Department of Stem Cell Biology, State Research Institute Centre for Innovative Medicine, LT-01102 Vilnius, Lithuania.
Faculty of Medicine, Vilnius University, LT-03101 Vilnius, Lithuania.
Function (Oxf). 2024 Jan 9;5(2):zqae002. doi: 10.1093/function/zqae002. eCollection 2024.
The pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 instigated the most serious global health crisis. Clinical presentation of COVID-19 frequently includes severe neurological and neuropsychiatric symptoms. However, it is presently unknown whether and to which extent pathological impairment of blood-brain barrier (BBB) contributes to the development of neuropathology during COVID-19 progression. In the present study, we used human induced pluripotent stem cells-derived brain endothelial cells (iBECs) to study the effects of blood plasma derived from COVID-19 patients on the BBB integrity in vitro. We also performed a comprehensive analysis of the cytokine and chemokine profiles in the plasma of COVID-19 patients, healthy and recovered individuals. We found significantly increased levels of interferon γ-induced protein 10 kDa, hepatocyte growth factor, and interleukin-18 in the plasma of COVID-19 patients. However, blood plasma from COVID-19 patients did not affect transendothelial electrical resistance in iBEC monolayers. Our results demonstrate that COVID-19-associated blood plasma inflammatory factors do not affect BBB paracellular pathway directly and suggest that pathological remodeling (if any) of BBB during COVID-19 may occur through indirect or yet unknown mechanisms.
由严重急性呼吸综合征冠状病毒 2 引起的 2019 年冠状病毒病(COVID-19)大流行引发了最严重的全球卫生危机。COVID-19 的临床特征经常包括严重的神经和神经精神症状。然而,目前尚不清楚病理上血脑屏障(BBB)的损伤是否以及在多大程度上促进了 COVID-19 进展过程中的神经病理学发展。在本研究中,我们使用人类诱导多能干细胞衍生的脑内皮细胞(iBECs)来研究源自 COVID-19 患者的血浆对体外 BBB 完整性的影响。我们还对 COVID-19 患者、健康人和康复者的血浆中的细胞因子和趋化因子谱进行了全面分析。我们发现 COVID-19 患者血浆中干扰素 γ诱导蛋白 10 kDa、肝细胞生长因子和白细胞介素 18 的水平显著升高。然而,COVID-19 患者的血浆并未影响 iBEC 单层细胞的跨内皮电阻。我们的结果表明,与 COVID-19 相关的血浆炎症因子不会直接影响 BBB 的旁细胞途径,并表明 COVID-19 期间 BBB 的病理性重塑(如果有)可能通过间接或未知的机制发生。