Fekete Monika, Lehoczki Andrea, Szappanos Ágnes, Toth Attila, Mahdi Mohamed, Sótonyi Péter, Benyó Zoltán, Yabluchanskiy Andriy, Tarantini Stefano, Ungvari Zoltan
Institute of Preventive Medicine and Public Health, Semmelweis University, Budapest, Hungary.
Doctoral College, Health Sciences Program, Semmelweis University, Budapest, Hungary.
Geroscience. 2025 Feb;47(1):745-779. doi: 10.1007/s11357-024-01487-4. Epub 2025 Jan 7.
Long COVID (also known as post-acute sequelae of SARS-CoV-2 infection [PASC] or post-COVID syndrome) is characterized by persistent symptoms that extend beyond the acute phase of SARS-CoV-2 infection, affecting approximately 10% to over 30% of those infected. It presents a significant clinical challenge, notably due to pronounced neurocognitive symptoms such as brain fog. The mechanisms underlying these effects are multifactorial, with mounting evidence pointing to a central role of cerebromicrovascular dysfunction. This review investigates key pathophysiological mechanisms contributing to cerebrovascular dysfunction in long COVID and their impacts on brain health. We discuss how endothelial tropism of SARS-CoV-2 and direct vascular infection trigger endothelial dysfunction, impaired neurovascular coupling, and blood-brain barrier disruption, resulting in compromised cerebral perfusion. Furthermore, the infection appears to induce mitochondrial dysfunction, enhancing oxidative stress and inflammation within cerebral endothelial cells. Autoantibody formation following infection also potentially exacerbates neurovascular injury, contributing to chronic vascular inflammation and ongoing blood-brain barrier compromise. These factors collectively contribute to the emergence of white matter hyperintensities, promote amyloid pathology, and may accelerate neurodegenerative processes, including Alzheimer's disease. This review also emphasizes the critical role of advanced imaging techniques in assessing cerebromicrovascular health and the need for targeted interventions to address these cerebrovascular complications. A deeper understanding of the cerebrovascular mechanisms of long COVID is essential to advance targeted treatments and mitigate its long-term neurocognitive consequences.
长期新冠（也称为新冠病毒2感染后急性后遗症[PASC]或新冠后综合征）的特征是持续症状，这些症状在新冠病毒2感染的急性期之后仍会持续，影响约10%至超过30%的感染者。它带来了重大的临床挑战，尤其是由于明显的神经认知症状，如脑雾。这些影响背后的机制是多因素的，越来越多的证据表明脑微血管功能障碍起着核心作用。本综述研究了导致长期新冠脑血管功能障碍的关键病理生理机制及其对大脑健康的影响。我们讨论了新冠病毒2的内皮嗜性和直接血管感染如何引发内皮功能障碍、神经血管耦合受损和血脑屏障破坏，从而导致脑灌注受损。此外，感染似乎会诱导线粒体功能障碍，增强脑内皮细胞内的氧化应激和炎症。感染后自身抗体的形成也可能加剧神经血管损伤，导致慢性血管炎症和持续的血脑屏障损害。这些因素共同导致白质高信号的出现，促进淀粉样蛋白病理变化，并可能加速神经退行性过程，包括阿尔茨海默病。本综述还强调了先进成像技术在评估脑微血管健康方面的关键作用，以及针对这些脑血管并发症进行靶向干预的必要性。深入了解长期新冠的脑血管机制对于推进靶向治疗和减轻其长期神经认知后果至关重要。
