Vascular disruption has been implicated in coronavirus disease 2019 (COVID-19) pathogenesis and may predispose to the neurological sequelae associated with long COVID, yet it is unclear how blood–brain barrier (BBB) function is affected in these conditions. Here we show that BBB disruption is evident during acute infection and in patients with long COVID with cognitive impairment, commonly referred to as brain fog. Using dynamic contrast-enhanced magnetic resonance imaging, we show BBB disruption in patients with long COVID-associated brain fog. Transcriptomic analysis of peripheral blood mononuclear cells revealed dysregulation of the coagulation system and a dampened adaptive immune response in individuals with brain fog. Accordingly, peripheral blood mononuclear cells showed increased adhesion to human brain endothelial cells in vitro, while exposure of brain endothelial cells to serum from patients with long COVID induced expression of inflammatory markers. Together, our data suggest that sustained systemic inflammation and persistent localized BBB dysfunction is a key feature of long COVID-associated brain fog.

血管破坏与 2019 年冠状病毒病 (COVID-19) 的发病机制有关，并可能导致与长期 COVID 相关的神经系统后遗症，但尚不清楚在这些情况下血脑屏障 (BBB) 功能如何受到影响。在这里，我们发现，在急性感染期间和患有认知障碍（通常称为脑雾）的长期新冠患者中，血脑屏障破坏是明显的。使用动态对比增强磁共振成像，我们显示了与新冠病毒相关的长期脑雾患者的血脑屏障受损。外周血单核细胞的转录组分析揭示了脑雾患者的凝血系统失调和适应性免疫反应减弱。因此，外周血单核细胞在体外表现出与人脑内皮细胞的粘附增加，而将脑内皮细胞暴露于长期新冠患者的血清中会诱导炎症标志物的表达。总之，我们的数据表明，持续的全身炎症和持续的局部血脑屏障功能障碍是与新冠病毒相关的长期脑雾的一个关键特征。