Comparison of alternative acute phase reactants in the evaluation of the prognosis of COVID-19 patients
Keywords:COVID-19,, acute phase reactants, neopterin, adenosine deaminase, chitotriosidase
Aim: Acute phase reactants (APR) and their release pattern is important in cytokine storm related with poor prognosis in COVID-19 patients. The cytokine storm is basically caused by interleukin-6 (IL-6). However, a variety of APRs are thought to be related to disease severity. The present study is focused on evaluation of alternative acute phase reactants in COVID-19 patients.
Materials and Methods: 121 participants were included in the study. They were divided in to 3 groups as IL-6 level < 35 pg/ml (group 1) , IL-6 level > 35 pg/mL (group 2) , and healthy controls (group 3) . Levels of altenatice APRs neopterin, adenosine deaminase (ADA) and Chitotriosidase were evaluated in study groups together with routinely studied inflammation markers.
Results: Neopterin values were significantly different in all study groups. Chitotriosidase levels were similar bewteen group 1 and group 2 while there was a statistically significant difference between group 1 and group 3, group 2 and group 3 and also a difference in comparison of all groups together. ADA levels were only significantly different between group 1 and group 3. Among the study parameters, neopterin showed moderate correlation wtih IL-6. Neopterin also showed week moderate correlations with NLR and fibrinogen.
Conclusion: Neopterin can be a candidate APR and a prognostic marker for COVID-19. It can can be accepted as a marker of poor prognosis, lung damage, and high morbidity in COVID-19, alongside IL-6.
Chen Y, Liu Q, Guo D. Emerging coronaviruses: genome structure, replication, and pathogenesis. J. Med. Virol. 2020; 92(4): 418–423.
Cray C, Zaias J, Altman NH. Acute phase response in animals: a review. Comp Med. 2009; 59(6): 517-526.
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.
Li X, Geng M, Peng Y, Meng L, Lu S. Molecular immune pathogenesis and diagnosis of COVID-19. J. Pharm. Analysis. 2020; 10(2): 102-108.
Panigrahy D, Gilligan MM, Huang S, Gartung A, Cortes-Puch I, Sime PJ, et al. Inflammation resolution: a dual-pronged approach to averting cytokine storms in COVID-19? Cancer Metastasis Rev. 2020; 39(2): 337-340.
Nemeth E, Rivera S, Gabayan V, Keller C, Taudorf S, Pedersen BK, et al. IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. J Clin Invest. 2004;113(9):1271–1276.
Tanaka T, Narazaki M, Kishimoto T. IL-6 in inflammation, immunity, and disease. Cold Spring Harb Perspect Biol. 2014; 4(6): a016295.
Hojyo S, Uchida M, Tanaka K, Hasebe R, Tanaka Y, Murakami M. How COVID-19 induces cytokine storm with high mortality. Inflamm Regen 2020;1 (40):37
Guirao JJ, Cabrera CM, Jimenez N, Rincon L, Urra JM. High serum IL-6 values increase the risk of mortality and the severity of pneumonia in patients diagnosed with COVID-19. Mol Immunol. 2020;128:64–68.
Herold T, Jurinovic V, Arnreich C, Lipworth BJ, Hellmuth JC, von Bergwelt-Baildon M, et al. Elevated levels of IL-6 and CRP predict the need for mechanical ventilation in COVID-19. J Allergy Clin Immunol. 2020;146. 12836.e4
Cunha JG. Adenosine deaminase. A pluridisciplinary enzyme. Acta Med Port. 1991; 4 (6): 315-323.
Hovi T, Smyth JF, Allison AC, Williams SC. Role of adenosine deaminase in lymphocyte proliferation. Clin Exp Immunol.1976; 23(3): 395–403.
Chuang SC, Boeing H, Vollset SE, Midttun Ø, Ueland PM, Bueno-de-Mesquita B, et al. Cellular immune activity biomarker neopterin is associated hyperlipidemia: results from a large population-based study. Immun Ageing. 2016; 13:5
El-Lebedy D, Hussein J, Ashmawy I, Mohammed AM. Serum level of neopterin is not a marker of disease activity in treated rheumatoid arthritis patients. Clin Rheumatol. 2017; 36 (9): 1975-1979.
Godai K, Uemasu J, Kawasaki H. Clinical significance of serum and urinary neopterins in patients with chronic renal disease. Clin Nephrol. 1991; 36(3): 141-146.
Eisenhut M. Neopterin in Diagnosis and Monitoring of Infectious Diseases. J Biomark. 2013;2013:196432.
Kuusk S, Sørlie M, Väljamäe P.Human Chitotriosidase Is an Endo-Processive Enzyme. PLoS One. 2017; 12(1): e0171042.
Van Dyken SJ, Liang HE, Naikawadi RP, Woodruff PG, Wolters PJ, Erle DJ, et al. Spontaneous chitin accumulation in airways and age-related fibrotic lung disease. Cell. 2017;169(3): 497–509.
Shi Y, Wang Y, Shao C. COVID-19 infection: the perspectives on immune responses. Cell Death Differ. 2020; 27(5): 1451–1454.
Uciechowski P, Dempke WCM. Interleukin-6: a masterplayer in the cytokine network. Oncology. 2020;98(3):131–137.
Zhou L, Huntington K, Zhang S, Carlsen L, So E-Y, Parker C, et al. MEK inhibitors reduce cellular expression of ACE2, pERK, pRb while stimulating NK-mediated cytotoxicity and attenuating inflammatory cytokines relevant to SARS-CoV-2 infection. Oncotarget. 2020;11(46):4201–4223.
Zheng B, Cao KY, Chan CPY, Choi CWY, Leung W, Leung M, et al. Serum neopterin for early assessment of severity of severe acute respiratory syndrome. Clinical Immunology. 2005; 116 (1):18–26.
Chang D, Sharma L, Dela Cruz CS. Chitotriosidase: a marker and modulator of lung disease. Eur Respir Rev. 2020;29 (156): 190143.
Kunihiro Y, Tanaka N, Kawano R, Yujiri T, Kubo M, Ueda K, et al. Differential diagnosis of pulmonary infections in immunocompromised patients using high-resolution computed tomography. Eur Radiol. 2019; 29: 6089–6099.
Kaljas Y, Liu C, Skaldin M, Wu C, et al. Human adenosine deaminases ADA1 and ADA2 bind to different subsets of immune cells. Cell Mol Life Sci.2016; 74(3): 555–570.
Martinez-Navio JM, Casanova V, Pacheco R, Naval-Macabuhay I, et al. Adenosine deaminase potentiates the generation of effector, memory, and regulatory CD4+ T cells. J Leukoc Biol. 2011; 89(1): 127–136.
Niedzwicki JG, Mayer KH, Abushanab E, Abernethy DR. Plasma adenosine deaminase, is a marker for human immunodeficiency virus-I seroconversion. Am Hematol. 1991;37(3): 152–155.
How to Cite
Copyright (c) 2022 Journal of Social and Analytical Health
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.