Interleukin-6 and severe COVID-19: a systematic review and meta-analysis.
Identifieur interne : 000476 ( Main/Exploration ); précédent : 000475; suivant : 000477Interleukin-6 and severe COVID-19: a systematic review and meta-analysis.
Auteurs : Helia Mojtabavi [Iran] ; Amene Saghazadeh [Iran] ; Nima Rezaei [Iran]Source :
- European cytokine network [ 1952-4005 ] ; 2020.
Descripteurs français
- KwdFr :
- Adulte d'âge moyen (MeSH), Analyse de survie (MeSH), Anti-inflammatoires (usage thérapeutique), Anticorps monoclonaux humanisés (administration et posologie), Antiviraux (usage thérapeutique), Betacoronavirus (immunologie), Betacoronavirus (pathogénicité), Expression des gènes (MeSH), Femelle (MeSH), Humains (MeSH), Indice de gravité de la maladie (MeSH), Infections à coronavirus (immunologie), Infections à coronavirus (mortalité), Infections à coronavirus (traitement médicamenteux), Infections à coronavirus (virologie), Interleukine-6 (antagonistes et inhibiteurs), Interleukine-6 (génétique), Interleukine-6 (immunologie), Mâle (MeSH), Pandémies (MeSH), Pneumopathie virale (immunologie), Pneumopathie virale (mortalité), Pneumopathie virale (traitement médicamenteux), Pneumopathie virale (virologie), Récepteurs à l'interleukine-6 (génétique), Récepteurs à l'interleukine-6 (immunologie), Résultat thérapeutique (MeSH), Sujet âgé (MeSH), Unités de soins intensifs (MeSH).
- MESH :
- administration et posologie : Anticorps monoclonaux humanisés.
- antagonistes et inhibiteurs : Interleukine-6.
- génétique : Interleukine-6, Récepteurs à l'interleukine-6.
- immunologie : Betacoronavirus, Infections à coronavirus, Interleukine-6, Pneumopathie virale, Récepteurs à l'interleukine-6.
- mortalité : Infections à coronavirus, Pneumopathie virale.
- pathogénicité : Betacoronavirus.
- traitement médicamenteux : Infections à coronavirus, Pneumopathie virale.
- usage thérapeutique : Anti-inflammatoires, Antiviraux.
- virologie : Infections à coronavirus, Pneumopathie virale.
- Adulte d'âge moyen, Analyse de survie, Expression des gènes, Femelle, Humains, Indice de gravité de la maladie, Mâle, Pandémies, Résultat thérapeutique, Sujet âgé, Unités de soins intensifs.
English descriptors
- KwdEn :
- Aged (MeSH), Anti-Inflammatory Agents (therapeutic use), Antibodies, Monoclonal, Humanized (administration & dosage), Antiviral Agents (therapeutic use), Betacoronavirus (immunology), Betacoronavirus (pathogenicity), Coronavirus Infections (drug therapy), Coronavirus Infections (immunology), Coronavirus Infections (mortality), Coronavirus Infections (virology), Cytokine Release Syndrome (drug therapy), Cytokine Release Syndrome (immunology), Cytokine Release Syndrome (mortality), Cytokine Release Syndrome (virology), Female (MeSH), Gene Expression (MeSH), Humans (MeSH), Intensive Care Units (MeSH), Interleukin-6 (antagonists & inhibitors), Interleukin-6 (genetics), Interleukin-6 (immunology), Male (MeSH), Middle Aged (MeSH), Pandemics (MeSH), Pneumonia, Viral (drug therapy), Pneumonia, Viral (immunology), Pneumonia, Viral (mortality), Pneumonia, Viral (virology), Receptors, Interleukin-6 (genetics), Receptors, Interleukin-6 (immunology), Severity of Illness Index (MeSH), Survival Analysis (MeSH), Treatment Outcome (MeSH).
- MESH :
- chemical , administration & dosage : Antibodies, Monoclonal, Humanized.
- chemical , antagonists & inhibitors : Interleukin-6.
- chemical , genetics : Interleukin-6, Receptors, Interleukin-6.
- chemical , immunology : Interleukin-6, Receptors, Interleukin-6.
- chemical , therapeutic use : Anti-Inflammatory Agents, Antiviral Agents.
- drug therapy : Coronavirus Infections, Cytokine Release Syndrome, Pneumonia, Viral.
- immunology : Betacoronavirus, Coronavirus Infections, Cytokine Release Syndrome, Pneumonia, Viral.
- mortality : Coronavirus Infections, Cytokine Release Syndrome, Pneumonia, Viral.
- pathogenicity : Betacoronavirus.
- virology : Coronavirus Infections, Cytokine Release Syndrome, Pneumonia, Viral.
