{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T06:47:47Z","timestamp":1789714067423,"version":"4.0.1"},"reference-count":64,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2022,9,7]],"date-time":"2022-09-07T00:00:00Z","timestamp":1662508800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ProA Capital and Startlite Foundation","award":["B2020\/MITICAD-CM"],"award-info":[{"award-number":["B2020\/MITICAD-CM"]}]},{"name":"ProA Capital and Startlite Foundation","award":["COVID-19 UAH 2019\/00003\/016\/001\/026"],"award-info":[{"award-number":["COVID-19 UAH 2019\/00003\/016\/001\/026"]}]},{"name":"ProA Capital and Startlite Foundation","award":["COVID-19 2021-2020\/00003\/016\/001\/027"],"award-info":[{"award-number":["COVID-19 2021-2020\/00003\/016\/001\/027"]}]},{"name":"Universidad de Alcala COVID-19 UAH","award":["B2020\/MITICAD-CM"],"award-info":[{"award-number":["B2020\/MITICAD-CM"]}]},{"name":"Universidad de Alcala COVID-19 UAH","award":["COVID-19 UAH 2019\/00003\/016\/001\/026"],"award-info":[{"award-number":["COVID-19 UAH 2019\/00003\/016\/001\/026"]}]},{"name":"Universidad de Alcala COVID-19 UAH","award":["COVID-19 2021-2020\/00003\/016\/001\/027"],"award-info":[{"award-number":["COVID-19 2021-2020\/00003\/016\/001\/027"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>SARS-CoV-2 is a new coronavirus characterized by a high infection and transmission capacity. A significant number of patients develop inadequate immune responses that produce massive releases of cytokines that compromise their survival. Soluble factors are clinically and pathologically relevant in COVID-19 survival but remain only partially characterized. The objective of this work was to simultaneously study 62 circulating soluble factors, including innate and adaptive cytokines and their soluble receptors, chemokines and growth and wound-healing\/repair factors, in severe COVID-19 patients who survived compared to those with fatal outcomes. Serum samples were obtained from 286 COVID-19 patients and 40 healthy controls. The 62 circulating soluble factors were quantified using a Luminex Milliplex assay. Results. The patients who survived had decreased levels of the following 30 soluble factors of the 62 studied compared to those with fatal outcomes, therefore, these decreases were observed for cytokines and receptors predominantly produced by the innate immune system\u2014IL-1\u03b1, IL-1\u03b1, IL-18, IL-15, IL-12p40, IL-6, IL-27, IL-1Ra, IL-1RI, IL-1RII, TNF\u03b1, TGF\u03b1, IL-10, sRAGE, sTNF-RI and sTNF-RII\u2014for the chemokines IL-8, IP-10, MCP-1, MCP-3, MIG and fractalkine; for the growth factors M-CSF and the soluble receptor sIL2Ra; for the cytokines involved in the adaptive immune system IFN\u03b3, IL-17 and sIL-4R; and for the wound-repair factor FGF2. On the other hand, the patients who survived had elevated levels of the soluble factors TNF\u03b2, sCD40L, MDC, RANTES, G-CSF, GM-CSF, EGF, PDGFAA and PDGFABBB compared to those who died. Conclusions. Increases in the circulating levels of the sCD40L cytokine; MDC and RANTES chemokines; the G-CSF and GM-CSF growth factors, EGF, PDGFAA and PDGFABBB; and tissue-repair factors are strongly associated with survival. By contrast, large increases in IL-15, IL-6, IL-18, IL-27 and IL-10; the sIL-1RI, sIL1RII and sTNF-RII receptors; the MCP3, IL-8, MIG and IP-10 chemokines; the M-CSF and sIL-2Ra growth factors; and the wound-healing factor FGF2 favor fatal outcomes of the disease.<\/jats:p>","DOI":"10.3390\/ijms231810344","type":"journal-article","created":{"date-parts":[[2022,9,8]],"date-time":"2022-09-08T01:40:13Z","timestamp":1662601213000},"page":"10344","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Role of Innate and Adaptive Cytokines in the Survival of COVID-19 Patients"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1775-4645","authenticated-orcid":false,"given":"Jorge","family":"Monserrat","sequence":"first","affiliation":[{"name":"Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcal\u00e1 de Henares, Spain"},{"name":"Ram\u00f3n y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"G\u00f3mez-Lahoz","sequence":"additional","affiliation":[{"name":"Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcal\u00e1 de Henares, Spain"},{"name":"Ram\u00f3n