SARS-CoV-2 genomic characterization and clinical manifestation of the COVID-19 outbreak in Uruguay

COVID-19 is a respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and declared by the World Health Organization a global public health emergency. Among the severe outbreaks across South America, Uruguay has become known for curtailing SARS-CoV-2 exceptionally well. To understand the SARS-CoV-2 introductions, local transmissions, and associations with genomic and clinical parameters in Uruguay, we sequenced the viral genomes of 44 outpatients and inpatients in a private healthcare system in its capital, Montevideo, from March to May 2020. We performed a phylogeographic analysis using sequences from our cohort and other studies that indicate a minimum of 23 independent introductions into Uruguay, resulting in five major transmission clusters. Our data suggest that most introductions resulting in chains of transmission originate from other South American countries, with the earliest seeding of the virus in late February 2020, weeks before the borders were closed to all non-citizens and a partial lockdown implemented. Genetic analyses suggest a dominance of S and G clades (G, GH, GR) that make up >90% of the viral strains in our study. In our cohort, lethal outcome of SARS-CoV-2 infection significantly correlated with arterial hypertension, kidney failure, and ICU admission (FDRCOVID-19是由严重急性呼吸综合征冠状病毒2（severe acute respiratory syndrome coronavirus 2, SARS-CoV-2）引发的呼吸道疾病，现已被世界卫生组织（World Health Organization）列为全球公共卫生紧急事件。在南美多国暴发严重疫情的背景下，乌拉圭因防控SARS-CoV-2疫情成效极为突出而广受关注。为探究乌拉圭境内SARS-CoV-2的输入情况、本地传播链条，以及其与基因组学及临床参数的关联，本研究于2020年3月至5月期间，在该国首都蒙得维的亚的一家私立医疗系统内，对44名门诊及住院患者的病毒基因组进行了测序。本研究结合本次队列（cohort）的序列数据与其他相关研究的序列开展系统发育地理学分析（phylogeographic analysis），结果显示乌拉圭境内至少存在23次独立的病毒输入事件，由此形成5个主要传播簇。研究数据表明，多数引发持续传播链的病毒输入均源自其他南美国家，病毒最早的定植时间为2020年2月末，也就是该国对所有非本国公民关闭边境并实施部分封控措施的数周之前。遗传分析显示，S及G进化枝（clade，包含G、GH、GR亚型）占本研究收录病毒毒株的90%以上，为优势流行克隆型。在本研究队列中，SARS-CoV-2感染的致死结局与动脉高血压、肾衰竭及ICU收治呈显著相关性（错误发现率（False Discovery Rate, FDR））