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Demystifying Excess Immune Response in COVID-19 to Reposition an Orphan Drug for Down-Regulation of NF-κB: A Systematic Review

The immunological findings from autopsies, biopsies, and various studies in COVID-19 patients show that the major cause of morbidity and mortality in COVID-19 is excess immune response resulting in hyper-inflammation. With the objective to review various mechanisms of excess immune response in adult...

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Autores principales: Peddapalli, Apparao, Gehani, Manish, Kalle, Arunasree M., Peddapalli, Siva R., Peter, Angela E., Sharad, Shashwat
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997247/
https://www.ncbi.nlm.nih.gov/pubmed/33673529
http://dx.doi.org/10.3390/v13030378
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author Peddapalli, Apparao
Gehani, Manish
Kalle, Arunasree M.
Peddapalli, Siva R.
Peter, Angela E.
Sharad, Shashwat
author_facet Peddapalli, Apparao
Gehani, Manish
Kalle, Arunasree M.
Peddapalli, Siva R.
Peter, Angela E.
Sharad, Shashwat
author_sort Peddapalli, Apparao
collection PubMed
description The immunological findings from autopsies, biopsies, and various studies in COVID-19 patients show that the major cause of morbidity and mortality in COVID-19 is excess immune response resulting in hyper-inflammation. With the objective to review various mechanisms of excess immune response in adult COVID-19 patients, Pubmed was searched for free full articles not related to therapeutics or co-morbid sub-groups, published in English until 27 October 2020, irrespective of type of article, country, or region. Joanna Briggs Institute’s design-specific checklists were used to assess the risk of bias. Out of 122 records screened for eligibility, 42 articles were included in the final review. The review found that eventually, most mechanisms result in cytokine excess and up-regulation of Nuclear Factor-κB (NF-κB) signaling as a common pathway of excess immune response. Molecules blocking NF-κB or targeting downstream effectors like Tumour Necrosis Factor α (TNFα) are either undergoing clinical trials or lack specificity and cause unwanted side effects. Neutralization of upstream histamine by histamine-conjugated normal human immunoglobulin has been demonstrated to inhibit the nuclear translocation of NF-κB, thereby preventing the release of pro-inflammatory cytokines Interleukin (IL) 1β, TNF-α, and IL-6 and IL-10 in a safer manner. The authors recommend repositioning it in COVID-19.
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spelling pubmed-79972472021-03-27 Demystifying Excess Immune Response in COVID-19 to Reposition an Orphan Drug for Down-Regulation of NF-κB: A Systematic Review Peddapalli, Apparao Gehani, Manish Kalle, Arunasree M. Peddapalli, Siva R. Peter, Angela E. Sharad, Shashwat Viruses Review The immunological findings from autopsies, biopsies, and various studies in COVID-19 patients show that the major cause of morbidity and mortality in COVID-19 is excess immune response resulting in hyper-inflammation. With the objective to review various mechanisms of excess immune response in adult COVID-19 patients, Pubmed was searched for free full articles not related to therapeutics or co-morbid sub-groups, published in English until 27 October 2020, irrespective of type of article, country, or region. Joanna Briggs Institute’s design-specific checklists were used to assess the risk of bias. Out of 122 records screened for eligibility, 42 articles were included in the final review. The review found that eventually, most mechanisms result in cytokine excess and up-regulation of Nuclear Factor-κB (NF-κB) signaling as a common pathway of excess immune response. Molecules blocking NF-κB or targeting downstream effectors like Tumour Necrosis Factor α (TNFα) are either undergoing clinical trials or lack specificity and cause unwanted side effects. Neutralization of upstream histamine by histamine-conjugated normal human immunoglobulin has been demonstrated to inhibit the nuclear translocation of NF-κB, thereby preventing the release of pro-inflammatory cytokines Interleukin (IL) 1β, TNF-α, and IL-6 and IL-10 in a safer manner. The authors recommend repositioning it in COVID-19. MDPI 2021-02-27 /pmc/articles/PMC7997247/ /pubmed/33673529 http://dx.doi.org/10.3390/v13030378 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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 (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Review
Peddapalli, Apparao
Gehani, Manish
Kalle, Arunasree M.
Peddapalli, Siva R.
Peter, Angela E.
Sharad, Shashwat
Demystifying Excess Immune Response in COVID-19 to Reposition an Orphan Drug for Down-Regulation of NF-κB: A Systematic Review
title Demystifying Excess Immune Response in COVID-19 to Reposition an Orphan Drug for Down-Regulation of NF-κB: A Systematic Review
title_full Demystifying Excess Immune Response in COVID-19 to Reposition an Orphan Drug for Down-Regulation of NF-κB: A Systematic Review
title_fullStr Demystifying Excess Immune Response in COVID-19 to Reposition an Orphan Drug for Down-Regulation of NF-κB: A Systematic Review
title_full_unstemmed Demystifying Excess Immune Response in COVID-19 to Reposition an Orphan Drug for Down-Regulation of NF-κB: A Systematic Review
title_short Demystifying Excess Immune Response in COVID-19 to Reposition an Orphan Drug for Down-Regulation of NF-κB: A Systematic Review
title_sort demystifying excess immune response in covid-19 to reposition an orphan drug for down-regulation of nf-κb: a systematic review
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997247/
https://www.ncbi.nlm.nih.gov/pubmed/33673529
http://dx.doi.org/10.3390/v13030378
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