Results:

On 32,379 participants in the analysis, 88.7% were in the US, 6.8% in Chile, and 4.5% in Peru. Mean age was 50.2 ± 15.9 years (22.4% of participants ≥65 years), and 55.6% were male; 79.0% were White, 8.3% Black, 4.4% Asian, 4.0% Native American or Native Alaskan, 2.4% multiple races or ethnic groups; and 22.3% were Hispanic or Latinx. Median follow-up was 61 (interquartile range, 1-129) days after the second injection. AZD1222 was associated with low incidences of serious and medically attended adverse events and adverse events of special interest (<0.1% thrombotic and thrombocytopenic events); with incidences similar to those observed in the placebo group. Solicited local and systemic reactions generally were mild or moderate in both groups. Overall estimated vaccine efficacy was 74.0% (95% confidence interval [CI], 65.3-80.5; p < 0.001) and estimated vaccine efficacy was 83.5% (95% CI, 54.2-94.1) in participants ≥65 years of age. High vaccine efficacy was consistent across a range of demographic subgroups. In the fully vaccinated analysis subgroup, no severe or critical symptomatic COVID-19 cases were observed among the 17,662 participants in the AZD1222 group; eight cases were noted among the 8,550 participants in the placebo group (<0.1%). The estimated vaccine efficacy for preventing SARS-CoV-2 infection (nucleocapsid antibody seroconversion) was 64.3% (95% CI, 56.1-71.0; p < 0.001). SARS-CoV-2 spike protein binding and neutralizing antibodies increased after the first dose and increased further when measured 28 days after the second dose.