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Abstract
Background: Seasonal influenza may cause severe complications in case of cytokine storm, a hyperinflammatory reaction that increases tissue damage and dysfunction of multiple organs.
Objective: The research aims were to determine the correlation between seasonal influenza and cytokine storm through clinical and molecular investigations.
Methods: A cross-sectional observational study was carried out on 120 patients with RT-PCR-confirmed seasonal influenza in December 2023-March 2024. ELISA was used to determine serum levels of IL-6, TNF-α, IFN- g, IL-1, and IL-18. Demographics and clinical information, such as ARDS, coagulopathy, acute kidney injury, CNS manifestations, etc., were documented. Statistical significance of p = 0.05 was used to test statistical significance with SPSS v26.0 (t-test, Mann- Whitney, Pearson/Spearman correlation).
Results: The patients with cytokine storm (n = XX) had much more serum cytokines than their uncomplicated influenza counterparts (IL-6: 142 ± 35 vs. 18 ± 6 pg/mL, p < 0.001; TNF-α a: 96 ± 22 vs. 15 ± 5 pg/mL, p < 0.001). The incidence of coagulopathy (70% vs. 5%), AKI (40% vs. 5%), and CNS (confusion 45% vs. 10%) was significantly higher. High IL-6 levels were greatly associated with ARDS (r = 0.68, p < 0.01).
Conclusion: In seasonal influenza, cytokine storm is related to hyper-release of IL-6, TNF-α, IFN- gamma, IL- 1 8, and IL-1α, which cause dysfunction of multiple organs and increased complications. The timely identification of the signs of cytokine storm would enhance the outcome of patients and inform the use of specific immunomodulatory treatment.
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Copyright (c) 2025 Wurood Kadhim Abed (Author)

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References
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- Hasan TH, Kadhum HA, Al-Khilkhali HJB. Epidemiology of varicella-zoster virus in Najaf Governorate, Iraq. Lat Am J Pharm. 2023;42(Spec Issue):188–190.
- Hassan LA, Darweesh MF, Hasan TH. Immunomodulator activity of Pseudomonas aeruginosa extracted protein: azurin charming protein. Lat Am J Pharm. 2023;42(Spec Issue):245–251.
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- Iwasaki A, Pillai PS. Inflammatory responses and liver injury in viral infection. J Hepatol. 2021;75(3):712–722. https://doi.org/10.1016/j.jhep.2021.04.031
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- Stegeman SK, Kourko O, Amsden H, Pellizzari Delano IE, Mamatis JE, Roth M, et al. RNA viruses, TLRs, and cytokines: the perfect storm? J Innate Immun. 2025;39:1–?
- Teijaro JR. Cytokine storms in infectious diseases. Semin Immunopathol. 2016;38(5):513–515. https://doi.org/10.1007/s00281-016-0559-1
- Tikki KA, Mohammed EH, Mahdi AA, Hasan TH. Effects of COVID-19 infection on hematologic parameters. Egypt J Hosp Med. 2022;89(1):5488–5492. https://doi.org/10.21608/ejhm.2022.264846
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References
Abed WK, Hussein HK. Detection of human metapneumovirus RNA sequence in nasopharyngeal swab samples from children with acute respiratory tract infections in Najaf Province, Iraq. AIP Conf Proc. 2023;2977:040009. https://doi.org/10.1063/5.0182237
Abusaiba THH. Prevalence of hepatitis B and C viruses in patients in Al-Najaf Governorate, Iraq. Int J Pharm Res. 2020;12(3):1297–1303.https://doi.org/10.31838/ijpr/2020.12.03.195
Al-Ethari AS, Hasan TH, Tikki KA, Bustani GS. Genotypic detection of qnrA and qnrC genes in Citrobacter koseri isolated from patients with urinary tract infection. Razi Arch Inst. 2022;77(2).https//doi.org/10.22092/ARI.2022.357122.1979.
