Role of vitamin D, folic acid, ferritin, inflammation and oxidative stress in the pathogenesis of COVID-19
Main Article Content
Keywords
ferritin, COVID-19, Oxidative stress, vitamin D, folic acid
Abstract
The COVID-19 pandemic is one of the most devastating and significant events of recent times. COVID-19 has so far become one of the worst infectious disease outbreaks of recent times, with more than 103 million cases and more than 2.2 million deaths. Viruses cause an explosion of inflammatory cytokines and reactive oxygen types. Oxidative stress is thought to have a key role in COVID-19. vitamin D, folic acid, calcium (Ca), magnesium (Mg) and ferritin levels are thought to be associated with COVID-19. The aim of this study is to investigate the role of oxidative stress, inflammation, vitamin D and folic acid, ferritin, Ca, Mg in the pathogenesis of COVID-19.45 patients diagnosed with COVID-19 and 45 healthy persons (control group) were included in the study. Vitamin D, ferritin, folic acid, CRP, Ca, Mg, Phosphorus were measured in an autoanalyzer, and SOD, GSH-Px and MDA were spectrophotometrically measured in the serum of the participants. TNF-α, IL-1β and IL6 levels were studied by ELISA method.The activity of SOD, GSH-px, antioxidant enzymes, Serum vitamin D, folic acid, Ca, Mg of the COVID-19 group was found to be significantly lower than the control group (p<0.05).Again, the levels of MDA, TNF-α, IL-1β, IL-6, CRP, ferritin in the Covid-19 group were found to be significantly higher than the control group (p<0.05).Antioxidant enzyme activities were low and oxidative stress was high in patients with COVID-19. At the same time, level of serum ferritin, CRP, TNF-α, IL-1β and IL6 were high, and level of Ca and Mg were low in patients with COVID-19.According to these results, we hypothesise think that the level of oxidative stress, inflammation, vitamin D, and serum ferritin, Ca, and Mg levels play a role in the pathogenesis of COVID-19. Future clinical trials should be conducted to further clarify the pathogenesis in patients with COVID-19.
References
1.Ziegler CGK, Allon SJ, Nyquist SK, et al (2020) SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues. Cell 181:1016-1035.e19. doi:10.1016/j.cell.2020.04.035
2.Zu ZY, Jiang MD, Xu PP, Chen W et al (2020) Coronavirus disease 2019 (COVID-19): a perspective from China. Radiology 296:E15–E25 • https://doi.org/10.1148/radiol.2020200490
3.Margaritelis NV, Paschalis V, Theodorou AA, Vassiliou V, Kyparos A, Nikolaidis MG (2020) Rapid decreases of key antioxidant molecules in critically ill patients: A personalized approach. Clin Nutr 39:1146-1154. doi: 10.1016/j.clnu.2019.04.029. Epub 2019 Apr 29. PMID: 31080038.
4.Pizzino G, Irrera N, Cucinotta M, Pallio G, Mannino F, Arcoraci V, Squadrito F, Altavilla D, Bitto A (2017) Oxidative Stress: Harms and Benefits for Human Health. Oxid Med Cell Longev 2017:8416763. doi: 10.1155/2017/8416763. Epub 2017 Jul 27. PMID: 28819546; PMCID: PMC5551541.
5.Unsal V, Dalkıran T, Çiçek M, Kölükçü E (2020) The Role of Natural Antioxidants Against Reactive Oxygen Species Produced by Cadmium Toxicity: A Review. Adv Pharm Bull 10:184-202. doi:10.34172/apb.2020.023
6.Chen G, Wu D, Guo W et al (2020) Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest 130:2620-2629. doi:10.1172/JCI137244
7.Diao B, Wang C, Tan Y (2020) Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID-19). Front Immunol 11:827. Published 2020 May 1. doi:10.3389/fimmu.2020.00827
8.Zhou F, Yu T, Du R et al (2020) Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 395:1054–62.
9.Ruan Q, Yang K, Wang W et al (2020) Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med 46:846–8.
10.C Zhang, Z Wu, J W Li, H Zhao, G.-Q Wang, The cytokine release syndrome (CRS) of severe COVID-19 and interleukin-6 receptor (IL-6R) antagonist tocilizumab may be the key to reduce the mortality, Int J Antimicrob Agents 55:105954 doi:https://doi.org/10.1016/j.ijantimicag.2020.105954
11.Cheng, L., Li, H., Li, L., Liu, C., Yan, S., Chen, H., & Li, Y. (2020). Ferritin in the coronavirus disease 2019 (COVID‐19): A systematic review and meta‐analysis. Journal of clinical laboratory analysis, 34(10), e23618.
12.Cullis, J. O., Fitzsimons, E. J., Griffiths, W. J., Tsochatzis, E., Thomas, D. W., & British Society for Haematology. (2018). Investigation and management of a raised serum ferritin. British journal of haematology, 181(3), 331-340.
13.Li, Y., Hu, Y., Yu, J., & Ma, T. (2020). Retrospective analysis of laboratory testing in 54 patients with severe-or critical-type 2019 novel coronavirus pneumonia. Laboratory Investigation, 1-7.
14.Vargas-Vargas M and Cortés-Rojo C (2020) Ferritin levels and COVID-19. Rev Panam Salud Publica 44:e72. https://doi. org/10.26633/RPSP.2020.72
15.Ali, N. Role of vitamin D in preventing of COVID-19 infection, progression and severity. Journal of infection and public health. 2020;13:1373-1380
16.Grant WB, Lahore H, McDonnell SL et al (2020) Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths. Nutrients 12(4):988. Published 2020 Apr 2. doi:10.3390/nu12040988
17.Li Y, Li Q, Zhang N, Liu Z (2020) Sunlight and vitamin D in the prevention of coronavirus disease (COVID-19) infection and mortality in the United States. Research Square DOI: 10.21203/rs.3.rs-32499/v1.
