Unveiling COVID-19 Secrets: Harnessing Cytokines as Powerful Biomarkers for Diagnosis and Predicting Severity

References

• Tang Y, Liu J, Zhang D, Xu Z, Ji J, Wen C. Cytokine storm in COVID-19: the current evidence and treatment strategies. Front Immunol. 2020;11:11. doi:10.3389/fimmu.2020.01708
   PubMed Web of Science ®Google Scholar
• Costela-Ruiz VJ, Illescas-Montes R, Puerta-Puerta JM, Ruiz C, Melguizo-Rodríguez L. SARS-CoV-2 infection: the role of cytokines in COVID-19 disease. Cytokine Growth Factor Rev. 2020;54. doi:10.1016/j.cytogfr.2020.06.001
   Web of Science ®Google Scholar
• Soy M, Keser G, Atagündüz P. Pathogenesis and treatment of cytokine storm in covid-19. Turk J Biol. 2021;45(SI–1):372–389. doi:10.3906/biy-2105-37
   PubMedGoogle Scholar
• Kim JS, Lee JY, Yang JW, et al. Immunopathogenesis and treatment of cytokine storm in COVID-19. Theranostics. 2020;11(1). doi:10.7150/thno.49713
   Web of Science ®Google Scholar
• Valizadeh H, Abdolmohammadi-vahid S, Danshina S, et al. Nano-curcumin therapy, a promising method in modulating inflammatory cytokines in COVID-19 patients. Int Immunopharmacol. 2020:89. doi:10.1016/j.intimp.2020.107088
   Web of Science ®Google Scholar
• Choi JH, Lee YH, Kwon TW, Ko SG, Nah SY, Cho IH. Can Panax ginseng help control cytokine storm in COVID-19? J Ginseng Res. 2022;46(3):337–347. doi:10.1016/j.jgr.2022.02.006
   PubMed Web of Science ®Google Scholar
• Tang L, Yin Z, Hu Y, Mei H, Zhu L. Controlling Cytokine Storm Is Vital in COVID-19. Front Immunol. 2020;11:11. doi:10.3389/fimmu.2020.570993
   PubMed Web of Science ®Google Scholar
• Soy M, Keser G, Atagündüz P, Tabak F, Atagündüz I, Kayhan S. Cytokine storm in COVID-19: pathogenesis and overview of anti-inflammatory agents used in treatment. Clin Rheumatol. 2020;39(7):2085–2094. doi:10.1007/s10067-020-05190-5
   PubMed Web of Science ®Google Scholar
• Kutleša M. The cytokine storm and COVID-19. Medicus. 2020;29:2.
   Google Scholar
• Rodda LB, Netland J, Shehata L, et al. Functional SARS-CoV-2-specific immune memory persists after mild COVID-19. Cell. 2020;184(1):169–183.e17. doi:10.1016/J.CELL.2020.11.029
   PubMed Web of Science ®Google Scholar
• Conti P, Ronconi G, Caraffa A, et al. Induction of pro-inflammatory cytokines (IL-1 and IL-6) and lung inflammation by Coronavirus-19 (COVI-19 or SARS-CoV-2): anti-inflammatory strategies. J Biol Regul Homeost Agents. 2020;34(2):327–331. doi:10.23812/CONTI-E
   PubMed Web of Science ®Google Scholar
• Xiao T, Yan Z, Xiao S, Xia Y. Proinflammatory cytokines regulate epidermal stem cells in wound epithelialization. Stem Cell Res Ther. 2020;11(1). doi:10.1186/s13287-020-01755-y
   Web of Science ®Google Scholar
• Bradding P, Roberts JA, Britten KM, et al. Interleukin-4, −5, and −6 and tumor necrosis factor-alpha in normal and asthmatic airways: evidence for the human mast cell as a source of these cytokines. Am J Respir Cell Mol Biol. 1994;10(5):471–480. doi:10.1165/AJRCMB.10.5.8179909
   PubMed Web of Science ®Google Scholar
• Zanza C, Romenskaya T, Manetti AC, et al. Cytokine Storm in COVID-19: immunopathogenesis and Therapy. Medicina. 2022;58(2). doi:10.3390/medicina58020144