y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2588-1708","authenticated-orcid":false,"given":"Miguel","family":"Ortega","sequence":"additional","affiliation":[{"name":"Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcal\u00e1 de Henares, Spain"},{"name":"Ram\u00f3n y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain"},{"name":"Cancer Registry and Pathology Department, Hospital Universitario Principe de Asturias, 28806 Alcal\u00e1 de Henares, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3180-184X","authenticated-orcid":false,"given":"Jos\u00e9","family":"Sanz","sequence":"additional","affiliation":[{"name":"Service of Internal Medicine and Immune System Diseases-Rheumatology, University Hospital Pr\u00edncipe de Asturias (CIBEREHD), 28806 Alcal\u00e1 de Henares, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Service of Internal Medicine and Immune System Diseases-Rheumatology, University Hospital Pr\u00edncipe de Asturias (CIBEREHD), 28806 Alcal\u00e1 de Henares, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2563-7860","authenticated-orcid":false,"given":"Juan","family":"Ar\u00e9valo-Serrano","sequence":"additional","affiliation":[{"name":"Service of Internal Medicine and Immune System Diseases-Rheumatology, University Hospital Pr\u00edncipe de Asturias (CIBEREHD), 28806 Alcal\u00e1 de Henares, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8446-3373","authenticated-orcid":false,"given":"Jos\u00e9","family":"Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Service of Internal Medicine and Immune System Diseases-Rheumatology, University Hospital Pr\u00edncipe de Asturias (CIBEREHD), 28806 Alcal\u00e1 de Henares, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose","family":"Gasalla","sequence":"additional","affiliation":[{"name":"Service of Internal Medicine and Immune System Diseases-Rheumatology, University Hospital Pr\u00edncipe de Asturias (CIBEREHD), 28806 Alcal\u00e1 de Henares, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d3scar","family":"Gasulla","sequence":"additional","affiliation":[{"name":"Hospital Universitari de Bellvitge, Universitat de Barcelona, 08907 L\u2019Hospitalet de Llobregat, Spain"},{"name":"Department of Surgery, Medical and Social Sciences, Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcal\u00e1 de Henares, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Arranz","sequence":"additional","affiliation":[{"name":"Department of Surgery, Medical and Social Sciences, Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcal\u00e1 de Henares, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4181-1593","authenticated-orcid":false,"given":"Jordi","family":"Fortuny-Profit\u00f3s","sequence":"additional","affiliation":[{"name":"Campus Nord, Universitat Polit\u00e8cnica de Catalunya, 08034 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferran","family":"Mazaira-Font","sequence":"additional","affiliation":[{"name":"Departament d\u2019Econometria, Estad\u00edstica I Economia Aplicada, Universitat de Barcelona, 08007 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Teixid\u00f3 Rom\u00e1n","sequence":"additional","affiliation":[{"name":"Campus Nord, Universitat Polit\u00e8cnica de Catalunya, 08034 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2121-189X","authenticated-orcid":false,"given":"Carlos","family":"Mart\u00ednez-A","sequence":"additional","affiliation":[{"name":"Department of Immunology and Oncology, Centro Nacional de Biotecnolog\u00eda\/CSIC, 28006 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitri","family":"Balomenos","sequence":"additional","affiliation":[{"name":"Department of Immunology and Oncology, Centro Nacional de Biotecnolog\u00eda\/CSIC, 28006 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7898-4685","authenticated-orcid":false,"given":"Angel","family":"Asunsolo","sequence":"additional","affiliation":[{"name":"Ram\u00f3n y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain"},{"name":"Cancer Registry and Pathology Department, Hospital Universitario Principe de Asturias, 28806 Alcal\u00e1 de Henares, Spain"},{"name":"Department of Epidemiology and Biostatistics, Graduate School of Public Health and Health Policy, University of New York, New York, NY 10027, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1309-7510","authenticated-orcid":false,"given":"Melchor","family":"\u00c1lvarez-Mon","sequence":"additional","affiliation":[{"name":"Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcal\u00e1 de Henares, Spain"},{"name":"Ram\u00f3n y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain"},{"name":"Service of Internal Medicine and Immune System Diseases-Rheumatology, University Hospital Pr\u00edncipe de Asturias (CIBEREHD), 28806 Alcal\u00e1 de Henares, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the COVID-19 HUPA 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Engl. J. Med."