Serial measurement of cytokines strongly predict COVID-19 outcome
Purpose Cytokines are major mediators of COVID-19 pathogenesis and several of them are already being regarded as predictive markers for the clinical course and outcome of COVID-19 cases. A major pitfall of many COVID-19 cytokine studies is the lack of a benchmark sampling timing. Since cytokines and...
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| creator | Ozger, Hasan Selcuk Karakus, Resul Kuscu, Elif Nazli Bagriacik, Umit Emin Oruklu, Nihan Yaman, Melek Turkoglu, Melda Erbas, Gonca Atak, Aysegul Yucel Senol, Esin |
| description | Purpose Cytokines are major mediators of COVID-19 pathogenesis and several of them are already being regarded as predictive markers for the clinical course and outcome of COVID-19 cases. A major pitfall of many COVID-19 cytokine studies is the lack of a benchmark sampling timing. Since cytokines and their relative change during an infectious disease course is quite dynamic, we evaluated the predictive value of serially measured cytokines for COVID-19 cases. Methods In this single-center, prospective study, a broad spectrum of cytokines were determined by multiplex ELISA assay in samples collected at admission and at the third day of hospitalization. Appropriateness of cytokine levels in predicting mortality were assessed by receiver-operating characteristic (ROC) analyses for both sampling times in paralel to conventional biomarkers. Results At both sampling points, higher levels of IL-6, IL-7, IL-10, IL-15, IL-27 IP-10, MCP-1, and GCSF were found to be more predictive for mortality (p |
| doi_str_mv | 10.1371/journal.pone.0260623 |
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A major pitfall of many COVID-19 cytokine studies is the lack of a benchmark sampling timing. Since cytokines and their relative change during an infectious disease course is quite dynamic, we evaluated the predictive value of serially measured cytokines for COVID-19 cases. Methods In this single-center, prospective study, a broad spectrum of cytokines were determined by multiplex ELISA assay in samples collected at admission and at the third day of hospitalization. Appropriateness of cytokine levels in predicting mortality were assessed by receiver-operating characteristic (ROC) analyses for both sampling times in paralel to conventional biomarkers. Results At both sampling points, higher levels of IL-6, IL-7, IL-10, IL-15, IL-27 IP-10, MCP-1, and GCSF were found to be more predictive for mortality (p<0.05). Some of these cytokines, such as IL-6, IL-10, IL-7 and GCSF, had higher sensitivity and specificity in predicting mortality. AUC values of IL-6, IL-10, IL-7 and GCSF were 0.85 (0.65 to 0.92), 0.88 (0.73 to 0.96), 0.80 (0.63 to 0.91) and 0.86 (0.70 to 0.95), respectively at hospital admission. Compared to hospital admission, on the 3rd day of hospitalization serum levels of IL-6 and, IL-10 decreased significantly in the survivor group, unlike the non-survivor group (IL-6, p = 0.015, and IL-10, p = 0.016). Conclusion Our study results suggest that single-sample-based cytokine analyzes can be misleading and that cytokine levels measured serially at different sampling times provide a more precise and accurate estimate for the outcome of COVID-19 patients.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0260623</identifier><identifier>PMID: 34855834</identifier><language>eng</language><publisher>San Francisco: Public Library of Science</publisher><subject>Biology and Life Sciences ; Biomarkers ; Chemokines ; Coronaviruses ; COVID-19 ; Cytokines ; Enzyme-linked immunosorbent assay ; Health aspects ; Hospitalization ; Immunology ; Infections ; Infectious diseases ; Interleukin 10 ; Interleukin 15 ; Interleukin 27 ; Interleukin 6 ; Interleukin 7 ; IP-10 protein ; Measurement ; Medicine ; Medicine and Health Sciences ; Monocyte chemoattractant protein 1 ; Mortality ; Normal distribution ; Pathogenesis ; Pneumonia ; Proteins ; Public health ; Respiratory diseases ; Sampling ; Serum levels ; Severe acute respiratory syndrome coronavirus 2 ; Tumor necrosis factor-TNF</subject><ispartof>PloS one, 2021-12, Vol.16 (12), p.e0260623-e0260623</ispartof><rights>COPYRIGHT 2021 Public Library of Science</rights><rights>2021 Ozger 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>2021 Ozger et al 2021 Ozger et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c669t-8b3c36486ae7203f5fc589e1536921cafdf783d82768af29a7464a66a75e8bf23</citedby><cites>FETCH-LOGICAL-c669t-8b3c36486ae7203f5fc589e1536921cafdf783d82768af29a7464a66a75e8bf23</cites><orcidid>0000-0003-2654-6119 ; 