Neurologic complications of symptomatic COVID-19 are common. Brain tissues from 13 autopsies of people who died of COVID-19 were examined. Cultured endothelial and neuronal cells were incubated with and wild type mice were injected IV with different spike subunits. In situ analyses were used to detect SARS-CoV-2 proteins and the host response. In 13/13 brains from fatal COVID-19, pseudovirions (spike, envelope, and membrane proteins without viral RNA) were present in the endothelia of microvessels ranging from 0 to 14 positive cells/200× field (mean 4.3). The pseudovirions strongly co-localized with caspase-3, ACE2, IL6, TNFα, and C5b-9. The surrounding neurons demonstrated increased NMDAR2 and neuronal NOS plus decreased MFSD2a and SHIP1 proteins. Tail vein injection of the full length S1 spike subunit in mice led to neurologic signs (increased thirst, stressed behavior) not evident in those injected with the S2 subunit. The S1 subunit localized to the endothelia of microvessels in the mice brain and showed co-localization with caspase-3, ACE2, IL6, TNFα, and C5b-9. The surrounding neurons showed increased neuronal NOS and decreased MFSD2a. It is concluded that ACE2+ endothelial damage is a central part of SARS-CoV2 pathology and may be induced by the spike protein alone. Thus, the diagnostic pathologist can use either hematoxylin and eosin stain or immunohistochemistry for caspase 3 and ACE2 to document the endothelial cell damage of COVID-19.

有症状的 COVID-19 的神经系统并发症很常见。检查了 13 例死于 COVID-19 的人的脑组织。培养的内皮细胞和神经元细胞与野生型小鼠一起孵育，并给野生型小鼠静脉注射不同的刺突亚基。原位分析用于检测 SARS-CoV-2 蛋白和宿主反应。在来自致命 COVID-19 的 13/13 大脑中，假病毒颗粒（不含病毒 RNA 的刺突蛋白、包膜蛋白和膜蛋白）存在于微血管内皮细胞中，范围为 0 至 14 个阳性细胞/200× 视野（平均 4.3）。假病毒颗粒与 caspase-3、ACE2、IL6、TNFα 和 C5b-9 强烈共定位。周围的神经元表现出增加的 NMDAR2 和神经元 NOS 以及减少的 MFSD2a 和 SHIP1 蛋白。在小鼠尾部静脉注射全长 S1 刺突亚基导致神经系统症状（口渴增加、应激行为）在注射 S2 亚基的小鼠中不明显。S1 亚基定位于小鼠大脑微血管的内皮细胞，并与 caspase-3、ACE2、IL6、TNFα 和 C5b-9 共定位。周围神经元显示神经元 NOS 增加和 MFSD2a 减少。得出的结论是，ACE2+ 内皮损伤是 SARS-CoV2 病理学的核心部分，可能仅由刺突蛋白诱导。因此，诊断病理学家可以使用苏木精和伊红染色或半胱天冬酶 3 和 ACE2 的免疫组织化学来记录 COVID-19 的内皮细胞损伤。S1 亚基定位于小鼠大脑微血管的内皮细胞，并显示与 caspase-3、ACE2、IL6、TNFα 和 C5b-9 共定位。周围神经元显示神经元 NOS 增加和 MFSD2a 减少。得出的结论是，ACE2+ 内皮损伤是 SARS-CoV2 病理学的核心部分，可能仅由刺突蛋白诱导。因此，诊断病理学家可以使用苏木精和伊红染色或半胱天冬酶 3 和 ACE2 的免疫组织化学来记录 COVID-19 的内皮细胞损伤。S1 亚基定位于小鼠大脑微血管的内皮细胞，并与 caspase-3、ACE2、IL6、TNFα 和 C5b-9 共定位。周围神经元显示神经元 NOS 增加和 MFSD2a 减少。得出的结论是，ACE2+ 内皮损伤是 SARS-CoV2 病理学的核心部分，可能仅由刺突蛋白诱导。因此，诊断病理学家可以使用苏木精和伊红染色或半胱天冬酶 3 和 ACE2 的免疫组织化学来记录 COVID-19 的内皮细胞损伤。