Blood–brain barrier injury and neuroinflammation induced by SARS-CoV-2 in a lung–brain microphysiological system

Peng Wang, Lin Jin, Min Zhang, Yunsong Wu, Zilei Duan, Yaqiong Guo, Chaoming Wang, Yingqi Guo, Wenwen Chen, Zhiyi Liao, Yaqing Wang, Ren Lai, Luke P. Lee, Jianhua Qin

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

In some patients, COVID-19 can trigger neurological symptoms with unclear pathogenesis. Here we describe a microphysiological system integrating alveolus and blood–brain barrier (BBB) tissue chips that recapitulates neuropathogenesis associated with infection by SARS-CoV-2. Direct exposure of the BBB chip to SARS-CoV-2 caused mild changes to the BBB, and infusion of medium from the infected alveolus chip led to more severe injuries on the BBB chip, including endothelial dysfunction, pericyte detachment and neuroinflammation. Transcriptomic analyses indicated downregulated expression of the actin cytoskeleton in brain endothelium and upregulated expression of inflammatory genes in glial cells. We also observed early cerebral microvascular damage following lung infection with a low viral load in the brains of transgenic mice expressing human angiotensin-converting enzyme 2. Our findings suggest that systemic inflammation is probably contributing to neuropathogenesis following SARS-CoV-2 infection, and that direct viral neural invasion might not be a prerequisite for this neuropathogenesis. Lung–brain microphysiological systems should aid the further understanding of the systemic effects and neurological complications of viral infection.

Original languageEnglish
JournalNature Biomedical Engineering
DOIs
StateAccepted/In press - 2023

Bibliographical note

Publisher Copyright:
© 2023, The Author(s), under exclusive licence to Springer Nature Limited.

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