   Google Scholar
• Niles MA, Gogesch P, Kronhart S, et al. Macrophages and dendritic cells are not the major source of pro-inflammatory cytokines upon SARS-CoV-2 infection. Front Immunol. 2021:12. doi:10.3389/fimmu.2021.647824
   Google Scholar
• Song P, Li W, Xie J, Hou Y, You C. Cytokine storm induced by SARS-CoV-2. Clin. Chim. Acta. 2020;509. doi:10.1016/j.cca.2020.06.017
   Web of Science ®Google Scholar
• Olbei M, Hautefort I, Modos D, et al. SARS-CoV-2 Causes a different cytokine response compared to other cytokine storm-causing respiratory viruses in severely ill patients. Front Immunol. 2021:12. doi:10.3389/fimmu.2021.629193
   Google Scholar
• Pum A, Ennemoser M, Adage T, Kungl AJ. Cytokines and chemokines in SARS-CoV-2 infections—therapeutic strategies targeting cytokine storm. Biomolecules. 2021;11(1):91. doi:10.3390/biom11010091
   PubMed Web of Science ®Google Scholar
• Ngo B, Lapp SA, Siegel B, et al. Cerebrospinal fluid cytokine, chemokine, and SARS-CoV-2 antibody profiles in children with neuropsychiatric symptoms associated with COVID-19. Mult Scler Relat Disord. 2021:55. doi:10.1016/j.msard.2021.103169
   Web of Science ®Google Scholar
• Sherwani S, Khan MWA. Cytokine response in SARS-CoV-2 infection in the Elderly. J Inflamm Res. 2020;13. doi:10.2147/JIR.S276091
   Web of Science ®Google Scholar
• Zhang L, Xu D, Zhang T, Hou W, Yixi L. Correlation between interleukin-6, interleukin-8, and modified early warning score of patients with acute ischemic stroke and their condition and prognosis. Ann Palliat Med. 2021;10(1). doi:10.21037/apm-20-2200
   Web of Science ®Google Scholar
• Kosidło JW, Wolszczak-Biedrzycka B, Dymicka-Piekarska V, Dorf J, Matowicka-Karna J. Clinical significance and diagnostic utility of NLR, LMR, PLR and SII in the Course of COVID-19: a Literature Review. J Inflamm Res. 2023;16:539–562. doi:10.2147/JIR.S395331
   PubMed Web of Science ®Google Scholar
• Hasanvand A. COVID-19 and the role of cytokines in this disease. Inflammopharmacology. 2022;30(3):789–798. doi:10.1007/s10787-022-00992-2
   PubMed Web of Science ®Google Scholar
• Potere N, Batticciotto A, Vecchié A, et al. The role of IL-6 and IL-6 blockade in COVID-19. Expert Rev Clin Immunol. 2021;17(6):601–618. doi:10.1080/1744666X.2021.1919086
   PubMed Web of Science ®Google Scholar
• Wang X, Tang G, Liu Y, et al. The role of IL-6 in coronavirus, especially in COVID-19. Front Pharmacol. 2022:13. doi:10.3389/fphar.2022.1033674
   Web of Science ®Google Scholar
• Smail SW, Babaei E, Amin K, Abdulahad WH. Serum IL-23, IL-10, and TNF-α predict in-hospital mortality in COVID-19 patients. Front Immunol. 2023;14:1145840. doi:10.3389/FIMMU.2023.1145840/BIBTEX
   PubMedGoogle Scholar
• Du P, Geng J, Wang F, Chen X, Huang Z, Wang Y. Role of IL-6 inhibitor in treatment of COVID-19-related cytokine release syndrome. Int J Med Sci. 2021;18(6):1356–1362. doi:10.7150/ijms.53564
   PubMed Web of Science ®Google Scholar
• Kunnumakkara AB, Rana V, Parama D, et al. COVID-19, cytokines, inflammation, and spices: how are they related? Life Sci. 2021:284. doi:10.1016/j.lfs.2021.119201
