Impaired immune cell cytotoxicity in severe COVID-19 is IL-6 dependent
BACKGROUNDCoronavirus disease 19 (COVID-19) is an emerging infectious disease caused by SARS-CoV-2. Antiviral immune response is crucial to achieve pathogen clearance; however, in some patients an excessive and aberrant host immune response can lead to an acute respiratory distress syndrome. The com...
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| Veröffentlicht in: | The Journal of clinical investigation 2020-09, Vol.130 (9), p.4694-4703 |
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| creator | Mazzoni, Alessio Salvati, Lorenzo Maggi, Laura Capone, Manuela Vanni, Anna Spinicci, Michele Mencarini, Jessica Caporale, Roberto Peruzzi, Benedetta Antonelli, Alberto Trotta, Michele Zammarchi, Lorenzo Ciani, Luca Gori, Leonardo Lazzeri, Chiara Matucci, Andrea Vultaggio, Alessandra Rossi, Oliviero Almerigogna, Fabio Parronchi, Paola Fontanari, Paolo Lavorini, Federico Peris, Adriano Rossolini, Gian Maria Bartoloni, Alessandro Romagnani, Sergio Liotta, Francesco Annunziato, Francesco Cosmi, Lorenzo |
| description | BACKGROUNDCoronavirus disease 19 (COVID-19) is an emerging infectious disease caused by SARS-CoV-2. Antiviral immune response is crucial to achieve pathogen clearance; however, in some patients an excessive and aberrant host immune response can lead to an acute respiratory distress syndrome. The comprehension of the mechanisms that regulate pathogen elimination, immunity, and pathology is essential to better characterize disease progression and widen the spectrum of therapeutic options.METHODSWe performed a flow cytometric characterization of immune cell subsets from 30 patients with COVID-19 and correlated these data with clinical outcomes.RESULTSPatients with COVID-19 showed decreased numbers of circulating T, B, and NK cells and exhibited a skewing of CD8+ T cells toward a terminally differentiated/senescent phenotype. In agreement, CD4+ T and CD8+ T, but also NK cells, displayed reduced antiviral cytokine production capability. Moreover, a reduced cytotoxic potential was identified in patients with COVID-19, particularly in those who required intensive care. The latter group of patients also showed increased serum IL-6 levels that inversely correlated to the frequency of granzyme A-expressing NK cells. Off-label treatment with tocilizumab restored the cytotoxic potential of NK cells.CONCLUSIONThe association between IL-6 serum levels and the impairment of cytotoxic activity suggests the possibility that targeting this cytokine may restore antiviral mechanisms.FUNDINGThis study was supported by funds from the Department of Experimental and Clinical Medicine of University of Florence (the ex-60% fund and the "Excellence Departments 2018-2022 Project") derived from Ministero dell'Istruzione, dell'Università e della Ricerca (Italy). |
| doi_str_mv | 10.1172/JCI138554 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7456250</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A635668695</galeid><sourcerecordid>A635668695</sourcerecordid><originalsourceid>FETCH-LOGICAL-c647t-bc841e4554965d7ecd8864d9f6f0aff3733640eb6795ee3aa6182dfe2fe97f4e3</originalsourceid><addsrcrecordid>eNqNkk1rGzEQhkVpaNy0h_6BslAo9LCptPpY7aUQ3KbdYDD0I1cha0e2wq7krrQh_vdVaerE4EPQYUDzzDvDzIvQG4LPCamrj1fzllDJOXuGZoRzWcqKyudohnFFyqam8hS9jPEGY8IYZy_QKa2YoBLTGbpsh612I3SFG4bJQ2Gg7wuzSyGFO2dc2hXOFxFuYYRivrxuP5ekKVws2kUpig624Dvw6RU6sbqP8Po-nqFfl19-zr-Vi-XXdn6xKI1gdSpXRjICLE_aCN7VYDopBesaKyzW1tKaUsEwrETdcACqtSCy6ixUFpraMqBn6NM_3e20GqAzufWoe7Ud3aDHnQraqcOMdxu1DreqZlxUHGeBd_cCY_g9QUzqJkyjzzOrijFC84aIfKDWugflvA1ZzAwuGnUhKBdCioZnqjxCrcFD7hw8WJe_D_jzI3x-HQzOHC34cFCQmQR3aa2nGFX74_vT2eX1Ifv-EbsB3adNDP2UXPDxqKgZQ4wj2P2mCVZ_raf21svs28en2ZP_vUb_AKwEzk8</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2441314418</pqid></control><display><type>article</type><title>Impaired