Critically ill COVID-19 patients with neutralizing autoantibodies against type I interferons have increased risk of herpesvirus disease
Autoantibodies neutralizing the antiviral action of type I interferons (IFNs) have been associated with predisposition to severe Coronavirus Disease 2019 (COVID-19). Here, we screened for such autoantibodies in 103 critically ill COVID-19 patients in a tertiary intensive care unit (ICU) in Switzerla...
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| description | Autoantibodies neutralizing the antiviral action of type I interferons (IFNs) have been associated with predisposition to severe Coronavirus Disease 2019 (COVID-19). Here, we screened for such autoantibodies in 103 critically ill COVID-19 patients in a tertiary intensive care unit (ICU) in Switzerland. Eleven patients (10.7%), but no healthy donors, had neutralizing anti-IFN[alpha] or anti-IFN[alpha]/anti-IFN[omega] IgG in plasma/serum, but anti-IFN IgM or IgA was rare. One patient had non-neutralizing anti-IFN[alpha] IgG. Strikingly, all patients with plasma anti-IFN[alpha] IgG also had anti-IFN[alpha] IgG in tracheobronchial secretions, identifying these autoantibodies at anatomical sites relevant for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Longitudinal analyses revealed patient heterogeneity in terms of increasing, decreasing, or stable anti-IFN IgG levels throughout the length of hospitalization. Notably, presence of anti-IFN autoantibodies in this critically ill COVID-19 cohort appeared to predict herpesvirus disease (caused by herpes simplex viruses types 1 and 2 (HSV-1/-2) and/or cytomegalovirus (CMV)), which has been linked to worse clinical outcomes. Indeed, all 7 tested COVID-19 patients with anti-IFN IgG in our cohort (100%) suffered from one or more herpesviruses, and analysis revealed that these patients were more likely to experience CMV than COVID-19 patients without anti-IFN autoantibodies, even when adjusting for age, gender, and systemic steroid treatment (odds ratio (OR) 7.28, 95% confidence interval (CI) 1.14 to 46.31, p = 0.036). As the IFN system deficiency caused by neutralizing anti-IFN autoantibodies likely directly and indirectly exacerbates the likelihood of latent herpesvirus reactivations in critically ill patients, early diagnosis of anti-IFN IgG could be rapidly used to inform risk-group stratification and treatment options. |
| doi_str_mv | 10.1371/journal.pbio.3001709 |
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Here, we screened for such autoantibodies in 103 critically ill COVID-19 patients in a tertiary intensive care unit (ICU) in Switzerland. Eleven patients (10.7%), but no healthy donors, had neutralizing anti-IFN[alpha] or anti-IFN[alpha]/anti-IFN[omega] IgG in plasma/serum, but anti-IFN IgM or IgA was rare. One patient had non-neutralizing anti-IFN[alpha] IgG. Strikingly, all patients with plasma anti-IFN[alpha] IgG also had anti-IFN[alpha] IgG in tracheobronchial secretions, identifying these autoantibodies at anatomical sites relevant for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Longitudinal analyses revealed patient heterogeneity in terms of increasing, decreasing, or stable anti-IFN IgG levels throughout the length of hospitalization. Notably, presence of anti-IFN autoantibodies in this critically ill COVID-19 cohort appeared to predict herpesvirus disease (caused by herpes simplex viruses types 1 and 2 (HSV-1/-2) and/or cytomegalovirus (CMV)), which has been linked to worse clinical outcomes. Indeed, all 7 tested COVID-19 patients with anti-IFN IgG in our cohort (100%) suffered from one or more herpesviruses, and analysis revealed that these patients were more likely to experience CMV than COVID-19 patients without anti-IFN autoantibodies, even when adjusting for age, gender, and systemic steroid treatment (odds ratio (OR) 7.28, 95% confidence interval (CI) 1.14 to 46.31, p = 0.036). As the IFN system deficiency caused by neutralizing anti-IFN autoantibodies likely directly and indirectly exacerbates the likelihood of latent herpesvirus reactivations in critically ill patients, early diagnosis of anti-IFN IgG could be rapidly used to inform risk-group stratification and treatment options.