   Web of Science ®Google Scholar
• Flisiak R, Parczewski M, Horban A, et al. Management of SARS-CoV-2 infection: recommendations of the Polish association of epidemiologists and infectiologists. Annex no. 2 as of October 13, 2020. Pol Arch Intern Med. 2020;130(10):915–918. doi:10.20452/PAMW.15658
   PubMedGoogle Scholar
• Wolszczak-Biedrzycka B, Dorf J, Milewska A, et al. The diagnostic value of inflammatory markers (CRP, IL6, CRP/IL6, CRP/L, LCR) for assessing the severity of COVID-19 symptoms based on the MEWS and predicting the risk of mortality. J Inflamm Res. 2023;16:2173–2188. doi:10.2147/jir.s406658
   PubMed Web of Science ®Google Scholar
• Dymicka-Piekarska V, Dorf J, Milewska A, et al. Neutrophil/Lymphocyte Ratio (NLR) and Lymphocyte/Monocyte Ratio (LMR) – risk of death inflammatory biomarkers in patients with COVID-19. J Inflamm Res. 2023;16:2209–2222. doi:10.2147/jir.s409871
   PubMed Web of Science ®Google Scholar
• Shawcross DL, Davies NA, Williams R, Jalan R. Systemic inflammatory response exacerbates the neuropsychological effects of induced hyperammonemia in cirrhosis. J Hepatol. 2004;40(2):247–254. doi:10.1016/j.jhep.2003.10.016
   PubMed Web of Science ®Google Scholar
• Lu Q, Zhu Z, Tan C, et al. Changes of serum IL-10, IL-1β, IL-6, MCP-1, TNF-α, IP-10 and IL-4 in COVID-19 patients. Int J Clin Pract. 2021;75(9). doi:10.1111/ijcp.14462
   Web of Science ®Google Scholar
• Potere N, Del Buono MG, Caricchio R, et al. Interleukin-1 and the NLRP3 inflammasome in COVID-19: pathogenetic and therapeutic implications: IL-1 and NLRP3 inflammasome in COVID-19. EBioMedicine. 2022:85. doi:10.1016/j.ebiom.2022.104299
   Web of Science ®Google Scholar
• Della-Torre E, Lanzillotta M, Campochiaro C, et al. Respiratory impairment predicts response to IL-1 and IL-6 Blockade in COVID-19 patients with severe pneumonia and hyper-inflammation. Front Immunol. 2021:12. doi:10.3389/fimmu.2021.675678
   Web of Science ®Google Scholar
• Liu J, Li S, Liu J, et al. Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients. EBioMedicine. 2020:55. doi:10.1016/j.ebiom.2020.102763
   Web of Science ®Google Scholar
• Cavalli G, Dagna L. The right place for IL-1 inhibition in COVID-19. Lancet Respir Med. 2021;9(3):223–224. doi:10.1016/S2213-2600(21)00035-7
   PubMed Web of Science ®Google Scholar
• Satış H, Özger HS, Aysert Yıldız P, et al. Prognostic value of interleukin-18 and its association with other inflammatory markers and disease severity in COVID-19. Cytokine. 2021:137. doi:10.1016/j.cyto.2020.155302
   Web of Science ®Google Scholar
• Kerget B, Kerget F, Aksakal A, Aşkın S, Sağlam L, Akgün M. Evaluation of alpha defensin, IL-1 receptor antagonist, and IL-18 levels in COVID-19 patients with macrophage activation syndrome and acute respiratory distress syndrome. J Med Virol. 2021;93(4):2090–2098. doi:10.1002/jmv.26589
   PubMed Web of Science ®Google Scholar
• Li S, Jiang L, Beckmann K, et al. A novel anti-human IL-1R7 antibody reduces IL-18-mediated inflammatory signaling. J Biol Chem. 2021:296. doi:10.1016/J.JBC.2021.100630
   Web of Science ®Google Scholar