immune cell cytotoxicity in severe COVID-19 is IL-6 dependent</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><creator>Mazzoni, Alessio ; Salvati, Lorenzo ; Maggi, Laura ; Capone, Manuela ; Vanni, Anna ; Spinicci, Michele ; Mencarini, Jessica ; Caporale, Roberto ; Peruzzi, Benedetta ; Antonelli, Alberto ; Trotta, Michele ; Zammarchi, Lorenzo ; Ciani, Luca ; Gori, Leonardo ; Lazzeri, Chiara ; Matucci, Andrea ; Vultaggio, Alessandra ; Rossi, Oliviero ; Almerigogna, Fabio ; Parronchi, Paola ; Fontanari, Paolo ; Lavorini, Federico ; Peris, Adriano ; Rossolini, Gian Maria ; Bartoloni, Alessandro ; Romagnani, Sergio ; Liotta, Francesco ; Annunziato, Francesco ; Cosmi, Lorenzo</creator><creatorcontrib>Mazzoni, Alessio ; Salvati, Lorenzo ; Maggi, Laura ; Capone, Manuela ; Vanni, Anna ; Spinicci, Michele ; Mencarini, Jessica ; Caporale, Roberto ; Peruzzi, Benedetta ; Antonelli, Alberto ; Trotta, Michele ; Zammarchi, Lorenzo ; Ciani, Luca ; Gori, Leonardo ; Lazzeri, Chiara ; Matucci, Andrea ; Vultaggio, Alessandra ; Rossi, Oliviero ; Almerigogna, Fabio ; Parronchi, Paola ; Fontanari, Paolo ; Lavorini, Federico ; Peris, Adriano ; Rossolini, Gian Maria ; Bartoloni, Alessandro ; Romagnani, Sergio ; Liotta, Francesco ; Annunziato, Francesco ; Cosmi, Lorenzo</creatorcontrib><description>BACKGROUNDCoronavirus disease 19 (COVID-19) is an emerging infectious disease caused by SARS-CoV-2. Antiviral immune response is crucial to achieve pathogen clearance; however, in some patients an excessive and aberrant host immune response can lead to an acute respiratory distress syndrome. The comprehension of the mechanisms that regulate pathogen elimination, immunity, and pathology is essential to better characterize disease progression and widen the spectrum of therapeutic options.METHODSWe performed a flow cytometric characterization of immune cell subsets from 30 patients with COVID-19 and correlated these data with clinical outcomes.RESULTSPatients with COVID-19 showed decreased numbers of circulating T, B, and NK cells and exhibited a skewing of CD8+ T cells toward a terminally differentiated/senescent phenotype. In agreement, CD4+ T and CD8+ T, but also NK cells, displayed reduced antiviral cytokine production capability. Moreover, a reduced cytotoxic potential was identified in patients with COVID-19, particularly in those who required intensive care. The latter group of patients also showed increased serum IL-6 levels that inversely correlated to the frequency of granzyme A-expressing NK cells. Off-label treatment with tocilizumab restored the cytotoxic potential of NK cells.CONCLUSIONThe association between IL-6 serum levels and the impairment of cytotoxic activity suggests the possibility that targeting this cytokine may restore antiviral mechanisms.FUNDINGThis study was supported by funds from the Department of Experimental and Clinical Medicine of University of Florence (the ex-60% fund and the "Excellence Departments 2018-2022 Project") derived from Ministero dell'Istruzione, dell'Università e della Ricerca (Italy).