The blood-gas barrier in COVID-19: an overview of the effects of SARS-CoV-2 infection on the alveolar epithelial and endothelial cells of the lung

ABSTRACT

Blood-gas barrier (BGB) or alveolar-capillary barrier is the primary tissue barrier affected by coronavirus disease 2019 (COVID-19). Comprising alveolar epithelial cells (AECs), endothelial cells (ECs) and the extracellular matrix (ECM) in between, the BGB is damaged following the action of multiple pro-inflammatory cytokines during acute inflammation. The infection of AECs and ECs with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen behind COVID-19, triggers an inflammatory response at the BGB, inducing the release of interleukin 1 (IL-1), IL-6, tumor necrosis factor alpha (TNF-α), transforming growth factor beta (TGF-β), high mobility group box 1 (HMGB1), matrix metalloproteinases (MMPs), intercellular adhesion molecule-1 (ICAM-1) and platelet activating factor (PAF). The end result is the disassembly of adherens junctions (AJs) and tight junctions (TJs) in both AECs and ECs, AEC hyperplasia, EC pyroptosis, ECM remodeling and deposition of fibrin clots in the alveolar capillaries, leading to disintegration and thickening of the BGB, and ultimately, hypoxia. This commentary seeks to provide a brief account of how the BGB might become affected in COVID-19.

KEYWORDS:

• Blood-gas barrier
• alveolar-capillary barrier
• alveolar epithelial cell
• endothelial cell
• adherens junction
• tight junction
• extracellular matrix
• severe acute respiratory syndrome coronavirus 2
• COVID-19
• coronavirus disease 2019

Disclosure of potential conflicts of interest

No conflicts of interest, financial or otherwise, are declared by the author. The author has no financial relationship with a biotechnology and/or pharmaceutical manufacturer that has an interest in the subject matter or materials discussed in the submitted manuscript.