Study: SARS-CoV-2 vaccine breakthrough by Omicron and Delta variants: comparative assessments with New York State genomic surveillance data. Image Credit: JIMMOYHT/Shutterstock

Research shows that the Omicron variant can break through vaccine protection more effectively than the Delta variant

In a recent study posted to the medRxiv* preprint server, researchers rated the efficacy of vaccinations against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta and Omicron variants of care (VOCs).

Study: SARS-CoV-2 Vaccine Breakthrough by Omicron and Delta Variants: Comparative Reviews with New York State Genomic Surveillance Data† Image Credit: JIMMOYHT/Shutterstock


Previous studies have reported that vaccinations provided significant protection against the original SARS-CoV-2 strain (Wuhan-Hu-1); however, the recently emerged SARS-CoV-2 strains have demonstrated greater potential to cause breakthrough infections in the vaccine. Omicron has been found to contain several mutations responsible for the increased infectivity, enhanced immune evasion and decreased efficacy of monoclonal antibodies and plasma antibody transfers.

About the study

Researchers assessed the efficacy of vaccination against Delta and Omicron in the current case-control study.

For the analysis, the New York State (NYS) genomic sequence dataset was matched with the participants’ vaccination and demographic data. The adjusted associations of age, type of vaccination (Moderna, Janssen, Pfizer), vaccination status, and elapsed time since vaccination with SARS-CoV-2 strains were evaluated using odds ratios (OR). Data were analyzed using logistic regression models of the Delta wave and Omicron wave, and the best fit models were determined using the Akaike Information Criterion (AIC) scoring system.

Respiratory swabs were obtained from the study participants for real-time PCR analysis, after which SARS-CoV-2 positive swabs were subjected to whole-genome sequencing (WGS) for genomic surveillance. The samples were matched with demographic data in the Electronic Communicable Disease Surveillance System (CDESS) and vaccination data in the NYS Immunization System (NYSIIS).

Omicron emergence analysis was performed between November 28, 2021 and January 24, 2022. Individuals with Omicron infections (all BA sublines) (cases, n = 1439) were matched with individuals infected with a different strain (controls, n = 728) during the Omicron rule period. Cases were matched to controls based on sample date, gender, age, and economic regions.

Delta emergence analysis was performed between March 19, 2021 and August 15, 2021, in which cases (n=603) were individuals infected with Delta (all AY sublines) and those affected with another SARS-CoV-2 strain except Delta during the Delta predominance period were considered controls (n=1816). Variables related to booster vaccination were excluded from the Delta emergence analysis because booster doses were not readily available during this period.


In the Omicron emergence analysis, most participants (>80%) were 18 to 69 years old, 22% and 8% of cases and controls, respectively, had received booster vaccinations, and the corresponding proportion of unvaccinated subjects was 30% and 56%, respectively. Of the vaccinated subjects, 177, 109 and 22 received Pfizer, Moderna and Janssen vaccinations, respectively. All controls in the dataset were infected by Delta.

Complete vaccinations and booster vaccinations were substantially associated with Omicron infections, with OR values ​​of 3.1 and 6.7, respectively. The risk of Omicron infections in relation to Delta infections showed a declining trend with aging (OR 0.96). The greater likelihood of Omicron infections in young people compared to adults may be due to increased socialization and other behavioral risk factors in individuals 18 to 29 years of age.

By limiting the analysis to only subjects who had been vaccinated, the probability of Omicron infections decreased with an increase in the time elapsed since the last vaccination (OR 0.99). Furthermore, the risk of Omicron infections was lower with Janssen vaccinations (OR 0.35) compared to Pfizer vaccinations; (OR 0.4) with respect to a vaccination with messenger ribonucleic acid (mRNA).

In the Delta emergence analysis, most of the individuals (75%) were also 18 to 69 years old, and 61.8% and 75% of the cases and controls, respectively, were unvaccinated. Of the controls, 62%, 20%, 3.5%, and 1% of subjects were infected with the Alpha, Iota, Gamma, and Beta strains, respectively, and the remainder were not infected with other SARS-CoV-2 -VOC strains.

Neither the type of vaccination nor the time elapsed since the last vaccination showed a significant association with a higher probability of Delta infections compared to infection with another SARS-CoV-2 strain. However, when age was not considered for case-control matching, individuals who received Pfizer vaccines were 7.3 times more likely to develop Delta infections compared to other SARS-CoV-2 strain infections.


Overall, the study results showed that Omicron was immune-evasive than Delta and was able to breach SARS-CoV-2 vaccine protection (including booster doses) more efficiently compared to Delta, although Delta may be better able to breach vaccines than previous SARS -CoV-2 strains such as Alpha.

However, the effect of elapsed time since vaccination was not assessed by stratifying individuals based on whether or not they received booster doses. The study population was small to assess the effects of vaccination by vaccine type. Therefore, further research with larger sample sizes and comparison between vaccine types and between boosted and unboosted individuals is needed to better inform vaccine developers.

*Important announcement

medRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered conclusive, should guide clinical practice/health-related behavior, or be treated as established information.

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