The spatial landscape of lung pathology during the progression of COVID-19

Recent studies have provided insight into the pathology and immune response to coronavirus disease 2019 (COVID-19)^1–8. However, a thorough examination of the interaction between infected cells and the immune system at sites of infection is lacking. We use high-parameter imaging mass cytometry⁹ targeting the expression of 36 proteins, to study at single cell resolution, the cellular composition and the spatial architecture of human acute lung injury, including SARS-CoV-2. These spatially resolved single-cell data reveal the disordered structure of the infected and injured lung as well as the distribution of extensive immune infiltration. Infiltration of neutrophils and macrophages is the hallmark of bacterial pneumonia and COVID-19, respectively. We provide evidence that SARS-CoV-2 primarily infects alveolar epithelial cells and induces a localized hyper-inflammatory cellular state associated with lung damage. Taking advantage of the time range of severe fatal disease of COVID-19 from the time of symptom onset, we observe an increase in extravasation of macrophages, mesenchymal cells and the abundance of fibroblasts concomitant with increased proximity between these cell types as the disease progresses, perhaps as an attempt. to repair damaged lung tissue. These spatially resolved single-cell data have enabled us to develop a biologically interpretable landscape of pulmonary pathology from a structural, immunological and clinical perspective. This unicellular spatial landscape has enabled the pathophysiological characterization of the human lung from its macroscopic presentation to the single cell, providing an important basis for understanding COVID-19 and pulmonary pathology in general.