Center for Neurodegeneration and Regeneration, Zilkha Neurogenetic Institute, Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
J Med Virol. 2024 May;96(5):e29671. doi: 10.1002/jmv.29671.
The coronavirus disease of 2019 (COVID-19) pandemic has led to more than 700 million confirmed cases and nearly 7 million deaths. Although severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus mainly infects the respiratory system, neurological complications are widely reported in both acute infection and long-COVID cases. Despite the success of vaccines and antiviral treatments, neuroinvasiveness of SARS-CoV-2 remains an important question, which is also centered on the mystery of whether the virus is capable of breaching the barriers into the central nervous system. By studying the K18-hACE2 infection model, we observed clear evidence of microvascular damage and breakdown of the blood-brain barrier (BBB). Mechanistically, SARS-CoV-2 infection caused pericyte damage, tight junction loss, endothelial activation and vascular inflammation, which together drive microvascular injury and BBB impairment. In addition, the blood-cerebrospinal fluid barrier at the choroid plexus was also impaired after infection. Therefore, cerebrovascular and choroid plexus dysfunctions are important aspects of COVID-19 and may contribute to neurological complications both acutely and in long COVID.
2019 年冠状病毒病（COVID-19）大流行导致超过 7 亿例确诊病例和近 700 万人死亡。尽管严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）病毒主要感染呼吸系统，但在急性感染和长 COVID 病例中广泛报道了神经系统并发症。尽管疫苗和抗病毒治疗取得了成功，但 SARS-CoV-2 的神经侵袭性仍然是一个重要问题，这也集中在病毒是否有能力突破进入中枢神经系统的障碍这一谜团上。通过研究 K18-hACE2 感染模型，我们观察到微血管损伤和血脑屏障（BBB）破裂的明显证据。从机制上讲，SARS-CoV-2 感染导致周细胞损伤、紧密连接丢失、内皮细胞激活和血管炎症，这些共同导致微血管损伤和 BBB 损伤。此外，感染后脉络丛的血脑脊液屏障也受到了损害。因此，脑血管和脉络丛功能障碍是 COVID-19 的重要方面，可能导致急性和长 COVID 期间的神经并发症。
