Should we stimulate or suppress immune responses in COVID-19? Cytokine and anti-cytokine interventions.
Identifieur interne : 000607 ( Main/Exploration ); précédent : 000606; suivant : 000608Should we stimulate or suppress immune responses in COVID-19? Cytokine and anti-cytokine interventions.
Auteurs : Yvan Jamilloux [France] ; Thomas Henry [France] ; Alexandre Belot [France] ; Sébastien Viel [France] ; Maxime Fauter [France] ; Thomas El Jammal [France] ; Thierry Walzer [France] ; Bruno François [France] ; Pascal Sève [France]Source :
- Autoimmunity reviews [ 1873-0183 ] ; 2020.
Descripteurs français
- KwdFr :
- Betacoronavirus (MeSH), Cytokines (antagonistes et inhibiteurs), Cytokines (usage thérapeutique), Humains (MeSH), Infections à coronavirus (immunologie), Infections à coronavirus (thérapie), Infections à coronavirus (traitement médicamenteux), Interférons (usage thérapeutique), Interleukine-1 bêta (MeSH), Interleukine-6 (MeSH), Pandémies (MeSH), Pneumopathie virale (immunologie), Pneumopathie virale (thérapie).
- MESH :
- antagonistes et inhibiteurs : Cytokines.
- immunologie : Infections à coronavirus, Pneumopathie virale.
- thérapie : Infections à coronavirus, Pneumopathie virale.
- traitement médicamenteux : Infections à coronavirus.
- usage thérapeutique : Cytokines, Interférons.
- Betacoronavirus, Humains, Interleukine-1 bêta, Interleukine-6, Pandémies.
English descriptors
- KwdEn :
- Betacoronavirus (MeSH), Coronavirus Infections (drug therapy), Coronavirus Infections (immunology), Coronavirus Infections (therapy), Cytokines (antagonists & inhibitors), Cytokines (therapeutic use), Humans (MeSH), Interferons (therapeutic use), Interleukin-1beta (MeSH), Interleukin-6 (MeSH), Pandemics (MeSH), Pneumonia, Viral (immunology), Pneumonia, Viral (therapy).
- MESH :
- chemical , antagonists & inhibitors : Cytokines.
- drug therapy : Coronavirus Infections.
- immunology : Coronavirus Infections, Pneumonia, Viral.
- chemical , therapeutic use : Cytokines, Interferons.
- therapy : Coronavirus Infections, Pneumonia, Viral.
- Betacoronavirus, Humans, Interleukin-1beta, Interleukin-6, Pandemics.
Abstract
The coronavirus disease-19 pandemic (COVID-19), which appeared in China in December 2019 and rapidly spread throughout the world, has forced clinicians and scientists to take up extraordinary challenges. This unprecedented situation led to the inception of numerous fundamental research protocols and many clinical trials. It quickly became apparent that although COVID-19, in the vast majority of cases, was a benign disease, it could also develop a severe form with sometimes fatal outcomes. Cytokines are central to the pathophysiology of COVID-19; while some of them are beneficial (type-I interferon, interleukin-7), others appear detrimental (interleukin-1β, -6, and TNF-α) particularly in the context of the so-called cytokine storm. Yet another characteristic of the disease has emerged: concomitant immunodeficiency, notably involving impaired type-I interferon response, and lymphopenia. This review provides an overview of current knowledge on COVID-19 immunopathology. We discuss the defective type-I IFN response, the theoretical role of IL-7 to restore lymphocyte repertoire, as well as we mention the two patterns observed in severe COVID-19 (i.e. interleukin-1β-driven macrophage activation syndrome vs. interleukin-6-driven immune dysregulation). Next, reviewing current evidence drawn from clinical trials, we examine a number of cytokine and anti-cytokine therapies, including interleukin-1, -6, and TNF inhibitors, as well as less targeted therapies, such as corticosteroids, chloroquine, or JAK inhibitors.
