Background This study aims to identify the causative strain of SARS-CoV-2 in a cluster of vaccine breakthroughs. Vaccine breakthrough by a highly transmissible SARS-CoV-2 strain is a risk to global public health. Methods Nasopharyngeal swabs from suspected vaccine breakthrough cases were tested for SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) by qPCR (quantitative polymerase chain reaction) for Wuhan-Hu1 and alpha variant. Positive samples were then sequenced by Swift Normalase Amplicon Panels to determine the causal variant. GATK (genome analysis toolkit) variants were filtered with allele fraction ≥80 and min read depth 30x. Results Viral sequencing revealed an infection cluster of 6 vaccinated patients infected with the delta (B.1.617.2) SARS-CoV-2 variant. With no history of vaccine breakthrough, this suggests the delta variant may possess immune evasion in patients that received the Pfizer BNT162b2, Moderna mRNA-1273, and Covaxin BBV152. Conclusions Delta variant may pose the highest risk out of any currently circulating SARS-CoV-2 variants, with previously described increased transmissibility over alpha variant and now, possible vaccine breakthrough. Funding Parts of this work was supported by the National Institute of Allergy and Infectious Diseases (1U19AI144297) and Baylor College of Medicine internal funding. Supplementary Information The online version contains supplementary material available at 10.1186/s12916-021-02103-4.
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