![]() The degree to which SARS-CoV-2 infection and the immune response to COVID-19 resemble or differ from other insults in the lung is therefore unclear. Although most patients with severe COVID-19 develop ARDS, administering routine clinical supportive care as for other ARDS does not entirely aid in patient recovery. However, thorough analysis of infected tissue and the immune system in a spatial context has only recently been started 4, 19, 20, 21 and is currently lacking for most infected organs, including the lung. Immune profiling in peripheral blood 1, 2, 3, 5, 7, 16 or bronchoalveolar lavage fluid 17 have revealed major changes in the immune system excessive neutrophil activation 18, lymphopenia 3 and aberrant responses of the adaptive immune system 2 are among the most prominent changes. Persistent inflammation can result in damage to lung tissue 13, the exudation of pulmonary-oedema fluid that leads to dyspnoea, and acute respiratory distress syndrome (ARDS) 14, 15. A growing body of evidence indicates that the severity of COVID-19 is driven by an inflammatory syndrome caused by hyperactivation of the immune system 8, 12 in an attempt to clear the virus. SARS-CoV-2 is the coronavirus that causes COVID-19, which has become a global pandemic: as of February 2021, over 100 million people have been infected and there have been more than 2 million fatalities 10, 11. 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. ![]() ![]() Our data enable us to develop a biologically interpretable landscape of lung pathology from a structural, immunological and clinical standpoint. 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. 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. Neutrophil and macrophage infiltration are hallmarks of bacterial pneumonia and COVID-19, respectively. These spatially resolved single-cell data unravel the disordered structure of the infected and injured lung, alongside the distribution of extensive immune infiltration. Here we use high-parameter imaging mass cytometry 9 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. However, a thorough investigation of the interplay between infected cells and the immune system at sites of infection has been lacking. Recent studies have provided insights into the pathology of and immune response to COVID-19 1, 2, 3, 4, 5, 6, 7, 8. ![]()
0 Comments
Leave a Reply. |