0000-0003-3894-0092</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/PMC8639000/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8639000/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2100,2926,23865,27923,27924,53790,53792,79371,79372</link.rule.ids></links><search><contributor>Ito, Etsuro</contributor><creatorcontrib>Ozger, Hasan Selcuk</creatorcontrib><creatorcontrib>Karakus, Resul</creatorcontrib><creatorcontrib>Kuscu, Elif Nazli</creatorcontrib><creatorcontrib>Bagriacik, Umit Emin</creatorcontrib><creatorcontrib>Oruklu, Nihan</creatorcontrib><creatorcontrib>Yaman, Melek</creatorcontrib><creatorcontrib>Turkoglu, Melda</creatorcontrib><creatorcontrib>Erbas, Gonca</creatorcontrib><creatorcontrib>Atak, Aysegul Yucel</creatorcontrib><creatorcontrib>Senol, Esin</creatorcontrib><title>Serial measurement of cytokines strongly predict COVID-19 outcome</title><title>PloS one</title><description>Purpose Cytokines are major mediators of COVID-19 pathogenesis and several of them are already being regarded as predictive markers for the clinical course and outcome of COVID-19 cases. A major pitfall of many COVID-19 cytokine studies is the lack of a benchmark sampling timing. Since cytokines and their relative change during an infectious disease course is quite dynamic, we evaluated the predictive value of serially measured cytokines for COVID-19 cases. Methods In this single-center, prospective study, a broad spectrum of cytokines were determined by multiplex ELISA assay in samples collected at admission and at the third day of hospitalization. Appropriateness of cytokine levels in predicting mortality were assessed by receiver-operating characteristic (ROC) analyses for both sampling times in paralel to conventional biomarkers. Results At both sampling points, higher levels of IL-6, IL-7, IL-10, IL-15, IL-27 IP-10, MCP-1, and GCSF were found to be more predictive for mortality (p<0.05). Some of these cytokines, such as IL-6, IL-10, IL-7 and GCSF, had higher sensitivity and specificity in predicting mortality. AUC values of IL-6, IL-10, IL-7 and GCSF were 0.85 (0.65 to 0.92), 0.88 (0.73 to 0.96), 0.80 (0.63 to 0.91) and 0.86 (0.70 to 0.95), respectively at hospital admission. Compared to hospital admission, on the 3rd day of hospitalization serum levels of IL-6 and, IL-10 decreased significantly in the survivor group, unlike the non-survivor group (IL-6, p = 0.015, and IL-10, p = 0.016). Conclusion Our study results suggest that single-sample-based cytokine analyzes can be misleading and that cytokine levels measured serially at different sampling times provide a more precise and accurate estimate for the outcome of COVID-19 patients.</description><subject>Biology and Life Sciences</subject><subject>Biomarkers</subject><subject>Chemokines</subject><subject>Coronaviruses</subject><subject>COVID-19</subject><subject>Cytokines</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Health aspects</subject><subject>Hospitalization</subject><subject>Immunology</subject><subject>Infections</subject><subject>Infectious diseases</subject><subject>Interleukin 10</subject><subject>Interleukin 15</subject><subject>Interleukin 27</subject><subject>Interleukin 6</subject><subject>Interleukin 7</subject><subject>IP-10 protein</subject><subject>Measurement</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Monocyte chemoattractant protein 1</subject><subject>Mortality</subject><subject>Normal distribution</subject><subject>Pathogenesis</subject><subject>Pneumonia</subject><subject>Proteins</subject><subject>Public health</subject><subject>Respiratory diseases</subject><subject>Sampling</subject><subject>Serum levels</subject><subject>Severe acute respiratory syndrome coronavirus 2</subject><subject>Tumor necrosis 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measurement of cytokines strongly predict COVID-19 outcome</title><author>Ozger, Hasan Selcuk ; Karakus, Resul ; Kuscu, Elif Nazli ; Bagriacik, Umit Emin ; Oruklu, Nihan ; Yaman, Melek ; Turkoglu, Melda ; Erbas, Gonca ; Atak, Aysegul Yucel ; Senol, Esin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c669t-8b3c36486ae7203f5fc589e1536921cafdf783d82768af29a7464a66a75e8bf23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Biology and Life Sciences</topic><topic>Biomarkers</topic><topic>Chemokines</topic><topic>Coronaviruses</topic><topic>COVID-19</topic><topic>Cytokines</topic><topic>Enzyme-linked immunosorbent assay</topic><topic>Health aspects</topic><topic>Hospitalization</topic><topic>Immunology</topic><topic>Infections</topic><topic>Infectious diseases</topic><topic>Interleukin 10</topic><topic>Interleukin 15</topic><topic>Interleukin 27</topic><topic>Interleukin 6</topic><topic>Interleukin 7</topic><topic>IP-10 