</description><identifier>ISSN: 0021-9738</identifier><identifier>EISSN: 1558-8238</identifier><identifier>DOI: 10.1172/JCI138554</identifier><identifier>PMID: 32463803</identifier><language>eng</language><publisher>United States: American Society for Clinical Investigation</publisher><subject>Adult ; Adult respiratory distress syndrome ; Aged ; Aged, 80 and over ; Antiviral agents ; B-Lymphocytes - immunology ; Betacoronavirus ; Biomedical research ; CD4 antigen ; CD4-Positive T-Lymphocytes - immunology ; CD8 antigen ; CD8-Positive T-Lymphocytes - immunology ; Cell differentiation ; Clinical Medicine ; Communicable diseases ; Coronavirus Infections - blood ; Coronavirus Infections - epidemiology ; Coronavirus Infections - immunology ; Coronaviruses ; COVID-19 ; Critical Care ; Cytokines - blood ; Cytokines - immunology ; Cytotoxicity ; Cytotoxicity, Immunologic ; Development and progression ; Disease susceptibility ; Evaluation ; Female ; Flow cytometry ; Granzymes - blood ; Granzymes - immunology ; Health aspects ; Humans ; Immune clearance ; Immune response ; Infectious diseases ; Interleukin 6 ; Interleukin-6 - blood ; Interleukin-6 - immunology ; Killer Cells, Natural - immunology ; Lymphocytes ; Lymphocytes T ; Male ; Middle Aged ; Models, Immunological ; Pandemics ; Pathogens ; Patients ; Phenotypes ; Pneumonia, Viral - blood ; Pneumonia, Viral - epidemiology ; Pneumonia, Viral - immunology ; Respiratory distress syndrome ; SARS-CoV-2 ; Serum levels ; Severe acute respiratory syndrome coronavirus 2 ; Viral infections</subject><ispartof>The Journal of clinical investigation, 2020-09, Vol.130 (9), p.4694-4703</ispartof><rights>COPYRIGHT 2020 American Society for Clinical Investigation</rights><rights>Copyright American Society for Clinical Investigation Sep 2020</rights><rights>2020 American Society for Clinical Investigation 2020 American Society for Clinical Investigation</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c647t-bc841e4554965d7ecd8864d9f6f0aff3733640eb6795ee3aa6182dfe2fe97f4e3</citedby><cites>FETCH-LOGICAL-c647t-bc841e4554965d7ecd8864d9f6f0aff3733640eb6795ee3aa6182dfe2fe97f4e3</cites><orcidid>0000-0003-0892-8404 ; 0000-0001-7768-3805 ; 0000-0001-9758-1523 ; 0000-0001-5831-0392 ; 0000-0003-4059-7094</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456250/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456250/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32463803$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mazzoni, Alessio</creatorcontrib><creatorcontrib>Salvati, Lorenzo</creatorcontrib><creatorcontrib>Maggi, Laura</creatorcontrib><creatorcontrib>Capone, Manuela</creatorcontrib><creatorcontrib>Vanni, Anna</creatorcontrib><creatorcontrib>Spinicci, Michele</creatorcontrib><creatorcontrib>Mencarini, Jessica</creatorcontrib><creatorcontrib>Caporale, Roberto</creatorcontrib><creatorcontrib>Peruzzi, Benedetta</creatorcontrib><creatorcontrib>Antonelli, Alberto</creatorcontrib><creatorcontrib>Trotta, Michele</creatorcontrib><creatorcontrib>Zammarchi, Lorenzo</creatorcontrib><creatorcontrib>Ciani, Luca</creatorcontrib><creatorcontrib>Gori, Leonardo</creatorcontrib><creatorcontrib>Lazzeri, Chiara</creatorcontrib><creatorcontrib>Matucci, Andrea</creatorcontrib><creatorcontrib>Vultaggio, Alessandra</creatorcontrib><creatorcontrib>Rossi, Oliviero</creatorcontrib><creatorcontrib>Almerigogna, Fabio</creatorcontrib><creatorcontrib>Parronchi, Paola</creatorcontrib><creatorcontrib>Fontanari, Paolo</creatorcontrib><creatorcontrib>Lavorini, Federico</creatorcontrib><creatorcontrib>Peris, Adriano</creatorcontrib><creatorcontrib>Rossolini, Gian Maria</creatorcontrib><creatorcontrib>Bartoloni, Alessandro</creatorcontrib><creatorcontrib>Romagnani, Sergio</creatorcontrib><creatorcontrib>Liotta, Francesco</creatorcontrib><creatorcontrib>Annunziato, Francesco</creatorcontrib><creatorcontrib>Cosmi, Lorenzo</creatorcontrib><title>Impaired immune cell cytotoxicity in severe COVID-19 is IL-6 dependent</title><title>The Journal of