},{"key":"ref_2","unstructured":"(2022, July 17). World Health Organization Fact Sheet. WHO Health Emergency Dashboard. Available online: https:\/\/extranet.who.int\/publicemergency."},{"key":"ref_3","first-page":"1917","article-title":"Role of the immune system in SARS-CoV-2 infection: Immunopathology of COVID-19","volume":"13","author":"Sanz","year":"2021","journal-title":"Medicine"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1038\/s41577-020-0311-8","article-title":"The trinity of COVID-19: Immunity, inflammation and intervention","volume":"20","author":"Tay","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.2147\/JIR.S301784","article-title":"Attenuating the Effects of Novel COVID-19 (SARS-CoV-2) Infection-Induced Cytokine Storm and the Implications","volume":"14","author":"Rowaiye","year":"2021","journal-title":"J. Inflamm. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2485","DOI":"10.2147\/IDR.S258639","article-title":"Role of Monocytes\/Macrophages in COVID-19 Pathogenesis: Implications for Therapy","volume":"13","author":"Salas","year":"2020","journal-title":"Infect. Drug Resist."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1038\/nrrheum.2015.179","article-title":"Macrophage activation syndrome in the era of biologic therapy","volume":"12","author":"Grom","year":"2016","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s41232-020-00131-w","article-title":"Macrophage activation syndrome and COVID-19","volume":"40","author":"Otsuka","year":"2020","journal-title":"Inflamm. Regen."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1146\/annurev-med-061813-012806","article-title":"Pathogenesis of macrophage activation syndrome and potential for cytokine-directed therapies","volume":"66","author":"Schulert","year":"2015","journal-title":"Annu. Rev. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"104799","DOI":"10.1016\/j.micpath.2021.104799","article-title":"The pro-inflammatory cytokines in COVID-19 pathogenesis: What goes wrong?","volume":"153","author":"Darif","year":"2021","journal-title":"Microb. Pathog."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e148980","DOI":"10.1172\/jci.insight.148980","article-title":"Cardiovascular complications of COVID-19","volume":"6","author":"Farshidfar","year":"2021","journal-title":"JCI Insight"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1111\/j.1365-2249.1992.tb07922.x","article-title":"Cytokine receptors: Structure and signal transduction","volume":"90","author":"Foxwell","year":"1992","journal-title":"Clin. Exp. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1038\/cmi.2018.9","article-title":"Chemokines: The past, the present and the future","volume":"15","author":"Tang","year":"2018","journal-title":"Cell Mol. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Zanza, C., Romenskaya, T., Manetti, A.C., Franceschi, F., La Russa, R., Bertozzi, G., Maiese, A., Savioli, G., Volonnino, G., and Longhitano, Y. (2022). Cytokine Storm in COVID-19: Immunopathogenesis and Therapy. Medicina, 58.","DOI":"10.3390\/medicina58020144"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"818890","DOI":"10.3389\/fcvm.2022.818890","article-title":"The Role of Interleukin-6 Family Members in Cardiovascular Diseases","volume":"9","author":"Feng","year":"2022","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/s41568-021-00363-z","article-title":"Interleukins in cancer: From biology to therapy","volume":"21","author":"Briukhovetska","year":"2021","journal-title":"Nat. Rev. Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"McInnes, I. (2013). Cytokines. Kelley\u2019s Textbook of Rheumatology, Elsevier Inc.","DOI":"10.1016\/B978-1-4377-1738-9.00026-8"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Ozger, H.S., Karakus, R., Kuscu, E.N., Bagriacik, U.E., Oruklu, N., Yaman, M., Turkoglu, M., Erbas, G., Atak, A.Y., and Senol, E. (2021). Serial measurement of cytokines strongly predict COVID-19 outcome. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0260623"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1038\/nri.2017.49","article-title":"Chemokines in the cancer microenvironment and their relevance in cancer immunotherapy","volume":"17","author":"Nagarsheth","year":"2017","journal-title":"Nat. Rev. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"832394","DOI":"10.3389\/fimmu.2022.832394","article-title":"The Role of Cytokines and Chemokines in Severe Acute Respiratory Syndrome Coronavirus 2 Infections","volume":"13","author":"Hsu","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1016\/j.csbj.2021.01.034","article-title":"Chemokines and chemokine receptors during COVID-19 infection","volume":"19","author":"Khalil","year":"2021","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1038\/s41577-020-0331-4","article-title":"Pathological inflammation in patients with COVID-19: A key role for monocytes and macrophages","volume":"20","author":"Merad","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Meizlish, M.L., Pine, A.B., Goshua, G., Chang, C.H., Zhang, H., Bishai, J., Bahel, P., Patel, A., Gbyli, R., and Kwan, J. (2020). Circulating Markers of Angiogenesis and Endotheliopathy in COVID-19. medRxiv.","DOI":"10.1101\/2020.06.29.20140376"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1002\/JLB.3COVA0820-410RRR","article-title":"Cytokine release syndrome in COVID-19: Innate immune, vascular, and platelet pathogenic factors differ in severity of disease and sex","volume":"109","author":"Petrey","year":"2021","journal-title":"J. Leukoc. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Tamayo-Velasco, A., Mart\u00ednez-Paz, P., Pe\u00f1arrubia-Ponce, M., de la Fuente, I., P\u00e9rez-Gonz\u00e1lez, S., Fern\u00e1ndez, I., Due\u00f1as, C., G\u00f3mez-S\u00e1nchez, E., Lorenzo-L\u00f3pez, M., and G\u00f3mez-Pesquera, E. (2021). HGF, IL-1\u03b1, and IL-27 Are Robust Biomarkers in Early Severity Stratification of COVID-19 Patients. J. Clin. Med., 10.","DOI":"10.21203\/rs.3.rs-374650\/v1"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"20793","DOI":"10.1038\/s41598-021-00190-0","article-title":"Cytokine signature and COVID-19 prediction models in the two waves of pandemics","volume":"11","author":"Cabaro","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"702507","DOI":"10.3389\/fcvm.2021.702507","article-title":"IL-10 and IL-12 (P70) Levels Predict the Risk of COVID-19 Progression in Hypertensive Patients: Insights From the BRACE-CORONA Trial","volume":"8","author":"Macedo","year":"2021","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"eabe3024","DOI":"10.1126\/sciadv.abe3024","article-title":"Distinct inflammatory profiles distinguish COVID-19 from influenza with limited contributions from cytokine storm","volume":"6","author":"Mudd","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.cmi.2020.09.051","article-title":"A whole blood test to measure SARS-CoV-2-specific response in COVID-19 patients","volume":"27","author":"Petrone","year":"2021","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1002\/med.21756","article-title":"SARS-CoV-2-mediated immune system activation and potential application in immunotherapy","volume":"41","author":"Tan","year":"2021","journal-title":"Med. Res. Rev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"103317","DOI":"10.1016\/j.ebiom.2021.103317","article-title":"Plasma biomarker profiling of PIMS-TS, COVID-19 and SARS-CoV2 seropositive children\u2014A cross-sectional observational study from southern India","volume":"66","author":"Venkataraman","year":"2021","journal-title":"EBioMedicine"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Youngs, J., Provine, N.M., Lim, N., Sharpe, H.R., Amini, A., Chen, Y.-L., Luo, J., Edmans, M.D., Zacharopoulou, P., and Chen, W. (2021). Identification of immune correlates of fatal outcomes in critically ill COVID-19 patients. PLoS Pathog., 17.","DOI":"10.1371\/journal.ppat.1009804"},{"key":"ref_33","unstructured":"World Health Organization (2022, July 17). Director-General\u2019s Remarks at the Media Briefing on 2019-nCoV on 11 February 2020. Available online: https:\/\/www.who.int\/director-general\/speeches\/detail\/who-director-general-s-remarks-at-the-media-briefing-on-2019-ncov-on-11-february-2020."