Berliand A N, Anufriev P L, Kanibolotskiy A A
Research Center of Neurology, Moscow, Russia.
Sklifosovsky Research Institute For Emergency Medicine, Moscow, Russia.
Arkh Patol. 2025;87(1):5-15. doi: 10.17116/patol2025870115.
There is no consolidated opinion on the pathogenesis of neurological manifestations of COVID-19, especially after infection. A significant contribution to understanding the mechanisms of neuropathology in COVID-19 can be made by detailed morphologic studies of the brain with assessment of changes in different brain regions during different periods of the infection process.
Clarification of the nature of brain morphologic changes and intracerebral virus invasion in COVID-19 and postinfection.
The study included 15 patients who died during the acute phase of COVID-19 (11 people) or after an infection (4 people) without a history of acute focal changes in the brain or neurological diseases. In each case, 9 brain areas were assessed, including the cortex, hippocampus, brainstem (pons and medulla oblongata), cerebellum, basal ganglia, and central parts of the olfactory system. In addition to the histological study, an immunohistochemical study was performed using antibodies against CD8, Iba1, as well as SARS-CoV-2 proteins (S1 and N) and a semi-quantitative assessment of circulatory disorders, microglial reaction and expression of the SARS-CoV-2 S1 protein in the brain.
The neuropathological picture was similar in the acute and post-infectious phases of COVID-19: microcirculatory disorders, diffuse cerebral edema, ischemic-hypoxic neuronal changes, accumulations of corpora amylacea, gliosis, small mainly perivascular lymphocytic infiltrates with a predominance of CD8 T cells, moderate microglial reaction, accumulation of SARS-CoV-2 S1 protein in the brain. The N protein of the virus was not detected in the brain. The most pronounced changes were observed in the brainstem, especially in the medulla oblongata, and the cerebellum. The severity of structural changes did not correlate with disease duration. S1 protein expression in the brain did not correlate with the severity of the microglial response or disease duration.
The identified neuropathological changes in COVID-19 in the acute and post-infectious phases are nonspecific with a predominance of vascular disorders and microglial reaction and are most pronounced in the brain stem and cerebellum. The SARS-CoV-2 S1 protein can accumulate in neurons and be detected in the brain a year or more after infection.
对于新型冠状病毒肺炎(COVID-19)神经表现的发病机制,尤其是感染后的机制,目前尚无统一意见。通过对大脑进行详细的形态学研究,并评估感染过程不同阶段不同脑区的变化,可为理解COVID-19神经病理学机制做出重要贡献。
明确COVID-19及感染后大脑形态学变化的性质以及脑内病毒侵袭情况。
该研究纳入了15例在COVID-19急性期(11例)或感染后(4例)死亡的患者,这些患者既往无脑部急性局灶性病变或神经疾病史。对每例患者的9个脑区进行评估,包括皮质、海马、脑干(脑桥和延髓)、小脑、基底神经节以及嗅觉系统的中央部分。除组织学研究外,还使用抗CD8、Iba1以及SARS-CoV-2蛋白(S1和N)的抗体进行了免疫组织化学研究,并对循环障碍、小胶质细胞反应以及脑内SARS-CoV-2 S1蛋白的表达进行了半定量评估。
COVID-19急性期和感染后阶段的神经病理学表现相似:微循环障碍、弥漫性脑水肿、缺血缺氧性神经元改变、淀粉样体积聚、胶质增生、主要为血管周围的小淋巴细胞浸润,以CD8 T细胞为主、中度小胶质细胞反应、脑内SARS-CoV-2 S1蛋白积聚。在脑中未检测到病毒的N蛋白。最明显的变化见于脑干,尤其是延髓以及小脑。结构变化的严重程度与病程无关。脑内S1蛋白表达与小胶质细胞反应的严重程度或病程无关。
在COVID-19急性期和感染后阶段所发现的神经病理学变化是非特异性的,以血管病变和小胶质细胞反应为主,且在脑干和小脑中最为明显。SARS-CoV-2 S1蛋白可在神经元中积聚,并在感染一年或更长时间后在脑中被检测到。