Asymptomatic Infection and Duration of Viral Shedding in Symptomatic Breakthrough Infections in a Phase 3 Study of AZD1222 (ChAdOx1 nCoV-19)

ABSTRACT

Background. SARS-CoV-2 vaccine efficacy (VE) against asymptomatic infection and impact on viral shedding during breakthrough infections have critical implications for pandemic control. AZD1222 (ChAdOx1 nCoV-19;2 doses, 4 weeks apart) demonstrated VE of 74.0% (95% CI 65.3, 80.5) against the primary endpoint of symptomatic RT-PCR-confirmed COVID-19 and safety in a Phase 3, 21 randomized, placebo-controlled study in the US, Chile and Peru (n=32,451). Here we present exploratory analyses on asymptomatic infections determined by nucleocapsid (N) seroconversion and time to viral clearance in participants with symptomatic infections determined by N seroconversion (primary data cut, March 5, 2021). Methods. N seroconversion was assessed at all scheduled and illness visits in the fully vaccinated analysis set (Table). In this analysis, symptomatic infections are defined as N seroconversion ≥ 15 days post second dose in participants who attended an illness visit with ≥ 1 qualifying COVID-19 symptom and had ≥ 1 positive RT-PCR result for SARS-CoV-2. Asymptomatic infections are defined as N seroconversion ≥ 15 days post second dose in participants who did not meet the criteria for symptomatic infections. In participants with symptomatic infections, viral shedding in saliva was assessed for 28 days and cumulative incidence of viral clearance was determined. Table. AZD1222 VE against symptomatic and potentially asymptomatic SARS-CoV-2 infections as determined by N seroconversion Results. Overall, 358 participants had SARS-CoV-2 infections as determined by N seroconversion (Table). Incidences per 1000 person-years of symptomatic infections were 25.62 for AZD1222 vs 103.42 for placebo (VE 75.23%;95% CI 65.33, 82.31) and of asymptomatic infections were 51.24 vs 111.95 (VE 54.24%;95% CI 39.99, 65.10) (Table). Sensitivity analyses for N seroconversion using the primary endpoint and CDC criteria for defining symptomatic/asymptomatic status were supportive. Median time to viral clearance in saliva in participants with symptomatic infections was 11 days (AZD1222, n=52) vs 16 days (placebo, n=92) (Figure). Conclusion. AZD1222 resulted in lower yet meaningful VE against asymptomatic compared to symptomatic infections, as determined by N seroconversion, and shortened viral shedding in symptomatic SARS-CoV-2 breakthrough infections vs placebo, highlighting its potential contribution to reducing viral transmission.