Table 5.

Summary on organ-an-a-chip for mimicking SARS-CoV-2 infection and drug screen.

Material	Fabrication method	Organ type	Key finding	Limitation	Ref.
PDMS	Soft lithographic	Lung	Treatment with remdesivir can inhibit viral replication and alleviate barrier disruption on chip	Use of only one cell type of alveolus epithelium and assess of only one type of antiviral candidates	104
PDMS	Soft lithographic	Lung	Rapid endotheliitis and vascular damage characterize SARS-CoV-2 infection	Lack of a complete recapitulation of resident innate immunity and the absence of an adaptive immune response and other cell types necessary for the complete recapitulation of vascular function	106
PDMS	Soft lithographic	Airway	Amodiaquine inhibited SARS-CoV-2 infection, but hydroxychloroquine did not.	Not use of native SARS-CoV-2 in BSL3 laboratories	107
Commercial device	Commercial device	Respiratory epithelial tissue	Models can recapitulate key, essential epithelial–capillary interactions specifically observed from in vivo pulmonology.	Timeline limit of three weeks	108
PDMS	Soft lithographic	Gut	In regard to the brain endothelium, the SARS-CoV-2 spike protein induced destabilization of the BBB, promoted a pro-inflammatory status but did not appear to alter cell viability acutely	Use of immortalized intestinal epithelial cell lines and lack of a comprehensive study on the complex responses of the immune cells involved in the host-virus interactions in this gut-on-a-chip system	110
PDMS	Soft lithographic	Blood–brain barrier	Introduction of spike proteins to in vitro models of the blood–brain barrier (BBB) showed significant changes to barrier properties	Ignorance on how permeability dynamics may change once these 3D microfluidic constructs are used with the whole SARS-CoV-2 virus	111
PDMS	Soft lithographic	Vasculature	Identification and inhibition of patient blood-specific coagulation in response to spike mutation or SARS-CoV-2	–	112
PDMS polystyrene	Soft lithographic Hot-embossing	Vasculature	Identification of angiopoietin-1-derived peptide as a therapeutic for SARS-CoV-2-induced inflammation	Use of HUVEC to understand SARS-CoV-2 pathogenesis while some studies have shown that endothelial cells may not be the primary target of SARS-CoV-2 infection in all organs; the complex interplay between parenchymal tissue and endothelial cells in the context of infection was not demonstrated	113
PDMS	Soft lithographic	Lung endothelial barrier	SARS-CoV-2 disrupts respiratory vascular barriers by suppressing Claudin-5 expression	Lack immune cells, the mechanism is not fully understood	114

‒, not applicable.