The Importance of Neopterin in COVID-19: The Prognostic Value and Relation with the Disease Severity

Overview

Journal Clin Biochem

Specialty Biochemistry

Date 2022 Mar 21

PMID 35307400

Authors

Yousef Rasmi

Nadia Heidari

Kevser Kubra Kirboga

Shima Hatamkhani

Burcu Tekin

Shahryar Alipour

Roya Naderi

Yeghaneh Farnamian

Ilknur Akca

Affiliations

Soon will be listed here.

Abstract

Coronavirus Disease 2019 [COVID-19], caused by severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2], has rapidly evolved into a global health emergency. Neopterin [NPT], produced by macrophages when stimulated with interferon [IFN-]gamma, is an essential cytokine in the antiviral immune response. NPT has been used as a marker for the early assessment of disease severity in different diseases. The leading cause of NPT production is the pro-inflammatory cytokine IFN-. Macrophage activation has also been revealed to be linked with disease severity in SARS-CoV-2 patients. We demonstrate the importance of NPT in the pathogenesis of SARS-CoV-2 and suggest that targeting NPT in SARS-CoV-2 infection may be critical in the early prediction of disease progression and provision of timely management of infected individuals.

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References

Al-Samkari H, Berliner N . Hemophagocytic Lymphohistiocytosis. Annu Rev Pathol. 2017; 13:27-49. DOI: 10.1146/annurev-pathol-020117-043625. View

Daniels L, Ren J, Kumar K, Bui Q, Zhang J, Zhang X . Relation of prior statin and anti-hypertensive use to severity of disease among patients hospitalized with COVID-19: Findings from the American Heart Association's COVID-19 Cardiovascular Disease Registry. PLoS One. 2021; 16(7):e0254635. PMC: 8281996. DOI: 10.1371/journal.pone.0254635. View

Lau J, Horvath C . Mechanisms of Type I interferon cell signaling and STAT-mediated transcriptional responses. Mt Sinai J Med. 2002; 69(3):156-68. View

Muller M, Curtius H, Herold M, Huber C . Neopterin in clinical practice. Clin Chim Acta. 1991; 201(1-2):1-16. DOI: 10.1016/0009-8981(91)90019-9. View

Matsushita H, Hosoi A, Ueha S, Abe J, Fujieda N, Tomura M . Cytotoxic T lymphocytes block tumor growth both by lytic activity and IFNγ-dependent cell-cycle arrest. Cancer Immunol Res. 2014; 3(1):26-36. DOI: 10.1158/2326-6066.CIR-14-0098. View

Suntharalingam G, Perry M, Ward S, Brett S, Castello-Cortes A, Brunner M . Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412. N Engl J Med. 2006; 355(10):1018-28. DOI: 10.1056/NEJMoa063842. View

Mahalanabis D, Lahiri M, Paul D, Gupta S, Gupta A, Wahed M . Randomized, double-blind, placebo-controlled clinical trial of the efficacy of treatment with zinc or vitamin A in infants and young children with severe acute lower respiratory infection. Am J Clin Nutr. 2004; 79(3):430-6. DOI: 10.1093/ajcn/79.3.430. View

Rainer T, Chan C, Leung M, Leung W, Ip M, Lee N . Diagnostic utility of CRP to neopterin ratio in patients with acute respiratory tract infections. J Infect. 2008; 58(2):123-30. DOI: 10.1016/j.jinf.2008.11.007. View

Reibnegger G, Auhuber I, Fuchs D, Hausen A, Judmaier G, Prior C . Urinary neopterin levels in acute viral hepatitis. Hepatology. 1988; 8(4):771-4. DOI: 10.1002/hep.1840080412. View

10.

El-Lebedy D, Hussein J, Ashmawy I, Mohammed A . Serum level of neopterin is not a marker of disease activity in treated rheumatoid arthritis patients. Clin Rheumatol. 2016; 36(9):1975-1979. DOI: 10.1007/s10067-016-3433-4. View

11.

Rerksuppaphol S, Rerksuppaphol L . A randomized controlled trial of zinc supplementation in the treatment of acute respiratory tract infection in Thai children. Pediatr Rep. 2019; 11(2):7954. PMC: 6548996. DOI: 10.4081/pr.2019.7954. View

12.

Hobarth K, Szabo N, Hallas A, Aulitzky W, Marberger M . Serum neopterin as a parameter for monitoring the course of renal cell carcinoma during interferon-gamma therapy. Clin Immunol Immunopathol. 1994; 70(3):241-4. DOI: 10.1006/clin.1994.1035. View

13.

Asci A, Baydar T, Cetinkaya R, Dolgun A, Sahin G . Evaluation of neopterin levels in patients undergoing hemodialysis. Hemodial Int. 2010; 14(2):240-6. DOI: 10.1111/j.1542-4758.2010.00439.x. View

14.

Eisenhut M . Neopterin in Diagnosis and Monitoring of Infectious Diseases. J Biomark. 2015; 2013:196432. PMC: 4437389. DOI: 10.1155/2013/196432. View

15.

Lin Z, Long F, Yang Y, Chen X, Xu L, Yang M . Serum ferritin as an independent risk factor for severity in COVID-19 patients. J Infect. 2020; 81(4):647-679. PMC: 7313486. DOI: 10.1016/j.jinf.2020.06.053. View

16.

Svoboda P, Ko S, Cho B, Yoo S, Choi S, Ye S . Neopterin, a marker of immune response, and 8-hydroxy-2'-deoxyguanosine, a marker of oxidative stress, correlate at high age as determined by automated simultaneous high-performance liquid chromatography analysis of human urine. Anal Biochem. 2008; 383(2):236-42. DOI: 10.1016/j.ab.2008.09.014. View

17.

Denz H, Fuchs D, Hausen A, HUBER H, Nachbaur D, Reibnegger G . Value of urinary neopterin in the differential diagnosis of bacterial and viral infections. Klin Wochenschr. 1990; 68(4):218-22. DOI: 10.1007/BF01662720. View

18.

Ponti G, Roli L, Oliva G, Manfredini M, Trenti T, Kaleci S . Homocysteine (Hcy) assessment to predict outcomes of hospitalized Covid-19 patients: a multicenter study on 313 Covid-19 patients. Clin Chem Lab Med. 2021; 59(9):e354-e357. DOI: 10.1515/cclm-2021-0168. View

19.

Centi S, Tombelli S, Puntoni M, Domenici C, Franek M, Palchetti I . Detection of biomarkers for inflammatory diseases by an electrochemical immunoassay: the case of neopterin. Talanta. 2015; 134:48-53. DOI: 10.1016/j.talanta.2014.10.053. View

20.

Eden A, Kanberg N, Gostner J, Fuchs D, Hagberg L, Andersson L . CSF Biomarkers in Patients With COVID-19 and Neurologic Symptoms: A Case Series. Neurology. 2020; 96(2):e294-e300. DOI: 10.1212/WNL.0000000000010977. View