protein</topic><topic>Measurement</topic><topic>Medicine</topic><topic>Medicine and Health Sciences</topic><topic>Monocyte chemoattractant protein 1</topic><topic>Mortality</topic><topic>Normal distribution</topic><topic>Pathogenesis</topic><topic>Pneumonia</topic><topic>Proteins</topic><topic>Public health</topic><topic>Respiratory diseases</topic><topic>Sampling</topic><topic>Serum levels</topic><topic>Severe acute respiratory syndrome coronavirus 2</topic><topic>Tumor necrosis factor-TNF</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ozger, Hasan Selcuk</creatorcontrib><creatorcontrib>Karakus, Resul</creatorcontrib><creatorcontrib>Kuscu, Elif Nazli</creatorcontrib><creatorcontrib>Bagriacik, Umit Emin</creatorcontrib><creatorcontrib>Oruklu, Nihan</creatorcontrib><creatorcontrib>Yaman, Melek</creatorcontrib><creatorcontrib>Turkoglu, Melda</creatorcontrib><creatorcontrib>Erbas, 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Esin</au><au>Ito, Etsuro</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Serial measurement of cytokines strongly predict COVID-19 outcome</atitle><jtitle>PloS one</jtitle><date>2021-12-02</date><risdate>2021</risdate><volume>16</volume><issue>12</issue><spage>e0260623</spage><epage>e0260623</epage><pages>e0260623-e0260623</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Purpose Cytokines are major mediators of COVID-19 pathogenesis and several of them are already being regarded as predictive markers for the clinical course and outcome of COVID-19 cases. A major pitfall of many COVID-19 cytokine studies is the lack of a benchmark sampling timing. Since cytokines and their relative change during an infectious disease course is quite dynamic, we evaluated the predictive value of serially measured cytokines for COVID-19 cases. Methods In this single-center, prospective study, a broad spectrum of cytokines were determined by multiplex ELISA assay in samples collected at admission and at the third day of hospitalization. Appropriateness of cytokine levels in predicting mortality were assessed by receiver-operating characteristic (ROC) analyses for both sampling times in paralel to conventional biomarkers. Results At both sampling points, higher levels of IL-6, IL-7, IL-10, IL-15, IL-27 IP-10, MCP-1, and GCSF were found to be more predictive for mortality (p<0.05). Some of these cytokines, such as IL-6, IL-10, IL-7 and GCSF, had higher sensitivity and specificity in predicting mortality. AUC values of IL-6, IL-10, IL-7 and GCSF were 0.85 (0.65 to 0.92), 0.88 (0.73 to 0.96), 0.80 (0.63 to 0.91) and 0.86 (0.70 to 0.95), respectively at hospital admission. Compared to hospital admission, on the 3rd day of hospitalization serum levels of IL-6 and, IL-10 decreased significantly in the survivor group, unlike the non-survivor group (IL-6, p = 0.015, and IL-10, p = 0.016). Conclusion Our study results suggest that single-sample-based cytokine analyzes can be misleading and that cytokine levels measured serially at different sampling times provide a more precise and accurate estimate for the outcome of COVID-19 patients.</abstract><cop>San Francisco</cop><pub>Public Library of Science</pub><pmid>34855834</pmid><doi>10.1371/journal.pone.0260623</doi><tpages>e0260623</tpages><orcidid>https://orcid.org/0000-0003-2654-6119</orcidid><orcidid>https://orcid.org/0000-0003-3894-0092</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Biology and Life Sciences Biomarkers Chemokines Coronaviruses COVID-19 Cytokines Enzyme-linked immunosorbent assay Health aspects Hospitalization Immunology Infections Infectious diseases Interleukin 10 Interleukin 15 Interleukin 27 Interleukin 6 Interleukin 7 IP-10 protein Measurement Medicine Medicine and Health Sciences Monocyte chemoattractant protein 1 Mortality Normal distribution Pathogenesis Pneumonia Proteins Public health Respiratory diseases Sampling Serum levels Severe acute respiratory syndrome coronavirus 2 Tumor necrosis factor-TNF |
| title | Serial measurement of cytokines strongly predict COVID-19 outcome |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-13T02%3A10%3A37IST&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=Serial%20measurement%20of%20cytokines%20strongly%20predict%20COVID-19%20outcome&rft.jtitle=PloS%20one&rft.au=Ozger,%20Hasan%20Selcuk&rft.date=2021-12-02&rft.volume=16&rft.issue=12&rft.spage=e0260623&rft.epage=e0260623&rft.pages=e0260623-e0260623&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0260623&rft_dat=%3Cgale_plos_%3EA684621315%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=2605598851&rft_id=info:pmid/34855834&rft_galeid=A684621315&rft_doaj_id=oai_doaj_org_article_bb3ae35fbb6d4d17b41297cf5ca27795&rfr_iscdi=true |