{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T22:44:27Z","timestamp":1784673867460,"version":"3.55.0"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T00:00:00Z","timestamp":1732492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Cytokines and chemokines as crucial participants in innate immune response play significant roles during SARS-CoV-2 infection, yet excessive immune response exacerbates the severity of COVID-19.<\/jats:p><\/jats:sec><jats:sec><jats:title>Purpose<\/jats:title><jats:p>This study aims to investigate the involvement of which cytokines\/chemokines in the cytokine storm of COVID-19, as well as the changes in cytokine\/chemokine levels during the course of COVID-19, simultaneously exploring the diagnostic and prognostic value of the relevant cytokines\/chemokines for COVID-19.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Flow cytometry was employed to detect the levels of cytokines and chemokines in the serum of 50 COVID-19 patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared with severe COVID-19 patients, the levels of cytokines IL-6, IL-8, IL-10, sCD25, and chemokines IP-10 and MIG in the peripheral blood of non-severe patients were significantly reduced, while only IL-6, IL-10, and IP-10 levels were significantly decreased compared to non-survivors of COVID-19. Meanwhile, serum concentrations of IP-10, MCP-1, sTREM-1, IL-10, and the neutrophil-to-lymphocyte ratio (NLR) in peripheral blood could distinguish between COVID-19 survivors and non-survivors and were significantly associated with mortality. Among them, the concentration of IP-10 was shown to be the most powerful indicator for predicting adverse outcomes in COVID-19 patients (AUC: 0.715); however, its combined detection with the conventional inflammatory marker NLR did not improve the predictive value for adverse outcomes in COVID-19 patients. Additionally, serum IP-10 levels were negatively correlated with peripheral blood NK cell count and total lymphocyte count, while sTREM-1 levels were positively correlated with peripheral blood CD4+ T cell count and CD3+ T cell count. Meanwhile, IL-8 levels were positively correlated with total lymphocyte count in peripheral blood. Finally, the serum levels of cytokines\/chemokines in non-survivors of COVID-19 increased significantly before death, while in survivors, they returned to normal levels before discharge.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Severely ill and non-surviving COVID-19 patients exhibit compromised immune function, with significantly higher levels of inflammation, cytokine\/chemokine storms, and immune dysregulation compared to non-severe patients. Serum concentrations of IP-10, MCP-1, sTREM-1, and IL-10 levels can serve as biomarkers to predict adverse outcomes in COVID-19.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1464545","type":"journal-article","created":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T06:24:21Z","timestamp":1732515861000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Characteristics of cytokines\/chemokines associated with disease severity and adverse prognosis in COVID-19 patients"],"prefix":"10.3389","volume":"15","author":[{"given":"Jianghao","family":"Cheng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haozhen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaodan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhua","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingli","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,11,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","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":"B2","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1186\/s12985-022-01814-1","article-title":"COVID-19 infection: an overview on cytokine storm and related interventions","volume":"19","author":"Montazersaheb","year":"2022","journal-title":"Virol J"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30211-7","article-title":"Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study","volume":"395","author":"Chen","year":"2020","journal-title":"Lancet"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.202012421","article-title":"The role of interleukin-6 in monitoring severe case of coronavirus disease 2019","volume":"12","author":"Liu","year":"2020","journal-title":"EMBO Mol Med"},{"key":"B5","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1210\/er.2006-0044","article-title":"Role of chemokines in endocrine autoimmune diseases","volume":"28","author":"Rotondi","year":"2007","journal-title":"Endocrine Rev"},{"key":"B6","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1016\/j.ccell.2019.05.004","article-title":"Cooperation between constitutive and inducible chemokines enables T cell engraftment and immune attack in solid tumors","volume":"35","author":"Dangaj","year":"2019","journal-title":"Cancer