Massachusetts General Hospital Cancer Center, Boston, MA, 02114, USA.
Department of Pathology, Massachusetts General Hospital, Boston, MA, 02114, USA.
Nat Commun. 2020 Dec 9;11(1):6319. doi: 10.1038/s41467-020-20139-7.
The relationship of SARS-CoV-2 pulmonary infection and severity of disease is not fully understood. Here we show analysis of autopsy specimens from 24 patients who succumbed to SARS-CoV-2 infection using a combination of different RNA and protein analytical platforms to characterize inter-patient and intra-patient heterogeneity of pulmonary virus infection. There is a spectrum of high and low virus cases associated with duration of disease. High viral cases have high activation of interferon pathway genes and a predominant M1-like macrophage infiltrate. Low viral cases are more heterogeneous likely reflecting inherent patient differences in the evolution of host response, but there is consistent indication of pulmonary epithelial cell recovery based on napsin A immunohistochemistry and RNA expression of surfactant and mucin genes. Using a digital spatial profiling platform, we find the virus corresponds to distinct spatial expression of interferon response genes demonstrating the intra-pulmonary heterogeneity of SARS-CoV-2 infection.
SARS-CoV-2 肺部感染与疾病严重程度的关系尚未完全阐明。在这里，我们使用多种 RNA 和蛋白质分析平台分析了 24 例死于 SARS-CoV-2 感染的患者的尸检标本，以描述肺病毒感染的患者间和患者内异质性。与疾病持续时间相关的高病毒和低病毒病例存在一定的范围。高病毒病例中干扰素途径基因的高激活和 M1 样巨噬细胞浸润占主导地位。低病毒病例则更加异质，可能反映了宿主反应演变中固有患者差异，但 napsin A 免疫组化和表面活性剂和粘蛋白基因的 RNA 表达一致表明肺上皮细胞的恢复。使用数字空间分析平台，我们发现病毒与干扰素反应基因的不同空间表达相对应，表明 SARS-CoV-2 感染的肺内异质性。
