Pathology and Medical Genetics Unit, University of Milan, Milan, Italy.
ASST Santi Paolo & Carlo and Department of Health Sciences, University of Milan, Milan, Italy.
J Neurol. 2021 Dec;268(12):4486-4491. doi: 10.1007/s00415-021-10604-8. Epub 2021 May 18.
SARS-CoV-2 might spread through the nervous system, reaching respiratory centers in the brainstem. Because we recently reported neurophysiological brainstem reflex abnormalities in COVID-19 patients, we here neuropathologically assessed structural brainstem damage in two COVID-19 patients.
We assessed neuropathological features in two patients who died of COVID-19 and in two COVID-19 negative patients as controls. Neuronal damage and corpora amylacea (CA) numbers /mm were histopathologically assessed. Other features studied were the immunohistochemical expression of the SARS-CoV-2 nucleoprotein (NP) and the Iba-1 antigen for glial activation.
Autopsies showed normal gross brainstem anatomy. Histopathological examination demonstrated increased neuronal and CA damage in Covid-19 patients' medulla oblongata. Immunohistochemistry disclosed SARS-CoV-2 NP in brainstem neurons and glial cells, and in cranial nerves. Glial elements also exhibited a widespread increase in Iba-1 expression. Sars-Co-V2 was immunohistochemically detected in the vagus nerve fibers.
Neuropathologic evidence showing SARS-CoV-2 in the brainstem and medullary damage in the area of respiratory centers strongly suggests that the pathophysiology of COVID-19-related respiratory failure includes a neurogenic component. Sars-Co-V2 detection in the vagus nerve, argues for viral trafficking between brainstem and lung.
SARS-CoV-2 可能通过神经系统传播,到达脑干中的呼吸中枢。由于我们最近报道了 COVID-19 患者存在神经生理学脑干反射异常,因此我们在此评估了两名 COVID-19 患者的脑干结构损伤。
我们评估了两名死于 COVID-19 的患者和两名 COVID-19 阴性对照患者的神经病理学特征。组织病理学评估了神经元损伤和脑体(CA)数量/mm。研究的其他特征包括 SARS-CoV-2 核蛋白(NP)的免疫组织化学表达和用于神经胶质激活的 Iba-1 抗原。
尸检显示脑干大体解剖正常。组织病理学检查显示 COVID-19 患者延髓的神经元和 CA 损伤增加。免疫组织化学显示 SARS-CoV-2 NP 存在于脑干神经元和神经胶质细胞以及颅神经中。神经胶质细胞也表现出广泛的 Iba-1 表达增加。Sars-Co-V2 在迷走神经纤维中被免疫组织化学检测到。
表明 SARS-CoV-2 存在于脑干和呼吸中枢区域的髓质损伤的神经病理学证据强烈表明,COVID-19 相关呼吸衰竭的病理生理学包括神经源性成分。在迷走神经中检测到 Sars-Co-V2,表明病毒在脑干和肺部之间的转移。