</description><identifier>ISSN: 1545-7885</identifier><identifier>ISSN: 1544-9173</identifier><identifier>EISSN: 1545-7885</identifier><identifier>DOI: 10.1371/journal.pbio.3001709</identifier><identifier>PMID: 35788562</identifier><language>eng</language><publisher>San Francisco: Public Library of Science</publisher><subject>Analysis ; Antiviral activity ; Autoantibodies ; Biology and Life Sciences ; Clinical outcomes ; Cloning ; Coronaviruses ; COVID-19 ; Critically ill ; Cytomegalovirus ; Discovery Report ; Disease ; Epidemics ; Gene expression ; Genetic aspects ; Health risks ; Health services ; Herpes ; Herpes simplex ; Herpes viruses ; Herpesvirus diseases ; Heterogeneity ; Hospitals ; Immunoglobulin A ; Immunoglobulin G ; Immunoglobulin M ; Influence ; Intensive care ; Interferon ; Medicine and Health Sciences ; Monoclonal antibodies ; Neutralizing ; Older people ; Patients ; Respiratory diseases ; Risk factors ; Secretions ; Severe acute respiratory syndrome ; Severe acute respiratory syndrome coronavirus 2 ; United States ; Viral diseases ; Viruses ; α-Interferon</subject><ispartof>PLoS biology, 2022-07, Vol.20 (7), p.e3001709-e3001709</ispartof><rights>COPYRIGHT 2022 Public Library of Science</rights><rights>2022 Busnadiego et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2022 Busnadiego et al 2022 Busnadiego et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c672t-5b09c3232cdaf70b8e69d070f07c7d4952b36be5d7fce3b153af034f941fcb1f3</citedby><cites>FETCH-LOGICAL-c672t-5b09c3232cdaf70b8e69d070f07c7d4952b36be5d7fce3b153af034f941fcb1f3</cites><orcidid>0000-0002-3891-9480</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/PMC9286229/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9286229/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79569,79570</link.rule.ids></links><search><creatorcontrib>Busnadiego, Idoia</creatorcontrib><creatorcontrib>Abela, Irene A</creatorcontrib><creatorcontrib>Frey, Pascal M</creatorcontrib><creatorcontrib>Hofmaenner, Daniel A</creatorcontrib><creatorcontrib>Scheier, Thomas C</creatorcontrib><creatorcontrib>Schuepbach, Reto A</creatorcontrib><creatorcontrib>Buehler, Philipp K</creatorcontrib><creatorcontrib>Brugger, Silvio D</creatorcontrib><creatorcontrib>Hale, Benjamin G</creatorcontrib><title>Critically ill COVID-19 patients with neutralizing autoantibodies against type I interferons have increased risk of herpesvirus disease</title><title>PLoS biology</title><description>Autoantibodies neutralizing the antiviral action of type I interferons (IFNs) have been associated with predisposition to severe Coronavirus Disease 2019 (COVID-19). Here, we screened for such autoantibodies in 103 critically ill COVID-19 patients in a tertiary intensive care unit (ICU) in Switzerland. Eleven patients (10.7%), but no healthy donors, had neutralizing anti-IFN[alpha] or anti-IFN[alpha]/anti-IFN[omega] IgG in plasma/serum, but anti-IFN IgM or IgA was rare. One patient had non-neutralizing anti-IFN[alpha] IgG. Strikingly, all patients with plasma anti-IFN[alpha] IgG also had anti-IFN[alpha] IgG in tracheobronchial secretions, identifying these autoantibodies at anatomical sites relevant for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Longitudinal analyses revealed patient heterogeneity in terms of increasing, decreasing, or stable anti-IFN IgG levels throughout the length of hospitalization. Notably, presence of anti-IFN autoantibodies in this critically ill COVID-19 cohort appeared to predict herpesvirus disease (caused by herpes simplex viruses types 1 and 2 (HSV-1/-2) and/or cytomegalovirus (CMV)), which has been linked to worse clinical outcomes. Indeed, all 7 tested COVID-19 patients with anti-IFN IgG in our cohort (100%) suffered from one or more herpesviruses, and analysis revealed that these patients were more likely to experience CMV than COVID-19 patients without anti-IFN autoantibodies, even when adjusting for age, gender, and systemic steroid treatment (odds ratio (OR) 7.28, 95% confidence interval (CI) 1.14 to 46.31, p = 0.036). As the IFN system deficiency caused by neutralizing anti-IFN autoantibodies likely directly and indirectly exacerbates the likelihood of latent herpesvirus reactivations in critically ill patients, early diagnosis of anti-IFN IgG could be rapidly used to inform risk-group stratification and treatment options.</description><subject>Analysis</subject><subject>Antiviral activity</subject><subject>Autoantibodies</subject><subject>Biology and Life Sciences</subject><subject>Clinical outcomes</subject><subject>Cloning</subject><subject>Coronaviruses</subject><subject>COVID-19</subject><subject>Critically ill</subject><subject>Cytomegalovirus</subject><subject>Discovery Report</subject><subject>Disease</subject><subject>Epidemics</subject><subject>Gene expression</subject><subject>Genetic aspects</subject><subject>Health risks</subject><subject>Health services</subject><subject>Herpes</subject><subject>Herpes simplex</subject><subject>Herpes viruses</subject><subject>Herpesvirus 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ill COVID-19 patients with neutralizing autoantibodies against type I interferons have increased risk of herpesvirus disease</title><author>Busnadiego, Idoia ; Abela, Irene A ; Frey, Pascal M ; Hofmaenner, Daniel A ; Scheier, Thomas C ; Schuepbach, Reto A ; Buehler, Philipp K ; Brugger, Silvio D ; Hale, Benjamin G</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c672t-5b09c3232cdaf70b8e69d070f07c7d4952b36be5d7fce3b153af034f941fcb1f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Analysis</topic><topic>Antiviral