patients hospitalised with SARS-CoV-2 infection during the Omicron (fourth) wave was assessed and compared to trends in the D614G (first), Beta (second), and Delta (third) waves in South Africa. Methods: Weekly incidence of 30 laboratory-confirmed SARS-CoV-2 cases/100,000 population defined the start and end of each wave. Hospital admission data were collected through an active national COVID-19-specific surveillance programme. Disease severity was compared across waves by post-imputation random effect multivariable logistic regression models. Severe disease was defined as one or more of acute respiratory distress, supplemental oxygen, mechanical ventilation, intensive-care admission or death. Results: 335,219 laboratory-confirmed SARS-CoV-2 admissions were analysed, constituting 10.4% of 3,216,179 cases recorded during the 4 waves. In the Omicron wave, 8.3% of cases were admitted to hospital (52,038/629,617) compared to 12.9% (71,411/553,530) in the D614G, 12.6% (91,843/726,772) in the Beta and 10.0% (131,083/1,306,260) in the Delta waves (p<0.001). During the Omicron wave, 33.6% of admissions experienced severe disease compared to 52.3%, 63.4% and 63.0% in the D614G, Beta and Delta waves (p<0.001). The in-hospital case fatality ratio during the Omicron wave was 10.7%, compared to 21.5%, 28.8% and 26.4% in the D614G, Beta and Delta waves (p<0.001). Compared to the Omicron wave, patients had more severe clinical presentations in the D614G (adjusted odds ratio [aOR] 2.07; 95% confidence interval [CI] 2.01-2.13), Beta (aOR 3.59; CI: 3.49-3.70) and Delta (aOR 3.47: CI: 3.38-3.57) waves. Conclusion: The trend of increasing cases and admissions across South Africa's first three waves shifted in Omicron fourth wave, with a higher and quicker peak but fewer admitted patients, who experienced less clinically severe illness and had a lower case-fatality ratio. Omicron marked a change in the SARS-CoV-2 epidemic curve, clinical profile and deaths in South Africa. Extrapolations to other populations should factor in differing vaccination and prior infection levels.