Risk factors for severe respiratory syncytial virus-associated respiratory tract infection in a high HIV prevalence setting, prior to the SARS-CoV-2 pandemic, South Africa, 2012 – 2018

Abstract Background Identifying risk factors for respiratory syncytial virus (RSV)–associated severe acute respiratory illness (SARI) will assist with targeting vaccine interventions. Methods Using surveillance data from South Africa (2012-2018). We compared the characteristics of individuals with RSV-associated ILI (reference group) to those with RSV-associated SARI to describe factors associated with SARI using a multivariable analysis. Results RSV was detected in 6% (483/7792) of ILI cases and 15% (844/5672) of SARI cases. Factors associated with SARI in children included age <2 months, compared to age 2–4 years (adjusted odds ratio (aOR) 54.4; 95% confidence interval (CI) 23.5–125.8), malnutrition (aOR 1.9; 95% CI 1.2–3.2), prematurity (aOR 2.4; 95% CI 1.3–4.6) and living with HIV (LWH) (aOR 22.5; 95% CI 2.9–174.3). In individuals ≥5 years, factors associated with SARI included age ≥65 years compared to age 5–24 years (aOR 10.7; 95% CI 1.1–107.5), symptom duration ≥5 days (aOR 2.7; 95% CI 1.1–6.3), underlying illness (aOR 2.7; 95% CI 1.5–26.1) and LWH (aOR 16.8, 95% CI: 4.8–58.2). Conclusion Individuals at the extremes of age and those with identified risk factors a might benefit most from RSV prevention interventions.