Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation,Cell

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Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation
Cell ( IF 45.5 ) Pub Date : 2022-06-13 , DOI: 10.1016/j.cell.2022.06.008
Anthony Fernández-Castañeda ₁ , Peiwen Lu ₂ , Anna C Geraghty ₁ , Eric Song ₂ , Myoung-Hwa Lee ₃ , Jamie Wood ₄ , Michael R O'Dea ₅ , Selena Dutton ₁ , Kiarash Shamardani ₁ , Kamsi Nwangwu ₁ , Rebecca Mancusi ₁ , Belgin Yalçın ₁ , Kathryn R Taylor ₁ , Lehi Acosta-Alvarez ₁ , Karen Malacon ₁ , Michael B Keough ₁ , Lijun Ni ₁ , Pamelyn J Woo ₁ , Daniel Contreras-Esquivel ₁ , Angus Martin Shaw Toland ₆ , Jeff R Gehlhausen ₂ , Jon Klein ₂ , Takehiro Takahashi ₂ , Julio Silva ₂ , Benjamin Israelow ₂ , Carolina Lucas ₂ , Tianyang Mao ₂ , Mario A Peña-Hernández ₂ , Alexandra Tabachnikova ₂ , Robert J Homer ₇ , Laura Tabacof ₄ , Jenna Tosto-Mancuso ₄ , Erica Breyman ₄ , Amy Kontorovich ₈ , Dayna McCarthy ₄ , Martha Quezado ₉ , Hannes Vogel ₆ , Marco M Hefti ₁₀ , Daniel P Perl ₁₁ , Shane Liddelow ₁₂ , Rebecca Folkerth ₁₃ , David Putrino ₄ , Avindra Nath ₃ , Akiko Iwasaki ₁₄ , Michelle Monje ₁₅

Affiliation

Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA.
Department of Immunobiology, Yale University, New Haven, CT, USA.
National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA.
Abilities Research Center, Department of Rehabilitation and Human Performance, Mount Sinai School of Medicine, New York, NY, USA.
Neuroscience Institute, NYU Grossman School of Medicine, New York, NY, USA.
Department of Pathology, Stanford University, Stanford, CA, USA.
Department of Pathology, Yale University, New Haven, CT, USA.
Cardiovascular Research Institute, Mount Sinai School of Medicine, New York, NY, USA.
National Cancer Institute, Bethesda, MD, USA.
Department of Pathology, University of Iowa, Iowa City, IA, USA.
Department of Pathology, Uniformed Services University of Health Sciences, Bethesda, MD, USA.
Neuroscience Institute, NYU Grossman School of Medicine, New York, NY, USA; Departments of Neuroscience & Physiology and of Ophthalmology, NYU Grossman School of Medicine, New York, NY, USA; Parekh Center for Interdisciplinary Neurology, NYU Grossman School of Medicine, New York, NY, USA.
Office of Chief Medical Examiner, New York, NY, USA.
Department of Immunobiology, Yale University, New Haven, CT, USA; Howard Hughes Medical Institute, Yale University, New Haven, CT, USA.
Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA; Department of Pathology, Stanford University, Stanford, CA, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA.

COVID survivors frequently experience lingering neurological symptoms that resemble cancer-therapy-related cognitive impairment, a syndrome for which white matter microglial reactivity and consequent neural dysregulation is central. Here, we explored the neurobiological effects of respiratory SARS-CoV-2 infection and found white-matter-selective microglial reactivity in mice and humans. Following mild respiratory COVID in mice, persistently impaired hippocampal neurogenesis, decreased oligodendrocytes, and myelin loss were evident together with elevated CSF cytokines/chemokines including CCL11. Systemic CCL11 administration specifically caused hippocampal microglial reactivity and impaired neurogenesis. Concordantly, humans with lasting cognitive symptoms post-COVID exhibit elevated CCL11 levels. Compared with SARS-CoV-2, mild respiratory influenza in mice caused similar patterns of white-matter-selective microglial reactivity, oligodendrocyte loss, impaired neurogenesis, and elevated CCL11 at early time points, but after influenza, only elevated CCL11 and hippocampal pathology persisted. These findings illustrate similar neuropathophysiology after cancer therapy and respiratory SARS-CoV-2 infection which may contribute to cognitive impairment following even mild COVID.

中文翻译：

轻度呼吸道新冠肺炎可导致多谱系神经细胞和髓磷脂失调

新冠肺炎幸存者经常会出现挥之不去的神经系统症状，类似于癌症治疗相关的认知障碍，这种综合征的核心是白质小胶质细胞反应和随之而来的神经失调。在这里，我们探索了呼吸道 SARS-CoV-2 感染的神经生物学影响，并发现小鼠和人类的白质选择性小胶质细胞反应性。小鼠出现轻度呼吸道新冠肺炎后，海马神经发生持续受损、少突胶质细胞减少和髓鞘质丢失，以及包括 CCL11 在内的脑脊液细胞因子/趋化因子升高。全身性 CCL11 给药会特别引起海马小胶质细胞反应性并损害神经发生。相应地，在新冠病毒感染后出现持续认知症状的人表现出 CCL11 水平升高。与 SARS-CoV-2 相比，小鼠中的轻度呼吸道流感在早期时间点引起了类似的白质选择性小胶质细胞反应、少突胶质细胞丢失、神经发生受损和 CCL11 升高的模式，但在流感后，仅持续升高的 CCL11 和海马病理学。这些发现说明了癌症治疗和呼吸道 SARS-CoV-2 感染后相似的神经病理生理学，即使是轻微的新冠病毒感染也可能导致认知障碍。

更新日期：2022-06-13

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