Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Authors:Zhang et al.  

Journal/ Pre-Print:bioRxiv preprint 

TagsModelling, Immunology/Immunity, Cell Biology 

Research Highlights 

  1. The establishment of the first microengineered human pulmonary model of SARS-CoV-2 infection on a chip. Which provides a promising and alternative platform for COVID-19 research.  

  1. Epithelial and endothelial cells displayed distinct transcriptome responses after SARS-CoV-2 infectionAlveolar epithelial cells showed un enrichment of type I interferon (IFN-I) signalling pathway and cytokine-mediated signalling pathway, while the activation of JAK-STAT signalling pathway was observed in pulmonary microvascular endothelial cells.  

  1. Circulating immune cells play a crucial role in mediating the damage of alveolar barrier function after SARS-CoV-2 infection. 


In this study, the authors created a microengineered human disease model of SARS-CoV-2 infectionThey showed that this human organ on chip model closely recapitulated the human relevant lung pathophysiology and immune responses associated with COVID-19, such as viral replication in human alveolar epithelium, alveolar-capillary barrier injury, vascular dysfunction, recruitment of immune cells, and increased inflammatory cytokine release in a physiologically-relevant manner. Interestingly, alveolar epithelial and endothelial cells have a distinct role and response in the pathogenesis of COVID-19.  While alveolar epithelial cells displayed strong innate immune responses and antiviral responses following viral infection, endothelial cells display a positive regulation of JAK-STAT cascade and adaptive immune response. Moreover, they found that human circulating immune cells play a key role in exacerbating inflammatory responses and the injury of alveolar-capillary-barrier induced by SARS-CoV-2. Lastly, they could validate the antiviral efficacy of remdesivir in their infected chip model. 

Impact for SARS-CoV2/COVID19 research efforts  

Understand the virology and/or cell biology of SARS-CoV2/COVID19:   

In this study, they showed that the human alveolar epithelial cells were more susceptible to SARS-CoV-2 infection than endothelial cells Moreover, transcriptome analysis demonstrated a distinctive response of alveolar epithelial and endothelial cells to SARS-CoV-2 infection. 

Understand the immune response to SARS-CoV2/COVID19:  

The study revealed the critical roles of human circulating immune cells in exacerbating inflammatory responses and mediating alveolar injury and microvascular endothelial dysfunction induced by SARS-CoV-2 at organ-level. 

Study Type  

  • In vitro study (human organ on chip) 

Strengths and limitations of the paper 

Novelty: This work provides a proof-of-concept to establish the first human alveolus chip capable to model human lung pathophysiology and study host-immune responses to SARS-CoV-2 infection at organ level.  

Standing in the field: The results obtained from this first microengineered human pulmonary model of SARS-CoV-2 are in agreement with the published clinical results in COVID-19 patients 

Viral model used: SARS-CoV2 strain 

Translatability: This microengineered human disease model provide a promising and alternative platform for evaluating candidate drugs and repurposing approved drugs to face COVID19 pandemic 

Main limitations: The main limitation is the use of HPAEpiC which is immortalized human alveolar epithelial cells and HULEC-5a the human lung microvasculature cell line. which didn’t mimic the real human primary alveolar tissues that contains multiple types of pneumocytes.