DOI: 10.1016/j.autrev.2020.102567
PubMed: 32376392
PubMed Central: PMC7196557
Affiliations:
- France
- Auvergne-Rhône-Alpes, Limousin, Nouvelle-Aquitaine, Rhône-Alpes
- Limoges, Lyon
- Université Claude Bernard Lyon 1
Links toward previous steps (curation, corpus...)
Le document en format XML
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Service d'Immunologie Biologique, Centre, Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite, France; National Referee Centre for Rheumatic and AutoImmune and Systemic diseases in childrEn (RAISE), Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Centre International de Recherche en Infectiologie (CIRI), Inserm U1111, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Université Claude Bernard-Lyon 1, Lyon, France; Service d'Immunologie Biologique, Centre, Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite, France; National Referee Centre for Rheumatic and AutoImmune and Systemic diseases in childrEn (RAISE), Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName><orgName type="university">Université Claude Bernard Lyon 1</orgName></affiliation></author><author><name sortKey="Fauter, Maxime" sort="Fauter, Maxime" uniqKey="Fauter M" first="Maxime" last="Fauter">Maxime Fauter</name><affiliation wicri:level="3"><nlm:affiliation>Department of Internal Medicine, Lyon University Hospital, Lyon, France; Centre International de Recherche en Infectiologie (CIRI), Inserm U1111, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Université Claude Bernard-Lyon 1, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Internal Medicine, Lyon University Hospital, Lyon, France; Centre International de Recherche en Infectiologie (CIRI), Inserm U1111, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Université Claude Bernard-Lyon 1, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="El Jammal, Thomas" sort="El Jammal, Thomas" uniqKey="El Jammal T" first="Thomas" last="El Jammal">Thomas El Jammal</name><affiliation wicri:level="3"><nlm:affiliation>Department of Internal Medicine, Lyon University Hospital, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Internal Medicine, Lyon University Hospital, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Walzer, Thierry" sort="Walzer, Thierry" uniqKey="Walzer T" first="Thierry" last="Walzer">Thierry Walzer</name><affiliation wicri:level="4"><nlm:affiliation>Centre International de Recherche en Infectiologie (CIRI), Inserm U1111, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Université Claude Bernard-Lyon 1, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Centre International de Recherche en Infectiologie (CIRI), Inserm U1111, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Université Claude Bernard-Lyon 1, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName><orgName type="university">Université Claude Bernard Lyon 1</orgName></affiliation></author><author><name sortKey="Francois, Bruno" sort="Francois, Bruno" uniqKey="Francois B" first="Bruno" last="François">Bruno François</name><affiliation wicri:level="3"><nlm:affiliation>Intensive care unit & Inserm CIC 1435 & Inserm UMR 1092, Dupuytren University Hospital, Limoges, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Intensive care unit & Inserm CIC 1435 & Inserm UMR 1092, Dupuytren University Hospital, Limoges</wicri:regionArea><placeName><region type="region">Nouvelle-Aquitaine</region><region type="old region">Limousin</region><settlement type="city">Limoges</settlement></placeName></affiliation></author><author><name sortKey="Seve, Pascal" sort="Seve, Pascal" uniqKey="Seve P" first="Pascal" last="Sève">Pascal Sève</name><affiliation wicri:level="3"><nlm:affiliation>Department of Internal Medicine, Lyon University Hospital, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Internal Medicine, Lyon University Hospital, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2020">2020</date><idno type="RBID">pubmed:32376392</idno><idno type="pmid">32376392</idno><idno type="doi">10.1016/j.autrev.2020.102567</idno><idno type="pmc">PMC7196557</idno><idno type="wicri:Area/Main/Corpus">001423</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">001423</idno><idno type="wicri:Area/Main/Curation">001423</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">001423</idno><idno type="wicri:Area/Main/Exploration">001423</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Should we stimulate or suppress immune responses in COVID-19? Cytokine and anti-cytokine interventions.</title><author><name sortKey="Jamilloux, Yvan" sort="Jamilloux, Yvan" uniqKey="Jamilloux Y" first="Yvan" last="Jamilloux">Yvan Jamilloux</name><affiliation wicri:level="3"><nlm:affiliation>Department of Internal Medicine, Lyon University Hospital, Lyon, France; Centre International de Recherche en Infectiologie (CIRI), Inserm U1111, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Université Claude Bernard-Lyon 1, Lyon, France. Electronic address: yvan.jamilloux@chu-lyon.fr.