18.Darling AL, Ahmadi KR, Ward KA et al (2020) Vitamin D status, body mass index, ethnicity and COVID-19: Initial analysis of the first-reported UK Biobank COVID-19 positive cases (n 580) compared with negative controls (n 723). medRxiv; 2020. DOI: 10.1101/2020.04.29.20084277.
19. Beltrán-García J, Osca-Verdegal R, Pallardó FV et al (2020) Oxidative Stress and Inflammation in COVID-19-Associated Sepsis: The Potential Role of Anti-Oxidant Therapy in Avoiding Disease Progression. Antioxidants (Basel, Switzerland). 9(10). DOI: 10.3390/antiox9100936.
20.Sun YI, Oberley LW, Li YA (1998) simple method for clinical assay of superoxide dismutase. Clinical chemistry 34: 497-500.
21-Paglia DE, Valentine, WN (1967) Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 70: 158-169.
22. Esterbauer H, Cheeseman KH (1990) Determination of aldehydic lipid peroxidation products: malonaldehyde and 4-hydroxynonenal. Methods Enzymol 186:407–421.
23.Crimi E, Sica V, Williams-Ignarro S, Zhang H, Slutsky AS, Ignarro LJ, Napoli C (2006) The role of oxidative stress in adult critical care. Free Radic Biol Med 40:398-406. doi: 10.1016/j.freeradbiomed.2005.10.054. Epub 2005 Nov 18. PMID: 16443154.
24.Schönrich G, Raftery MJ, Samstag Y (2020) Devilishly radical NETwork in COVID-19: Oxidative stress, neutrophil extracellular traps (NETs), and T cell suppression. Advances in Biological Regulation 77: 100741 doi: 10.1016/j.jbior.2020.100741.
25.Berger JP, Simet SM, DeVasure JM, Boten JA, Sweeter JM, Kharbanda KK, Sisson JH, Wyatt TA (2014) Malondialdehyde-acetaldehyde (MAA) adducted proteins bind to scavenger receptor A in airway epithelial cells. Alcohol 48:493-500. doi: 10.1016/j.alcohol.2014.02.005.
26.Ighodaro OM and Akinloye OA (2018) First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): Their fundamental role in the entire antioxidant defence grid. Alexandria journal of medicine 54: 287-293.
27.Violi F, Oliva A, Cangemi R, Ceccarelli G, Pignatelli P, Carnevale R, Cammisotto V, Lichtner M, Alessandri F, De Angelis M, Miele MC, D'Ettorre G, Ruberto F, Venditti M, Pugliese F, Mastroianni CM (2020) Nox2 activation in Covid-19. Redox Biol 36:101655. doi: 10.1016/j.redox.2020.101655
28. Shenoy S (2020) Coronavirus (Covid-19) sepsis: revisiting mitochondrial dysfunction in pathogenesis, aging, inflammation, and mortality. Inflamm Res 69 :1077-1085. doi:10.1007/s00011-020-01389-z
29.de Las Heras N, Martín Giménez VM, Ferder L, Manucha W, Lahera V (2020) Implications of Oxidative Stress and Potential Role of Mitochondrial Dysfunction in COVID-19: Therapeutic Effects of Vitamin D. Antioxidants (Basel) 9(9):897 doi:10.3390/antiox9090897
30.Wagener, F. A., Carels, C. E., & Lundvig, D. (2013). Targeting the redox balance in inflammatory skin conditions. International journal of molecular sciences, 14(5), 9126-9167.
31.Chelombitko, M. A. (2018). Role of reactive oxygen species in inflammation: a minireview. Moscow University Biological Sciences Bulletin, 73(4), 199-202.
32.Naik, E., & Dixit, V. M. (2011). Mitochondrial reactive oxygen species drive proinflammatory cytokine production. Journal of Experimental Medicine, 208(3), 417-420.
33-Imai Y, Kuba K, Neely GG et al (2008) Identification of oxidative stress and Toll-like receptor 4 signaling as a key pathway of acute lung injury. Cell 133: 235–249 doi:https://doi.org/10.1016/j.cell.2008.02.043
34.Yang Y, Shen C, Li J et al (2020) Exuberant elevation of IP-10, MCP-3 and IL-1ra during SARS-CoV-2 infection is associated with disease severity and fatal outcome. medRxiv DOI: 10.1101/2020.03.02.20029975.
35.Qin C, Zhou L, Hu Z et al (2020) Dysregulation of Immune Response in Patients With Coronavirus 2019 (COVID-19) in Wuhan, China. Clin Infect Dis 71:762-768. doi:10.1093/cid/ciaa248
36.J Gong, H Dong, SQ Xia, YZ Huang, D Wang, Y Zhao et al (2020) Correlation Analysis Between Disease Severity and Inflammation-related Parameters in Patients with COVID-19 Pneumonia. medRxiv
37.Huang C, Wang Y, Li X, Ren L (2020) Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 395(10223): 497-506. 395
38. Zhang W, Zhao Y, Zhang F (2020) The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): The Perspectives of clinical immunologists from China. Clin Immunol 214:108393. doi:10.1016/j.clim.2020.108393
39- Li X, Xu S, Yu M et al (2020) Risk factors for severity and mortality in adult COVID-19 inpatients in Wuhan. J Allergy Clin Immunol 146:110-118. doi:10.1016/j.jaci.2020.04.006
40.Del Valle DM, Kim-Schulze S, Huang HH et al (2020) An inflammatory cytokine signature predicts COVID-19 severity and survival. Nat Med 26:1636-1643. doi:10.1038/s41591-020-1051-9
41-Torti FM, Torti SV (2002) Regulation of ferritin genes and protein. Blood 99:3505-3516. doi:10.1182/blood.v99.10.3505
42-Winter, W. E., Bazydlo, L. A., & Harris, N. S. (2014). The molecular biology of human iron metabolism. Laboratory medicine, 45(2), 92-102.
