Understanding the Immunologic Characteristics of Neurologic Manifestations of SARS-CoV-2 and Potential Immunological Mec
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Understanding the Immunologic Characteristics of Neurologic Manifestations of SARS-CoV-2 and Potential Immunological Mechanisms Soheil Mohammadi 1,2 & Fatemeh Moosaie 1,2 & Mohammad Hadi Aarabi 1 Received: 7 July 2020 / Accepted: 25 August 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Similar to its predecessors, coronavirus disease 2019 (COVID-19) exhibits neurotrophic properties, which lead to progression of neurologic sequelae. Besides direct viral invasion to the central nervous system (CNS), indirect CNS involvement through viral-mediated immune response is plausible. Aberrant immune pathways such as extreme release of cytokines (cytokine storm), autoimmunity mediated by cross-reactivity between CNS components and viral particles, and microglial activation propagate CNS damage in these patients. Here, we review the currently available evidence to discuss the plausible immunologic pathways that may contribute to the development of COVID-19 neurological complications, namely Alzheimer’s disease, Parkinson’s disease, stroke, multiple sclerosis, Guillain-Barre syndrome, seizure, and brainstem involvement. Keywords Cytokines . Coronavirus disease 2019 . Immunologic pathways . Neurological complications . Central nervous system . SARS-CoV-2
Introduction In December 2019, the outbreak of novel coronavirus disease 2019 (COVID-19) emerged in Wuhan, China. To date, the outbreak has turned into a pandemic, infecting millions of people globally [1]. Although the virus, also known as severe acute respiratory syndrome coronavirus 2 (SARSCoV-2), mainly manifests as an acute respiratory infection [2], recent evidence suggests that 36% of affected patients exhibit neurological sequelae [3]. Neurologic symptoms are more common among severe cases of the disease, regarding that 84% of the intensive care unit (ICU)–admitted SARSCoV-2 patients exhibited at least one neurologic symptom [4]. In line with these, brain magnetic resonance imaging (MRI) investigations in SARS-CoV-2 patients show multifocal hyperintense white matter lesions and cortical signal
* Mohammad Hadi Aarabi [email protected] 1
Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
2
NeuroImaging Network (NIN), Universal Scientific Education and Research Network (USERN), Tehran, Iran
abnormalities (particularly in the medial temporal lobe) on fluid-attenuated inversion recovery (FLAIR), along with intracerebral hemorrhagic and microhemorrhagic lesions, and leptomeningeal enhancement [5, 6]. Electroencephalogram (EEG) studies demonstrate high amplitude monomorphic delta waves, indicating the central nervous system (CNS) involvement in SARS-CoV-2 patients [7]. Also, functional magnetic resonance imaging (fMRI) is recently proposed as an independent predictor of neurologic outcomes [8]. SARS-CoV-2 patients present with elevated plasma levels of neurofilament light chain protein (NfL) and glial fibrillary acidic protein (GFAP), which are known as biochemical indicators of neuronal injury and glial
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