SARS-CoV-2 Vaccine Breakthrough by Omicron and Delta Variants, New York, USA

Alexander C. Keyel; Alexis Russell; Jonathan Plitnick; Jemma V. Rowlands; Daryl M. Lamson; Eli Rosenberg; Kirsten St. George


Emerging Infectious Diseases. 2022;28(10):1990-1998. 

In This Article

Abstract and Introduction


Recently emerged SARS-CoV-2 variants have greater potential than earlier variants to cause vaccine breakthrough infections. During emergence of the Delta and Omicron variants, a matched case–control analysis used a viral genomic sequence dataset linked with demographic and vaccination information from New York, USA, to examine associations between virus lineage and patient vaccination status, patient age, vaccine type, and time since vaccination. Case-patients were persons infected with the emerging virus lineage, and controls were persons infected with any other virus lineage. Infections in fully vaccinated and boosted persons were significantly associated with the Omicron lineage. Odds of infection with Omicron relative to Delta generally decreased with increasing patient age. A similar pattern was observed with vaccination status during Delta emergence but was not significant. Vaccines offered less protection against Omicron, thereby increasing the number of potential hosts for emerging variants.


As of August 10, 2022, the SARS-CoV-2 pandemic had claimed >6.4 million human lives globally, >1 million in the United States, and >70,000 in New York state.[1] Virus evolution and adaptation have been observed in persistently infected immunocompromised persons[2] and animal reservoirs,[3,4] leading to the potential for new, highly adapted variants.

Novel variants of SARS-CoV-2 have shown increased rates of transmission and immune evasion.[5,6] In particular, Omicron has evolved a suite of unique mutations, which have greatly increased its infectiousness,[7] increased its ability to evade current vaccines,[5,6] and decreased the effectiveness of convalescent plasma transfusions and monoclonal antibody treatments.[8,9] To a lesser degree, the Delta variant showed some of these same patterns of increased infectiousness[10] and potential for immune evasion compared with earlier strains that preceded Delta.[11]

Prior literature has also shown differences in vaccine effectiveness for SARS-CoV-2 lineages associated with variation in vaccine type, time since vaccination, and patient age. Before emergence of the Delta and Omicron variants, data showed reduced neutralizing antibody protection for the Janssen vaccine (Johnson & Johnson, compared with the Pfizer (Pfizer-BioNTech, and Moderna ( vaccines[12] and slightly stronger protection for Moderna compared with Pfizer vaccines.[12] An effect of time since vaccination has been demonstrated for the Delta variant[11] Younger persons were found to be more likely to be infected with Omicron.[13,14]

To test the associations between vaccination status, vaccine type, and time since vaccination with lineage identity during the emergence of new variants of SARS-CoV-2, we conducted a matched case–control study. We performed analyses for the emergence of the Omicron and Delta variants in New York, USA. The study was waived by the New York State Department of Health (NYSDOH) Institutional Review Board for Human Subjects Research review.