43.Ferreira C, Santambrogio P, Martin ME, et al (2001) H ferritin knockout mice: a model of hyperferritinemia in the absence of iron overload. Blood 98(3):525-532. doi:10.1182/blood.v98.3.525
44.Kell DB, Pretorius E (2014) Serum ferritin is an important inflammatory disease marker, as it is mainly a leakage product from damaged cells. Metallomics 6(4):748-773. doi:10.1039/c3mt00347g
45.Cragg SJ, Wagstaff M, Worwood M (1981) Detection of a glycosylated subunit in human serum ferritin. Biochem J 199:565-571. doi:10.1042/bj1990565
46.Garcia PC , Longhi F , Branco RG , Piva JP , Lacks D , Tasker RC (2007) Ferritin levels in children with severe sepsis and septic shock. ACTA Paediatr 96 :1829–31 .
47.Lin Z, Long F, Yang Y, Chen X, Xu L,Yang M (2020) Serum ferritin as an independent risk factor for severity in COVID-19 patients. J Infect 81(4). 647-679.
48.Fox SE, Akmatbekov A, Harbert JL, Li G, Brown JQ, Vander Heide RS (2020) Pulmonary and Cardiac Pathology in Covid-19: The First Autopsy Series from New Orleans. medRxiv 8(7): 681-686 doi: https://doi.org/10.1101/2020.04.06.20050575
49.Wu C, Chen X, Cai Y et al (2020) Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Intern Med 180(7):934-943. doi:10.1001/jamainternmed.2020.0994
50.Kernan KF, Carcillo JA (2017) Hyperferritinemia and inflammation. Int Immunol 1;29:401-409. doi: 10.1093/intimm/dxx031.
51.Lucas C, Wong P, Klein J et al (2020) Longitudinal analyses reveal immunological misfiring in severe COVID-19. Nature 584:463-469. doi:10.1038/s41586-020-2588-y
52.Henry BM, de Oliveira MHS, Benoit S, Plebani M, Lippi G (2020) Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): a meta-analysis. Clin Chem Lab Med 58(7):1021-1028. doi:10.1515/cclm-2020-0369
53.Filgueiras MS, Rocha NP, Novaes JF, Bressan J (2020) Vitamin D status, oxidative stress, and inflammation in children and adolescents: A systematic review. Crit Rev Food Sci Nutr 60:660-669. doi: 10.1080/10408398.2018.1546671. Epub 2018 Dec 30. PMID: 30596263.
54. Aranow C (2011) Vitamin D and the immune system. J Investig Med. 2011;59:881-886. doi:10.2310/JIM.0b013e31821b8755
55.Ferder M, Inserra F, Manucha W, Ferder L (2013) The world pandemic of vitamin D deficiency could possibly be explained by cellular inflammatory response activity induced by the renin-angiotensin system. Am J Physiol Cell Physiol 304:C1027-39. doi: 10.1152/ajpcell.00403.2011.
56. Wimalawansa SJ (2019) Vitamin D Deficiency: Effects on Oxidative Stress, Epigenetics, Gene Regulation, and Aging. Biology (Basel) 11;8:30. doi: 10.3390/biology8020030. PMID: 31083546; PMCID: PMC6627346.
57-Liu Y, Hyde AS, Simpson MA, Barycki JJ (2014) Emerging regulatory paradigms in glutathione metabolism. Adv Cancer Res 122:69-101. doi: 10.1016/B978-0-12-420117-0.00002-5
58.Shakoor H, Feehan J, Al Dhaheri AS et al (2021) Immune-boosting role of vitamins D, C, E, zinc, selenium and omega-3 fatty acids: Could they help against COVID-19?. Maturitas 143:1-9. doi:10.1016/j.maturitas.2020.08.003
59.D'Avolio A, Avataneo V, Manca A, Cusato J, De Nicolò A, Lucchini R, Keller F, Cantù M (2020) 25-Hydroxyvitamin D Concentrations Are Lower in Patients with Positive PCR for SARS-CoV-2. Nutrients 12(5):1359. doi: 10.3390/nu12051359
60.Bergman P, Norlin AC, Hansen S, Björkhem-Bergman L (2015) Vitamin D supplementation improves well-being in patients with frequent respiratory tract infections: a post hoc analysis of a randomized, placebo-controlled trial. BMC Res Notes 8:498. doi:10.1186/s13104-015-1504-2
61.Jolliffe DA, Camargo CA, Sluyter JD, et al (2020) Vitamin D supplementation to prevent acute respiratory infections: systematic review and meta-analysis of aggregate data from randomised controlled trials. Preprint. medRxiv 2020.07.14.20152728. Published 2020 Nov 25. doi:10.1101/2020.07.14.20152728
62.Jain A, Chaurasia R, Sengar NS, Singh M, Mahor S, Narain S (2020) Analysis of vitamin D level among asymptomatic and critically ill COVID-19 patients and its correlation with inflammatory markers. Sci Rep 10:20191 doi:10.1038/s41598-020-77093-z
63.Foroozanfard F, Jamilian M, Bahmani F et al (2015) Calcium plus vitamin D supplementation influences biomarkers of inflammation and oxidative stress in overweight and vitamin D-deficient women with polycystic ovary syndrome: a randomized double-blind placebo-controlled clinical trial. Clin Endocrinol (Oxf) 83:888-894. doi:10.1111/cen.12840
