Preliminary observations on IGRA testing for TB infection in patients with severe COVID-19 eligible for immunosuppressive therapy
COVID-19, the novel coronavirus pandemic, has already spread around the globe affecting more than 18 million people. As previously observed with other coronaviruses, SARS-CoV-2 deeply dysregulate the immune system eliciting respiratory failure and a state of systemic hyperinflammation in severely il...
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| Veröffentlicht in: | Respiratory medicine 2020-12, Vol.175, p.106204-106204, Article 106204 |
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| creator | Torre, Alessandro Aliberti, Stefano Castellotti, Paola Francesca Cirillo, Daniela Maria Grisolia, Antonella Mangioni, Davide Marchetti, Giulia Rossotti, Roberto Santus, Pierachille Besozzi, Giorgio Villa, Simone Codecasa, Luigi Ruffo Bandera, Alessandra Blasi, Francesco Campisi, Daniela Ferrarese, Maurizio Gramegna, Andrea Lombardi, Alessandra Mancon, Alessandro Mantero, Marco Muscatello, Antonio Passerini, Matteo Piscaglia, Marco Saporiti, Matteo Schiuma, Marco |
| description | COVID-19, the novel coronavirus pandemic, has already spread around the globe affecting more than 18 million people. As previously observed with other coronaviruses, SARS-CoV-2 deeply dysregulate the immune system eliciting respiratory failure and a state of systemic hyperinflammation in severely ill individuals. Immunotherapy is often used to downgrade the detrimental effects of the disease sustained by high-level of cytokines. Those treatments, however, are known to undermine patients’ ability to contain tuberculosis (TB) infection. This study aims to describe interferon-γ release assay (IGRA) results in severe COVID-19 patients eligible for immunosuppressive treatment. Aggregate data were gathered from five hospitals in Milan, Italy, from March 1 to May 15, 2020 and retrospectively analyses. Results were summarized using absolute frequencies and percentages and compared using a two-sided Chi-squared test. Overall, 462 COVID-19 patients were eligible for immunosuppressive therapy, among which 335 were tested using IGRA testing. More than one-third of them (122/335; 36.4%) had an indeterminate IGRA result because of insufficient immune response to mitogen control, 19 (5.7%) tested positive and 194 (57.9) negative. The majority of patients with lymphocytopenia (i.e., total lymphocyte count [TLC] below 1000 cells/mm3) had indeterminate IGRAs (81/155; 52.3%). The proportion becomes even higher in patients with severe lymphocytopenia (i.e., TLC |
| doi_str_mv | 10.1016/j.rmed.2020.106204 |
| format | Article |
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•So far, no data on the effect of COVID-19 and anti-IL-1/-6 agents in TB progression.•IGRA indeterminate was associated to severe lymphocytopenia in COVID-19 patients.•Patients with indeterminate IGRA treated with anti-IL-1/-6 were more likely to die.•A monitoring program is needed to avoid late diagnosis and poor outcome of TB.</description><identifier>ISSN: 0954-6111</identifier><identifier>EISSN: 1532-3064</identifier><identifier>DOI: 10.1016/j.rmed.2020.106204</identifier><identifier>PMID: 33186846</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Anakinra ; Antibodies, Monoclonal, Humanized - therapeutic use ; Antirheumatic Agents - therapeutic use ; Cell number ; Chi-square test ; Coronaviridae ; Coronaviruses ; COVID-19 ; COVID-19 - diagnosis ; COVID-19 - epidemiology ; COVID-19 - therapy ; COVID-19 - virology ; Cytokine-blocking agents ; Cytokines ; Drug dosages ; Editing ; Epidemiology ; Female ; Humans ; IGRA ; Immune response ; Immune system ; Immunity - physiology ; Immunosuppression - methods ; Immunosuppressive agents ; Immunotherapy ; Infections ; Interferon ; Interferon-gamma Release Tests - methods ; Interferon-gamma Release Tests - statistics & numerical data ; Interleukin 1 Receptor Antagonist Protein - therapeutic use ; Italy - epidemiology ; Latent Tuberculosis - diagnosis ; Latent Tuberculosis - epidemiology ; Latent Tuberculosis - immunology ; Latent Tuberculosis - prevention & control ; Lymphocytes ; Lymphopenia ; Lymphopenia - immunology ; Male ; Medical treatment ; Monoclonal antibodies ; Pandemics ; Patients ; Public health ; Respiratory failure ; Retrospective Studies ; SARS-CoV-2 - genetics ; Severe acute respiratory syndrome coronavirus 2 ; Severity of Illness Index ; Short Communication ; Statistical tests ; Supervision ; Tocilizumab ; Tuberculosis ; Viral infections ; Writing ; γ-Interferon</subject><ispartof>Respiratory medicine, 2020-12, Vol.175, p.106204-106204, Article 106204</ispartof><rights>2020 Elsevier Ltd</rights><rights>Copyright © 2020 Elsevier Ltd. All rights reserved.