Published date: Jun 30 2023

Journal Title: Sudan Journal of Medical Sciences

Issue title: Sudan JMS: Volume 18 (2023), Issue No. 2

Pages: 190–202

DOI: 10.18502/sjms.v18i2.13603

Walaa Mohammedsaeedwmohammedsaeed@taibahu.edu.saClinical Biochemistry, Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, Taibah University, Madinah, Saudi Arabia

Ziab Zakey AlahmadeyLaboratory Department, Ohud Hospital Madinah, Saudi Arabia

Nikhat ManzoorMedical Mycology Lab, Department of Biosciences, Jamia Millia Islamia, New Delhi, India

Background: The severity of Coronavirus disease 2019 (COVID-19) has been proposed to be associated with cytokine dysregulation. A significant number of patients become serious and need intensive care in hospitals.

Methods: The concentrations of cytokines interleukin (IL-6, IL-10) and tumor necrosis factor (TNF) were estimated using enzyme-linked immunosorbent assay (ELISA) in serum samples of 60 adult patients infected with SARS-CoV-2 along with 50 healthy controls of the same age. The mean age of the subjects was 50-52 years and included an equal number of males and females. The patients were further grouped as severe (38 patients) and non-severe cases (22 patients).

Results: The mean serum cytokine levels were significantly higher in the COVID-19 patients than in the healthy controls. IL-6 was excessively elevated in comparison to IL-10 and TNF. Comparative analysis of severe versus non-severe cases revealed only slight alterations in the cytokine levels: IL-6 being the most elevated in severe cases. The concentration of the liver enzyme ALT was higher than AST in both severe and non-severe cases. The mean concentration of serum electrolytes (Na, K, and Ca) did not vary much between the patients and healthy controls.

Conclusion: There was a significant positive correlation between the levels of cytokines serum biomarkers in COVID-19 patients. It may be suggested that early detection of cytokines, especially IL-6 and serum biomarkers can help predict disease prognosis and severity in COVID-19 patients.

Keywords: COVID-19, Cytokines, disease severity, diagnosis, liver function, kidney function

[1] Wang, C., Wang, Z., Wang, G., Lau, J. Y., Zhang, K., & Li, W. (2021). COVID-19 in early 2021: Current status and looking forward. Signal Transduction and Targeted Therapy, 6, 114.

[2] Mokhtari, T., Hassani, F., Ghaffari, N., Ebrahimi, B., Yarahmadi, A., & Hassanzadeh, G. (2020). COVID-19 and multiorgan failure: A narrative review on potential mechanisms. Journal of Molecular Histology, 51, 613–628.

[3] Rothan, H. A., & Byrareddy, S. N. (2020). The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. Journal of Autoimmunity, 109, 102433.

[4] Wang, C., Horby, P. W., Hayden, F. G., & Gao, G. F. (2020). A novel coronavirus outbreak of global health concern. Lancet, 395, 470–473.

[5] Lopes-Pacheco, M., Silva, P. L., Cruz, F. F., Battaglini, D., Robba, C., Pelosi, P., Morales, M. M., Caruso Neves, C., & Rocco, P. R. M. (2021). Pathogenesis of multiple organ injury in COVID-19 and potential therapeutic strategies. Frontiers in Physiology, 12, 593223.

[6] Nicholls, J. M., Poon, L. L., Lee, K. C., Ng, W. F., Lai, S. T., Leung, C. Y., Chu, C. M., Hui, P. K., Mak, K. L., Lim, W., Yan, K. W., Chan, K. H., Tsang, N. C., Guan, Y., Yuen, K. Y., & Peiris, J. S. (2003). Lung pathology of fatal severe acute respiratory syndrome. Lancet, 361, 1773–1778.

[7] Zhang, Y., Li, J., Zhan, Y., Wu, L., Yu, X., Zhang, W., Ye, L., Xu, S., Sun, R., Wang, Y., & Lou, J. (2004). Analysis of serum cytokines in patients with severe acute respiratory syndrome. Infection and Immunity, 72, 4410–4415.

[8] Velazquez-Salinas, L., Verdugo-Rodriguez, A., Rodriguez, L. L., & Borca, M. V. (2019). The role of interleukin 6 during viral infections. Frontiers in Microbiology, 10, 1057.

[9] Brydon, E. W., Morris, S. J., & Sweet, C. (2005). Role of apoptosis and cytokines in influenza virus morbidity. FEMS Microbiology Reviews, 29, 837–850.

[10] Kany, S., Vollrath, J. T., & Relja, B. (2019). Cytokines in inflammatory disease. International Journal of Molecular Sciences, 20, 6008.

[11] Mortaz, E., Tabarsi, P., Varahram, M., Folkerts, G., & Adcock, I. M. (2020). The immune response and immunopathology of COVID-19. Frontiers in Immunology, 11, 2037.

[12] Ye, Q., Wang, B., & Mao, J. (2020). The pathogenesis and treatment of the ‘Cytokine Storm’ in COVID-19. The Journal of Infection, 80, 607–613.

[13] Sinha, P., Matthay, M. A., & Calfee, C. S. (2020). Is a “cytokine storm” relevant to COVID-19? JAMA Internal Medicine, 180, 1152–1154.