64.Ke CY, Yang FL, Wu WT et al (2016) Vitamin D3 Reduces Tissue Damage and Oxidative Stress Caused by Exhaustive Exercise. Int J Med Sci 13:147-153. doi:10.7150/ijms.13746
65.Alatawi FS, Faridi UA, Alatawi MS (2018) Effect of treatment with vitamin D plus calcium on oxidative stress in streptozotocin-induced diabetic rats. Saudi Pharm J 26:1208-1213. doi:10.1016/j.jsps.2018.07.012
66. Reid IR, Bolland MJ (2020) Calcium and/or Vitamin D Supplementation for the Prevention of Fragility Fractures: Who Needs It?. Nutrients 12:1011. doi:10.3390/nu12041011
67.Sankaran RT, Mattana J, Pollack S et al (1997) Laboratory abnormalities in patients with bacterial pneumonia. Chest 111:595-600. doi:10.1378/chest.111.3.595
68.Forsythe RM, Wessel CB, Billiar TR, Angus DC, Rosengart MR (2008) Parenteral calcium for intensive care unit patients. Cochrane Database Syst Rev (4):CD006163. Published 2008 Oct 8. doi:10.1002/14651858.CD006163.pub2
69.Sun JK, Zhang WH, Zou L et al (2020) Serum calcium as a biomarker of clinical severity and prognosis in patients with coronavirus disease 2019. Aging (Albany NY) 12:11287-11295. doi:10.18632/aging.103526
70.Chen D, Li X, Song Q et al (2020) Hypokalemia and Clinical Implications in Patients with Coronavirus Disease 2019 (COVID-19). medRxiv; 2020. DOI: 10.1101/2020.02.27.20028530.
71.Liu J, Han P, Wu J, Gong J, Tian D (2020) Prevalence and predictive value of hypocalcemia in severe COVID-19 patients. J Infect Public Health 13:1224-1228. doi:10.1016/j.jiph.2020.05.029
72.Whang R, Whang DD, Ryan MP (1992) Refractory potassium repletion. A consequence of magnesium deficiency. Arch Intern Med 152:40-5. PMID: 1728927.
73.Cojocaru IM, Cojocaru M, Tănăsescu R, Iacob SA, Iliescu I (2009) Changes of magnesium serum levels in patients with acute ischemic stroke and acute infections. Rom J Intern Med 47:169-171.
74.Mazur A, Maier JA, Rock E, Gueux E, Nowacki W, Rayssiguier Y (2007) Magnesium and the inflammatory response: potential physiopathological implications. Arch Biochem Biophys. 458:48-56. doi:10.1016/j.abb.2006.03.031
75.Yang X, Soohoo M, Streja E, et al (2016)Serum Magnesium Levels and Hospitalization and Mortality in Incident Peritoneal Dialysis Patients: A Cohort Study. Am J Kidney Dis. 68:619-627. doi:10.1053/j.ajkd.2016.03.428
76.DiNicolantonio JJ, O'Keefe JH, Wilson W (2018) Subclinical magnesium deficiency: a principal driver of cardiovascular disease and a public health crisis [published correction appears in Open Heart. 2018 Apr 5;5(1):e000668corr1]. Open Heart 5:e000668. doi:10.1136/openhrt-2017-000668
77.Micke O, Vormann J, Kisters K (2020) Magnesium and COVID-19 - Some Further Comments - A Commentary on Wallace TC. Combating COVID-19 and Building Immune Resilience: A Potential Role for Magnesium Nutrition? J Am Coll Nutr 1-9. doi:10.1080/07315724.2020.1785971
78.Velissaris D, Karamouzos V, Pierrakos C, Aretha D, Karanikolas M (2015) Hypomagnesemia in Critically Ill Sepsis Patients. J Clin Med Res 7:911-918. doi:10.14740/jocmr2351w
79.Limaye CS, Londhey VA, Nadkart MY, Borges NE (2011) Hypomagnesemia in critically ill medical patients. J Assoc Physicians India 59:19-22
80.Chacko SA, Song Y, Nathan L, Tinker L, de Boer IH, Tylavsky F, Wallace R, Liu S (2010) Relations of dietary magnesium intake to biomarkers of inflammation and endothelial dysfunction in an ethnically diverse cohort of postmenopausal women. Diabetes Care 33:304-10. doi: 10.2337/dc09-1402.
81.Nielsen FH (2018) Magnesium deficiency and increased inflammation: current perspectives. J Inflamm Res 18:25-34. doi: 10.2147/JIR.S136742
82.Wallace TC (2020) Combating COVID-19 and Building Immune Resilience: A Potential Role for Magnesium Nutrition? J Am Coll Nutr 10:1-9. doi:10.1080/07315724.2020.1785971.
83.Rodríguez-Morán M, Guerrero-Romero F (2008) Serum magnesium and C-reactive protein levels. Arch Dis Child 93:676-680. doi:10.1136/adc.2006.109371
84.Müller C, Schibli R, Maurer B (2020) Can Nuclear Imaging of Activated Macrophages with Folic Acid-Based Radiotracers Serve as a Prognostic Means to Identify COVID-19 Patients at Risk? Pharmaceuticals (Basel). 13:238. doi: 10.3390/ph13090238.
