Previously, single-cell RNA sequencing (scRNA-seq) analyses of healthy individuals have revealed the tissue distribution of host receptors that are required for SARS-CoV-2 entry 5, 6, 7, and examination of bronchoalveolar lavage fluid and blood from patients with COVID-19 of varying severity has identified the effects of SARS-CoV-2 infection on immune responses and cytokine dysregulation 8, 9, 10, 11, 12. Approximately 15% of infected individuals develop severe disease, which can manifest as acute respiratory distress syndrome (ARDS) and is associated with substantial morbidity and mortality 2, 4. Globally, the pandemic of COVID-19, which results from infection with SARS-CoV-2, has led to more than 145 million cases (32 million in the USA) and 3.1 million deaths (570,000 in the USA figures as of 26 April 2021) 1. This atlas enables the dissection of lethal COVID-19, may inform our understanding of long-term complications of COVID-19 survivors, and provides an important resource for therapeutic development. Inference of protein activity and ligand–receptor interactions identified putative drug targets to disrupt deleterious circuits. Furthermore, we identified expansion of recently described CTHRC1 + pathological fibroblasts 3 contributing to rapidly ensuing pulmonary fibrosis in COVID-19.
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Alveolar type 2 cells adopted an inflammation-associated transient progenitor cell state and failed to undergo full transition into alveolar type 1 cells, resulting in impaired lung regeneration. Monocyte/macrophage-derived interleukin-1β and epithelial cell-derived interleukin-6 were unique features of SARS-CoV-2 infection compared to other viral and bacterial causes of pneumonia. The lungs from individuals with COVID-19 were highly inflamed, with dense infiltration of aberrantly activated monocyte-derived macrophages and alveolar macrophages, but had impaired T cell responses. Integrated analyses identified substantial alterations in cellular composition, transcriptional cell states, and cell-to-cell interactions, thereby providing insight into the biology of lethal COVID-19. Here we performed single-nucleus RNA sequencing of about 116,000 nuclei from the lungs of nineteen individuals who died of COVID-19 and underwent rapid autopsy and seven control individuals. Respiratory failure is the leading cause of death in patients with severe SARS-CoV-2 infection 1, 2, but the host response at the lung tissue level is poorly understood. Nature volume 595, pages 114–119 ( 2021) Cite this article A molecular single-cell lung atlas of lethal COVID-19
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