SARS-CoV-2 vaccine breakthrough by Omicron and Delta variants: comparative assessments with New York State genomic surveillance data

Background Recently emerged variants of SARS-CoV-2 have shown greater potential to cause vaccine breakthrough infections. Methods A matched cohort analysis used a genomic sequence dataset linked with demographic and vaccination information from New York State (NYS). Two sets of conditional logistic regression analyses were performed, one during the emergence of Delta and another during the emergence of Omicron. For each set, cases were defined as individuals with the emerging lineage, and controls were individuals infected with any other lineage. The adjusted associations of vaccination status, vaccine type, time since vaccination, and age with lineage were assessed using odds ratios (OR) and 95% confidence intervals (CI). Results Fully vaccinated status (OR: 3, 95% CI: 2.0 - 4.9) and Boosted status (OR 6.7, 95% CI: 3.4 – 13.0) were significantly associated with having the Omicron lineage during the Omicron emergence period. Risk of Omicron infection relative to Delta generally decreased with increasing age (OR: 0.964, 95% CI 0.950 – 0.978). The Delta emergence analysis had low statistical power for the observed effect size. Conclusions Vaccines offered less protection against Omicron, thereby increasing the number of potential hosts for the emerging variant. Lay Summary There are different variants, or types, of the virus that causes COVID-19. These variants may differ in their ability to infect a person, cause severe disease, or evade vaccine protection. From previous studies, we know that vaccines provide substantial protection against the original COVID-19 virus. In this study, we wanted to know how some of the new variants compare to one another in this regard. We found that the Omicron variant could break through vaccine protection more effectively than the Delta variant. The data suggested that Delta may be better able to break through vaccines compared to previous variants, including Alpha, but our sample sizes were low, so this pattern was not statistically significant. Individuals with a booster shot had much stronger protection against Delta compared to their protection against Omicron. We also found that younger people were more likely to be infected with Omicron than Delta.