Cell"},{"key":"B7","doi-asserted-by":"publisher","first-page":"144","DOI":"10.3390\/medicina58020144","article-title":"Cytokine storm in COVID-19: immunopathogenesis and therapy","volume":"58","author":"Zanza","year":"2022","journal-title":"Medicina (Kaunas Lithuania)"},{"key":"B8","doi-asserted-by":"publisher","first-page":"6777","DOI":"10.3390\/jcm11226777","article-title":"A retrospective assessment of laboratory findings and cytokine markers in severe SARS-CoV-2 infection among patients of roma population","volume":"11","author":"Mocanu","year":"2022","journal-title":"J Clin Med"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1093\/nsr\/nwaa037","article-title":"Elevated plasma levels of selective cytokines in COVID-19 patients reflect viral load and lung injury","volume":"7","author":"Liu","year":"2020","journal-title":"Natl Sci Rev"},{"key":"B10","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/j.mayocp.2020.10.022","article-title":"Clinical characteristics, treatment, and outcomes of critically ill patients with COVID-19: A scoping review","volume":"96","author":"Huang","year":"2021","journal-title":"Mayo Clinic Proc"},{"key":"B11","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.cyto.2018.11.018","article-title":"IP-10 is highly involved in HIV infection","volume":"115","author":"Lei","year":"2019","journal-title":"Cytokine"},{"key":"B12","doi-asserted-by":"publisher","first-page":"10942","DOI":"10.1038\/srep10942","article-title":"The serum profile of hypercytokinemia factors identified in H7N9-infected patients can predict fatal outcomes","volume":"5","author":"Guo","year":"2015","journal-title":"Sci Rep"},{"key":"B13","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1016\/j.jaci.2006.05.025","article-title":"Respiratory viral infections drive chemokine expression and exacerbate the asthmatic response","volume":"118","author":"Schaller","year":"2006","journal-title":"J Allergy Clin Immunol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005774","article-title":"Elevated basal pre-infection CXCL10 in plasma and in the small intestine after infection are associated with more rapid HIV\/SIV disease onset","volume":"12","author":"Ploquin","year":"2016","journal-title":"PLoS Pathog"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2014.01.001","article-title":"Predictive value of interferon-gamma inducible protein 10 kD for hepatitis B e antigen clearance and hepatitis B surface antigen decline during pegylated interferon alpha therapy in chronic hepatitis B patients","volume":"103","author":"Wang","year":"2014","journal-title":"Antiviral Res"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3390\/cimb46080525","article-title":"Dysregulated inflammatory cytokine levels may be useful markers in a better up-dated management of COVID-19","volume":"46","author":"Iuliano","year":"2024","journal-title":"Curr Issues Mol Biol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"3946320241279893","DOI":"10.1177\/03946320241279893","article-title":"Implication of IL-12A, IL-12B, IL-6, and TNF single-nucleotide polymorphisms in severity and susceptibility to COVID-19","volume":"38","author":"Benmansour","year":"2024","journal-title":"Int J immunopathology Pharmacol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.3A0414-232RR","article-title":"High IP-10 levels decrease T cell function in HIV-1-infected individuals on ART","volume":"96","author":"Ramirez","year":"2014","journal-title":"J leukocyte Biol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0903831","article-title":"CXC chemokine ligand (CXCL) 9 and CXCL10 are antagonistic costimulation molecules during the priming of alloreactive T cell effectors","volume":"184","author":"Rosenblum","year":"2010","journal-title":"J Immunol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.2016.5.issue-11","article-title":"CXCL9: evidence and contradictions for its role in tumor progression","volume":"5","author":"Ding","year":"2016","journal-title":"Cancer Med"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2002.07054.x","article-title":"Increased expression of T cell chemokines and their receptors in chronic hepatitis C: relationship with the histological activity of liver disease","volume":"97","author":"Apolinario","year":"2002","journal-title":"Am J Gastroenterol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1053457","article-title":"CCL2: An important cytokine in normal and pathological pregnancies: A review","volume":"13","author":"Lin","year":"2022","journal-title":"Front Immunol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0047748","article-title":"Soluble IL-2R\u03b1 (sCD25) exacerbates autoimmunity and enhances the development of Th17 responses in mice","volume":"7","author":"Russell","year":"2012","journal-title":"PLoS