The SARS-CoV-2 spike (S) protein, the viral mediator for binding and entry into the host cell, has sparked great interest as a target for vaccine development and treatments with neutralizing antibodies. Initial data suggest that the virus has low mutation rates, but its large genome could facilitate recombination, insertions, and deletions, as has been described in other coronaviruses. Here, we deep-sequenced the complete SARS-CoV-2 S gene from 18 patients (10 with mild and 8 with severe COVID-19), and found that the virus accumulates deletions upstream and very close to the S1/S2 cleavage site (PRRAR/S), generating a frameshift with appearance of a stop codon. These deletions were found in a small percentage of the viral quasispecies (2.2%) in samples from all the mild and only half the severe COVID-19 patients. Our results suggest that the virus may generate free S1 protein released to the circulation. We suggest that natural selection has favoured a “Don’t burn down the house” strategy, in which free S1 protein may compete with viral particles for the ACE2 receptor, thus reducing the severity of the infection and tissue damage without losing transmission capability.

SARS-CoV-2 刺突 (S) 蛋白是结合和进入宿主细胞的病毒介质，作为疫苗开发和中和抗体治疗的靶点引起了人们的极大兴趣。初步数据表明，该病毒的突变率较低，但其庞大的基因组可以促进重组、插入和缺失，正如在其他冠状病毒中所描述的那样。在这里，我们对完整的 SARS-CoV-2 S 进行了深度测序来自 18 名患者（10 名轻度 COVID-19 患者和 8 名重度 COVID-19 患者）的基因，发现病毒在上游积累缺失并非常靠近 S1/S2 切割位点 (PRRAR/S)，产生具有终止密码子外观的移码. 在来自所有轻度 COVID-19 患者和仅一半重度 COVID-19 患者的样本中，在一小部分病毒准种 (2.2%) 中发现了这些缺失。我们的结果表明，病毒可能会产生释放到循环中的游离 S1 蛋白。我们建议自然选择偏爱“不要烧毁房子”的策略，其中游离 S1 蛋白可能与病毒颗粒竞争 ACE2 受体，从而在不失去传播能力的情况下降低感染和组织损伤的严重程度。