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1186\/s10020-020-00230-x","article-title":"IP-10 and MCP-1 as biomarkers associated with disease severity of COVID-19","volume":"26","author":"Chen","year":"2020","journal-title":"Mol. Med."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Jang, H.J., Leem, A.Y., Chung, K.S., Ahn, J.Y., Jung, J.Y., Kang, Y.A., Park, M.S., Kim, Y.S., and Lee, S.H. (2021). Soluble IL-2R Levels Predict in-Hospital Mortality in COVID-19 Patients with Respiratory Failure. J. Clin. Med., 10.","DOI":"10.21203\/rs.3.rs-709180\/v1"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Monserrat, J., Asunsolo, A., G\u00f3mez-Lahoz, A., Ortega, M.A., Gasalla, J.M., Gasulla, \u00d3., Fortuny-Profit\u00f3s, J., Mazaira-Font, F.A., Teixid\u00f3 Rom\u00e1n, M., and Arranz, A. (2021). Impact of the Innate Inflammatory Response on ICU Admission and Death in Hospitalized Patients with COVID-19. Biomedicines, 9.","DOI":"10.3390\/biomedicines9111675"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.ijid.2020.10.003","article-title":"A score combining early detection of cytokines accurately predicts COVID-19 severity and intensive care unit transfer","volume":"101","author":"Nagant","year":"2020","journal-title":"Int. J. Infect. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.jaci.2020.04.027","article-title":"Plasma IP-10 and MCP-3 levels are highly associated with disease severity and predict the progression of COVID-19","volume":"146","author":"Yang","year":"2020","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1038\/s41584-019-0277-8","article-title":"The IL-1 family of cytokines and receptors in rheumatic diseases","volume":"15","author":"Dinarello","year":"2019","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1016\/j.immuni.2019.03.012","article-title":"Interleukin-1 and Related Cytokines in the Regulation of Inflammation and Immunity","volume":"50","author":"Mantovani","year":"2019","journal-title":"Immunity"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Challagundla, N., Saha, B., and Agrawal-Rajput, R. (2022). Insights into inflammasome regulation: Cellular, molecular, and pathogenic control of inflammasome activation. Immunol. Res., 1\u201329.","DOI":"10.1007\/s12026-022-09286-9"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.cytogfr.2015.07.004","article-title":"Interleukin-6: Biology, signaling and strategies of blockade","volume":"26","author":"Schaper","year":"2015","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.cyto.2014.05.024","article-title":"Interleukin-6 and its receptors: A highly regulated and dynamic system","volume":"70","author":"Wolf","year":"2014","journal-title":"Cytokine"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Marc, F., Moldovan, C.M., Hoza, A., Magheru, S., Ciavoi, G., Farcas, D.M., Sachelarie, L., Calin, G., Romila, L., and Damir, D. (2022). Comparative Study of Cytokine Storm Treatment in Patients with COVID-19 Pneumonia Using Immunomodulators. J. Clin. Med., 11.","DOI":"10.3390\/jcm11102945"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1186\/s42269-022-00781-5","article-title":"Could anakinra outmatch dexamethasone\/tocilizumab in COVID-19?","volume":"46","author":"Gupta","year":"2022","journal-title":"Bull Natl. Res. Cent."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e24434","DOI":"10.1002\/jcla.24434","article-title":"Anakinra treatment efficacy in reduction of inflammatory biomarkers in COVID-19 patients: A meta-analysis","volume":"36","author":"Naveed","year":"2022","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"479","DOI":"10.3389\/fimmu.2016.00479","article-title":"Expanding Diversity in Molecular Structures and Functions of the IL-6\/IL-12 Heterodimeric Cytokine Family","volume":"7","author":"Hasegawa","year":"2016","journal-title":"Front. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"930","DOI":"10.3389\/fimmu.2017.00930","article-title":"Developmental and Functional Control of Natural Killer Cells by Cytokines","volume":"8","author":"Wu","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1016\/j.humimm.2011.07.311","article-title":"Interleukin (IL)-2 and IL-15 have different effects on human natural killer lymphocytes","volume":"72","author":"Pillet","year":"2011","journal-title":"Hum. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1111\/imr.12757","article-title":"Exploring the complex role of chemokines and chemoattractants in vivo on leukocyte dynamics","volume":"289","author":"David","year":"2019","journal-title":"Immunol. Rev."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1146\/annurev-immunol-032713-120145","article-title":"Chemokines and chemokine receptors: Positioning cells for host defense and immunity","volume":"32","author":"Griffith","year":"2014","journal-title":"Annu. Rev. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"241","DOI":"10.3389\/fpsyt.2018.00241","article-title":"Revisiting the Role of Eotaxin-1\/CCL11 in Psychiatric Disorders","volume":"9","author":"Teixeira","year":"2018","journal-title":"Front. Psychiatry"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"104569","DOI":"10.1016\/j.meegid.2020.104569","article-title":"Role of Fractalkine in promoting inflammation in sepsis-induced multiple organ dysfunction","volume":"85","author":"Chen","year":"2020","journal-title":"Infect. Genet. Evol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"110570","DOI":"10.1016\/j.mehy.2021.110570","article-title":"Could SARS-CoV-2 blocking of ACE2 in endothelial cells result in upregulation of CX3CL1, promoting thrombosis in COVID-19 patients?","volume":"151","author":"Valdes","year":"2021","journal-title":"Med. Hypotheses"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1984","DOI":"10.1002\/pro.3519","article-title":"The molecular details of cytokine signaling via the JAK\/STAT pathway","volume":"27","author":"Morris","year":"2018","journal-title":"Protein Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1038\/s41584-021-00707-x","article-title":"Interleukin-2 and regulatory T cells in rheumatic diseases","volume":"17","author":"Kolios","year":"2021","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1159\/000510352","article-title":"G-CSF and GM-CSF Are Different. Which One Is Better for COVID-19?","volume":"144","author":"Lazarus","year":"2021","journal-title":"Acta Haematol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"a028449","DOI":"10.1101\/cshperspect.a028449","article-title":"The Common Cytokine Receptor gamma Chain Family of Cytokines","volume":"10","author":"Lin","year":"2018","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1186\/s12985-021-01561-9","article-title":"Lymphocyte-monocyte-neutrophil index: A predictor of severity of coronavirus disease 2019 patients produced by sparse principal component analysis","volume":"18","author":"Qi","year":"2021","journal-title":"Virol. J."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.cell.2021.01.007","article-title":"Adaptive immunity to SARS-CoV-2 and COVID-19","volume":"184","author":"Sette","year":"2021","journal-title":"Cell"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2063","DOI":"10.3389\/fimmu.2020.02063","article-title":"Excessive Neutrophils and Neutrophil Extracellular Traps in COVID-19","volume":"11","author":"Wang","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1046\/j.1365-3148.2001.00340.x","article-title":"Platelet chemokines and their receptors: What is their relevance to platelet storage and transfusion practice?","volume":"11","author":"Boehlen","year":"2001","journal-title":"Transfus. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.blre.2009.04.001","article-title":"Platelet \u03b1-granules: Basic biology and clinical correlates","volume":"23","author":"Blair","year":"2009","journal-title":"Blood Rev."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s41232-020-00146-3","article-title":"How COVID-19 induces cytokine storm with high mortality","volume":"40","author":"Hojyo","year":"2020","journal-title":"Inflamm. Regen."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/18\/10344\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:25:18Z","timestamp":1760142318000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/18\/10344"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,7]]},"references-count":64,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2022,9]]}},"alternative-id":["ijms231810344"],"URL":"https:\/\/doi.org\/10.3390\/ijms231810344","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,7]]}}}