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Internal Medicine, Lyon University Hospital, Lyon, France; Centre International de Recherche en Infectiologie (CIRI), Inserm U1111, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Université Claude Bernard-Lyon 1, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Henry, Thomas" sort="Henry, Thomas" uniqKey="Henry T" first="Thomas" last="Henry">Thomas Henry</name><affiliation wicri:level="4"><nlm:affiliation>Centre International de Recherche en Infectiologie (CIRI), Inserm U1111, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Université Claude Bernard-Lyon 1, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Centre International de Recherche en Infectiologie (CIRI), Inserm U1111, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Université Claude Bernard-Lyon 1, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName><orgName type="university">Université Claude Bernard Lyon 1</orgName></affiliation></author><author><name sortKey="Belot, Alexandre" sort="Belot, Alexandre" uniqKey="Belot A" first="Alexandre" last="Belot">Alexandre Belot</name><affiliation wicri:level="4"><nlm:affiliation>Centre International de Recherche en Infectiologie (CIRI), Inserm U1111, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Université Claude Bernard-Lyon 1, Lyon, France; Department of Pediatric rheumatology, nephrology, and dermatology, Lyon University Hospital, Lyon, France; National Referee Centre for Rheumatic and AutoImmune and Systemic diseases in childrEn (RAISE), Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Centre International de Recherche en Infectiologie (CIRI), Inserm U1111, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Université Claude Bernard-Lyon 1, Lyon, France; Department of Pediatric rheumatology, nephrology, and dermatology, Lyon University Hospital, Lyon, France; National Referee Centre for Rheumatic and AutoImmune and Systemic diseases in childrEn (RAISE), Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName><orgName type="university">Université Claude Bernard Lyon 1</orgName></affiliation></author><author><name sortKey="Viel, Sebastien" sort="Viel, Sebastien" uniqKey="Viel S" first="Sébastien" last="Viel">Sébastien Viel</name><affiliation wicri:level="4"><nlm:affiliation>Centre International de Recherche en Infectiologie (CIRI), Inserm U1111, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Université Claude Bernard-Lyon 1, Lyon, France; Service d'Immunologie Biologique, Centre, Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite, France; National Referee Centre for Rheumatic and AutoImmune and Systemic diseases in childrEn (RAISE), Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Centre International de Recherche en Infectiologie (CIRI), Inserm U1111, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Université Claude Bernard-Lyon 1, Lyon, France; Service d'Immunologie Biologique, Centre, Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite, France; National Referee Centre for Rheumatic and AutoImmune and Systemic diseases in childrEn (RAISE), Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName><orgName type="university">Université Claude Bernard Lyon 1</orgName></affiliation></author><author><name sortKey="Fauter, Maxime" sort="Fauter, Maxime" uniqKey="Fauter M" first="Maxime" last="Fauter">Maxime Fauter</name><affiliation wicri:level="3"><nlm:affiliation>Department of Internal Medicine, Lyon University Hospital, Lyon, France; Centre International de Recherche en Infectiologie (CIRI), Inserm U1111, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Université Claude Bernard-Lyon 1, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Internal Medicine, Lyon University Hospital, Lyon, France; Centre International de Recherche en Infectiologie (CIRI), Inserm U1111, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Université Claude Bernard-Lyon 1, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="El Jammal, Thomas" sort="El Jammal, Thomas" uniqKey="El Jammal T" first="Thomas" last="El Jammal">Thomas El Jammal</name><affiliation wicri:level="3"><nlm:affiliation>Department of Internal Medicine, Lyon University Hospital, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Internal Medicine, Lyon University Hospital, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Walzer, Thierry" sort="Walzer, Thierry" uniqKey="Walzer T" first="Thierry" last="Walzer">Thierry Walzer</name><affiliation wicri:level="4"><nlm:affiliation>Centre