Modelling SARS-CoV-2 infection in a human alveolus microphysiological system.

Area of Science:

• * Respiratory biology
• * Virology
• * Biomedical engineering

Background:

• * The COVID-19 pandemic necessitates advanced in vitro models for preclinical research.
• * Current models often lack the physiological relevance of the human lung.
• * Microphysiological systems (MPS) offer a promising avenue for more accurate disease modeling.

Purpose of the Study:

• * To adapt and validate a human alveolus MPS for studying SARS-CoV-2 infection.
• * To assess the model's ability to recapitulate key aspects of lung infection.
• * To evaluate the model's utility in preclinical research for respiratory viruses.

Main Methods:

• * Adaptation of a human alveolus MPS using primary human alveolar epithelial and lung microvascular endothelial cells.
• * Culture of cells at the air-liquid interface with breathing-like stretch.
• * Infection with SARS-CoV-2 within a Biosafety Level 3 facility.
• * Analysis of cytopathic effects, viral replication, and host immune responses.

Main Results:

• * The MPS model demonstrated clinically relevant cytopathic effects, including alveolar type 2 cell rounding and occludin disruption.
• * SARS-CoV-2 replication was confirmed via immunocytochemical staining and increased virus shedding within 2 days.
• * Changes in innate host immune responses were observed post-infection.
• * The model successfully mimicked SARS-CoV-2 infection in human alveolar lung cells.

Conclusions:

• * The developed human alveolus MPS is a viable and physiologically relevant model for SARS-CoV-2 infection.
• * This model can recapitulate key pathological features and viral dynamics of lung infection.
• * The MPS platform holds significant potential for advancing preclinical research on respiratory viral diseases.