Breakthrough infections of SARS-CoV-2 are well-documented. The current study estimates breakthrough incidence across pandemic waves, and evaluates predictors of breakthrough and severe breakthrough infections (defined as those requiring hospitalization).
89,762 participants underwent longitudinal antibody surveillance. Incidence rates were calculated using total person-days contributed. Bias-corrected and age-adjusted logistic regression determined multivariable predictors of breakthrough and severe breakthrough infection, respectively.
The incidence was 0.45 (0.38, 0.50) during pre-Delta, 2.80 (2.25, 3.14) during Delta, and 11.2 (8.80, 12.95) during Omicron, per 10,000 person-days. Factors associated with elevated odds of breakthrough included Hispanic ethnicity (vs non-Hispanic White, OR=1.243[1.073, 1.441]), larger household size (OR=1.251 [1.048, 1.494] for 3-5 vs. 1 and OR=1.726 [1.317, 2.262] for more than 5 vs. 1 person), rural vs urban living (OR=1.383 [1.122, 1.704]), receiving Pfizer or Johnson&Johnson vs. Moderna, and multiple comorbidities. Of the 1,700 breakthrough infections, 1,665 reported on severity; 112 (6.73%) were severe. Higher BMI, Hispanic ethnicity, vaccine type, asthma, and hypertension predicted severe breakthroughs.
Breakthrough infection was 4-25 times more common during the Omicron-dominant wave versus earlier waves. Higher burden of severe breakthrough infections was identified in subgroups.
Published by Oxford University Press on behalf of Infectious Diseases Society of America 2023.