</rights><rights>2020. Elsevier Ltd</rights><rights>2020 Elsevier Ltd. All rights reserved. 2020 Elsevier Ltd</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c483t-b9dad32ab38814370d68bbaf34102c1beefa6ab4b33709b748634eae1a89c4fb3</citedby><cites>FETCH-LOGICAL-c483t-b9dad32ab38814370d68bbaf34102c1beefa6ab4b33709b748634eae1a89c4fb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0954611120303449$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33186846$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Torre, Alessandro</creatorcontrib><creatorcontrib>Aliberti, Stefano</creatorcontrib><creatorcontrib>Castellotti, Paola Francesca</creatorcontrib><creatorcontrib>Cirillo, Daniela Maria</creatorcontrib><creatorcontrib>Grisolia, Antonella</creatorcontrib><creatorcontrib>Mangioni, Davide</creatorcontrib><creatorcontrib>Marchetti, Giulia</creatorcontrib><creatorcontrib>Rossotti, Roberto</creatorcontrib><creatorcontrib>Santus, Pierachille</creatorcontrib><creatorcontrib>Besozzi, Giorgio</creatorcontrib><creatorcontrib>Villa, Simone</creatorcontrib><creatorcontrib>Codecasa, Luigi Ruffo</creatorcontrib><creatorcontrib>Bandera, Alessandra</creatorcontrib><creatorcontrib>Blasi, Francesco</creatorcontrib><creatorcontrib>Campisi, Daniela</creatorcontrib><creatorcontrib>Ferrarese, Maurizio</creatorcontrib><creatorcontrib>Gramegna, Andrea</creatorcontrib><creatorcontrib>Lombardi, Alessandra</creatorcontrib><creatorcontrib>Mancon, Alessandro</creatorcontrib><creatorcontrib>Mantero, Marco</creatorcontrib><creatorcontrib>Muscatello, Antonio</creatorcontrib><creatorcontrib>Passerini, Matteo</creatorcontrib><creatorcontrib>Piscaglia, Marco</creatorcontrib><creatorcontrib>Saporiti, Matteo</creatorcontrib><creatorcontrib>Schiuma, Marco</creatorcontrib><creatorcontrib>Milan TB-COVID-19 study group</creatorcontrib><title>Preliminary observations on IGRA testing for TB infection in patients with severe COVID-19 eligible for immunosuppressive therapy</title><title>Respiratory medicine</title><addtitle>Respir Med</addtitle><description>COVID-19, the novel coronavirus pandemic, has already spread around the globe affecting more than 18 million people. As previously observed with other coronaviruses, SARS-CoV-2 deeply dysregulate the immune system eliciting respiratory failure and a state of systemic hyperinflammation in severely ill individuals. Immunotherapy is often used to downgrade the detrimental effects of the disease sustained by high-level of cytokines. Those treatments, however, are known to undermine patients’ ability to contain tuberculosis (TB) infection. This study aims to describe interferon-γ release assay (IGRA) results in severe COVID-19 patients eligible for immunosuppressive treatment. Aggregate data were gathered from five hospitals in Milan, Italy, from March 1 to May 15, 2020 and retrospectively analyses. Results were summarized using absolute frequencies and percentages and compared using a two-sided Chi-squared test. Overall, 462 COVID-19 patients were eligible for immunosuppressive therapy, among which 335 were tested using IGRA testing. More than one-third of them (122/335; 36.4%) had an indeterminate IGRA result because of insufficient immune response to mitogen control, 19 (5.7%) tested positive and 194 (57.9) negative. The majority of patients with lymphocytopenia (i.e., total lymphocyte count [TLC] below 1000 cells/mm3) had indeterminate IGRAs (81/155; 52.3%). The proportion becomes even higher in patients with severe lymphocytopenia (i.e., TLC<500 cells/mm3) (36/57; 63%). Our results suggest a possible negative impact of COVID-19 related immune dysregulation on TB infection assessment and management. Close monitoring of individuals with or without retesting of individuals with indeterminate IGRAs and further basic science investigations should to be sought to better comprehend their implication on TB epidemiology.
