System-wide transcriptome damage and tissue identity loss in COVID-19 patients. Park et al.

The molecular mechanisms underlying the clinical manifestations of COVID-19 and what distinguishes them from common seasonal influenza virus and other lung injury states such as Acute Respiratory Distress Syndrome remains poorly understood. To address these challenges, we combine transcriptional profiling of 646 clinical nasopharyngeal swabs and 39 patient autopsy tissues to define body-wide transcriptome changes in response to COVID-19. We then match this data with spatial protein and expression profiling across 357 tissue sections from 16 representative patient lung samples and identify tissue compartment-specific damage wrought by SARS-CoV-2 infection, evident as a function of varying viral loads during the clinical course of infection and tissue type-specific expression states. Overall, our findings reveal a systemic disruption of canonical cellular and transcriptional pathways across all tissues, which can inform subsequent studies to combat the mortality of COVID-19 and to better understand the molecular dynamics of lethal SARS-CoV-2 and other respiratory infections.新型冠状病毒肺炎（COVID-19）的临床表现背后的分子机制，以及其与普通季节性流感病毒、急性呼吸窘迫综合征（Acute Respiratory Distress Syndrome）等其他肺损伤状态的差异，目前仍不甚明晰。为应对这些科学挑战，本研究整合了646份临床鼻咽拭子与39例患者尸检组织的转录谱分析数据，以明确机体针对COVID-19的全转录组变化特征。随后，本研究将该数据集与16例代表性患者肺组织样本的357份组织切片的空间蛋白质组与表达谱数据进行匹配分析，鉴定出严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染引发的组织分区特异性损伤，该损伤程度随感染临床进程中病毒载量的变化以及组织类型特异性表达状态而呈现差异。综上，本研究结果揭示了全身所有组织中经典细胞通路与转录通路的系统性紊乱，该发现可为后续降低COVID-19病死率的研究提供理论参考，也有助于更深入理解致死性SARS-CoV-2感染与其他呼吸道感染的分子动力学机制。