International de Recherche en Infectiologie (CIRI), Inserm U1111, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Université Claude Bernard-Lyon 1, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Centre International de Recherche en Infectiologie (CIRI), Inserm U1111, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Université Claude Bernard-Lyon 1, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName><orgName type="university">Université Claude Bernard Lyon 1</orgName></affiliation></author><author><name sortKey="Francois, Bruno" sort="Francois, Bruno" uniqKey="Francois B" first="Bruno" last="François">Bruno François</name><affiliation wicri:level="3"><nlm:affiliation>Intensive care unit & Inserm CIC 1435 & Inserm UMR 1092, Dupuytren University Hospital, Limoges, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Intensive care unit & Inserm CIC 1435 & Inserm UMR 1092, Dupuytren University Hospital, Limoges</wicri:regionArea><placeName><region type="region">Nouvelle-Aquitaine</region><region type="old region">Limousin</region><settlement type="city">Limoges</settlement></placeName></affiliation></author><author><name sortKey="Seve, Pascal" sort="Seve, Pascal" uniqKey="Seve P" first="Pascal" last="Sève">Pascal Sève</name><affiliation wicri:level="3"><nlm:affiliation>Department of Internal Medicine, Lyon University Hospital, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Internal Medicine, Lyon University Hospital, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author></analytic><series><title level="j">Autoimmunity reviews</title><idno type="eISSN">1873-0183</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Betacoronavirus (MeSH)</term><term>Coronavirus Infections (drug therapy)</term><term>Coronavirus Infections (immunology)</term><term>Coronavirus Infections (therapy)</term><term>Cytokines (antagonists & inhibitors)</term><term>Cytokines (therapeutic use)</term><term>Humans (MeSH)</term><term>Interferons (therapeutic use)</term><term>Interleukin-1beta (MeSH)</term><term>Interleukin-6 (MeSH)</term><term>Pandemics (MeSH)</term><term>Pneumonia, Viral (immunology)</term><term>Pneumonia, Viral (therapy)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Betacoronavirus (MeSH)</term><term>Cytokines (antagonistes et inhibiteurs)</term><term>Cytokines (usage thérapeutique)</term><term>Humains (MeSH)</term><term>Infections à coronavirus (immunologie)</term><term>Infections à coronavirus (thérapie)</term><term>Infections à coronavirus (traitement médicamenteux)</term><term>Interférons (usage thérapeutique)</term><term>Interleukine-1 bêta (MeSH)</term><term>Interleukine-6 (MeSH)</term><term>Pandémies (MeSH)</term><term>Pneumopathie virale (immunologie)</term><term>Pneumopathie virale (thérapie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Cytokines</term></keywords><keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Cytokines</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Coronavirus Infections</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Infections à coronavirus</term><term>Pneumopathie virale</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Coronavirus Infections</term><term>Pneumonia, Viral</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Cytokines</term><term>Interferons</term></keywords><keywords scheme="MESH" qualifier="therapy" xml:lang="en"><term>Coronavirus Infections</term><term>Pneumonia, Viral</term></keywords><keywords scheme="MESH" qualifier="thérapie" xml:lang="fr"><term>Infections à coronavirus</term><term>Pneumopathie virale</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Infections à coronavirus</term></keywords><keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Cytokines</term><term>Interférons</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Betacoronavirus</term><term>Humans</term><term>Interleukin-1beta</term><term>Interleukin-6</term><term>Pandemics</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Betacoronavirus</term><term>Humains</term><term>Interleukine-1 bêta</term><term>Interleukine-6</term><term>Pandémies</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The coronavirus disease-19 pandemic (COVID-19), which appeared in China in December 2019 and rapidly spread throughout the world, has forced clinicians and scientists to take up extraordinary challenges. This unprecedented situation led to the inception of numerous fundamental research protocols and many clinical trials. It quickly became apparent that although COVID-19, in the vast majority of cases, was a benign disease, it could also develop a severe form with sometimes fatal outcomes. Cytokines are central to the pathophysiology of COVID-19; while some of them are beneficial (type-I interferon, interleukin-7), others