clinical investigation</title><addtitle>J Clin Invest</addtitle><description>BACKGROUNDCoronavirus disease 19 (COVID-19) is an emerging infectious disease caused by SARS-CoV-2. Antiviral immune response is crucial to achieve pathogen clearance; however, in some patients an excessive and aberrant host immune response can lead to an acute respiratory distress syndrome. The comprehension of the mechanisms that regulate pathogen elimination, immunity, and pathology is essential to better characterize disease progression and widen the spectrum of therapeutic options.METHODSWe performed a flow cytometric characterization of immune cell subsets from 30 patients with COVID-19 and correlated these data with clinical outcomes.RESULTSPatients with COVID-19 showed decreased numbers of circulating T, B, and NK cells and exhibited a skewing of CD8+ T cells toward a terminally differentiated/senescent phenotype. In agreement, CD4+ T and CD8+ T, but also NK cells, displayed reduced antiviral cytokine production capability. Moreover, a reduced cytotoxic potential was identified in patients with COVID-19, particularly in those who required intensive care. The latter group of patients also showed increased serum IL-6 levels that inversely correlated to the frequency of granzyme A-expressing NK cells. Off-label treatment with tocilizumab restored the cytotoxic potential of NK cells.CONCLUSIONThe association between IL-6 serum levels and the impairment of cytotoxic activity suggests the possibility that targeting this cytokine may restore antiviral mechanisms.FUNDINGThis study was supported by funds from the Department of Experimental and Clinical Medicine of University of Florence (the ex-60% fund and the "Excellence Departments 2018-2022 Project") derived from Ministero dell'Istruzione, dell'Università e della Ricerca (Italy).</description><subject>Adult</subject><subject>Adult respiratory distress syndrome</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Antiviral agents</subject><subject>B-Lymphocytes - immunology</subject><subject>Betacoronavirus</subject><subject>Biomedical research</subject><subject>CD4 antigen</subject><subject>CD4-Positive T-Lymphocytes - immunology</subject><subject>CD8 antigen</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>Cell differentiation</subject><subject>Clinical Medicine</subject><subject>Communicable diseases</subject><subject>Coronavirus Infections - blood</subject><subject>Coronavirus Infections - epidemiology</subject><subject>Coronavirus Infections - immunology</subject><subject>Coronaviruses</subject><subject>COVID-19</subject><subject>Critical Care</subject><subject>Cytokines - blood</subject><subject>Cytokines - immunology</subject><subject>Cytotoxicity</subject><subject>Cytotoxicity, Immunologic</subject><subject>Development and progression</subject><subject>Disease susceptibility</subject><subject>Evaluation</subject><subject>Female</subject><subject>Flow cytometry</subject><subject>Granzymes - blood</subject><subject>Granzymes - immunology</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Immune clearance</subject><subject>Immune response</subject><subject>Infectious diseases</subject><subject>Interleukin 6</subject><subject>Interleukin-6 - blood</subject><subject>Interleukin-6 - immunology</subject><subject>Killer Cells, Natural - immunology</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Models, Immunological</subject><subject>Pandemics</subject><subject>Pathogens</subject><subject>Patients</subject><subject>Phenotypes</subject><subject>Pneumonia, Viral - blood</subject><subject>Pneumonia, Viral - epidemiology</subject><subject>Pneumonia, Viral - immunology</subject><subject>Respiratory distress syndrome</subject><subject>SARS-CoV-2</subject><subject>Serum levels</subject><subject>Severe acute respiratory syndrome coronavirus 2</subject><subject>Viral 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immune cell cytotoxicity in severe COVID-19 is IL-6 dependent</title><author>Mazzoni, Alessio ; Salvati, Lorenzo ; Maggi, Laura ; Capone, Manuela ; Vanni, Anna ; Spinicci, Michele ; Mencarini, Jessica ; Caporale, Roberto ; Peruzzi, Benedetta ; Antonelli, Alberto ; Trotta, Michele ; Zammarchi, Lorenzo ; Ciani, Luca ; Gori, Leonardo ; Lazzeri, Chiara ; Matucci, Andrea ; Vultaggio, Alessandra ; Rossi, Oliviero ; Almerigogna, Fabio ; Parronchi, Paola ; Fontanari, Paolo ; Lavorini, Federico ; Peris, Adriano ; Rossolini, Gian Maria ; Bartoloni, Alessandro ; Romagnani, Sergio ; Liotta, Francesco ; Annunziato, Francesco ; Cosmi, Lorenzo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c647t-bc841e4554965d7ecd8864d9f6f0aff3733640eb6795ee3aa6182dfe2fe97f4e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adult</topic><topic>Adult respiratory distress syndrome</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Antiviral agents</topic><topic>B-Lymphocytes - immunology</topic><topic>Betacoronavirus</topic><topic>Biomedical research</topic><topic>CD4 antigen</topic><topic>CD4-Positive T-Lymphocytes - immunology</topic><topic>CD8 antigen</topic><topic>CD8-Positive T-Lymphocytes - immunology</topic><topic>Cell differentiation</topic><topic>Clinical Medicine</topic><topic>Communicable diseases</topic><topic>Coronavirus Infections - blood</topic><topic>Coronavirus Infections - epidemiology</topic><topic>Coronavirus Infections - immunology</topic><topic>Coronaviruses</topic><topic>COVID-19</topic><topic>Critical Care</topic><topic>Cytokines - blood</topic><topic>Cytokines - immunology</topic><topic>Cytotoxicity</topic><topic>Cytotoxicity, Immunologic</topic><topic>Development and progression</topic><topic>Disease susceptibility</topic><topic>Evaluation</topic><topic>Female</topic><topic>Flow cytometry</topic><topic>Granzymes - 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Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>SIRS Editorial</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of clinical investigation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mazzoni, Alessio</au><au>Salvati, Lorenzo</au><au>Maggi, Laura</au><au>Capone, Manuela</au><au>Vanni, Anna</au><au>Spinicci, Michele</au><au>Mencarini, Jessica</au><au>Caporale, Roberto</au><au>Peruzzi, Benedetta</au><au>Antonelli, Alberto</au><au>Trotta, Michele</au><au>Zammarchi, Lorenzo</au><au>Ciani, Luca</au><au>Gori, Leonardo</au><au>Lazzeri, Chiara</au><au>Matucci, Andrea</au><au>Vultaggio, Alessandra</au><au>Rossi, Oliviero</au><au>Almerigogna, Fabio</au><au>Parronchi, Paola</au><au>Fontanari, Paolo</au><au>Lavorini, Federico</au><au>Peris, Adriano</au><au>Rossolini, Gian Maria</au><au>Bartoloni, Alessandro</au><au>Romagnani, Sergio</au><au>Liotta, Francesco</au><au>Annunziato, Francesco</au><au>Cosmi, Lorenzo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Impaired immune cell cytotoxicity in severe COVID-19 is IL-6 dependent</atitle><jtitle>The Journal of clinical investigation</jtitle><addtitle>J Clin Invest</addtitle><date>2020-09-01</date><risdate>2020</risdate><volume>130</volume><issue>9</issue><spage>4694</spage><epage>4703</epage><pages>4694-4703</pages><issn>0021-9738</issn><eissn>1558-8238</eissn><abstract>BACKGROUNDCoronavirus disease 19 (COVID-19) is an emerging infectious disease caused by SARS-CoV-2. Antiviral immune response is crucial to achieve