A SARS-CoV-2 ultra-deep sequencing study of the mutant spectrum of amplicons spike (S)-coding regions of five fully vaccinated cases with BNT162b2 (Pfizer-BioNTech) in March 2021 who mounted an effective antiviral response, and subsequently were infected with SARS-CoV-2 in April 2021, and developed COVID-19 clinical symptoms

Replication of SARS-CoV-2 in human population is defined by distributions of mutants that are present at different frequencies within the infected host, and can be detected by ultra-deep sequencing techniques. In this paper, we examined the SARS-CoV-2 mutant spectra of amplicons from the spike (S)-coding region of five nasopharyngeal isolates derived from vaccine-breakthrough patients. Interestingly, all patients became infected with the alpha variant but amino acid substitutions that correspond to the Iota, Delta Plus and Omicron variants were also found in their mutant spectra. Deep sequencing analysis of SARS-CoV-2 from vaccine-breakthrough patients may inform of tolerated substitutions that can be represented in epidemiological dominant variants.