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

This article has been Reviewed by the following groups

Read the full article See related articles

Listed in

This article is not in any list yet, why not save it to one of your lists.
Log in to save this article

Abstract

The coronavirus 2019 pandemic has highlighted the importance of physiologically relevant in vitro 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.

Article activity feed

  1. The reviewers have raised some concerns, pleaase make sure you address them carefully. In particular those that relate to clarity, data visualisation as well as inclusion of statistical analysis data (reviewer 2 lines 195-197).

  2. Comments to Author

    This manuscript describes 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. In general, the data is well presented and reflects the innovation and advantages of using this model. However, while reviewing this work one major critique was identified. Furthermore, several minor critiques should also be addressed to provide clarity to the text. These critiques are outlined below. Mayor critique: - Given that the main contribution of this manuscript is the description of a microphysiological system to study infection with SARS-CoV-2, it is essential to include a figure where this model is extensively described. This will allow the reader get familiarized with …

  3. Comments to Author

    This is a well written paper which describes validation of an MPS model for lung tissue infected with SARS-CoV-2. While generally reasonable in conclusions and goals there remains some issues to address. The authors point out the discrepancies between the cytokine responses observed in this study and comparable studies (lines 283-286) and suggest that this is connected to lack of immune cells in the model described here. While this is plausible this is also a critical observation for this study and a reasonable discussion should expand on this point. This is particularly important given the study seeks to demonstrate that the model recapitulates key clinical features, of which comparable cytokine responses must be considered a critical component. There are a number of issues with presentation of …