OBJECTIVES: To identify demographic, clinical and immunological factors associated with adverse COVID-19 outcomes. METHODS: A large randomised controlled trial of ChAdOx1 nCoV-19 was undertaken in Brazil. Participants were randomised 1:1 either to receive ChAdOx1 nCov-19 or to a control group. COVID-19 infections were confirmed by nucleic acid amplification test (NAAT) and classified using the WHO clinical progression scale. Anti-spike antibody responses and serum neutralising activity were measured 28 days after second vaccination in some participants. Exploratory analyses were conducted into factors associated with COVID-19 infection severity and hospitalisation, using logistic regression models adjusted for demographic and clinical factors. RESULTS: 10,416 participants were enrolled; 1790 had NAAT-positive COVID-19 infection; 63 cases required hospitalisation. More severe infection was associated with greater body-mass index (BMI) (odds ratio [OR] = 1.06 [95 %CI: 1.01-1.10], p = 0.01) and diabetes (OR = 3.67 [1.59-8.07], p = 0.003). Hospitalisation risk increased with greater age (OR = 1.06 [1.03-1.08], p < 0.001) and BMI (OR = 1.10 [1.05-1.16], p < 0.001). More severe infection and hospitalisation risks increased >180 days after last vaccination. In the fully vaccinated subgroup (n = 841), only greater age predicted hospitalisation (OR = 1.07 [1.03-1.12], p < 0.001). Serological responses to two vaccine doses diminished with age. CONCLUSIONS: Unvaccinated individuals with high BMI and diabetes risked more severe COVID-19 outcomes. Vaccination mitigated this risk. CLINICAL TRIAL REGISTRATION NUMBER: NCT04536051.