•So far, no data on the effect of COVID-19 and anti-IL-1/-6 agents in TB progression.•IGRA indeterminate was associated to severe lymphocytopenia in COVID-19 patients.•Patients with indeterminate IGRA treated with anti-IL-1/-6 were more likely to die.•A monitoring program is needed to avoid late diagnosis and poor outcome of TB.</description><subject>Anakinra</subject><subject>Antibodies, Monoclonal, Humanized - therapeutic use</subject><subject>Antirheumatic Agents - therapeutic use</subject><subject>Cell number</subject><subject>Chi-square test</subject><subject>Coronaviridae</subject><subject>Coronaviruses</subject><subject>COVID-19</subject><subject>COVID-19 - diagnosis</subject><subject>COVID-19 - epidemiology</subject><subject>COVID-19 - therapy</subject><subject>COVID-19 - virology</subject><subject>Cytokine-blocking agents</subject><subject>Cytokines</subject><subject>Drug dosages</subject><subject>Editing</subject><subject>Epidemiology</subject><subject>Female</subject><subject>Humans</subject><subject>IGRA</subject><subject>Immune response</subject><subject>Immune system</subject><subject>Immunity - physiology</subject><subject>Immunosuppression - methods</subject><subject>Immunosuppressive agents</subject><subject>Immunotherapy</subject><subject>Infections</subject><subject>Interferon</subject><subject>Interferon-gamma Release Tests - methods</subject><subject>Interferon-gamma Release Tests - statistics & numerical data</subject><subject>Interleukin 1 Receptor Antagonist Protein - therapeutic use</subject><subject>Italy - epidemiology</subject><subject>Latent Tuberculosis - diagnosis</subject><subject>Latent Tuberculosis - epidemiology</subject><subject>Latent Tuberculosis - immunology</subject><subject>Latent Tuberculosis - prevention & control</subject><subject>Lymphocytes</subject><subject>Lymphopenia</subject><subject>Lymphopenia - immunology</subject><subject>Male</subject><subject>Medical treatment</subject><subject>Monoclonal antibodies</subject><subject>Pandemics</subject><subject>Patients</subject><subject>Public health</subject><subject>Respiratory failure</subject><subject>Retrospective Studies</subject><subject>SARS-CoV-2 - genetics</subject><subject>Severe acute respiratory syndrome coronavirus 2</subject><subject>Severity of Illness Index</subject><subject>Short Communication</subject><subject>Statistical tests</subject><subject>Supervision</subject><subject>Tocilizumab</subject><subject>Tuberculosis</subject><subject>Viral infections</subject><subject>Writing</subject><subject>γ-Interferon</subject><issn>0954-6111</issn><issn>1532-3064</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU1v1DAQhi0EotvCH-CALHHhksVf6yQSQioLLStVKkKFq2Unk12vEju1k6Ae-89xuqVqOXCyZT_zamYehN5QsqSEyg_7ZeigXjLC5gfJiHiGFnTFWcaJFM_RgpQrkUlK6RE6jnFPCCmFIC_REee0kIWQC3T7PUBrO-t0uMHeRAiTHqx3EXuHN-c_TvEAcbBuixsf8NVnbF0D1UykG-4TC26I-LcddjjCBAHw-vLX5ktGS5yCt9a0cFdqu250Po59HyBGOwEedhB0f_MKvWh0G-H1_XmCfp59vVp_yy4uzzfr04usEgUfMlPWuuZMG14UVPCc1LIwRjdcUMIqagAaLbURhqe_0uSikFyABqqLshKN4Sfo0yG3H01aW5X6DrpVfbBdml15bdXTH2d3ausnlUuxYvkqBby_Dwj-ekxbUZ2NFbStduDHqJiQJJe8ICKh7_5B934MLo03U4mjpGSJYgeqCj7GAM1DM5So2bDaq9mwmg2rg-FU9PbxGA8lf5Um4OMBgLTMyUJQsUqSKqhtSOZU7e3_8v8AKi251g</recordid><startdate>20201201</startdate><enddate>20201201</enddate><creator>Torre, Alessandro</creator><creator>Aliberti, Stefano</creator><creator>Castellotti, Paola Francesca</creator><creator>Cirillo, Daniela Maria</creator><creator>Grisolia, Antonella</creator><creator>Mangioni, Davide</creator><creator>Marchetti, Giulia</creator><creator>Rossotti, Roberto</creator><creator>Santus, Pierachille</creator><creator>Besozzi, Giorgio</creator><creator>Villa, Simone</creator><creator>Codecasa, Luigi