Department of Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
Department of Pathology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
Proc Natl Acad Sci U S A. 2022 Aug 16;119(33):e2203437119. doi: 10.1073/pnas.2203437119. Epub 2022 Jul 27.
The mortality of coronavirus disease 2019 (COVID-19) is strongly correlated with pulmonary vascular pathology accompanied by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-triggered immune dysregulation and aberrant activation of platelets. We combined histological analyses using field emission scanning electron microscopy with energy-dispersive X-ray spectroscopy analyses of the lungs from autopsy samples and single-cell RNA sequencing of peripheral blood mononuclear cells to investigate the pathogenesis of vasculitis and immunothrombosis in COVID-19. We found that SARS-CoV-2 accumulated in the pulmonary vessels, causing exudative vasculitis accompanied by the emergence of thrombospondin-1-expressing noncanonical monocytes and the formation of myosin light chain 9 (Myl9)-containing microthrombi in the lung of COVID-19 patients with fatal disease. The amount of plasma Myl9 in COVID-19 was correlated with the clinical severity, and measuring plasma Myl9 together with other markers allowed us to predict the severity of the disease more accurately. This study provides detailed insight into the pathogenesis of vasculitis and immunothrombosis, which may lead to optimal medical treatment for COVID-19.
新型冠状病毒病 2019（COVID-19）的死亡率与肺血管病理学密切相关，其伴随严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）感染引发的免疫失调和血小板异常激活。我们结合使用场发射扫描电子显微镜的组织学分析以及来自尸检样本的肺部能量色散 X 射线光谱分析和外周血单核细胞的单细胞 RNA 测序，研究了 COVID-19 中的血管炎和免疫血栓形成的发病机制。我们发现 SARS-CoV-2 在肺部血管中积聚，导致渗出性血管炎，并伴有血栓调理素-1 表达的非经典单核细胞的出现以及 COVID-19 患者肺部肌球蛋白轻链 9（Myl9）的形成包含微血栓。COVID-19 中的血浆 Myl9 量与临床严重程度相关，并且测量血浆 Myl9 与其他标志物一起可更准确地预测疾病的严重程度。这项研究深入了解了血管炎和免疫血栓形成的发病机制，这可能为 COVID-19 的最佳治疗提供指导。
