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. ### Competing Interest Statement ACK, AR, JP, JVR, ER, DML, and KAM declare no conflicts of interest. KSG receives research support from ThermoFisher for the evaluation of new assays for the diagnosis and characterization of viruses and has a royalty generating collaborative agreement with Zeptometrix. ### Funding Statement Initial funding for sequencing was generously provided by the New York Community Trust. The work for this publication was also supported by Cooperative Agreement number NU50CK000516, funded by the Centers for Disease Control and Prevention. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the Centers for Disease Control and Prevention or the Department of Health and Human Services. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was waived by the New York State Department of Health Institutional Review Board for Human Subjects Research review I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All de-identified data produced in the present study are available upon reasonable request to the authors, subject to NYSDOH approval.