Abstract：
The seasonal human coronaviruses (HCoVs) have zoonotic origins, repeated infections, and global transmission. The objectives of this study are to elaborate the epidemiological and evolutionary characteristics of HCoVs from patients with acute respiratory illness. We conducted a multicenter surveillance at 36 sentinel hospitals of Beijing Metropolis, China, during 2016-2019. Patients with influenza-like illness (ILI) and severe acute respiratory infection (SARI) were included, and submitted respiratory samples for screening HCoVs by multiplex real-time reverse transcription-polymerase chain reaction assays. All the positive samples were used for metatranscriptomic sequencing to get whole genomes of HCoVs for genetical and evolutionary analyses. Totally, 321 of 15 677 patients with ILI or SARI were found to be positive for HCoVs, with an infection rate of 2.0% (95% confidence interval, 1.8%-2.3%). HCoV-229E, HCoV-NL63, HCoV-OC43, and HCoV-HKU1 infections accounted for 18.7%, 38.3%, 40.5%, and 2.5%, respectively. In comparison to ILI cases, SARI cases were significantly older, more likely caused by HCoV-229E and HCoV-OC43, and more often co-infected with other respiratory pathogens. A total of 179 full genome sequences of HCoVs were obtained from 321 positive patients. The phylogenetical analyses revealed that HCoV-229E, HCoV-NL63 and HCoV-OC43 continuously yielded novel lineages, respectively. The nonsynonymous to synonymous ratio of all key genes in each HCoV was less than one, indicating that all four HCoVs were under negative selection pressure. Multiple substitution modes were observed in spike glycoprotein among the four HCoVs. Our findings highlight the importance of enhancing surveillance on HCoVs, and imply that more variants might occur in the future.
摘要：
季节性人类冠状病毒（HCoV）起源于人畜共患，反复感染,和全球传播。这项研究的目的是阐述急性呼吸道疾病患者HCoV的流行病学和进化特征。我们在北京大都会的36家哨点医院进行了多中心监测，中国,2016-2019年。包括流感样疾病（ILI）和严重急性呼吸道感染（SARI）的患者。并提交了呼吸道样本，用于通过多重实时逆转录聚合酶链反应测定法筛选HCoV。所有阳性样品均用于超转录组测序，以获得HCoV的全基因组用于遗传和进化分析。完全正确,15677例ILI或SARI患者中有321例HCoV阳性，感染率为2.0%(95%置信区间，1.8%-2.3%）。HCoV-229E,HCoV-NL63、HCoV-OC43和HCoV-HKU1感染占18.7%,38.3%,40.5%,和2.5%，分别。与ILI病例相比，SARI病例明显年龄较大，更可能由HCoV-229E和HCoV-OC43引起，并且更常与其他呼吸道病原体共感染。从321名阳性患者中获得了总共179个HCoV的全基因组序列。系统发育分析表明，HCoV-229E，HCoV-NL63和HCoV-OC43不断产生新的谱系，分别。每个HCoV中所有关键基因的非同义与同义比率小于1，表明所有四个HCoV都处于负选择压力下。在四个HCoV中的刺突糖蛋白中观察到多种取代模式。我们的发现强调了加强对HCoV监测的重要性，并暗示未来可能会出现更多的变体。
