The spatial landscape of lung pathology during COVID-19 progression - immune activation IMC data

Recent studies have provided insights into the pathology and immune response to coronavirus disease 2019 (COVID-19). However thorough interrogation of the interplay between infected cells and the immune system at sites of infection is lacking. We use high parameter imaging mass cytometry targeting the expression of 36 proteins, to investigate at single cell resolution, the cellular composition and spatial architecture of human acute lung injury including SARS-CoV-2. This spatially resolved, single-cell data unravels the disordered structure of the infected and injured lung alongside the distribution of extensive immune infiltration. Neutrophil and macrophage infiltration are hallmarks of bacterial pneumonia and COVID-19, respectively. We provide evidence that SARS-CoV-2 infects predominantly alveolar epithelial cells and induces a localized hyper-inflammatory cell state associated with lung damage. By leveraging the temporal range of COVID-19 severe fatal disease in relation to the time of symptom onset, we observe increased macrophage extravasation, mesenchymal cells, and fibroblasts abundance concomitant with increased proximity between these cell types as the disease progresses, possibly as an attempt to repair the damaged lung tissue. This spatially resolved single-cell data allowed us to develop a biologically interpretable landscape of lung pathology from a structural, immunological and clinical standpoint. This spatial single-cell landscape enabled the pathophysiological characterization of the human lung from its macroscopic presentation to the single-cell, providing an important basis for the understanding of COVID-19, and lung pathology in general.近期研究已为2019冠状病毒病（coronavirus disease 2019, COVID-19）的病理特征与免疫应答提供了诸多见解，但针对感染部位受感染细胞与免疫系统间的相互作用开展全面解析的研究仍存在空白。本研究采用靶向36种蛋白表达的高参数成像质谱流式细胞术（imaging mass cytometry），以单细胞分辨率探究包括严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）感染在内的人类急性肺损伤的细胞组成与空间架构。该空间分辨单细胞数据揭示了受感染与损伤肺组织的紊乱结构，以及广泛免疫浸润的分布特征。中性粒细胞浸润与巨噬细胞浸润分别为细菌性肺炎与COVID-19的典型病理标志。本研究证实，SARS-CoV-2主要感染肺泡上皮细胞，并诱导与肺损伤相关的局部高炎症细胞状态。通过结合重症致死型COVID-19的病程与症状发作时间，我们观察到随着疾病进展，巨噬细胞外渗、间充质细胞与成纤维细胞的丰度显著升高，且这些细胞类型间的邻近相互作用亦随之增强，这一现象可能是机体修复受损肺组织的代偿性机制。本项空间分辨单细胞数据使我们能够从结构、免疫与临床视角构建具有生物学可解释性的肺病理图谱。该空间单细胞图谱实现了人类肺部从宏观表达到单细胞层面的病理生理特征表征，为全面理解COVID-19及一般性肺病理改变提供了重要研究基础。