appear detrimental (interleukin-1β, -6, and TNF-α) particularly in the context of the so-called cytokine storm. Yet another characteristic of the disease has emerged: concomitant immunodeficiency, notably involving impaired type-I interferon response, and lymphopenia. This review provides an overview of current knowledge on COVID-19 immunopathology. We discuss the defective type-I IFN response, the theoretical role of IL-7 to restore lymphocyte repertoire, as well as we mention the two patterns observed in severe COVID-19 (i.e. interleukin-1β-driven macrophage activation syndrome vs. interleukin-6-driven immune dysregulation). Next, reviewing current evidence drawn from clinical trials, we examine a number of cytokine and anti-cytokine therapies, including interleukin-1, -6, and TNF inhibitors, as well as less targeted therapies, such as corticosteroids, chloroquine, or JAK inhibitors.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" IndexingMethod="Curated" Owner="NLM"><PMID Version="1">32376392</PMID><DateCompleted><Year>2020</Year><Month>06</Month><Day>10</Day></DateCompleted><DateRevised><Year>2020</Year><Month>06</Month><Day>10</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1873-0183</ISSN><JournalIssue CitedMedium="Internet"><Volume>19</Volume><Issue>7</Issue><PubDate><Year>2020</Year><Month>Jul</Month></PubDate></JournalIssue><Title>Autoimmunity reviews</Title><ISOAbbreviation>Autoimmun Rev</ISOAbbreviation></Journal><ArticleTitle>Should we stimulate or suppress immune responses in COVID-19? Cytokine and anti-cytokine interventions.</ArticleTitle><Pagination><MedlinePgn>102567</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">S1568-9972(20)30129-4</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.autrev.2020.102567</ELocationID><Abstract><AbstractText>The coronavirus disease-19 pandemic (COVID-19), which appeared in China in December 2019 and rapidly spread throughout the world, has forced clinicians and scientists to take up extraordinary challenges. This unprecedented situation led to the inception of numerous fundamental research protocols and many clinical trials. It quickly became apparent that although COVID-19, in the vast majority of cases, was a benign disease, it could also develop a severe form with sometimes fatal outcomes. Cytokines are central to the pathophysiology of COVID-19; while some of them are beneficial (type-I interferon, interleukin-7), others appear detrimental (interleukin-1β, -6, and TNF-α) particularly in the context of the so-called cytokine storm. Yet another characteristic of the disease has emerged: concomitant immunodeficiency, notably involving impaired type-I interferon response, and lymphopenia. This review provides an overview of current knowledge on COVID-19 immunopathology. We discuss the defective type-I IFN response, the theoretical role of IL-7 to restore lymphocyte repertoire, as well as we mention the two patterns observed in severe COVID-19 (i.e. interleukin-1β-driven macrophage activation syndrome vs. interleukin-6-driven immune dysregulation). Next, reviewing current evidence drawn from clinical trials, we examine a number of cytokine and anti-cytokine therapies, including interleukin-1, -6, and TNF inhibitors, as well as less targeted therapies, such as corticosteroids, chloroquine, or JAK inhibitors.</AbstractText><CopyrightInformation>Copyright © 2020 Elsevier B.V. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Jamilloux</LastName><ForeName>Yvan</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Internal Medicine, Lyon University Hospital, Lyon, France; Centre International de Recherche en Infectiologie (CIRI), Inserm U1111, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Université Claude Bernard-Lyon 1, Lyon, France. Electronic address: yvan.jamilloux@chu-lyon.fr.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Henry</LastName><ForeName>Thomas</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Centre International de Recherche en Infectiologie (CIRI), Inserm U1111, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Université Claude Bernard-Lyon 1, Lyon, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Belot</LastName><ForeName>Alexandre</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Centre International de Recherche en Infectiologie (CIRI), Inserm U1111, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Université Claude Bernard-Lyon 1, Lyon, France; Department of Pediatric rheumatology, nephrology, and dermatology, Lyon University Hospital, Lyon, France; National Referee Centre for Rheumatic and AutoImmune and Systemic diseases in childrEn (RAISE), Lyon, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Viel</LastName><ForeName>Sébastien</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Centre