We present an asthmatic 39 year old female frontline healthcare worker in contact with COVID-19 patients, who suffered from respiratory problems for a few days, after which she was found dead by her spouse. Post-mortem (PM) examination showed lung consolidation and histological evidence of diffuse alveolar damage (DAD), in form of hyaline membrane disease, as well as atypical cells, thrombi and fibrin plugs inside pulmonary capillaries. Swab sample testing for SARS-CoV-2 confirmed the infection status. SARS-CoV-2 is a novel coronavirus which first emerged in Wuhan, China, and PM is contributing immensely to uncovering the pathophysiological mechanism of this disease. SARS-CoV-2 enters host cells via the angiotensin-converting enzyme 2 (ACE2), and can lead to a fatal pneumonia characterized histologically by DAD (the most consistent PM finding). This is due to invasion by the virus of type II pneumocytes, which leads to the death of both type I and II pneumocytes and increased capillary permeability. This compromises gas exchange which can lead eventually to cardiorespiratory failure and death.
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http://dx.doi.org/10.1016/j.mpdhp.2021.07.003 | DOI Listing |
Sci Transl Med
January 2025
Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease in which repetitive epithelial injury and incomplete alveolar repair result in accumulation of profibrotic intermediate/transitional "aberrant" epithelial cell states. The mechanisms leading to the emergence and persistence of aberrant epithelial populations in the distal lung remain incompletely understood. By interrogating single-cell RNA sequencing (scRNA-seq) data from patients with IPF and a mouse model of repeated lung epithelial injury, we identified persistent activation of hypoxia-inducible factor (HIF) signaling in these aberrant epithelial cells.
View Article and Find Full Text PDFJ Transl Med
January 2025
Emergency Department, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510630, China.
Background: Acute respiratory distress syndrome (ARDS) is a life-threatening and heterogeneous disorder leading to lung injury. To date, effective therapies for ARDS remain limited. Sepsis is a frequent inducer of ARDS.
View Article and Find Full Text PDFYakugaku Zasshi
January 2025
Department of Pharmaceutics and Drug Delivery, Faculty of Pharmaceutical Sciences, Tokyo University of Science.
Chronic obstructive pulmonary disease (COPD) is characterized by chronic bronchitis and emphysema, and current drug treatments is limited to symptomatic therapy. Thus, there is an urgent need for development of new treatments to repair alveolar destruction. To regenerate the destroyed alveoli, we focused on the differentiation of alveolar epithelial progenitor cells into type I or type II alveolar epithelial cells that constitute the alveoli.
View Article and Find Full Text PDFSci Rep
January 2025
Harbin Medical University, Harbin, Heilongjiang Province, China.
Interstitial lung disease (ILD) is known to be a major complication of systemic sclerosis (SSc) and a leading cause of death in SSc patients. As the most common type of ILD, the pathogenesis of idiopathic pulmonary fibrosis (IPF) has not been fully elucidated. In this study, weighted correlation network analysis (WGCNA), protein‒protein interaction, Kaplan-Meier curve, univariate Cox analysis and machine learning methods were used on datasets from the Gene Expression Omnibus database.
View Article and Find Full Text PDFmBio
December 2024
Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, North Carolina, USA.
Unlabelled: Respiratory epithelial cells can survive direct infection by influenza viruses, and the long-term consequences of that infection have been characterized in a subset of proximal airway cell types. The impact on the cells that survive viral infection in the distal lung epithelia, however, is much less well-characterized. Utilizing a Cre-expressing influenza B virus (IBV) and a lox-stop-lox tdTomato reporter mouse model, we identified that alveolar type 2 (AT2) pneumocytes, a progenitor cell type in the distal lung, can survive viral infection.
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