85.Sheybani Z, Dokoohaki MH, Negahdaripour M et al (2020) The Role of Folic Acid in the Management of Respiratory Disease Caused by COVID-19. ChemRxiv DOI: 10.26434/chemrxiv.12034980.v1
86. Wu C, Zheng M, Yang Y et al (2020) Furin: A Potential Therapeutic Target for COVID-19. iScience. 23:101642. doi:10.1016/j.isci.2020.101642
87.Shakoor H, Feehan J, Mikkelsen K et al (2021) Be well: A potential role for vitamin B in COVID-19. Maturitas 144:108-111. doi:10.1016/j.maturitas.2020.08.007
88-Acosta-Elias J, Espinosa-Tanguma R (2020) The Folate Concentration and/or Folic Acid Metabolites in Plasma as Factor for COVID-19 Infection. Front Pharmacol 11:1062. Published 2020 Jul 16. doi:10.3389/fphar.2020.01062
2.Zu ZY, Jiang MD, Xu PP, Chen W et al (2020) Coronavirus disease 2019 (COVID-19): a perspective from China. Radiology 296:E15–E25 • https://doi.org/10.1148/radiol.2020200490
3.Margaritelis NV, Paschalis V, Theodorou AA, Vassiliou V, Kyparos A, Nikolaidis MG (2020) Rapid decreases of key antioxidant molecules in critically ill patients: A personalized approach. Clin Nutr 39:1146-1154. doi: 10.1016/j.clnu.2019.04.029. Epub 2019 Apr 29. PMID: 31080038.
4.Pizzino G, Irrera N, Cucinotta M, Pallio G, Mannino F, Arcoraci V, Squadrito F, Altavilla D, Bitto A (2017) Oxidative Stress: Harms and Benefits for Human Health. Oxid Med Cell Longev 2017:8416763. doi: 10.1155/2017/8416763. Epub 2017 Jul 27. PMID: 28819546; PMCID: PMC5551541.
5.Unsal V, Dalkıran T, Çiçek M, Kölükçü E (2020) The Role of Natural Antioxidants Against Reactive Oxygen Species Produced by Cadmium Toxicity: A Review. Adv Pharm Bull 10:184-202. doi:10.34172/apb.2020.023
6.Chen G, Wu D, Guo W et al (2020) Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest 130:2620-2629. doi:10.1172/JCI137244
7.Diao B, Wang C, Tan Y (2020) Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID-19). Front Immunol 11:827. Published 2020 May 1. doi:10.3389/fimmu.2020.00827
8.Zhou F, Yu T, Du R et al (2020) Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 395:1054–62.
9.Ruan Q, Yang K, Wang W et al (2020) Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med 46:846–8.
10.C Zhang, Z Wu, J W Li, H Zhao, G.-Q Wang, The cytokine release syndrome (CRS) of severe COVID-19 and interleukin-6 receptor (IL-6R) antagonist tocilizumab may be the key to reduce the mortality, Int J Antimicrob Agents 55:105954 doi:https://doi.org/10.1016/j.ijantimicag.2020.105954
11.Cheng, L., Li, H., Li, L., Liu, C., Yan, S., Chen, H., & Li, Y. (2020). Ferritin in the coronavirus disease 2019 (COVID‐19): A systematic review and meta‐analysis. Journal of clinical laboratory analysis, 34(10), e23618.
12.Cullis, J. O., Fitzsimons, E. J., Griffiths, W. J., Tsochatzis, E., Thomas, D. W., & British Society for Haematology. (2018). Investigation and management of a raised serum ferritin. British journal of haematology, 181(3), 331-340.
13.Li, Y., Hu, Y., Yu, J., & Ma, T. (2020). Retrospective analysis of laboratory testing in 54 patients with severe-or critical-type 2019 novel coronavirus pneumonia. Laboratory Investigation, 1-7.
14.Vargas-Vargas M and Cortés-Rojo C (2020) Ferritin levels and COVID-19. Rev Panam Salud Publica 44:e72. https://doi. org/10.26633/RPSP.2020.72
15.Ali, N. Role of vitamin D in preventing of COVID-19 infection, progression and severity. Journal of infection and public health. 2020;13:1373-1380
16.Grant WB, Lahore H, McDonnell SL et al (2020) Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths. Nutrients 12(4):988. Published 2020 Apr 2. doi:10.3390/nu12040988
17.Li Y, Li Q, Zhang N, Liu Z (2020) Sunlight and vitamin D in the prevention of coronavirus disease (COVID-19) infection and mortality in the United States. Research Square DOI: 10.21203/rs.3.rs-32499/v1.
18.Darling AL, Ahmadi KR, Ward KA et al (2020) Vitamin D status, body mass index, ethnicity and COVID-19: Initial analysis of the first-reported UK Biobank COVID-19 positive cases (n 580) compared with negative controls (n 723). medRxiv; 2020. DOI: 10.1101/2020.04.29.20084277.
19. Beltrán-García J, Osca-Verdegal R, Pallardó FV et al (2020) Oxidative Stress and Inflammation in COVID-19-Associated Sepsis: The Potential Role of Anti-Oxidant Therapy in Avoiding Disease Progression. Antioxidants (Basel, Switzerland). 9(10). DOI: 10.3390/antiox9100936.
20.Sun YI, Oberley LW, Li YA (1998) simple method for clinical assay of superoxide dismutase. Clinical chemistry 34: 497-500.
21-Paglia DE, Valentine, WN (1967) Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 70: 158-169.
22. Esterbauer H, Cheeseman KH (1990) Determination of aldehydic lipid peroxidation products: malonaldehyde and 4-hydroxynonenal. Methods Enzymol 186:407–421.
23.Crimi E, Sica V, Williams-Ignarro S, Zhang H, Slutsky AS, Ignarro LJ, Napoli C (2006) The role of oxidative stress in adult critical care. Free Radic Biol Med 40:398-406. doi: 10.1016/j.freeradbiomed.2005.10.054. Epub 2005 Nov 18. PMID: 16443154.
