Lung epithelial and endothelial damage, loss of tissue repair, inhibition of fibrinolysis, and cellular senescence in fatal COVID-19 Journal Article


Authors: D'Agnillo, F.; Walters, K. A.; Xiao, Y.; Sheng, Z. M.; Scherler, K.; Park, J.; Gygli, S.; Rosas, L. A.; Sadtler, K.; Kalish, H.; Blatti, C. A. 3rd; Zhu, R.; Gatzke, L.; Bushell, C.; Memoli, M. J.; O'Day, S. J.; Fischer, T. D.; Hammond, T. C.; Lee, R. C.; Cash, J. C.; Powers, M. E.; O'Keefe, G. E.; Butnor, K. J.; Rapkiewicz, A. V.; Travis, W. D.; Layne, S. P.; Kash, J. C.; Taubenberger, J. K.
Article Title: Lung epithelial and endothelial damage, loss of tissue repair, inhibition of fibrinolysis, and cellular senescence in fatal COVID-19
Abstract: Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is characterized by respiratory distress, multiorgan dysfunction, and, in some cases, death. The pathological mechanisms underlying COVID-19 respiratory distress and the interplay with aggravating risk factors have not been fully defined. Lung autopsy samples from 18 patients with fatal COVID-19, with symptom onset-to-death times ranging from 3 to 47 days, and antemortem plasma samples from 6 of these cases were evaluated using deep sequencing of SARS-CoV-2 RNA, multiplex plasma protein measurements, and pulmonary gene expression and imaging analyses. Prominent histopathological features in this case series included progressive diffuse alveolar damage with excessive thrombosis and late-onset pulmonary tissue and vascular remodeling. Acute damage at the alveolar-capillary barrier was characterized by the loss of surfactant protein expression with injury to alveolar epithelial cells, endothelial cells, respiratory epithelial basal cells, and defective tissue repair processes. Other key findings included impaired clot fibrinolysis with increased concentrations of plasma and lung plasminogen activator inhibitor-1 and modulation of cellular senescence markers, including p21 and sirtuin-1, in both lung epithelial and endothelial cells. Together, these findings further define the molecular pathological features underlying the pulmonary response to SARS-CoV-2 infection and provide important insights into signaling pathways that may be amenable to therapeutic intervention.
Keywords: health; china; expression; stem-cells; disease; recovery; alignment; plasminogen-activator inhibitor-1; cancer; pai-1
Journal Title: Science Translational Medicine
Volume: 13
Issue: 620
ISSN: 1946-6234
Publisher: American Association for the Advancement of Science  
Date Published: 2021-11-17
Start Page: eabj7790
Language: English
ACCESSION: WOS:000720389300006
DOI: 10.1126/scitranslmed.abj7790
PROVIDER: wos
PUBMED: 34648357
Notes: Article -- Source: Wos
Altmetric
Citation Impact
MSK Authors
  1. William D Travis
    674 Travis