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. Vaccine-breakthrough infections with SARS-CoV-2 Alpha mirror mutations in Delta Plus, Iota and Omicron

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.

人群中严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的复制特征，由感染宿主内以不同频率存在的突变体分布所决定，且可通过超深度测序技术实现检测。本研究针对5例疫苗突破感染患者的鼻咽分离株，对其刺突（S）编码区扩增子的SARS-CoV-2突变谱进行了分析。值得注意的是，所有受试患者初始感染毒株均为阿尔法（Alpha）变异株，但在其突变谱中同时检出了对应艾奥塔（Iota）、德尔塔+（Delta Plus）以及奥密克戎（Omicron）变异株的氨基酸替换突变。对疫苗突破感染患者体内SARS-CoV-2开展的深度测序分析，可为流行病学优势变异株中所携带的耐受型氨基酸替换突变提供参考依据。