Aljanaby IAJ, Al-Labban HMY, Hayder T, Hasan MJA, Aljanaby AAJ. Neural cell adhesion molecule in Mycobacterium tuberculosis patients. Lat Am J Pharm. 2023;42(Spec Issue):184–187.
Blanco-Melo D, Nilsson-Payant BE, Liu WC, Uhl S, Hoagland D, Møller R, et al. Imbalanced host response to SARS-CoV-2 drives development of COVID-19. Cell. 2020;181(5):1036–1045.e9. https://doi.org/10.1016/j.cell.2020.04.026
Chakraborty C, Bhattacharya M, Das A, Saha A. Regulation of miRNA in cytokine storm of COVID-19 and other viral infections: an exhaustive review. Rev Med Virol. 2025;35(2):e70026. https://doi.org/10.1002/rmv.70026
El-Maradny Y, Othman A, Gerges M, Belal F, Behery E, El-Fakharany E. COVID-19 coronavirus: pathogenesis, clinical features, diagnostics, epidemiology, prevention and control. Microb Biosyst. 2020;5(1):7–20. https://doi.org/10.21608/mb.2020.33405.1018
Freeman TL, Swartz TH. Targeting the NLRP3 inflammasome in severe influenza. Front Immunol. 2020;11:1159. https://doi.org/10.3389/fimmu.2020.01159
Goenka A, Michael BD, Ledger E, Hart IJ, Absoud M, Chow G, et al. Neurologic complications of influenza infection. J Pediatric Infect Dis Soc. 2021;10(1):46–53. https://doi.org/10.1093/jpids/piaa098
Gu Y, Zuo X, Zhang S, Ouyang Z, Jiang S, Wang F, et al. The mechanism behind influenza virus cytokine storm. Viruses. 2021;13(7):1362. https://doi.org/10.3390/v13071362
Guo M, Ye YD, Cai JP, Xu HT, Wei W, Sun JY, et al. PEG-SeNPs as therapeutic agents inhibiting apoptosis and inflammation of cells infected with H1N1 influenza A virus. Sci Rep. 2024;14(1):21318. https://doi.org/10.1038/s41598-024-71898-0
Hasan TH. Extended spectrum beta-lactamase Escherichia coli isolated from UTI patients in Najaf Province, Iraq. Int J Pharm Res. 2020;12(4):673–677.https://doi.org/10.31838/ijpr/2020.12.04.049
Hasan TH, Al-Harmoosh RA, Al-Khilkhali HJB. Identification of HIV virus in Najaf City, Iraq. Int J Res Pharm Sci. 2020;11(3):4866–4871.
Hasan TH, Kadhum HA, Al-Khilkhali HJB. Epidemiology of varicella-zoster virus in Najaf Governorate, Iraq. Lat Am J Pharm. 2023;42(Spec Issue):188–190.
Hassan LA, Darweesh MF, Hasan TH. Immunomodulator activity of Pseudomonas aeruginosa extracted protein: azurin charming protein. Lat Am J Pharm. 2023;42(Spec Issue):245–251.
Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497–506. https://doi.org/10.1016/S0140-6736(20)30183-5
Hussein AR, Al-Challabi K, Abed W, Mahdi H, Al-Hatimy A. Correlation of cytokines with thyroid hormones and autoantibodies in thyroid autoimmune diseases. Egypt J Med Microbiol. 2025;34(1):99–109. https://doi.org/10.21608/ejmm.2024.322552.1344
Iwasaki A, Pillai PS. Inflammatory responses and liver injury in viral infection. J Hepatol. 2021;75(3):712–722. https://doi.org/10.1016/j.jhep.2021.04.031
Kazantseva ED, Petrova AG, Rychkova LV, Darenskaya MA. Cytokines in influenza in children: a literature review. Cell Tissue Biol. 2024;18(6):632–645.
