Recent studies have provided insights into the pathology of and immune response to COVID-19^{1,2,3,4,5,6,7,8}. However, a thorough investigation of the interplay between infected cells and the immune system at sites of infection has been lacking. Here we use high-parameter imaging mass cytometry⁹ that targets the expression of 36 proteins to investigate the cellular composition and spatial architecture of acute lung injury in humans (including injuries derived from SARS-CoV-2 infection) at single-cell resolution. These spatially resolved single-cell data unravel 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 hyperinflammatory cell state that is associated with lung damage. We leverage the temporal range of fatal outcomes of COVID-19 in relation to the onset of symptoms, which reveals increased macrophage extravasation and increased numbers of mesenchymal cells and fibroblasts concomitant with increased proximity between these cell types as the disease progresses—possibly as a result of attempts to repair the damaged lung tissue. Our data enable us to develop a biologically interpretable landscape of lung pathology from a structural, immunological and clinical standpoint. We use this landscape to characterize the pathophysiology of the human lung from its macroscopic presentation to the single-cell level, which provides an important basis for understanding COVID-19 and lung pathology in general.

最近的研究为 COVID-19 的病理学和免疫反应提供了见解^{1,2,3,4,5,6,7,8}。然而，缺乏对感染细胞与感染部位免疫系统之间相互作用的彻底调查。在这里，我们使用高参数成像质谱流式细胞仪⁹该研究针对 36 种蛋白质的表达，以单细胞分辨率研究人类急性肺损伤（包括源自 SARS-CoV-2 感染的损伤）的细胞组成和空间结构。这些空间分辨的单细胞数据揭示了受感染和受伤肺的无序结构，以及广泛的免疫浸润分布。中性粒细胞和巨噬细胞浸润分别是细菌性肺炎和 COVID-19 的标志。我们提供的证据表明 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。我们利用与症状发作相关的 COVID-19 致命结果的时间范围，这表明随着疾病的进展，巨噬细胞外渗增加，间充质细胞和成纤维细胞数量增加，同时这些细胞类型之间的距离增加——可能是由于试图修复受损肺组织的结果。我们的数据使我们能够从结构、免疫学和临床的角度开发肺部病理学的生物学可解释图景。我们利用这一景观来表征人肺从宏观表现到单细胞水平的病理生理学特征，这为理解 COVID-19 和一般肺病理学提供了重要基础。我们的数据使我们能够从结构、免疫学和临床的角度开发肺部病理学的生物学可解释图景。我们利用这一景观来表征人肺从宏观表现到单细胞水平的病理生理学特征，这为理解 COVID-19 和一般肺病理学提供了重要基础。我们的数据使我们能够从结构、免疫学和临床的角度开发肺部病理学的生物学可解释图景。我们利用这一景观来表征人肺从宏观表现到单细胞水平的病理生理学特征，这为理解 COVID-19 和一般肺病理学提供了重要基础。