24.Schönrich G, Raftery MJ, Samstag Y (2020) Devilishly radical NETwork in COVID-19: Oxidative stress, neutrophil extracellular traps (NETs), and T cell suppression. Advances in Biological Regulation 77: 100741 doi: 10.1016/j.jbior.2020.100741.
25.Berger JP, Simet SM, DeVasure JM, Boten JA, Sweeter JM, Kharbanda KK, Sisson JH, Wyatt TA (2014) Malondialdehyde-acetaldehyde (MAA) adducted proteins bind to scavenger receptor A in airway epithelial cells. Alcohol 48:493-500. doi: 10.1016/j.alcohol.2014.02.005.
26.Ighodaro OM and Akinloye OA (2018) First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): Their fundamental role in the entire antioxidant defence grid. Alexandria journal of medicine 54: 287-293.
27.Violi F, Oliva A, Cangemi R, Ceccarelli G, Pignatelli P, Carnevale R, Cammisotto V, Lichtner M, Alessandri F, De Angelis M, Miele MC, D'Ettorre G, Ruberto F, Venditti M, Pugliese F, Mastroianni CM (2020) Nox2 activation in Covid-19. Redox Biol 36:101655. doi: 10.1016/j.redox.2020.101655
28. Shenoy S (2020) Coronavirus (Covid-19) sepsis: revisiting mitochondrial dysfunction in pathogenesis, aging, inflammation, and mortality. Inflamm Res 69 :1077-1085. doi:10.1007/s00011-020-01389-z
29.de Las Heras N, Martín Giménez VM, Ferder L, Manucha W, Lahera V (2020) Implications of Oxidative Stress and Potential Role of Mitochondrial Dysfunction in COVID-19: Therapeutic Effects of Vitamin D. Antioxidants (Basel) 9(9):897 doi:10.3390/antiox9090897
30.Wagener, F. A., Carels, C. E., & Lundvig, D. (2013). Targeting the redox balance in inflammatory skin conditions. International journal of molecular sciences, 14(5), 9126-9167.
31.Chelombitko, M. A. (2018). Role of reactive oxygen species in inflammation: a minireview. Moscow University Biological Sciences Bulletin, 73(4), 199-202.
32.Naik, E., & Dixit, V. M. (2011). Mitochondrial reactive oxygen species drive proinflammatory cytokine production. Journal of Experimental Medicine, 208(3), 417-420.
33-Imai Y, Kuba K, Neely GG et al (2008) Identification of oxidative stress and Toll-like receptor 4 signaling as a key pathway of acute lung injury. Cell 133: 235–249 doi:https://doi.org/10.1016/j.cell.2008.02.043
34.Yang Y, Shen C, Li J et al (2020) Exuberant elevation of IP-10, MCP-3 and IL-1ra during SARS-CoV-2 infection is associated with disease severity and fatal outcome. medRxiv DOI: 10.1101/2020.03.02.20029975.
35.Qin C, Zhou L, Hu Z et al (2020) Dysregulation of Immune Response in Patients With Coronavirus 2019 (COVID-19) in Wuhan, China. Clin Infect Dis 71:762-768. doi:10.1093/cid/ciaa248
36.J Gong, H Dong, SQ Xia, YZ Huang, D Wang, Y Zhao et al (2020) Correlation Analysis Between Disease Severity and Inflammation-related Parameters in Patients with COVID-19 Pneumonia. medRxiv
37.Huang C, Wang Y, Li X, Ren L (2020) Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 395(10223): 497-506. 395
38. Zhang W, Zhao Y, Zhang F (2020) The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): The Perspectives of clinical immunologists from China. Clin Immunol 214:108393. doi:10.1016/j.clim.2020.108393
39- Li X, Xu S, Yu M et al (2020) Risk factors for severity and mortality in adult COVID-19 inpatients in Wuhan. J Allergy Clin Immunol 146:110-118. doi:10.1016/j.jaci.2020.04.006
40.Del Valle DM, Kim-Schulze S, Huang HH et al (2020) An inflammatory cytokine signature predicts COVID-19 severity and survival. Nat Med 26:1636-1643. doi:10.1038/s41591-020-1051-9
41-Torti FM, Torti SV (2002) Regulation of ferritin genes and protein. Blood 99:3505-3516. doi:10.1182/blood.v99.10.3505
42-Winter, W. E., Bazydlo, L. A., & Harris, N. S. (2014). The molecular biology of human iron metabolism. Laboratory medicine, 45(2), 92-102.
43.Ferreira C, Santambrogio P, Martin ME, et al (2001) H ferritin knockout mice: a model of hyperferritinemia in the absence of iron overload. Blood 98(3):525-532. doi:10.1182/blood.v98.3.525
44.Kell DB, Pretorius E (2014) Serum ferritin is an important inflammatory disease marker, as it is mainly a leakage product from damaged cells. Metallomics 6(4):748-773. doi:10.1039/c3mt00347g
45.Cragg SJ, Wagstaff M, Worwood M (1981) Detection of a glycosylated subunit in human serum ferritin. Biochem J 199:565-571. doi:10.1042/bj1990565
46.Garcia PC , Longhi F , Branco RG , Piva JP , Lacks D , Tasker RC (2007) Ferritin levels in children with severe sepsis and septic shock. ACTA Paediatr 96 :1829–31 .
47.Lin Z, Long F, Yang Y, Chen X, Xu L,Yang M (2020) Serum ferritin as an independent risk factor for severity in COVID-19 patients. J Infect 81(4). 647-679.
