严重急性呼吸综合征冠状病毒2 (SARS-CoV-2) 在大流行期间发生了显著变异，并导致了庞大的基因组序列数量。追踪持续感染病例中的SARS-CoV-2进化，可以揭示新变体的起源和动态。我们在此报告了一个正在接受化疗的B细胞急性淋巴细胞白血病患者，感染了超过两个月的SARS-CoV-2。对他连续的SARS-CoV-2阳性标本进行基因组监测发现，病毒尖峰蛋白N末端结构域（NTD）中出现了两个前所未有的大缺失Δ15-26和Δ138-145，并展示了它们在生成这些新变体中的动态变化。这些大缺失位于抗原超位点，预计会在三维蛋白结构预测中显著改变尖峰蛋白NTD，可能导致免疫逃逸，但会降低病毒的传播能力。总之，我们在此报道了一个接受化疗的患者中的新病毒进化轨迹。

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved significantly during the pandemic and resulted in daunting numbers of genomic sequences. Tracking SARS-CoV-2 evolution during persistent cases could provide insight into the origins and dynamics of new variants. We report here a case of B-cell acute lymphocytic leukemia on chemotherapy with infection of SARS-CoV-2 for more than two months. Genomic surveillance of his serial SARS-CoV-2-positive specimens revealed two unprecedented large deletions, Δ15-26 and Δ138-145, in the viral spike protein N-terminal domain (NTD) and demonstrated their dynamic shifts in generating these new variants. Located at antigenic supersites, these large deletions are anticipated to dramatically change the spike protein NTD in three-dimensional protein structure prediction, which may lead to immune escape but reduce their viral transmissibility. In summary, we present here a new viral evolutionary trajectory in a patient on chemotherapy.