SARS-CoV-2 may directly and indirectly damage lung tissue and other host organs, but there are few system-wide, untargeted studies of these effects on the human body. Here, we developed a parallelized mass spectrometry (MS) proteomics workflow enabling the rapid, quantitative analysis of hundreds of virus-infected FFPE tissues. The first layer of response to SARS-CoV-2 in all tissues was dominated by circulating inflammatory molecules. Beyond systemic inflammation, we differentiated between systemic and true tissue-specific effects to reflect distinct COVID-19-associated damage patterns. Proteomic changes in the lungs resembled those of diffuse alveolar damage (DAD) in non-COVID-19 patients. Extensive organ-specific changes were also evident in the kidneys, liver, and lymphatic and vascular systems. Secondary inflammatory effects in the brain were related to rearrangements in neurotransmitter receptors and myelin degradation. These MS-proteomics-derived results contribute substantially to our understanding of COVID-19 pathomechanisms and suggest strategies for organ-specific therapeutic interventions.

中文翻译：

---

致命性 COVID-19 的定量多器官蛋白质组学揭示了炎症以外的组织特异性影响

SARS-CoV-2可能直接或间接损害肺组织和其他宿主器官，但对这些对人体影响的全系统、无针对性的研究很少。在这里，我们开发了并行质谱 (MS) 蛋白质组学工作流程，能够对数百种病毒感染的 FFPE 组织进行快速定量分析。所有组织中对 SARS-CoV-2 的第一层反应主要是循环炎症分子。除了全身炎症之外，我们还区分了全身效应和真正的组织特异性效应，以反映与 COVID-19 相关的不同损伤模式。肺部的蛋白质组变化与非 COVID-19 患者的弥漫性肺泡损伤 (DAD) 相似。肾脏、肝脏、淋巴和血管系统也出现了广泛的器官特异性变化。大脑中的继发性炎症效应与神经递质受体的重排和髓磷脂降解有关。这些 MS 蛋白质组学结果极大地促进了我们对 COVID-19 病理机制的理解，并为器官特异性治疗干预策略提出了建议。