Lee YJ, Park SY, Kim YK, Kim S. Cytokine profiles in severe influenza A. Front Immunol. 2023;14:1134572. https://doi.org/10.3389/fimmu.2023.1134572
Levi M, van der Poll T. Coagulation and sepsis. N Engl J Med. 2022;387(1):77–88. https://doi.org/10.1056/NEJMra2107772
Lv C, Guo J, Luo R, Li Y, Zou X, Wang T, et al. Taurolidine inhibits influenza virus infection and prevents influenza-induced cytokine storm, vasoconstriction and lung damage. Cell Mol Life Sci. 2025;82(1):1–18.https://doi.org/10.1007/s00018-025-05636-6
Majeed HT, Hasan TH, Aljanaby AAJ. Epidemiological study in women infected with Toxoplasma gondii, rubella virus, and cytomegalovirus in Al-Najaf Governorate, Iraq. Int J Pharm Res. 2020;12:1442–1447.
Morris G, Bortolasci CC, Puri BK, Marx W, O’Neil A, Athan E, et al. Cytokine storms of COVID-19, H1N1 influenza, CRS and MAS compared. Cytokine. 2021;144:155593. https://doi.org/10.1016/j.cyto.2021.155593
Murdaca G, Paladin F, Tonacci A, Isola S, Allegra A, Gangemi S. Potential role of cytokine storm pathway in viral respiratory pandemics. Biomedicines. 2021;9(11):1688. https://doi.org/10.3390/biomedicines9111688
Olbei M, Hautefort I, Modos D, Treveil A, Poletti M, Gul L, et al. SARS-CoV-2 causes a different cytokine response compared to other respiratory viruses. Front Immunol. 2021;12:629193. https://doi.org/10.3389/fimmu.2021.629193
Shlash SA, Kadhum HA, Hasnawi NM, Hasan TH. Environmental and parasitic contamination of Euphrates River water using granular activated date seeds. Mater Today Proc. 2023;80:3646–3654.
Shlash SA, Zwain KA, Khayoon SQ, Hasan TH. Vitamin D deficiency with Blastocystis hominis infection. AIP Conf Proc. 2023;2845(1). https://doi.org/10.1063/5.0157297
Stegeman SK, Kourko O, Amsden H, Pellizzari Delano IE, Mamatis JE, Roth M, et al. RNA viruses, TLRs, and cytokines: the perfect storm? J Innate Immun. 2025;39:1–?
Teijaro JR. Cytokine storms in infectious diseases. Semin Immunopathol. 2016;38(5):513–515. https://doi.org/10.1007/s00281-016-0559-1
Tikki KA, Mohammed EH, Mahdi AA, Hasan TH. Effects of COVID-19 infection on hematologic parameters. Egypt J Hosp Med. 2022;89(1):5488–5492. https://doi.org/10.21608/ejhm.2022.264846
Wang S, Wang D, Wang X, Chen M, Wang Y, Zhou H, et al. Cytokine storm related to CD4+ T cells in influenza-associated acute necrotizing encephalopathy. Immune Netw. 2024;24(2):e18.https://doi.org/10.4110/in.2024.24.e18
Yin YZ, Luo RL, Li SQ, Li RF. Mechanism and suggestions of liver damage caused by influenza A virus: a narrative review. Infect Dis Trop Med. 2024;10:e1392.https://doi.org/10.32113/idtm_20244_1392
Yuan S, Jiang SC, Zhang ZW, Fu YF, Hu J, Li ZL. Quantification of cytokine storms during virus infections. Front Immunol. 2021;12:659419. https://doi.org/10.3389/fimmu.2021.659419
Zheng Y, He D, Zuo W, Wang W, Wu K, Wu H, et al. Influenza A virus dissemination leads to tissue-resident cell injury and dysfunction in viral sepsis. EBioMedicine. 2025;116:104715.https://doi.org/10.1016/j.ebiom.2025.105738
