Griggs Elizabeth, Trageser Kyle, Naughton Sean, Yang Eun-Jeong, Mathew Brian, Van Hyfte Grace, Hellmers Linh, Jette Nathalie, Estill Molly, Shen Li, Fischer Tracy, Pasinetti Giulio Maria
bioRxiv. 2022 Nov 23:2022.11.23.517706. doi: 10.1101/2022.11.23.517706.
Infection with the etiological agent of COVID-19, SARS-CoV-2, appears capable of impacting cognition, which some patients with Post-acute Sequelae of SARS-CoV-2 (PASC). To evaluate neuro-pathophysiological consequences of SARS-CoV-2 infection, we examine transcriptional and cellular signatures in the Broadman area 9 (BA9) of the frontal cortex and the hippocampal formation (HF) in SARS-CoV-2, Alzheimer's disease (AD) and SARS-CoV-2 infected AD individuals, compared to age- and gender-matched neurological cases. Here we show similar alterations of neuroinflammation and blood-brain barrier integrity in SARS-CoV-2, AD, and SARS-CoV-2 infected AD individuals. Distribution of microglial changes reflected by the increase of Iba-1 reveal nodular morphological alterations in SARS-CoV-2 infected AD individuals. Similarly, HIF-1α is significantly upregulated in the context of SARS-CoV-2 infection in the same brain regions regardless of AD status. The finding may help to inform decision-making regarding therapeutic treatments in patients with neuro-PASC, especially those at increased risk of developing AD.
SARS-CoV-2 and Alzheimer's disease share similar neuroinflammatory processes, which may help explain neuro-PASC.
感染2019冠状病毒病（COVID-19）的病原体严重急性呼吸综合征冠状病毒2（SARS-CoV-2）似乎能够影响认知，一些感染SARS-CoV-2后急性后遗症（PASC）的患者就有这种情况。为了评估SARS-CoV-2感染的神经病理生理后果，我们研究了SARS-CoV-2感染患者、阿尔茨海默病（AD）患者以及SARS-CoV-2感染的AD患者额叶皮质布罗德曼9区（BA9）和海马结构（HF）中的转录和细胞特征，并与年龄和性别匹配的神经病例进行比较。我们发现，SARS-CoV-2感染患者、AD患者以及SARS-CoV-2感染的AD患者在神经炎症和血脑屏障完整性方面存在相似的改变。由Iba-1增加所反映的小胶质细胞变化分布显示，SARS-CoV-2感染的AD患者存在结节状形态改变。同样，无论AD状态如何，在相同脑区中，HIF-1α在SARS-CoV-2感染的情况下均显著上调。这一发现可能有助于为神经PASC患者，尤其是那些患AD风险增加的患者的治疗决策提供参考。
SARS-CoV-2和阿尔茨海默病具有相似的神经炎症过程，这可能有助于解释神经PASC。