- Aged, Female, Gene Expression, Humans, Intensive Care Units, Male, Middle Aged, Pandemics, Severity of Illness Index, Survival Analysis, Treatment Outcome.
Abstract
BACKGROUND
Evidence links COVID-19 severity to hyper-inflammation. Treatment with tocilizumab, a monoclonal antibody directed against the interleukin-6 (IL-6) receptor, was shown to lead to clinical improvement in patients with severe COVID-19. We, therefore, performed the present systematic review and meta-analysis to investigate whether the circulating levels of IL-6 is a reliable indicator of disease severity among patients affected with COVID-19.
METHODS
A systematic search was conducted in PubMed, Scopus, Web of Science, and Google Scholar on April 19, 2020.
RESULTS
Eleven studies provided data of IL-6 levels in patients with severe to critical COVID-19 (severe) and patients with mild to moderate COVID-19 (non-severe). The included studies were of moderate to high quality. The mean patients' age was 60.9 years, ranging from 45.2 to 76.7 years in the severe group and 46.8 years, ranging from 37.9 to 61 years, in the nonsevere group. Fifty-two percent were male in the severe group, as compared to 46% in the non-severe group. An overall random effects meta-analysis showed significantly higher serum levels of IL-6 in the severe group than in the non-severe group with a mean difference of +23.1 pg/mL (95% CI: 12.42-33.79) and the overall effect of 4.24 (P-value < 0.001). Meta-regressions showed that neither age nor sex significantly influenced the mean difference of IL-6 between the groups.
CONCLUSIONS
Meta-analysis and meta-regression reveal a reliable relationship between IL-6 and COVID-19 severity, independent of age and sex. Future research is, however, required to assess the effect of BMI on the pattern of IL-6 production in patients with COVID-19. Also, there might be confounding factors that influence the relationship between IL-6 and COVID-19 severity and remain as yet unknown.
DOI: 10.1684/ecn.2020.0448
PubMed: 32933891
PubMed Central: PMC7530350
Affiliations:
Links toward previous steps (curation, corpus...)
Le document en format XML
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University of Medical Sciences, Children's Medical Center, Research Center for Immunodeficiencies, Tehran, Iran.</nlm:affiliation><country xml:lang="fr">Iran</country><wicri:regionArea>Universal Scientific Education and Research Network (USERN), Systematic Review and Meta-Analysis Expert Group (SRMEG), Tehran, Iran, Tehran University of Medical Sciences, Children's Medical Center, Research Center for Immunodeficiencies, Tehran</wicri:regionArea><wicri:noRegion>Tehran</wicri:noRegion></affiliation></author><author><name sortKey="Saghazadeh, Amene" sort="Saghazadeh, Amene" uniqKey="Saghazadeh A" first="Amene" last="Saghazadeh">Amene Saghazadeh</name><affiliation wicri:level="1"><nlm:affiliation>Universal Scientific Education and Research Network (USERN), Systematic Review and Meta-Analysis Expert Group (SRMEG), Tehran, Iran, Tehran University of Medical Sciences, Children's Medical Center, Research Center for Immunodeficiencies, Tehran, Iran.</nlm:affiliation><country 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Medical Sciences, Children's Medical Center, Research Center for Immunodeficiencies, Tehran, Iran, Tehran University of Medical Sciences, School of Medicine, Department of Immunology, Tehran, Iran, Universal Scientific Education and Research Network (USERN), Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Tehran</wicri:regionArea><wicri:noRegion>Tehran</wicri:noRegion></affiliation></author></analytic><series><title level="j">European cytokine network</title><idno type="eISSN">1952-4005</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aged (MeSH)</term><term>Anti-Inflammatory Agents (therapeutic use)</term><term>Antibodies, Monoclonal, Humanized (administration & dosage)</term><term>Antiviral Agents (therapeutic use)</term><term>Betacoronavirus (immunology)</term><term>Betacoronavirus (pathogenicity)</term><term>Coronavirus Infections (drug therapy)</term><term>Coronavirus Infections (immunology)</term><term>Coronavirus Infections (mortality)</term><term>Coronavirus Infections (virology)</term><term>Cytokine Release Syndrome (drug therapy)</term><term>Cytokine Release Syndrome (immunology)</term><term>Cytokine Release Syndrome (mortality)</term><term>Cytokine Release Syndrome (virology)</term><term>Female (MeSH)</term><term>Gene Expression (MeSH)</term><term>Humans (MeSH)</term><term>Intensive Care Units (MeSH)</term><term>Interleukin-6 (antagonists & inhibitors)</term><term>Interleukin-6 (genetics)</term><term>Interleukin-6 (immunology)</term><term>Male (MeSH)</term><term>Middle Aged (MeSH)</term><term>Pandemics (MeSH)</term><term>Pneumonia, Viral (drug therapy)</term><term>Pneumonia, Viral (immunology)</term><term>Pneumonia, Viral (mortality)</term><term>Pneumonia, Viral (virology)</term><term>Receptors, Interleukin-6 (genetics)</term><term>Receptors, Interleukin-6 (immunology)</term><term>Severity