Intracellular alterations, vacuolization and bypass mechanism by SARS-CoV-2 infection could be the possible basis of respiratory distress and hypoxia.

Summary

Across multiple pulmonary cell types infected with SARS-CoV-2, investigators observed AT2 cell vacuolization, cytoskeletal distortion, mitochondrial fragmentation, endothelial glycocalyx loss, and a putative virion egress ‘bypass’ pathway. They hypothesize these alterations impair gas transfer and tentatively propose nitroglycerin-based agents to modulate cytoplasmic viscosity.

Key Findings

• SARS-CoV-2 infection caused vacuolization in alveolar type II cells and cytoskeletal deformation.
• Mitochondrial fragmentation occurred in alveolar and pulmonary arterial endothelial cells.
• Loss of endothelial glycocalyx was observed after infection.
• Authors propose a unique virion ‘bypass’ exit mechanism from lung cells.
• Hypothesis that AT2 vacuoles occupied by virions impede gas transfer; suggestion to repurpose nitroglycerin to alter cytoplasmic viscosity.

Clinical Implications

Findings are hypothesis-generating; they do not support clinical use of nitroglycerin for ARDS. Future work could explore glycocalyx-preserving or mitochondria-protective strategies as adjuncts in COVID-19 respiratory failure.

Limitations

• In vitro model without in vivo or clinical validation.
• Sample size and quantitative effect sizes are not specified.
• Therapeutic proposal (nitroglycerin) is speculative and untested in disease models.

Future Directions

Validate mechanisms in primary human AT2 cells and lung organoids/animal models; quantify effects on gas exchange; test glycocalyx-preserving and mitochondrial-protective interventions before any clinical translation.