The spatial landscape of lung pathology during COVID-19 progression - targeted spatial transcriptomics 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.既往多项研究已为新型冠状病毒肺炎（Coronavirus Disease 2019, COVID-19）的病理特征与免疫应答机制提供了重要见解。然而，目前仍缺乏对感染部位受感染细胞与免疫系统间相互作用的全面解析。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），以单细胞分辨率解析包括严重急性呼吸综合征冠状病毒2型（Severe Acute Respiratory Syndrome Coronavirus 2, SARS-CoV-2）感染在内的人类急性肺损伤的细胞组成与空间结构特征。该空间分辨单细胞数据揭示了受感染及损伤肺组织的紊乱结构，以及广泛免疫细胞浸润的分布模式。中性粒细胞浸润与巨噬细胞浸润分别是细菌性肺炎与新型冠状病毒肺炎的典型病理标志。本研究证实，严重急性呼吸综合征冠状病毒2型主要感染肺泡上皮细胞，并诱导与肺损伤相关的局部过度炎症细胞状态。通过结合重症致死型新型冠状病毒肺炎患者从症状发作至死亡的时间跨度，本研究观察到随着疾病进展，巨噬细胞渗出、间充质细胞及成纤维细胞的丰度显著升高，且这些细胞间的近距离互作也随之增强，这可能是机体对受损肺组织的修复应答。该空间分辨单细胞数据使我们能够从结构、免疫及临床多个维度，构建肺病理特征的生物学可解释图谱。该空间单细胞图谱实现了人类肺部从宏观表型到单细胞层面的病理生理特征解析，为全面理解新型冠状病毒肺炎及一般性肺病理机制提供了重要依据。