of Illness Index (MeSH)</term><term>Survival Analysis (MeSH)</term><term>Treatment Outcome (MeSH)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Adulte d'âge moyen (MeSH)</term><term>Analyse de survie (MeSH)</term><term>Anti-inflammatoires (usage thérapeutique)</term><term>Anticorps monoclonaux humanisés (administration et posologie)</term><term>Antiviraux (usage thérapeutique)</term><term>Betacoronavirus (immunologie)</term><term>Betacoronavirus (pathogénicité)</term><term>Expression des gènes (MeSH)</term><term>Femelle (MeSH)</term><term>Humains (MeSH)</term><term>Indice de gravité de la maladie (MeSH)</term><term>Infections à coronavirus (immunologie)</term><term>Infections à coronavirus (mortalité)</term><term>Infections à coronavirus (traitement médicamenteux)</term><term>Infections à coronavirus (virologie)</term><term>Interleukine-6 (antagonistes et inhibiteurs)</term><term>Interleukine-6 (génétique)</term><term>Interleukine-6 (immunologie)</term><term>Mâle (MeSH)</term><term>Pandémies (MeSH)</term><term>Pneumopathie virale (immunologie)</term><term>Pneumopathie virale (mortalité)</term><term>Pneumopathie virale (traitement médicamenteux)</term><term>Pneumopathie virale (virologie)</term><term>Récepteurs à l'interleukine-6 (génétique)</term><term>Récepteurs à l'interleukine-6 (immunologie)</term><term>Résultat thérapeutique (MeSH)</term><term>Sujet âgé (MeSH)</term><term>Unités de soins intensifs (MeSH)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Antibodies, Monoclonal, Humanized</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Interleukin-6</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Interleukin-6</term><term>Receptors, Interleukin-6</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" 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virale</term><term>Récepteurs à l'interleukine-6</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Betacoronavirus</term><term>Coronavirus Infections</term><term>Cytokine Release Syndrome</term><term>Pneumonia, Viral</term></keywords><keywords scheme="MESH" qualifier="mortality" xml:lang="en"><term>Coronavirus Infections</term><term>Cytokine Release Syndrome</term><term>Pneumonia, Viral</term></keywords><keywords scheme="MESH" qualifier="mortalité" xml:lang="fr"><term>Infections à coronavirus</term><term>Pneumopathie virale</term></keywords><keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>Betacoronavirus</term></keywords><keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr"><term>Betacoronavirus</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Infections à coronavirus</term><term>Pneumopathie virale</term></keywords><keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Anti-inflammatoires</term><term>Antiviraux</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Infections à coronavirus</term><term>Pneumopathie virale</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Coronavirus Infections</term><term>Cytokine Release Syndrome</term><term>Pneumonia, Viral</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Aged</term><term>Female</term><term>Gene Expression</term><term>Humans</term><term>Intensive Care Units</term><term>Male</term><term>Middle Aged</term><term>Pandemics</term><term>Severity of Illness Index</term><term>Survival Analysis</term><term>Treatment Outcome</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adulte d'âge moyen</term><term>Analyse de survie</term><term>Expression des gènes</term><term>Femelle</term><term>Humains</term><term>Indice de gravité de la maladie</term><term>Mâle</term><term>Pandémies</term><term>Résultat thérapeutique</term><term>Sujet âgé</term><term>Unités de soins intensifs</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><b>BACKGROUND</b></p><p>Evidence links COVID-19 severity to hyper-inflammation. Treatment with tocilizumab, a monoclonal antibody directed against the interleukin-6 (IL-6) receptor, was shown to lead to clinical improvement in patients with severe COVID-19. We, therefore, performed the present systematic review and meta-analysis to investigate whether the circulating levels of IL-6 is a reliable indicator of disease severity among patients affected with COVID-19.</p></div><div type="abstract" xml:lang="en"><p><b>METHODS</b></p><p>A systematic search was conducted in PubMed, Scopus, Web of Science, and Google Scholar on April 19, 2020.</p></div><div type="abstract" xml:lang="en"><p><b>RESULTS</b></p><p>Eleven studies provided data of IL-6 levels in patients with severe to critical COVID-19 (severe) and patients with mild to moderate COVID-19 (non-severe). The included studies were of moderate to high quality. The mean patients' age was 60.9 years, ranging from 45.2 to 76.7 years in the severe group and 46.8 years, ranging from 37.9 to 61 years, in the nonsevere group. Fifty-two percent were male in the severe group, as compared to 46% in the non-severe group. An overall random effects meta-analysis showed significantly higher serum levels of IL-6 in the severe group than in the non-severe group with a mean difference of +23.1 pg/mL (95% CI: 12.42-33.79) and the overall effect of 4.24 (P-value < 0.001). Meta-regressions showed that neither age nor sex significantly influenced the mean difference of IL-6 between the groups.