• Coutinho LLC, Oliveira CN, Albuquerque PLMM, et al. Elevated IL-18 predicts poor prognosis in critically ill COVID-19 patients at a Brazilian hospital in 2020–21. Future Microbiol. 2022;17(16):1287–1294. doi:10.2217/fmb-2022-0057
   PubMed Web of Science ®Google Scholar
• Tao W, Zhang G, Wang X, et al. Analysis of the intestinal microbiota in COVID-19 patients and its correlation with the inflammatory factor IL-18. Med Microecol. 2020:5. doi:10.1016/j.medmic.2020.100023
   Google Scholar
• Smail SW, Babaei E, Amin K. Ct, IL-18 polymorphism, and laboratory biomarkers for predicting chemosensory dysfunctions and mortality in COVID-19. Future Sci OA. 2023;9(2). doi:10.2144/FSOA-2022-0082/ASSET/IMAGES/LARGE/FIGURE4.JPEG
   PubMed Web of Science ®Google Scholar
• Tanaka T, Narazaki M, Kishimoto T. IL-6 in inflammation, immunity, and disease. Cold Spring Harb Perspect Biol. 2014;6(10):a016295–a016295. doi:10.1101/CSHPERSPECT.A016295
   PubMed Web of Science ®Google Scholar
• Hirano T. IL-6 in inflammation, autoimmunity and cancer. Int Immunol. 2021;33(3):127–148. doi:10.1093/intimm/dxaa078
   PubMed Web of Science ®Google Scholar
• Chen J, Wei Y, Yang W, et al. IL-6: the link between inflammation, immunity and breast cancer. Front Oncol. 2022:12. doi:10.3389/fonc.2022.903800
   Google Scholar
• Maddaloni E, Buzzetti R. Covid-19 and diabetes mellitus: unveiling the interaction of two pandemics. Diabetes Metab Res Rev. 2020;36(7). doi:10.1002/dmrr.3321
   Web of Science ®Google Scholar
• Ma M, Sun Q, Li X, et al. Blockade of IL-6/IL-6R signaling attenuates acute antibody-mediated rejection in a mouse cardiac transplantation model. Front Immunol. 2021:12. doi:10.3389/fimmu.2021.778359
   Web of Science ®Google Scholar
• Kruglova TS, Fomina DS, Poteshkina NG, et al. Criteria for the optimal use of interleukin-6 receptor blockers in patients with COVID-19. Ter Arkh. 2021;93(11):1316–1324. doi:10.26442/00403660.2021.11.201248
   PubMed Web of Science ®Google Scholar
• University Hospital Inselspital B, AG RP. Tocilizumab in the treatment of coronavirus induced disease (COVID-19). ClinicalTrials. 2020;2020:1.
   Google Scholar
• Smail SW, Babaei E, Amin K. Hematological, inflammatory, coagulation, and oxidative/antioxidant biomarkers as predictors for severity and mortality in COVID-19: a prospective cohort-study. Int J Gen Med. 2023;16:565–580. doi:10.2147/IJGM.S402206
   PubMed Web of Science ®Google Scholar
• Smail SW, Babaei E, Amin K. Demographic, clinical and genetic factors associated with COVID-19 disease susceptibility and mortality in a Kurdish population. Ann Saudi Med. 2023;43(3):125–142. doi:10.5144/0256-4947.2023.125
   PubMed Web of Science ®Google Scholar
• Huang J, Li J, Zou Z, et al. Clinical characteristics of 3 patients infected with COVID-19: age, interleukin 6 (IL-6), lymphopenia, and variations in chest computed tomography (CT). Am J Case Rep. 2020:21. doi:10.12659/AJCR.924905
   Web of Science ®Google Scholar
• Pedersen SF, Ho YC. SARS-CoV-2: a storm is raging. J Clin Investig. 2020;130(5):2202–2205. doi:10.1172/JCI137647
   PubMed Web of Science ®Google Scholar
