SARS-CoV-2 Infection and Disease Modelling Using Stem Cell Technology and Organoids

Area of Science:

• Virology
• Pathogenesis
• Stem Cell Technology
• Organoid Models

Background:

• Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes a global pandemic with diverse clinical manifestations.
• Understanding the cellular tropism and pathogenesis of SARS-CoV-2 is crucial for developing effective treatments.
• Traditional in vitro models have limitations in recapitulating human organ complexity.

Purpose of the Study:

• To review how stem cell technology and organoids advance the understanding of SARS-CoV-2 cell tropisms.
• To elucidate the mechanisms of SARS-CoV-2 disease in the human host using organoid models.
• To support and clarify findings from clinical studies of SARS-CoV-2 infection.

Main Methods:

• Utilizing in vitro models of lung epithelia, including alveolar epithelial type II cells.
• Employing human small intestinal and colonic organoids to model gastrointestinal infection.
• Investigating SARS-CoV-2 pathogenesis in models of cardiomyocytes and choroid plexus epithelial cells.

Main Results:

• Alveolar epithelial type II cells are identified as key SARS-CoV-2 targets in the lungs, leading to apoptosis, inflammation, and impaired surfactant production.
• The gastrointestinal tract, specifically enterocytes and cholangiocytes, is susceptible to SARS-CoV-2 infection, causing cell damage and inflammation.
• Direct viral damage is observed in cardiomyocytes and choroid plexus epithelial cells, while endothelial cells and neurons show poor susceptibility.

Conclusions:

• Stem cell-derived organoids provide powerful tools to dissect SARS-CoV-2 pathogenesis at a cellular and organ level.
• Organoid models confirm specific cell types as primary targets, contributing to a deeper understanding of disease mechanisms.
• Findings suggest that indirect effects of systemic inflammation, rather than direct viral infection, may underlie neurological and vascular symptoms.