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

The coronavirus 2019 pandemic has highlighted the importance of physiologically relevant <i>in vitro</i> models to assist preclinical research. Here, we describe the adaptation of a human alveolus microphysiological system (MPS) model consisting of primary human alveolar epithelial and lung microvascular endothelial cells to study infection with SARS-CoV-2 at Biosafety Level 3 facility. This infection model recapitulates breathing-like stretch and culture of epithelial cells at the air-liquid interface and resulted in clinically relevant cytopathic effects including cell rounding of alveolar type 2 cells and disruption of the tight junction protein occludin. Viral replication was confirmed by immunocytochemical nucleocapsid staining in the epithelium and increased shedding of SARS-CoV-2 virus within 2 days post-infection, associated with changes in innate host immune responses. Together, these data demonstrate that, under the experimental conditions used in this work, this human alveolus MPS chip can successfully model SARS-CoV-2 infection of human alveolar lung cells.