• Zhou X, Ye G, Lv Y, et al. IL-6 drives T cell death to participate in lymphopenia in COVID-19. Int Immunopharmacol. 2022:111. doi:10.1016/j.intimp.2022.109132
   Web of Science ®Google Scholar
• Hanan N, Doud RL, Park IW, Jones HP, Mathew SO. The many faces of innate immunity in SARS-CoV-2 infection. Vaccines. 2021;9(6). doi:10.3390/vaccines9060596
   Web of Science ®Google Scholar
• Kokkotis G, Kitsou K, Xynogalas I, et al. Systematic review with meta-analysis: COVID-19 outcomes in patients receiving anti-TNF treatments. Aliment Pharmacol Ther. 2022;55(2):154–167. doi:10.1111/apt.16717
   PubMed Web of Science ®Google Scholar
• Robinson PC, Liew DFL, Liew JW, et al. The potential for repurposing anti-TNF as a therapy for the treatment of COVID-19. Med. 2020;1(1):90–102. doi:10.1016/j.medj.2020.11.005
   PubMedGoogle Scholar
• Mohd Zawawi Z, Kalyanasundram J, Mohd Zain R, Thayan R, Basri DF, Yap WB. Prospective roles of tumor necrosis factor-alpha (TNF-α) in COVID-19: prognosis, therapeutic and management. Int J Mol Sci. 2023;24(7):6142. doi:10.3390/ijms24076142
   PubMedGoogle Scholar
• Guo Y, Hu K, Li Y, et al. Targeting TNF-α for COVID-19: recent advanced and controversies. Front Public Health. 2022:10. doi:10.3389/fpubh.2022.833967
   Web of Science ®Google Scholar
• Ozpolat C, Altunbas E, Zhu A. Diagnostic utility of the Covichem score in predicting COVID-19 disease. Am J Emerg Med. 2022;57:60. doi:10.1016/j.ajem.2022.07.025
   PubMedGoogle Scholar
• Sun J, Peng L, Li T, et al. Performance of a chest radiograph AI diagnostic tool for COVID-19: a prospective observational study. Radiol Artif Intell. 2022;4(4). doi:10.1148/ryai.210217
   Google Scholar
• Kardos AS, Simon J, Nardocci C, et al. The diagnostic performance of deep-learning-based CT severity score to identify COVID-19 pneumonia. Brit J Radiol. 2022;95(1129). doi:10.1259/bjr.20210759
   PubMed Web of Science ®Google Scholar
• Godfred-Cato S, Abrams JY, Balachandran N, et al. Distinguishing multisystem inflammatory syndrome in children from COVID-19, Kawasaki disease and toxic shock syndrome. J Pediatr Infect Dis. 2022;41(4):315–323. doi:10.1097/INF.0000000000003449
   Google Scholar
• Wang L, Lv Q, Zhang X, et al. The utility of MEWS for predicting the mortality in the elderly adults with COVID-19: a retrospective cohort study with comparison to other predictive clinical scores. PeerJ. 2020;8. doi:10.7717/PEERJ.10018/SUPP-5
   Web of Science ®Google Scholar
• Ghahramani S, Tabrizi R, Lankarani KB, et al. Laboratory features of severe vs. non-severe COVID-19 patients in Asian populations: a systematic review and meta-analysis. Eur J Med Res. 2020;25(1):1–10. doi:10.1186/S40001-020-00432-3/TABLES/2
   PubMed Web of Science ®Google Scholar
• Velavan TP, Meyer CG. Mild versus severe COVID-19: laboratory markers. Int J Infect Dis. 2020;95:304–307. doi:10.1016/J.IJID.2020.04.061
   PubMed Web of Science ®Google Scholar
• Chen G, Wu D, Guo W, et al. Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest. 2020;130(5):2620–2629. doi:10.1172/JCI137244
   PubMed Web of Science ®Google Scholar