[14] Rismanbaf, A., & Zarei, S. (2020). Liver and kidney injuries in COVID-19 and their effects on drug therapy; a Letter to Editor. Archives of Academic Emergency Medicine, 8, e17.

[15] Martinez, M. A., & Franco, S. (2021). Impact of COVID-19 in liver disease progression. Hepatology Communications, 5, 1138–1150.

[16] Clark, R., Waters, B., & Stanfill, A. G. (2021). Elevated liver function tests in COVID-19: Causes, clinical evidence, and potential treatments. The Nurse Practitioner, 46, 21–26.

[17] Ghahramani, S., Tabrizi, R., Lankarani, K. B., Kashani, S. M. A., Rezaei, S., Zeidi, N., Akbari, M., Heydari, S. T., Akbari, H., Nowrouzi-Sohrabi, P., & Ahmadizar, F. (2020). Laboratory features of severe vs. non-severe COVID-19 patients in Asian populations: A systematic review and meta-analysis. European Journal of Medical Research, 25, 30.

[18] Zhang, X., Tan, Y., Ling, Y., Lu, G., Liu, F., Yi, Z., Jia, X., Wu, M., Shi, B., Xu, S., Chen, J., Wang, W., Chen, B., Jiang, L., Yu, S., Lu, J., Wang, J., Xu, M., Yuan, Z., . . . Lu, H. (2020). Viral and host factors related to the clinical outcome of COVID-19. Nature, 583, 437–440.

[19] MOH-approved scientific instruction manuals and guidelines for healthcare providers on how to deal with COVID-19 patients, 2020. Available from https://www.moh. gov.sa/en/Ministry/MediaCenter/Publications/Pages/covid19.aspx; 2020 [accessed 20 June 2020]).

[20] Wang, X., Yang, K., Wei, C., Huang, Y., & Zhao, D. (2010). Coinfection with EBV/CMV and other respiratory agents in children with suspected infectious mononucleosis. Virology Journal, 7, 247.

[21] Ye, Q., Wang, B., & Mao, J. (2020). The pathogenesis and treatment of the ‘cytokine storm’ in COVID-19. The Journal of Infection, 80, 607–613.

[22] Forbester, J. L., & Humphreys, I. R. (2021). Genetic influences on viral-induced cytokine responses in the lung. Mucosal Immunology, 14, 14–25.

[23] Melo, A. K. G., Milby, K. M., Caparroz, A. L. M. A., Pinto, A. C. P. N., Santos, R. R. P., Rocha, A. P., Ferreira, G. A., Souza, V. A., Valadares, L. D. A., Vieira, R. M. R. A., Pileggi, G. S., & Trevisani, V. F. M. (2021). Biomarkers of cytokine storm as red flags for severe and fatal COVID-19 cases: A living systematic review and meta-analysis. PLoS One, 16, e0253894.

[24] Ghazavi, A., Ganji, A., Keshavarzian, N., Rabiemajd, S., & Mosayebi, G. (2021). Cytokine profile and disease severity in patients with COVID-19. Cytokine, 137, 155323.

[25] Ponti, G., Maccaferri, M., Ruini, C., Tomasi, A., & Ozben, T. (2020). Biomarkers associated with COVID-19 disease progression. Critical Reviews in Clinical Laboratory Sciences, 57, 389–399.

[26] Tisoncik, J. R., Korth, M. J., Simmons, C. P., Farrar, J., Martin, T. R., & Katze, M. G. (2012). Into the eye of the cytokine storm. Microbiology and Molecular Biology Reviews, 76, 16–32.

[27] Lee, D. W., Gardner, R., Porter, D. L., Louis, C. U., Ahmed, N., Jensen, M., Grupp, S. A., & Mackall, C. L. (2014). Current concepts in the diagnosis and management of cytokine release syndrome. Blood, 124, 188–195.

[28] Del Valle, D. M., Kim-Schulze, S., Huang, H. H., Beckmann, N. D., Nirenberg, S., Wang, B., Lavin, Y., Swartz, T. H., Madduri, D., Stock, A., Marron, T. U., Xie, H., Patel, M., Tuballes, K., Van Oekelen, O., Rahman, A., Kovatch, P., Aberg, J. A., Schadt, E., . . . Gnjatic, S. (2020). An inflammatory cytokine signature predicts COVID-19 severity and survival. Nature Medicine, 26, 1636–1643.

[29] Islam, H., Chamberlain, T. C., Mui, A. L., & Little, J. P. (2021). Elevated interleukin-10 levels in COVID-19: Potentiation of pro-inflammatory responses or impaired anti-inflammatory action? Frontiers in Immunology, 12, 677008.

[30] Alfano, G., Ferrari, A., Fontana, F., Perrone, R., Mori, G., Ascione, E., Magistroni, R., Venturi, G., Pederzoli, S., Margiotta, G., Romeo, M., Piccinini, F., Franceschi, G., Volpi, S., Faltoni, M., Ciusa, G., Bacca, E., Tutone, M., Raimondi, A., . . . Guaraldi, G., & the Modena Covid-19 Working Group (MoCo19). (2021). Hypokalemia in patients with COVID-19. Clinical and Experimental Nephrology, 25, 401–409. https://doi.org/10.1007/s10157-020-01996-4