Impact Of Sars-Cov-2 Variants On Vaccine Breakthrough Infections

SARS-CoV-2 variants of concern are defined by their increased intrinsic transmissibility and ability to evade immune recognition and neutralization, yet the relative importance of these factors in determining variant fitness in population settings is unclear. We hypothesize that as population level immunity has increased throughout the course of the pandemic, immune escape has played an increasingly important role in the emergence and sustained circulation of variants. Here, we use logistic regression models to estimate the odds of vaccine breakthrough infections for several major variants of concern in a population of Connecticut residents. We investigate the impact of immune escape on sustained variant circulation across 18 months of the pandemic and in four periods of variant emergence in the context of increasing vaccination uptake rates. We show significantly increased odds of vaccine breakthrough infections associated with the Omicron BA.1 variant relative to the Delta variant [2 vaccine doses ≥5 months adjusted OR: 2.093, 95% CI: 1.11 - 3.94 | 3 vaccine doses ≤5 months adjusted OR: 7.118, 95% CI: 1.44 - 35.17] as well as the Omicron BA.4 and BA.5 variants relative to the Omicron BA.2 variant [3 vaccine doses adjusted OR: 1.66, 95% CI: 1.01 - 2.73]. We also show significantly decreased odds of vaccine breakthrough infections associated with the Alpha variant relative to the pre-Alpha variant lineages [adjusted OR: 0.796, 95% CI: 0.73, 0.86] as well as decreasing age and female sex. These findings suggest immune escape played an important role in the emergence of the Omicron BA.1 variant and imply an important association between demographic characteristics and vaccine breakthrough infections