Department of Biological Sciences, Sunway University, Petaling Jaya, Selangor 47500, Malaysia.
ACS Chem Neurosci. 2021 Feb 17;12(4):573-580. doi: 10.1021/acschemneuro.0c00793. Epub 2021 Feb 4.
Long-COVID is a postviral illness that can affect survivors of COVID-19, regardless of initial disease severity or age. Symptoms of long-COVID include fatigue, dyspnea, gastrointestinal and cardiac problems, cognitive impairments, myalgia, and others. While the possible causes of long-COVID include long-term tissue damage, viral persistence, and chronic inflammation, the review proposes, perhaps for the first time, that persistent brainstem dysfunction may also be involved. This hypothesis can be split into two parts. The first is the brainstem tropism and damage in COVID-19. As the brainstem has a relatively high expression of ACE2 receptor compared with other brain regions, SARS-CoV-2 may exhibit tropism therein. Evidence also exists that neuropilin-1, a co-receptor of SARS-CoV-2, may be expressed in the brainstem. Indeed, autopsy studies have found SARS-CoV-2 RNA and proteins in the brainstem. The brainstem is also highly prone to damage from pathological immune or vascular activation, which has also been observed in autopsy of COVID-19 cases. The second part concerns functions of the brainstem that overlap with symptoms of long-COVID. The brainstem contains numerous distinct nuclei and subparts that regulate the respiratory, cardiovascular, gastrointestinal, and neurological processes, which can be linked to long-COVID. As neurons do not readily regenerate, brainstem dysfunction may be long-lasting and, thus, is long-COVID. Indeed, brainstem dysfunction has been implicated in other similar disorders, such as chronic pain and migraine and myalgic encephalomyelitis or chronic fatigue syndrome.
长新冠是一种与病毒后(postviral)相关的疾病，可影响新冠幸存者，无论最初疾病严重程度或年龄如何。长新冠的症状包括疲劳、呼吸困难、胃肠道和心脏问题、认知障碍、肌肉疼痛等。虽然长新冠的可能原因包括长期组织损伤、病毒持续存在和慢性炎症，但该综述首次提出，持续性脑干功能障碍也可能与之相关。这一假说可以分为两部分。第一部分是新冠病毒感染中脑干的亲嗜性和损伤。由于与其他脑区相比，脑干中 ACE2 受体的表达相对较高，SARS-CoV-2 可能在其中表现出亲嗜性。也有证据表明，SARS-CoV-2 的共受体神经纤毛蛋白-1 (neuropilin-1)可能在脑干中表达。事实上，尸检研究已经在脑干中发现了 SARS-CoV-2 的 RNA 和蛋白。此外，脑干还极易受到病理性免疫或血管激活的损伤，在新冠病毒感染的尸检中也观察到了这种情况。第二部分涉及与长新冠症状重叠的脑干功能。脑干包含许多不同的核和亚区，调节呼吸、心血管、胃肠道和神经系统过程，这些过程与长新冠相关。由于神经元不易再生，脑干功能障碍可能持久存在，因此是长新冠。事实上，脑干功能障碍与其他类似疾病有关，如慢性疼痛、偏头痛、肌痛性脑脊髓炎或慢性疲劳综合征。
