Post-Vaccination Breakthrough SARS-CoV-2 Infections Enriched for Variants of Concern

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The researchers examined SARS-CoV-2 genomes isolated from individuals believed to have experienced vaccine breakthrough and compared them to the background of SARS-CoV-2 sequences from Washington State over the same time period.

Among the 20 breakthrough infections of SARS-CoV-2 detected in Washington State, the US among fully vaccinated individuals, all were caused by variants of concern (VOC). These findings were published in Clinical Infectious Diseases.

After February 2021, a SARS-CoV-2 genome sequencing program was launched. Individuals (n=20) who had been fully vaccinated with the Pfizer-BioNTech COVID-19 vaccine or the Moderna COVID-19 vaccine, and tested positive for SARS-CoV-2 underwent virus whole genome sequencing. A group of primary infection control individuals (n=5174) were used as a comparator group.

Patients were 13 women, 6 men, and 1 whose sex was not recorded, had a median age of 43 (interquartile range [IQR], 28-58) years, and median cycle threshold values were 20.2 (IQR, 17.1-23.3).

Most of the 18 individuals for whom clinical data were available reported symptoms (n=15) but none required hospitalization.

The detected VOC among breakthrough infections were B.1.1.7 (40%), B.1.429 (40%), B.1.427 (10%), B.1.351 (5%), and P.1 (5%). VOC were detected among 68% of the comparator sample, comprising 31% B.1.1.7, 27% B.1.429, 7% P.1, 3% B.1.427, and 1% B.1.351.

Compared with control group infections, VOC were increased 1.47-fold (95% CI, 1.45-1.50; P =.001) among breakthrough infections.

The distribution of variants differed significantly between cohorts (P =.001), in which variants that were less effectively neutralized by vaccine antibodies (B.1.351, B.1.427, B.1.429, P.1) were increased by 1.63-fold (95% CI, 1.14-2.34; P =.037) among breakthrough infections.

The specific W258L mutation that alters the spike protein was increased by 15.22-fold (95% CI, 3.91-59.10; P =.008) among the vaccinated cohort; however, the mutation was detected among only 2 individuals.

This study was limited by its small sample size and by the fact that most breakthrough infections were detected among health care workers, which may have biased these findings.

According to these results, breakthrough infections were more likely to be caused by VOC compared with infections among the nonvaccinated population. Continued surveillance is needed to ensure that particular VOC may be incorporated to new or booster SARS-CoV-2 vaccine formulations.

Disclosure: Some authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


McEwen AE, Cohen S, Bryson-Cahn C, et al. Variants of concern are overrepresented among post-vaccination breakthrough infections of SARS-CoV-2 in Washington State. Clin Infect Dis. Published online June 24, 2021. doi:10.1093/cid/ciab581