Ruffo</creator><creator>Bandera, Alessandra</creator><creator>Blasi, Francesco</creator><creator>Campisi, Daniela</creator><creator>Ferrarese, Maurizio</creator><creator>Gramegna, Andrea</creator><creator>Lombardi, Alessandra</creator><creator>Mancon, Alessandro</creator><creator>Mantero, Marco</creator><creator>Muscatello, Antonio</creator><creator>Passerini, Matteo</creator><creator>Piscaglia, Marco</creator><creator>Saporiti, Matteo</creator><creator>Schiuma, Marco</creator><general>Elsevier Ltd</general><general>Elsevier Limited</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7U9</scope><scope>ASE</scope><scope>FPQ</scope><scope>H94</scope><scope>K6X</scope><scope>K9.</scope><scope>M7N</scope><scope>NAPCQ</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20201201</creationdate><title>Preliminary observations on IGRA testing for TB infection in patients with severe COVID-19 eligible for immunosuppressive therapy</title><author>Torre, Alessandro ; Aliberti, Stefano ; Castellotti, Paola Francesca ; Cirillo, Daniela Maria ; Grisolia, Antonella ; Mangioni, Davide ; Marchetti, Giulia ; Rossotti, Roberto ; Santus, Pierachille ; Besozzi, Giorgio ; Villa, Simone ; Codecasa, Luigi Ruffo ; Bandera, Alessandra ; Blasi, Francesco ; Campisi, Daniela ; Ferrarese, Maurizio ; Gramegna, Andrea ; Lombardi, Alessandra ; Mancon, Alessandro ; Mantero, Marco ; Muscatello, Antonio ; Passerini, Matteo ; Piscaglia, Marco ; Saporiti, Matteo ; Schiuma, Marco</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c483t-b9dad32ab38814370d68bbaf34102c1beefa6ab4b33709b748634eae1a89c4fb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Anakinra</topic><topic>Antibodies, Monoclonal, Humanized - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Respiratory medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Torre, Alessandro</au><au>Aliberti, Stefano</au><au>Castellotti, Paola Francesca</au><au>Cirillo, Daniela Maria</au><au>Grisolia, Antonella</au><au>Mangioni, Davide</au><au>Marchetti, Giulia</au><au>Rossotti, Roberto</au><au>Santus, Pierachille</au><au>Besozzi, Giorgio</au><au>Villa, Simone</au><au>Codecasa, Luigi Ruffo</au><au>Bandera, Alessandra</au><au>Blasi, Francesco</au><au>Campisi, Daniela</au><au>Ferrarese, Maurizio</au><au>Gramegna, Andrea</au><au>Lombardi, Alessandra</au><au>Mancon, Alessandro</au><au>Mantero, Marco</au><au>Muscatello, Antonio</au><au>Passerini, Matteo</au><au>Piscaglia, Marco</au><au>Saporiti, Matteo</au><au>Schiuma, Marco</au><aucorp>Milan TB-COVID-19 study group</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Preliminary observations on IGRA testing for TB infection in patients with severe COVID-19 eligible for immunosuppressive therapy</atitle><jtitle>Respiratory medicine</jtitle><addtitle>Respir Med</addtitle><date>2020-12-01</date><risdate>2020</risdate><volume>175</volume><spage>106204</spage><epage>106204</epage><pages>106204-106204</pages><artnum>106204</artnum><issn>0954-6111</issn><eissn>1532-3064</eissn><abstract>COVID-19, the novel coronavirus pandemic, has already spread around the globe affecting more than 18 million people. As previously observed with other coronaviruses, SARS-CoV-2 deeply dysregulate the immune system eliciting respiratory failure and a state of systemic hyperinflammation in severely ill individuals. Immunotherapy is often used to downgrade the detrimental effects of the disease sustained by high-level of cytokines. Those treatments, however, are known to undermine patients’ ability to contain tuberculosis (TB) infection. This study aims to describe interferon-γ release assay (IGRA) results in severe COVID-19 patients eligible for immunosuppressive treatment. Aggregate data were gathered from five hospitals in Milan, Italy, from March 1 to May 15, 2020 and retrospectively analyses. Results were summarized using absolute frequencies and percentages and compared using a