One"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.10.4991","article-title":"Cutting edge: inflammatory responses can be triggered by TREM-1, a novel receptor expressed on neutrophils and monocytes","volume":"164","author":"Bouchon","year":"2000","journal-title":"J Immunol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1080\/1354750X.2016.1204005","article-title":"Soluble TREM-1 as a diagnostic and prognostic biomarker in patients with septic shock: an observational clinical study","volume":"22","author":"Brenner","year":"2017","journal-title":"Biomarkers"},{"key":"B26","doi-asserted-by":"publisher","first-page":"738","DOI":"10.1186\/s12879-021-06457-1","article-title":"Associations of immunological features with COVID-19 severity: a systematic review and meta-analysis","volume":"21","author":"Zhang","year":"2021","journal-title":"BMC Infect Dis"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1007\/s12291-022-01108-x","article-title":"Dynamic changes in circulatory cytokines and chemokines levels in mild to severe COVID-19 patients","volume":"38","author":"Tiwari","year":"2023","journal-title":"Indian J Clin biochemistry: IJCB"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.9.5019-5025.2002","article-title":"Pneumococcal infections in humans are associated with increased apoptosis and trafficking of type 1 cytokine-producing T cells","volume":"70","author":"Kemp","year":"2002","journal-title":"Infection Immun"},{"key":"B29","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1159\/000514193","article-title":"SARS-CoV-2-associated T-cell responses in the presence of humoral immunodeficiency","volume":"182","author":"Gupta","year":"2021","journal-title":"Int Arch Allergy Immunol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"3410","DOI":"10.1038\/s41467-020-17240-2","article-title":"Immunological and inflammatory profiles in mild and severe cases of COVID-19","volume":"11","author":"Song","year":"2020","journal-title":"Nat Commun"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1002\/stem.170127","article-title":"Leukemia inhibitory factor, Interleukin 6, and other cytokines using the GP130 transducing receptor: roles in inflammation and injury","volume":"17","author":"Gadient","year":"1999","journal-title":"Stem Cells"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1084\/jem.180.4.1243","article-title":"Defective inflammatory response in interleukin 6-deficient mice","volume":"180","author":"Fattori","year":"1994","journal-title":"J Exp Med"},{"key":"B33","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/0014-5793(92)80909-Z","article-title":"Interleukin-8, a chemotactic and inflammatory cytokine","volume":"307","author":"Baggiolini","year":"1992","journal-title":"FEBS Lett"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1038\/nri2711","article-title":"The regulation of IL-10 production by immune cells","volume":"10","author":"Saraiva","year":"2010","journal-title":"Nat Rev Immunol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00827","article-title":"Reduction and functional exhaustion of T cells in patients with coronavirus disease 2019 (COVID-19)","volume":"11","author":"Diao","year":"2020","journal-title":"Front Immunol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1080\/22221751.2020.1770129","article-title":"Profiling serum cytokines in COVID-19 patients reveals IL-6 and IL-10 are disease severity predictors","volume":"9","author":"Han","year":"2020","journal-title":"Emerging Microbes infections"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30628-0","article-title":"COVID-19: consider cytokine storm syndromes and immunosuppression","volume":"395","author":"Mehta","year":"2020","journal-title":"Lancet"},{"key":"B38","doi-asserted-by":"publisher","first-page":"2434","DOI":"10.1016\/j.cell.2022.05.022","article-title":"Humoral and cellular immune memory to four COVID-19 vaccines","volume":"185","author":"Zhang","year":"2022","journal-title":"Cell"},{"key":"B39","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1111\/hdi.2015.19.issue-1","article-title":"Association between depression and inflammatory\/anti-inflammatory cytokines in chronic kidney disease and end-stage renal disease patients: a review of literature","volume":"19","author":"Taraz","year":"2015","journal-title":"Hemodialysis Int Symposium Home Hemodialysis"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1464545\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T06:24:22Z","timestamp":1732515862000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1464545\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,25]]},"references-count":39,"alternative-id":["10.3389\/fimmu.2024.1464545"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2024.1464545","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,25]]},"article-number":"1464545"}}