48.Fox SE, Akmatbekov A, Harbert JL, Li G, Brown JQ, Vander Heide RS (2020) Pulmonary and Cardiac Pathology in Covid-19: The First Autopsy Series from New Orleans. medRxiv 8(7): 681-686 doi: https://doi.org/10.1101/2020.04.06.20050575
49.Wu C, Chen X, Cai Y et al (2020) Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Intern Med 180(7):934-943. doi:10.1001/jamainternmed.2020.0994
50.Kernan KF, Carcillo JA (2017) Hyperferritinemia and inflammation. Int Immunol 1;29:401-409. doi: 10.1093/intimm/dxx031.
51.Lucas C, Wong P, Klein J et al (2020) Longitudinal analyses reveal immunological misfiring in severe COVID-19. Nature 584:463-469. doi:10.1038/s41586-020-2588-y
52.Henry BM, de Oliveira MHS, Benoit S, Plebani M, Lippi G (2020) Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): a meta-analysis. Clin Chem Lab Med 58(7):1021-1028. doi:10.1515/cclm-2020-0369
53.Filgueiras MS, Rocha NP, Novaes JF, Bressan J (2020) Vitamin D status, oxidative stress, and inflammation in children and adolescents: A systematic review. Crit Rev Food Sci Nutr 60:660-669. doi: 10.1080/10408398.2018.1546671. Epub 2018 Dec 30. PMID: 30596263.
54. Aranow C (2011) Vitamin D and the immune system. J Investig Med. 2011;59:881-886. doi:10.2310/JIM.0b013e31821b8755
55.Ferder M, Inserra F, Manucha W, Ferder L (2013) The world pandemic of vitamin D deficiency could possibly be explained by cellular inflammatory response activity induced by the renin-angiotensin system. Am J Physiol Cell Physiol 304:C1027-39. doi: 10.1152/ajpcell.00403.2011.
56. Wimalawansa SJ (2019) Vitamin D Deficiency: Effects on Oxidative Stress, Epigenetics, Gene Regulation, and Aging. Biology (Basel) 11;8:30. doi: 10.3390/biology8020030. PMID: 31083546; PMCID: PMC6627346.
57-Liu Y, Hyde AS, Simpson MA, Barycki JJ (2014) Emerging regulatory paradigms in glutathione metabolism. Adv Cancer Res 122:69-101. doi: 10.1016/B978-0-12-420117-0.00002-5
58.Shakoor H, Feehan J, Al Dhaheri AS et al (2021) Immune-boosting role of vitamins D, C, E, zinc, selenium and omega-3 fatty acids: Could they help against COVID-19?. Maturitas 143:1-9. doi:10.1016/j.maturitas.2020.08.003
59.D'Avolio A, Avataneo V, Manca A, Cusato J, De Nicolò A, Lucchini R, Keller F, Cantù M (2020) 25-Hydroxyvitamin D Concentrations Are Lower in Patients with Positive PCR for SARS-CoV-2. Nutrients 12(5):1359. doi: 10.3390/nu12051359
60.Bergman P, Norlin AC, Hansen S, Björkhem-Bergman L (2015) Vitamin D supplementation improves well-being in patients with frequent respiratory tract infections: a post hoc analysis of a randomized, placebo-controlled trial. BMC Res Notes 8:498. doi:10.1186/s13104-015-1504-2
61.Jolliffe DA, Camargo CA, Sluyter JD, et al (2020) Vitamin D supplementation to prevent acute respiratory infections: systematic review and meta-analysis of aggregate data from randomised controlled trials. Preprint. medRxiv 2020.07.14.20152728. Published 2020 Nov 25. doi:10.1101/2020.07.14.20152728
62.Jain A, Chaurasia R, Sengar NS, Singh M, Mahor S, Narain S (2020) Analysis of vitamin D level among asymptomatic and critically ill COVID-19 patients and its correlation with inflammatory markers. Sci Rep 10:20191 doi:10.1038/s41598-020-77093-z
63.Foroozanfard F, Jamilian M, Bahmani F et al (2015) Calcium plus vitamin D supplementation influences biomarkers of inflammation and oxidative stress in overweight and vitamin D-deficient women with polycystic ovary syndrome: a randomized double-blind placebo-controlled clinical trial. Clin Endocrinol (Oxf) 83:888-894. doi:10.1111/cen.12840
64.Ke CY, Yang FL, Wu WT et al (2016) Vitamin D3 Reduces Tissue Damage and Oxidative Stress Caused by Exhaustive Exercise. Int J Med Sci 13:147-153. doi:10.7150/ijms.13746
65.Alatawi FS, Faridi UA, Alatawi MS (2018) Effect of treatment with vitamin D plus calcium on oxidative stress in streptozotocin-induced diabetic rats. Saudi Pharm J 26:1208-1213. doi:10.1016/j.jsps.2018.07.012
66. Reid IR, Bolland MJ (2020) Calcium and/or Vitamin D Supplementation for the Prevention of Fragility Fractures: Who Needs It?. Nutrients 12:1011. doi:10.3390/nu12041011
67.Sankaran RT, Mattana J, Pollack S et al (1997) Laboratory abnormalities in patients with bacterial pneumonia. Chest 111:595-600. doi:10.1378/chest.111.3.595
68.Forsythe RM, Wessel CB, Billiar TR, Angus DC, Rosengart MR (2008) Parenteral calcium for intensive care unit patients. Cochrane Database Syst Rev (4):CD006163. Published 2008 Oct 8. doi:10.1002/14651858.CD006163.pub2
69.Sun JK, Zhang WH, Zou L et al (2020) Serum calcium as a biomarker of clinical severity and prognosis in patients with coronavirus disease 2019. Aging (Albany NY) 12:11287-11295. doi:10.18632/aging.103526
70.Chen D, Li X, Song Q et al (2020) Hypokalemia and Clinical Implications in Patients with Coronavirus Disease 2019 (COVID-19). medRxiv; 2020. DOI: 10.1101/2020.02.27.20028530.
