Severe Acute Respiratory Syndrome Coronavirus-2 causes mild to severe Acute Respiratory Distress Syndrome, Pneumonia and lung tissue damage. This leads to sub performance in the pulmonary gaseous exchange by the alveolar cells causing hypoxia associated with clinical severities/mortality. The exact cellular basis of the pulmonary malfunction resulting into death of approximately 7.1 million people needs to be fully studied. Understanding the intracellular alterations in pulmonary cells caused by viral infection could prove to be a significant step in our attempts to revert the respiratory efficiency of the patients through appropriate therapeutic interventions. We have undertaken In-Vitro studies to understand the pathogenesis of SARS-CoV-2 in alveoli. We cultured the Alveolar Epithelium (A549 and L-132), Fibroblasts (WI-38), Human Pulmonary Artery Endothelial Cells (HPAEC-c), and African Green Monkey Kidney Epithelial Cells (Vero-E6) and infected them with SARS-CoV-2. Vacuoles in infected Alveolar Type-2 cells, cytoskeletal deformation, fragmentation of mitochondria in alveolar and arterial endothelial cells, loss of glycoclayx in endothelial cells and a unique bypass exit mechanism of virus were observed as major intracellular changes due to infection. The bypass exit of the daughter virions from lung cells along with loss of glycoclayx due to virus overburdening is reported as mechanism of propagation of infection towards multiple organs. We report that formation of numerous vacuoles in infected Alveolar Type-2 cells and the SARS-CoV-2 virions occupying these vacuoles could hamper the trans cytoplasmic trafficking of surfactant mixed inspired air and its subsequent transfer into venous blood through cell membranes of Alveolar Type -2 Cells and Capillary Wall Cells of pulmonary vein. The possible use of repurposed Nitroglycerine based drug to retrieve required intracellular cytoplasmic viscosity of the Alveolar type 2 cells has also been suggested.
Keywords: Alveoli; By pass exit; Gas exchange; Hypoxia; SARS-CoV-2; Vacuolization.
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