pathogen clearance; however, in some patients an excessive and aberrant host immune response can lead to an acute respiratory distress syndrome. The comprehension of the mechanisms that regulate pathogen elimination, immunity, and pathology is essential to better characterize disease progression and widen the spectrum of therapeutic options.METHODSWe performed a flow cytometric characterization of immune cell subsets from 30 patients with COVID-19 and correlated these data with clinical outcomes.RESULTSPatients with COVID-19 showed decreased numbers of circulating T, B, and NK cells and exhibited a skewing of CD8+ T cells toward a terminally differentiated/senescent phenotype. In agreement, CD4+ T and CD8+ T, but also NK cells, displayed reduced antiviral cytokine production capability. Moreover, a reduced cytotoxic potential was identified in patients with COVID-19, particularly in those who required intensive care. The latter group of patients also showed increased serum IL-6 levels that inversely correlated to the frequency of granzyme A-expressing NK cells. Off-label treatment with tocilizumab restored the cytotoxic potential of NK cells.CONCLUSIONThe association between IL-6 serum levels and the impairment of cytotoxic activity suggests the possibility that targeting this cytokine may restore antiviral mechanisms.FUNDINGThis study was supported by funds from the Department of Experimental and Clinical Medicine of University of Florence (the ex-60% fund and the "Excellence Departments 2018-2022 Project") derived from Ministero dell'Istruzione, dell'Università e della Ricerca (Italy).</abstract><cop>United States</cop><pub>American Society for Clinical Investigation</pub><pmid>32463803</pmid><doi>10.1172/JCI138554</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0003-0892-8404</orcidid><orcidid>https://orcid.org/0000-0001-7768-3805</orcidid><orcidid>https://orcid.org/0000-0001-9758-1523</orcidid><orcidid>https://orcid.org/0000-0001-5831-0392</orcidid><orcidid>https://orcid.org/0000-0003-4059-7094</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0021-9738 |
| ispartof | The Journal of clinical investigation, 2020-09, Vol.130 (9), p.4694-4703 |
| issn | 0021-9738 1558-8238 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7456250 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Alma/SFX Local Collection |
| subjects | Adult Adult respiratory distress syndrome Aged Aged, 80 and over Antiviral agents B-Lymphocytes - immunology Betacoronavirus Biomedical research CD4 antigen CD4-Positive T-Lymphocytes - immunology CD8 antigen CD8-Positive T-Lymphocytes - immunology Cell differentiation Clinical Medicine Communicable diseases Coronavirus Infections - blood Coronavirus Infections - epidemiology Coronavirus Infections - immunology Coronaviruses COVID-19 Critical Care Cytokines - blood Cytokines - immunology Cytotoxicity Cytotoxicity, Immunologic Development and progression Disease susceptibility Evaluation Female Flow cytometry Granzymes - blood Granzymes - immunology Health aspects Humans Immune clearance Immune response Infectious diseases Interleukin 6 Interleukin-6 - blood Interleukin-6 - immunology Killer Cells, Natural - immunology Lymphocytes Lymphocytes T Male Middle Aged Models, Immunological Pandemics Pathogens Patients Phenotypes Pneumonia, Viral - blood Pneumonia, Viral - epidemiology Pneumonia, Viral - immunology Respiratory distress syndrome SARS-CoV-2 Serum levels Severe acute respiratory syndrome coronavirus 2 Viral infections |
| title | Impaired immune cell cytotoxicity in severe COVID-19 is IL-6 dependent |
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