Risk Factors for Severe Coronavirus Disease 2019 Among Human Immunodeficiency Virus-Infected and -Uninfected Individuals in South Africa, April 2020–March 2022: Data From Sentinel Surveillance

BACKGROUND: Data on risk factors for coronavirus disease 2019 (COVID-19)-associated hospitalization and mortality in high human immunodeficiency virus (HIV) prevalence settings are limited. METHODS: Using existing syndromic surveillance programs for influenza-like-illness and severe respiratory illness at sentinel sites in South Africa, we identified factors associated with COVID-19 hospitalization and mortality. RESULTS: From April 2020 through March 2022, severe acute respiratory syndrome coronavirus 2 was detected in 24.0% (660 of 2746) of outpatient and 32.5% (2282 of 7025) of inpatient cases. Factors associated with COVID-19-associated hospitalization included the following: older age (25–44 [adjusted odds ratio {aOR}= 1.8, 95% confidence interval (CI) = 1.1–2.9], 45–64 [aOR = 6.8, 95% CI = 4.2–11.0] and ≥65 years [aOR = 26.6, 95% CI = 14.4–49.1] vs 15–24 years); black race (aOR, 3.3; 95% CI, 2.2–5.0); obesity (aOR, 2.3; 95% CI, 1.4–3.9); asthma (aOR, 3.5; 95% CI, 1.4–8.9); diabetes mellitus (aOR, 5.3; 95% CI, 3.1–9.3); HIV with CD4 ≥200/mm(3) (aOR, 1.5; 95% CI, 1.1–2.2) and CD4 <200/mm(3) (aOR, 10.5; 95% CI, 5.1–21.6) or tuberculosis (aOR, 12.8; 95% CI, 2.8–58.5). Infection with Beta (aOR, 0.5; 95% CI, .3–.7) vs Delta variant and being fully vaccinated (aOR, 0.1; 95% CI, .1–.3) were less associated with COVID-19 hospitalization. In-hospital mortality was increased in older age (45–64 years [aOR, 2.2; 95% CI, 1.6–3.2] and ≥65 years [aOR, 4.0; 95% CI, 2.8–5.8] vs 25–44 years) and male sex (aOR, 1.3; 95% CI, 1.0–1.6) and was lower in Omicron-infected (aOR, 0.3; 95% CI, .2–.6) vs Delta-infected individuals. CONCLUSIONS: Active syndromic surveillance encompassing clinical, laboratory, and genomic data identified setting-specific risk factors associated with COVID-19 severity that will inform prioritization of COVID-19 vaccine distribution. Elderly people with tuberculosis or people with HIV, especially severely immunosuppressed, should be prioritized for vaccination.