International de Recherche en Infectiologie (CIRI), Inserm U1111, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Université Claude Bernard-Lyon 1, Lyon, France; Service d'Immunologie Biologique, Centre, Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite, France; National Referee Centre for Rheumatic and AutoImmune and Systemic diseases in childrEn (RAISE), Lyon, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fauter</LastName><ForeName>Maxime</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Internal Medicine, Lyon University Hospital, Lyon, France; Centre International de Recherche en Infectiologie (CIRI), Inserm U1111, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Université Claude Bernard-Lyon 1, Lyon, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>El Jammal</LastName><ForeName>Thomas</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Department of Internal Medicine, Lyon University Hospital, Lyon, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Walzer</LastName><ForeName>Thierry</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Centre International de Recherche en Infectiologie (CIRI), Inserm U1111, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Université Claude Bernard-Lyon 1, Lyon, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>François</LastName><ForeName>Bruno</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Intensive care unit & Inserm CIC 1435 & Inserm UMR 1092, Dupuytren University Hospital, Limoges, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sève</LastName><ForeName>Pascal</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Department of Internal Medicine, Lyon University Hospital, Lyon, France.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D016454">Review</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>05</Month><Day>04</Day></ArticleDate></Article><MedlineJournalInfo><Country>Netherlands</Country><MedlineTA>Autoimmun Rev</MedlineTA><NlmUniqueID>101128967</NlmUniqueID><ISSNLinking>1568-9972</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D016207">Cytokines</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C508585">IL1B protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C508600">IL6 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D053583">Interleukin-1beta</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D015850">Interleukin-6</NameOfSubstance></Chemical><Chemical><RegistryNumber>9008-11-1</RegistryNumber><NameOfSubstance UI="D007372">Interferons</NameOfSubstance></Chemical></ChemicalList><SupplMeshList><SupplMeshName Type="Disease" UI="C000657245">COVID-19</SupplMeshName><SupplMeshName Type="Protocol" UI="C000705127">COVID-19 drug treatment</SupplMeshName><SupplMeshName Type="Organism" UI="C000656484">severe acute respiratory syndrome coronavirus 2</SupplMeshName></SupplMeshList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000073640" MajorTopicYN="N">Betacoronavirus</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018352" MajorTopicYN="N">Coronavirus Infections</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="N">drug therapy</QualifierName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName><QualifierName UI="Q000628" MajorTopicYN="Y">therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D016207" MajorTopicYN="N">Cytokines</DescriptorName><QualifierName UI="Q000037" MajorTopicYN="Y">antagonists & inhibitors</QualifierName><QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007372" MajorTopicYN="N">Interferons</DescriptorName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D053583" MajorTopicYN="N">Interleukin-1beta</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015850" MajorTopicYN="N">Interleukin-6</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D058873" MajorTopicYN="N">Pandemics</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011024" MajorTopicYN="N">Pneumonia, Viral</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName><QualifierName UI="Q000628" MajorTopicYN="Y">therapy</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Anakinra</Keyword><Keyword MajorTopicYN="N">COVID-19</Keyword><Keyword MajorTopicYN="N">Cytokine storm</Keyword><Keyword MajorTopicYN="N">IL-1</Keyword><Keyword MajorTopicYN="N">IL-6</Keyword><Keyword MajorTopicYN="N">Sars-CoV2</Keyword><Keyword MajorTopicYN="N">Tocilizumab</Keyword><Keyword MajorTopicYN="N">Type-I interferon</Keyword></KeywordList><CoiStatement>Declaration of Competing Interest The authors declare that they have no conflict of interest.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2020</Year><Month>04</Month><Day>26</Day></PubMedPubDate><PubMedPubDate 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