Background to new treatments for COVID-19, including its chronicity, through altering elements of the cytokine storm

dc.contributor.authorClark, Ian
dc.date.accessioned2023-04-12T01:51:38Z
dc.date.available2023-04-12T01:51:38Z
dc.date.issued2021
dc.date.updated2022-01-23T07:18:24Z
dc.description.abstractAnti-tumour necrosis factor (TNF) biologicals, Dexamethasone and rIL-7 are of considerable interest in treating COVID-19 patients who are in danger of, or have become, seriously ill. Yet reducing sepsis mortality by lowering circulating levels of TNF lost favour when positive endpoints in earlier simplistic models could not be reproduced in well-conducted human trials. Newer information with anti-TNF biologicals has encouraged reintroducing this concept for treating COVID-19. Viral models have had encouraging outcomes, as have the effects of anti-TNF biologicals on community-acquired COVID-19 during their long-term use to treat chronic inflammatory states. The positive outcome of a large scale trial of dexamethasone, and its higher potency late in the disease, harmonises well with its capacity to enhance levels of IL-7Rα, the receptor for IL-7, a cytokine that enhances lymphocyte development and is increased during the cytokine storm. Lymphoid germinal centres required for antibody-based immunity can be harmed by TNF, and restored by reducing TNF. Thus the IL-7- enhancing activity of dexamethasone may explain its higher potency when lymphocytes are depleted later in the infection, while employing anti-TNF, for several reasons, is much more logical earlier in the infection. This implies dexamethasone could prove to be synergistic with rIL-7, currently being trialed as a COVID-19 therapeutic. The principles behind these COVID-19 therapies are consistent with the observed chronic hypoxia through reduced mitochondrial function, and also the increased severity of this disease in ApoE4-positive individuals. Many of the debilitating persistent aspects of this disease are predictably susceptible to treatment with perispinal etanercept, since they have cerebral origins.en_AU
dc.format.mimetypeapplication/pdfen_AU
dc.identifier.issn1052-9276en_AU
dc.identifier.urihttp://hdl.handle.net/1885/288854
dc.language.isoen_AUen_AU
dc.provenanceThis is an open access article under the terms of the CreativeCommonsAttribution‐NonCommercialLicense,whichpermitsuse, distribution and reproduction in any medium,provided the original work is properly cited and is not used for commercial purposesen_AU
dc.publisherJohn Wiley & Sons Incen_AU
dc.rights© 2020 The authorsen_AU
dc.rights.licenseCreative Commons Attribution licenceen_AU
dc.rights.urihttps://creativecommons.org/licenses/by-nc/4.0/en_AU
dc.sourceReviews in Medical Virologyen_AU
dc.subjectanti‐TNFbiologicalsen_AU
dc.subjectCOVID‐19treatmenten_AU
dc.subjectdexamethasoneen_AU
dc.subjectIL‐7en_AU
dc.titleBackground to new treatments for COVID-19, including its chronicity, through altering elements of the cytokine stormen_AU
dc.typeJournal articleen_AU
dcterms.accessRightsOpen Accessen_AU
local.bibliographicCitation.issue5en_AU
local.bibliographicCitation.lastpage13en_AU
local.bibliographicCitation.startpage1en_AU
local.contributor.affiliationClark, Ian, College of Science, ANUen_AU
local.contributor.authoremailu7601622@anu.edu.auen_AU
local.contributor.authoruidClark, Ian, u7601622en_AU
local.description.notesImported from ARIESen_AU
local.identifier.absfor320900 - Neurosciencesen_AU
local.identifier.absfor320400 - Immunologyen_AU
local.identifier.ariespublicationa383154xPUB22070en_AU
local.identifier.citationvolume31en_AU
local.identifier.doi10.1002/rmv.2210en_AU
local.identifier.scopusID2-s2.0-85097976061
local.identifier.uidSubmittedBya383154en_AU
local.publisher.urlhttps://onlinelibrary.wiley.com/en_AU
local.type.statusPublished Versionen_AU

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