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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严重急性呼吸综合征冠状病毒-2（SARS-CoV-2）会导致轻度至重度的急性呼吸窘迫综合症、肺炎和肺组织损伤。这会导致肺泡细胞中的气体交换功能下降，从而引发与临床严重程度/死亡率相关的低氧血症。需要全面研究导致约710万人死亡的肺部功能障碍的确切细胞基础。了解病毒感染引起的肺细胞内变化可能是我们通过适当治疗干预恢复患者呼吸效率的重要一步。我们在体外进行了一项研究以理解SARS-CoV-2在肺泡中的发病机制。我们将肺泡上皮（A549和L-132）、成纤维细胞（WI-38）、人肺动脉内皮细胞（HPAEC-c）以及非洲绿猴肾上皮细胞（Vero-E6）培养并感染了SARS-CoV-2。在感染的II型肺泡细胞中观察到囊泡形成、细胞骨架变形，以及在肺泡和动脉内皮细胞中的线粒体断裂；内皮细胞的糖萼丧失以及病毒独特的旁路排出机制成为主要的细胞内变化。我们报道，在肺细胞中的子代病毒通过旁路排出路径离开并与由于病毒感染过载导致的内皮细胞糖萼丢失一起被报告为感染向多个器官传播的机制。我们也提出，感染的II型肺泡细胞中形成的众多囊泡以及占据这些囊泡内的SARS-CoV-2病毒颗粒可能会阻碍肺泡II型细胞和肺静脉壁细胞膜中的表面活性剂混合吸入空气的跨胞质转运及其随后转移到静脉血流中。还建议使用重新定位的硝酸甘油基药物来恢复肺泡II型细胞所需的细胞内细胞质粘度。

关键词： 肺泡；旁路排出；气体交换；低氧血症；SARS-CoV-2；囊泡化。