RT Journal Article
SR Electronic
T1 SARS-CoV-2 causes human BBB injury and neuroinflammation indirectly in a linked organ chip platform
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.10.05.463205
DO 10.1101/2021.10.05.463205
A1 Peng Wang
A1 Lin Jin
A1 Min Zhang
A1 Yunsong Wu
A1 Zilei Duan
A1 Wenwen Chen
A1 Chaoming Wang
A1 Zhiyi Liao
A1 Jianbao Han
A1 Yingqi Guo
A1 Yaqiong Guo
A1 Yaqing Wang
A1 Ren Lai
A1 Jianhua Qin
YR 2021
UL http://biorxiv.org/content/early/2021/10/06/2021.10.05.463205.abstract
AB COVID-19 is a multi-system disease affecting many organs outside of the lungs, and patients generally develop varying degrees of neurological symptoms. Whereas, the pathogenesis underlying these neurological manifestations remains elusive. Although in vitro models and animal models are widely used in studies of SARS-CoV-2 infection, human organ models that can reflect the pathological alterations in a multi-organ context are still lacking. In this study, we propose a new strategy to probe the effects of SARS-CoV-2 on human brains in a linked alveolus-BBB organ chip platform. The new multi-organ platform allows to recapitulate the essential features of human alveolar-capillary barrier and blood-brain barrier in a microfluidic condition by co-culturing the organ-specific cells. The results reveal direct SARS-CoV-2 exposure has no obvious effects on BBB chip alone. While, infusion of endothelial medium from infected alveolus chips can cause BBB dysfunction and neuroinflammation on the linked chip platform, including brain endothelium disruption, glial cell activation and inflammatory cytokines release. These new findings suggest that SARS-CoV-2 could induce neuropathological alterations, which might not result from direct viral infection through hematogenous route, but rather likely from systemic inflammation following lung infection. This work provides a new strategy to study the virus-host interaction and neuropathology at an organ-organ context, which is not easily obtained by other in vitro models. This will facilitate to understand the neurological pathogenesis in SARS-CoV-2 and accelerate the development of new therapeutics.SUMMARYA linked human alveolus-BBB chip platform is established to explore the influences of SARS-CoV-2 on human brains in an organ-organ context.SARS-CoV-2 infection could induce BBB injury and neuroinflammation.The neuropathological changes are caused by SARS-CoV-2 indirectly, which might be mediated by systemic inflammation following lung infection, but probably not by direct viral neuroinvasion.Competing Interest StatementThe authors have declared no competing interest.