Pathogenesis Underlying Neurological Manifestations of Long COVID Syndrome and Potential Therapeutics

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Leng, Albert
Shah, Manuj
Ahmad, Syed Ameen
Premraj, Lavienraj
Wildi, Karin
Li Bassi, Gianluigi
Pardo, Carlos A
Choi, Alex
Cho, Sung-Min
Griffith University Author(s)
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2023
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Abstract

The development of long-term symptoms of coronavirus disease 2019 (COVID-19) more than four weeks after primary infection, termed “long COVID” or post-acute sequela of COVID-19 (PASC), can implicate persistent neurological complications in up to one third of patients and present as fatigue, “brain fog”, headaches, cognitive impairment, dysautonomia, neuropsychiatric symptoms, anosmia, hypogeusia, and peripheral neuropathy. Pathogenic mechanisms of these symptoms of long COVID remain largely unclear; however, several hypotheses implicate both nervous system and systemic pathogenic mechanisms such as SARS-CoV2 viral persistence and neuroinvasion, abnormal immunological response, autoimmunity, coagulopathies, and endotheliopathy. Outside of the CNS, SARS-CoV-2 can invade the support and stem cells of the olfactory epithelium leading to persistent alterations to olfactory function. SARS-CoV-2 infection may induce abnormalities in innate and adaptive immunity including monocyte expansion, T-cell exhaustion, and prolonged cytokine release, which may cause neuroinflammatory responses and microglia activation, white matter abnormalities, and microvascular changes. Additionally, microvascular clot formation can occlude capillaries and endotheliopathy, due to SARS-CoV-2 protease activity and complement activation, can contribute to hypoxic neuronal injury and blood–brain barrier dysfunction, respectively. Current therapeutics target pathological mechanisms by employing antivirals, decreasing inflammation, and promoting olfactory epithelium regeneration. Thus, from laboratory evidence and clinical trials in the literature, we sought to synthesize the pathophysiological pathways underlying neurological symptoms of long COVID and potential therapeutics.

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Cells

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12

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5

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© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

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Neurology and neuromuscular diseases

Biological sciences

Biomedical and clinical sciences

Science & Technology

Life Sciences & Biomedicine

Cell Biology

COVID-19

SARS-CoV-2

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Leng, A; Shah, M; Ahmad, SA; Premraj, L; Wildi, K; Li Bassi, G; Pardo, CA; Choi, A; Cho, S-M, Pathogenesis Underlying Neurological Manifestations of Long COVID Syndrome and Potential Therapeutics, Cells, 2023, 12 (5), pp. 816

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