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A review of cytokine-based pathophysiology of Long COVID symptoms

The Long COVID/Post Acute Sequelae of COVID-19 (PASC) group includes patients with initial mild-to-moderate symptoms during the acute phase of the illness, in whom recovery is prolonged, or new symptoms are developed over months. Here, we propose a description of the pathophysiology of the Long COVI...

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Autores principales: Low, Russell N., Low, Ryan J., Akrami, Athena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10103649/
https://www.ncbi.nlm.nih.gov/pubmed/37064029
http://dx.doi.org/10.3389/fmed.2023.1011936
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author Low, Russell N.
Low, Ryan J.
Akrami, Athena
author_facet Low, Russell N.
Low, Ryan J.
Akrami, Athena
author_sort Low, Russell N.
collection PubMed
description The Long COVID/Post Acute Sequelae of COVID-19 (PASC) group includes patients with initial mild-to-moderate symptoms during the acute phase of the illness, in whom recovery is prolonged, or new symptoms are developed over months. Here, we propose a description of the pathophysiology of the Long COVID presentation based on inflammatory cytokine cascades and the p38 MAP kinase signaling pathways that regulate cytokine production. In this model, the SARS-CoV-2 viral infection is hypothesized to trigger a dysregulated peripheral immune system activation with subsequent cytokine release. Chronic low-grade inflammation leads to dysregulated brain microglia with an exaggerated release of central cytokines, producing neuroinflammation. Immunothrombosis linked to chronic inflammation with microclot formation leads to decreased tissue perfusion and ischemia. Intermittent fatigue, Post Exertional Malaise (PEM), CNS symptoms with “brain fog,” arthralgias, paresthesias, dysautonomia, and GI and ophthalmic problems can consequently arise as result of the elevated peripheral and central cytokines. There are abundant similarities between symptoms in Long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). DNA polymorphisms and viral-induced epigenetic changes to cytokine gene expression may lead to chronic inflammation in Long COVID patients, predisposing some to develop autoimmunity, which may be the gateway to ME/CFS.
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spelling pubmed-101036492023-04-15 A review of cytokine-based pathophysiology of Long COVID symptoms Low, Russell N. Low, Ryan J. Akrami, Athena Front Med (Lausanne) Medicine The Long COVID/Post Acute Sequelae of COVID-19 (PASC) group includes patients with initial mild-to-moderate symptoms during the acute phase of the illness, in whom recovery is prolonged, or new symptoms are developed over months. Here, we propose a description of the pathophysiology of the Long COVID presentation based on inflammatory cytokine cascades and the p38 MAP kinase signaling pathways that regulate cytokine production. In this model, the SARS-CoV-2 viral infection is hypothesized to trigger a dysregulated peripheral immune system activation with subsequent cytokine release. Chronic low-grade inflammation leads to dysregulated brain microglia with an exaggerated release of central cytokines, producing neuroinflammation. Immunothrombosis linked to chronic inflammation with microclot formation leads to decreased tissue perfusion and ischemia. Intermittent fatigue, Post Exertional Malaise (PEM), CNS symptoms with “brain fog,” arthralgias, paresthesias, dysautonomia, and GI and ophthalmic problems can consequently arise as result of the elevated peripheral and central cytokines. There are abundant similarities between symptoms in Long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). DNA polymorphisms and viral-induced epigenetic changes to cytokine gene expression may lead to chronic inflammation in Long COVID patients, predisposing some to develop autoimmunity, which may be the gateway to ME/CFS. Frontiers Media S.A. 2023-03-31 /pmc/articles/PMC10103649/ /pubmed/37064029 http://dx.doi.org/10.3389/fmed.2023.1011936 Text en Copyright © 2023 Low, Low and Akrami. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Medicine
Low, Russell N.
Low, Ryan J.
Akrami, Athena
A review of cytokine-based pathophysiology of Long COVID symptoms
title A review of cytokine-based pathophysiology of Long COVID symptoms
title_full A review of cytokine-based pathophysiology of Long COVID symptoms
title_fullStr A review of cytokine-based pathophysiology of Long COVID symptoms
title_full_unstemmed A review of cytokine-based pathophysiology of Long COVID symptoms
title_short A review of cytokine-based pathophysiology of Long COVID symptoms
title_sort review of cytokine-based pathophysiology of long covid symptoms
topic Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10103649/
https://www.ncbi.nlm.nih.gov/pubmed/37064029
http://dx.doi.org/10.3389/fmed.2023.1011936
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