</p></div><div type="abstract" xml:lang="en"><p><b>CONCLUSIONS</b></p><p>Meta-analysis and meta-regression reveal a reliable relationship between IL-6 and COVID-19 severity, independent of age and sex. Future research is, however, required to assess the effect of BMI on the pattern of IL-6 production in patients with COVID-19. Also, there might be confounding factors that influence the relationship between IL-6 and COVID-19 severity and remain as yet unknown.</p></div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">32933891</PMID><DateCompleted><Year>2020</Year><Month>09</Month><Day>23</Day></DateCompleted><DateRevised><Year>2020</Year><Month>10</Month><Day>03</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1952-4005</ISSN><JournalIssue CitedMedium="Internet"><Volume>31</Volume><Issue>2</Issue><PubDate><Year>2020</Year><Month>Jun</Month><Day>01</Day></PubDate></JournalIssue><Title>European cytokine network</Title><ISOAbbreviation>Eur Cytokine Netw</ISOAbbreviation></Journal><ArticleTitle>Interleukin-6 and severe COVID-19: a systematic review and meta-analysis.</ArticleTitle><Pagination><MedlinePgn>44-49</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1684/ecn.2020.0448</ELocationID><Abstract><AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">Evidence links COVID-19 severity to hyper-inflammation. Treatment with tocilizumab, a monoclonal antibody directed against the interleukin-6 (IL-6) receptor, was shown to lead to clinical improvement in patients with severe COVID-19. We, therefore, performed the present systematic review and meta-analysis to investigate whether the circulating levels of IL-6 is a reliable indicator of disease severity among patients affected with COVID-19.</AbstractText><AbstractText Label="METHODS" NlmCategory="METHODS">A systematic search was conducted in PubMed, Scopus, Web of Science, and Google Scholar on April 19, 2020.</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">Eleven studies provided data of IL-6 levels in patients with severe to critical COVID-19 (severe) and patients with mild to moderate COVID-19 (non-severe). The included studies were of moderate to high quality. The mean patients' age was 60.9 years, ranging from 45.2 to 76.7 years in the severe group and 46.8 years, ranging from 37.9 to 61 years, in the nonsevere group. Fifty-two percent were male in the severe group, as compared to 46% in the non-severe group. An overall random effects meta-analysis showed significantly higher serum levels of IL-6 in the severe group than in the non-severe group with a mean difference of +23.1 pg/mL (95% CI: 12.42-33.79) and the overall effect of 4.24 (P-value < 0.001). Meta-regressions showed that neither age nor sex significantly influenced the mean difference of IL-6 between the groups.</AbstractText><AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">Meta-analysis and meta-regression reveal a reliable relationship between IL-6 and COVID-19 severity, independent of age and sex. Future research is, however, required to assess the effect of BMI on the pattern of IL-6 production in patients with COVID-19. Also, there might be confounding factors that influence the relationship between IL-6 and COVID-19 severity and remain as yet unknown.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Mojtabavi</LastName><ForeName>Helia</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Universal Scientific Education and Research Network (USERN), Systematic Review and Meta-Analysis Expert Group (SRMEG), Tehran, Iran, Tehran University of Medical Sciences, Children's Medical Center, Research Center for Immunodeficiencies, Tehran, Iran.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Saghazadeh</LastName><ForeName>Amene</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Universal Scientific Education and Research Network (USERN), Systematic Review and Meta-Analysis Expert Group (SRMEG), Tehran, Iran, Tehran University of Medical Sciences, Children's Medical Center, Research Center for Immunodeficiencies, Tehran, Iran.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rezaei</LastName><ForeName>Nima</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Tehran University of Medical Sciences, Children's Medical Center, Research Center for Immunodeficiencies, Tehran, Iran, Tehran University of Medical Sciences, School of Medicine, Department of Immunology, Tehran, Iran, Universal Scientific Education and Research Network (USERN), Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Tehran, Iran.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D017418">Meta-Analysis</PublicationType><PublicationType UI="D000078182">Systematic Review</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>France</Country><MedlineTA>Eur Cytokine 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