ABSTRACT
BACKGROUND: In this study, we compared admission incidence risk and the risk of mortality in the Omicron BA.4/BA.5 wave to previous waves. METHODS: Data from South Africa's SARS-CoV-2 case linelist, national COVID-19 hospital surveillance system, and Electronic Vaccine Data System were linked and analyzed. Wave periods were defined when the country passed a weekly incidence of 30 cases/100 000 population. In-hospital case fatality ratios (CFRs) during the Delta, Omicron BA.1/BA.2, and Omicron BA.4/BA.5 waves were compared using post-imputation random effect multivariable logistic regression models. RESULTS: The CFR was 25.9% (N = 37 538 of 144 778), 10.9% (N = 6123 of 56 384), and 8.2% (N = 1212 of 14 879) in the Delta, Omicron BA.1/BA.2, and Omicron BA.4/BA.5 waves, respectively. After adjusting for age, sex, race, comorbidities, health sector, and province, compared with the Omicron BA.4/BA.5 wave, patients had higher risk of mortality in the Omicron BA.1/BA.2 wave (adjusted odds ratio [aOR], 1.3; 95% confidence interval [CI]: 1.2-1.4) and Delta wave (aOR, 3.0; 95% CI: 2.8-3.2). Being partially vaccinated (aOR, 0.9; 95% CI: .9-.9), fully vaccinated (aOR, 0.6; 95% CI: .6-.7), and boosted (aOR, 0.4; 95% CI: .4-.5) and having prior laboratory-confirmed infection (aOR, 0.4; 95% CI: .3-.4) were associated with reduced risks of mortality. CONCLUSIONS: Overall, admission incidence risk and in-hospital mortality, which had increased progressively in South Africa's first 3 waves, decreased in the fourth Omicron BA.1/BA.2 wave and declined even further in the fifth Omicron BA.4/BA.5 wave. Mortality risk was lower in those with natural infection and vaccination, declining further as the number of vaccine doses increased.