Dysregulated Interferon Response Underlying Severe COVID-19

Innate immune interferons (IFNs), including type I and III IFNs, constitute critical antiviral mechanisms. Recent studies reveal that IFN dysregulation is key to determine COVID-19 pathogenesis. Effective IFN stimulation or prophylactic administration of IFNs at the early stage prior to severe COVID...

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Main Authors: LeAnn Lopez, Peter C. Sang, Yun Tian, Yongming Sang
Format: Article
Language:English
Published: MDPI AG 2020-12-01
Series:Viruses
Subjects:
Online Access:https://www.mdpi.com/1999-4915/12/12/1433
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spelling doaj-c69a7c328d1e4d588a1a38ed00526aa62020-12-14T00:01:13ZengMDPI AGViruses1999-49152020-12-01121433143310.3390/v12121433Dysregulated Interferon Response Underlying Severe COVID-19LeAnn Lopez0Peter C. Sang1Yun Tian2Yongming Sang3Department of Agricultural and Environmental Sciences, College of Agriculture, Tennessee State University, 3500 John A. Merritt Boulevard, Nashville, TN 37209, USADepartment of Agricultural and Environmental Sciences, College of Agriculture, Tennessee State University, 3500 John A. Merritt Boulevard, Nashville, TN 37209, USADepartment of Agricultural and Environmental Sciences, College of Agriculture, Tennessee State University, 3500 John A. Merritt Boulevard, Nashville, TN 37209, USADepartment of Agricultural and Environmental Sciences, College of Agriculture, Tennessee State University, 3500 John A. Merritt Boulevard, Nashville, TN 37209, USAInnate immune interferons (IFNs), including type I and III IFNs, constitute critical antiviral mechanisms. Recent studies reveal that IFN dysregulation is key to determine COVID-19 pathogenesis. Effective IFN stimulation or prophylactic administration of IFNs at the early stage prior to severe COVID-19 may elicit an autonomous antiviral state, restrict the virus infection, and prevent COVID-19 progression. Inborn genetic flaws and autoreactive antibodies that block IFN response have been significantly associated with about 14% of patients with life-threatening COVID-19 pneumonia. In most severe COVID-19 patients without genetic errors in IFN-relevant gene loci, IFN dysregulation is progressively worsened and associated with the situation of pro-inflammation and immunopathy, which is prone to autoimmunity. In addition, the high correlation of severe COVID-19 with seniority, males, and individuals with pre-existing comorbidities will be plausibly explained by the coincidence of IFN aberrance in these situations. Collectively, current studies call for a better understanding of the IFN response regarding the spatiotemporal determination and subtype-specificity against SARS-CoV-2 infections, which are warranted to devise IFN-related prophylactics and therapies.https://www.mdpi.com/1999-4915/12/12/1433COVID-19interferonsinterferon signalingSARS-CoV-2immunopathy
collection DOAJ
language English
format Article
sources DOAJ
author LeAnn Lopez
Peter C. Sang
Yun Tian
Yongming Sang
spellingShingle LeAnn Lopez
Peter C. Sang
Yun Tian
Yongming Sang
Dysregulated Interferon Response Underlying Severe COVID-19
Viruses
COVID-19
interferons
interferon signaling
SARS-CoV-2
immunopathy
author_facet LeAnn Lopez
Peter C. Sang
Yun Tian
Yongming Sang
author_sort LeAnn Lopez
title Dysregulated Interferon Response Underlying Severe COVID-19
title_short Dysregulated Interferon Response Underlying Severe COVID-19
title_full Dysregulated Interferon Response Underlying Severe COVID-19
title_fullStr Dysregulated Interferon Response Underlying Severe COVID-19
title_full_unstemmed Dysregulated Interferon Response Underlying Severe COVID-19
title_sort dysregulated interferon response underlying severe covid-19
publisher MDPI AG
series Viruses
issn 1999-4915
publishDate 2020-12-01
description Innate immune interferons (IFNs), including type I and III IFNs, constitute critical antiviral mechanisms. Recent studies reveal that IFN dysregulation is key to determine COVID-19 pathogenesis. Effective IFN stimulation or prophylactic administration of IFNs at the early stage prior to severe COVID-19 may elicit an autonomous antiviral state, restrict the virus infection, and prevent COVID-19 progression. Inborn genetic flaws and autoreactive antibodies that block IFN response have been significantly associated with about 14% of patients with life-threatening COVID-19 pneumonia. In most severe COVID-19 patients without genetic errors in IFN-relevant gene loci, IFN dysregulation is progressively worsened and associated with the situation of pro-inflammation and immunopathy, which is prone to autoimmunity. In addition, the high correlation of severe COVID-19 with seniority, males, and individuals with pre-existing comorbidities will be plausibly explained by the coincidence of IFN aberrance in these situations. Collectively, current studies call for a better understanding of the IFN response regarding the spatiotemporal determination and subtype-specificity against SARS-CoV-2 infections, which are warranted to devise IFN-related prophylactics and therapies.
topic COVID-19
interferons
interferon signaling
SARS-CoV-2
immunopathy
url https://www.mdpi.com/1999-4915/12/12/1433
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AT petercsang dysregulatedinterferonresponseunderlyingseverecovid19
AT yuntian dysregulatedinterferonresponseunderlyingseverecovid19
AT yongmingsang dysregulatedinterferonresponseunderlyingseverecovid19
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