71.Liu J, Han P, Wu J, Gong J, Tian D (2020) Prevalence and predictive value of hypocalcemia in severe COVID-19 patients. J Infect Public Health 13:1224-1228. doi:10.1016/j.jiph.2020.05.029
72.Whang R, Whang DD, Ryan MP (1992) Refractory potassium repletion. A consequence of magnesium deficiency. Arch Intern Med 152:40-5. PMID: 1728927.
73.Cojocaru IM, Cojocaru M, Tănăsescu R, Iacob SA, Iliescu I (2009) Changes of magnesium serum levels in patients with acute ischemic stroke and acute infections. Rom J Intern Med 47:169-171.
74.Mazur A, Maier JA, Rock E, Gueux E, Nowacki W, Rayssiguier Y (2007) Magnesium and the inflammatory response: potential physiopathological implications. Arch Biochem Biophys. 458:48-56. doi:10.1016/j.abb.2006.03.031
75.Yang X, Soohoo M, Streja E, et al (2016)Serum Magnesium Levels and Hospitalization and Mortality in Incident Peritoneal Dialysis Patients: A Cohort Study. Am J Kidney Dis. 68:619-627. doi:10.1053/j.ajkd.2016.03.428
76.DiNicolantonio JJ, O'Keefe JH, Wilson W (2018) Subclinical magnesium deficiency: a principal driver of cardiovascular disease and a public health crisis [published correction appears in Open Heart. 2018 Apr 5;5(1):e000668corr1]. Open Heart 5:e000668. doi:10.1136/openhrt-2017-000668
77.Micke O, Vormann J, Kisters K (2020) Magnesium and COVID-19 - Some Further Comments - A Commentary on Wallace TC. Combating COVID-19 and Building Immune Resilience: A Potential Role for Magnesium Nutrition? J Am Coll Nutr 1-9. doi:10.1080/07315724.2020.1785971
78.Velissaris D, Karamouzos V, Pierrakos C, Aretha D, Karanikolas M (2015) Hypomagnesemia in Critically Ill Sepsis Patients. J Clin Med Res 7:911-918. doi:10.14740/jocmr2351w
79.Limaye CS, Londhey VA, Nadkart MY, Borges NE (2011) Hypomagnesemia in critically ill medical patients. J Assoc Physicians India 59:19-22
80.Chacko SA, Song Y, Nathan L, Tinker L, de Boer IH, Tylavsky F, Wallace R, Liu S (2010) Relations of dietary magnesium intake to biomarkers of inflammation and endothelial dysfunction in an ethnically diverse cohort of postmenopausal women. Diabetes Care 33:304-10. doi: 10.2337/dc09-1402.
81.Nielsen FH (2018) Magnesium deficiency and increased inflammation: current perspectives. J Inflamm Res 18:25-34. doi: 10.2147/JIR.S136742
82.Wallace TC (2020) Combating COVID-19 and Building Immune Resilience: A Potential Role for Magnesium Nutrition? J Am Coll Nutr 10:1-9. doi:10.1080/07315724.2020.1785971.
83.Rodríguez-Morán M, Guerrero-Romero F (2008) Serum magnesium and C-reactive protein levels. Arch Dis Child 93:676-680. doi:10.1136/adc.2006.109371
84.Müller C, Schibli R, Maurer B (2020) Can Nuclear Imaging of Activated Macrophages with Folic Acid-Based Radiotracers Serve as a Prognostic Means to Identify COVID-19 Patients at Risk? Pharmaceuticals (Basel). 13:238. doi: 10.3390/ph13090238.
85.Sheybani Z, Dokoohaki MH, Negahdaripour M et al (2020) The Role of Folic Acid in the Management of Respiratory Disease Caused by COVID-19. ChemRxiv DOI: 10.26434/chemrxiv.12034980.v1
86. Wu C, Zheng M, Yang Y et al (2020) Furin: A Potential Therapeutic Target for COVID-19. iScience. 23:101642. doi:10.1016/j.isci.2020.101642
87.Shakoor H, Feehan J, Mikkelsen K et al (2021) Be well: A potential role for vitamin B in COVID-19. Maturitas 144:108-111. doi:10.1016/j.maturitas.2020.08.007
88-Acosta-Elias J, Espinosa-Tanguma R (2020) The Folate Concentration and/or Folic Acid Metabolites in Plasma as Factor for COVID-19 Infection. Front Pharmacol 11:1062. Published 2020 Jul 16. doi:10.3389/fphar.2020.01062
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Unsal V, Sabancilar I, Ozbek E, Mermutluoglu C, Temiz H. Role of vitamin D, folic acid, ferritin, inflammation and oxidative stress in the pathogenesis of COVID-19. Progr Nutr [Internet]. 2022 Dec. 23 [cited 2024 Nov. 5];24(4):e2022126. Available from: https://mattioli1885journals.com/index.php/progressinnutrition/article/view/12306
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Unsal V, Sabancilar I, Ozbek E, Mermutluoglu C, Temiz H. Role of vitamin D, folic acid, ferritin, inflammation and oxidative stress in the pathogenesis of COVID-19. Progr Nutr [Internet]. 2022 Dec. 23 [cited 2024 Nov. 5];24(4):e2022126. Available from: https://mattioli1885journals.com/index.php/progressinnutrition/article/view/12306