two-sided Chi-squared test. Overall, 462 COVID-19 patients were eligible for immunosuppressive therapy, among which 335 were tested using IGRA testing. More than one-third of them (122/335; 36.4%) had an indeterminate IGRA result because of insufficient immune response to mitogen control, 19 (5.7%) tested positive and 194 (57.9) negative. The majority of patients with lymphocytopenia (i.e., total lymphocyte count [TLC] below 1000 cells/mm3) had indeterminate IGRAs (81/155; 52.3%). The proportion becomes even higher in patients with severe lymphocytopenia (i.e., TLC<500 cells/mm3) (36/57; 63%). Our results suggest a possible negative impact of COVID-19 related immune dysregulation on TB infection assessment and management. Close monitoring of individuals with or without retesting of individuals with indeterminate IGRAs and further basic science investigations should to be sought to better comprehend their implication on TB epidemiology.
•So far, no data on the effect of COVID-19 and anti-IL-1/-6 agents in TB progression.•IGRA indeterminate was associated to severe lymphocytopenia in COVID-19 patients.•Patients with indeterminate IGRA treated with anti-IL-1/-6 were more likely to die.•A monitoring program is needed to avoid late diagnosis and poor outcome of TB.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>33186846</pmid><doi>10.1016/j.rmed.2020.106204</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0954-6111 |
| ispartof | Respiratory medicine, 2020-12, Vol.175, p.106204-106204, Article 106204 |
| issn | 0954-6111 1532-3064 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7645275 |
| source | MEDLINE; Elsevier ScienceDirect Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Anakinra Antibodies, Monoclonal, Humanized - therapeutic use Antirheumatic Agents - therapeutic use Cell number Chi-square test Coronaviridae Coronaviruses COVID-19 COVID-19 - diagnosis COVID-19 - epidemiology COVID-19 - therapy COVID-19 - virology Cytokine-blocking agents Cytokines Drug dosages Editing Epidemiology Female Humans IGRA Immune response Immune system Immunity - physiology Immunosuppression - methods Immunosuppressive agents Immunotherapy Infections Interferon Interferon-gamma Release Tests - methods Interferon-gamma Release Tests - statistics & numerical data Interleukin 1 Receptor Antagonist Protein - therapeutic use Italy - epidemiology Latent Tuberculosis - diagnosis Latent Tuberculosis - epidemiology Latent Tuberculosis - immunology Latent Tuberculosis - prevention & control Lymphocytes Lymphopenia Lymphopenia - immunology Male Medical treatment Monoclonal antibodies Pandemics Patients Public health Respiratory failure Retrospective Studies SARS-CoV-2 - genetics Severe acute respiratory syndrome coronavirus 2 Severity of Illness Index Short Communication Statistical tests Supervision Tocilizumab Tuberculosis Viral infections Writing γ-Interferon |
| title | Preliminary observations on IGRA testing for TB infection in patients with severe COVID-19 eligible for immunosuppressive therapy |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-02T06%3A44%3A21IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Preliminary%20observations%20on%20IGRA%20testing%20for%20TB%20infection%20in%20patients%20with%20severe%20COVID-19%20eligible%20for%20immunosuppressive%20therapy&rft.jtitle=Respiratory%20medicine&rft.au=Torre,%20Alessandro&rft.aucorp=Milan%20TB-COVID-19%20study%20group&rft.date=2020-12-01&rft.volume=175&rft.spage=106204&rft.epage=106204&rft.pages=106204-106204&rft.artnum=106204&rft.issn=0954-6111&rft.eissn=1532-3064&rft_id=info:doi/10.1016/j.rmed.2020.106204&rft_dat=%3Cproquest_pubme%3E2460763804%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2464601092&rft_id=info:pmid/33186846&rft_els_id=S0954611120303449&rfr_iscdi=true |