• Giamarellos-Bourboulis EJ, Netea MG, Rovina N, et al. Complex immune dysregulation in COVID-19 patients with severe respiratory failure. Cell Host Microbe. 2020;27(6):992–1000.e3. doi:10.1016/J.CHOM.2020.04.009
   PubMed Web of Science ®Google Scholar
• Liu T, Zhang J, Yang Y, et al. The role of interleukin‐6 in monitoring severe case of coronavirus disease 2019. EMBO Mol Med. 2020;12(7). doi:10.15252/EMMM.202012421
   Web of Science ®Google Scholar
• Azmi A, Rismani M, Pourmontaseri H, Mirzaii E, Niknia S, Miladpour B. The role of vitamin D receptor and IL −6 in COVID-19. Mol Genet Genomic Med. 2023;11. doi:10.1002/mgg3.2172
   PubMed Web of Science ®Google Scholar
• Sanli DET, Altundag A, Kandemirli SG, et al. Relationship between disease severity and serum IL-6 levels in COVID-19 anosmia. Am J Otolaryngol. 2021;42(1). doi:10.1016/j.amjoto.2020.102796
   PubMed Web of Science ®Google Scholar
• Eljilany I, Elzouki AN. D-dimer, fibrinogen, and il-6 in covid-19 patients with suspected venous thromboembolism: a narrative review. Vasc Health Risk Manag. 2020;16:455–462. doi:10.2147/VHRM.S280962
   PubMed Web of Science ®Google Scholar
• Halim C, Mirza AF, Sari MI. The association between TNF-α, IL-6, and Vitamin D Levels and COVID-19 severity and mortality: a systematic review and meta-analysis. Pathogens. 2022;11(2):195. doi:10.3390/pathogens11020195
   PubMed Web of Science ®Google Scholar
• Scherger S, Henao-Martínez A, Franco-Paredes C, Shapiro L. Rethinking interleukin-6 blockade for treatment of COVID-19. Med Hypotheses. 2020;144. doi:10.1016/j.mehy.2020.110053
   Web of Science ®Google Scholar
• Tharmarajah E, Buazon A, Patel V, et al. IL-6 inhibition in the treatment of COVID-19: a meta-analysis and meta-regression. J Infect. 2021;82(5):178–185. doi:10.1016/j.jinf.2021.03.008
   PubMed Web of Science ®Google Scholar
• Schultheiß C, Willscher E, Paschold L, et al. The IL-1β, IL-6, and TNF cytokine triad is associated with post-acute sequelae of COVID-19. Cell Rep Med. 2022;3(6). doi:10.1016/j.xcrm.2022.100663
   PubMedGoogle Scholar
• Fishchuk L, Rossokha Z, Pokhylko V, et al. Modifying effects of TNF-α, IL-6 and VDR genes on the development risk and the course of COVID-19. Pilot study. Drug Metab Pers Ther. 2022;37(2). doi:10.1515/dmpt-2021-0127
   Google Scholar
• Zheng S, Zeng C, Liu M, Xiang P, Wang L, Li Z. Study on the role of IL-6/IL-6R/GP130 signal transduction pathway in neuroimmunomodulation. Acta Med Mediterr. 2021;37(4). doi:10.19193/0393-6384_2021_4_355
   Web of Science ®Google Scholar
• Chonov DC, Ignatova MMK, Ananiev JR, Gulubova MV. IL-6 activities in the tumour microenvironment. part 1. Open Access Maced J Med Sci. 2019;7(14):2391–2398. doi:10.3889/oamjms.2019.589
   PubMedGoogle Scholar
• Hwang MS, Strainic MG, Pohlmann E, et al. Research article vegfr2 survival and mitotic signaling depends on joint activation of associated C3ar1/C5ar1 and IL-6R-gp130. J Cell Sci. 2019;132(6). doi:10.1242/jcs.219352
   PubMed Web of Science ®Google Scholar
• Vatansever HS, Becer E. Relationship between IL-6 and COVID-19: to be considered during treatment. Future Virol. 2020;15(12):817–822. doi:10.2217/fvl-2020-0168
   Web of Science ®Google Scholar