activity</topic><topic>Autoantibodies</topic><topic>Biology and Life Sciences</topic><topic>Clinical outcomes</topic><topic>Cloning</topic><topic>Coronaviruses</topic><topic>COVID-19</topic><topic>Critically ill</topic><topic>Cytomegalovirus</topic><topic>Discovery Report</topic><topic>Disease</topic><topic>Epidemics</topic><topic>Gene 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Philipp K</au><au>Brugger, Silvio D</au><au>Hale, Benjamin G</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Critically ill COVID-19 patients with neutralizing autoantibodies against type I interferons have increased risk of herpesvirus disease</atitle><jtitle>PLoS biology</jtitle><date>2022-07-05</date><risdate>2022</risdate><volume>20</volume><issue>7</issue><spage>e3001709</spage><epage>e3001709</epage><pages>e3001709-e3001709</pages><issn>1545-7885</issn><issn>1544-9173</issn><eissn>1545-7885</eissn><abstract>Autoantibodies neutralizing the antiviral action of type I interferons (IFNs) have been associated with predisposition to severe Coronavirus Disease 2019 (COVID-19). Here, we screened for such autoantibodies in 103 critically ill COVID-19 patients in a tertiary intensive care unit (ICU) in Switzerland. Eleven patients (10.7%), but no healthy donors, had neutralizing anti-IFN[alpha] or anti-IFN[alpha]/anti-IFN[omega] IgG in plasma/serum, but anti-IFN IgM or IgA was rare. One patient had non-neutralizing anti-IFN[alpha] IgG. Strikingly, all patients with plasma anti-IFN[alpha] IgG also had anti-IFN[alpha] IgG in tracheobronchial secretions, identifying these autoantibodies at anatomical sites relevant for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Longitudinal analyses revealed patient heterogeneity in terms of increasing, decreasing, or stable anti-IFN IgG levels throughout the length of hospitalization. Notably, presence of anti-IFN autoantibodies in this critically ill COVID-19 cohort appeared to predict herpesvirus disease (caused by herpes simplex viruses types 1 and 2 (HSV-1/-2) and/or cytomegalovirus (CMV)), which has been linked to worse clinical outcomes. Indeed, all 7 tested COVID-19 patients with anti-IFN IgG in our cohort (100%) suffered from one or more herpesviruses, and analysis revealed that these patients were more likely to experience CMV than COVID-19 patients without anti-IFN autoantibodies, even when adjusting for age, gender, and systemic steroid treatment (odds ratio (OR) 7.28, 95% confidence interval (CI) 1.14 to 46.31, p = 0.036). As the IFN system deficiency caused by neutralizing anti-IFN autoantibodies likely directly and indirectly exacerbates the likelihood of latent herpesvirus reactivations in critically ill patients, early diagnosis of anti-IFN IgG could be rapidly used to inform risk-group stratification and treatment options.</abstract><cop>San Francisco</cop><pub>Public Library of Science</pub><pmid>35788562</pmid><doi>10.1371/journal.pbio.3001709</doi><orcidid>https://orcid.org/0000-0002-3891-9480</orcidid><oa>free_for_read</oa></addata></record> |
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| issn | 1545-7885 1544-9173 1545-7885 |
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| subjects | Analysis Antiviral activity Autoantibodies Biology and Life Sciences Clinical outcomes Cloning Coronaviruses COVID-19 Critically ill Cytomegalovirus Discovery Report Disease Epidemics Gene expression Genetic aspects Health risks Health services Herpes Herpes simplex Herpes viruses Herpesvirus diseases Heterogeneity Hospitals Immunoglobulin A Immunoglobulin G Immunoglobulin M Influence Intensive care Interferon Medicine and Health Sciences Monoclonal antibodies Neutralizing Older people Patients Respiratory diseases Risk factors Secretions Severe acute respiratory syndrome Severe acute respiratory syndrome coronavirus 2 United States Viral diseases Viruses α-Interferon |
| title | Critically ill COVID-19 patients with neutralizing autoantibodies against type I interferons have increased risk of herpesvirus disease |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-13T17%3A06%3A39IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Critically%20ill%20COVID-19%20patients%20with%20neutralizing%20autoantibodies%20against%20type%20I%20interferons%20have%20increased%20risk%20of%20herpesvirus%20disease&rft.jtitle=PLoS%20biology&rft.au=Busnadiego,%20Idoia&rft.date=2022-07-05&rft.volume=20&rft.issue=7&rft.spage=e3001709&rft.epage=e3001709&rft.pages=e3001709-e3001709&rft.issn=1545-7885&rft.eissn=1545-7885&rft_id=info:doi/10.1371/journal.pbio.3001709&rft_dat=%3Cgale_plos_%3EA713615745%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2703198930&rft_id=info:pmid/35788562&rft_galeid=A713615745&rft_doaj_id=oai_doaj_org_article_b3408de1604843568c24aa541f6d426c&rfr_iscdi=true |