Covid-19 Hastalığı Tedavisinde Vitaminlerin Rolü

Lu R, Zhao X, Li J, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: Implications for virus origins and receptor binding. Lancet. 2020;395:565–574. doi: 10.1016/S0140-6736(20)30251-

Duffy S. Why are RNA virus mutation rates so damn high? PLoS Biol. 2018;16:e3000003. doi: 10.1371/journal. pbio.3000003

Chen Y, Li L. SARS-CoV-2: Virus dynamics and host response. Lancet Infect. Dis. 2020;20:515–516. doi: 10.1016/S1473-3099(20)30235-8

Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study. Lancet. 2020;395 1054–1062. doi: 10.1016/S0140-6736(20)30566-

Calder P.C. Immunonutrition. Br. Med. J. 2003;327:117–118. doi: 10.1136/ bmj. 327.7407.117.

Soares A.D.N, Costa K.A, Wanner S.P et al. Dietary glutamine prevents the loss of intestinal barrier function and attenuates the increase in core body temperature induced by acute heat exposure. Br. J. Nutr. 2014;112:1601–1610. doi: 10.1017/S0007114514002608.

Mizock B.A. Immunonutrition and critical illness: An update. Nutrition. 2010;26:701–707. doi: 10.1016/j.nut.2009.11.010.

Beale R.J, Bryg D.J, Bihari D.J. Immunonutrition in the critically ill: A systematic review of clinical outcome. Crit. Care Med. 1999;27:2799–2805. doi: 10.1097/00003246-199912000-00032

Heyland D.K, Dhaliwal R, Suchner U, et al. Antioxidant nutrients: A systematic review of trace elements and vitamins in the critically ill patient. Intensive Care Med. 2005;31:327–337.doi:10.1007/s00134-004

Pontes-Arruda A, Aragão A.M.A, Albuquerque J.D. Effects of enteral feeding with eicosapentaenoic acid, γ-linolenic acid, and antioxidants in mechanically ventilated patients with severe sepsis and septic shock. Crit. Care Med. 2006;34:2325-2333. doi:10.1097/01.CCM.0000234033.656 57

Li C, Bo L, Liu W, et al. Enteral immunomodulatory diet (omega-3 fatty acid, γ-linolenic acid and antioxidant supplementation) for acute lung injury and acute respiratory distress syndrome: An updated systematic review and meta-analysis. Nutrients. 2015;7:5572–5585. doi: 10.3390/nu 7075239.

Nelson J.L, DeMichele S.J, Pacht E.R, et al. Effect of enteral feeding with eicosapentaenoic acid, γ-linolenic acid, and antioxidants on antioxidant status in patients with acute respiratory distress syndrome. J. Parenter. Enter. Nutr. 2003;27:98–104. doi: 10.1177/014860710302700298.

Michienzi SM, Badowski ME. Can vitamins and/or supplements provide hope against coronavirus? Drugs in Context. 2020;9:1–29. doi: 10.7573/dic.2020-5-7.

Tay M.Z, et al (2020) Inflammation and intervention, pp 363–374

Ni W, Yang X, Yang D, et al. Role of angiotensin-converting enzyme 2 (ACE2) in COVID-19. Crit Care. 2020;24(1):1–10. doi: 10.1186/s13054-020-03120-0.

Yuki K, Fujiogi M, Koutsogiannaki S, COVID-19 pathophysiology: a review. In: Clinical immunology. Academic Press Inc., pp 108427. 10.1016/j.clim.2020.108427.

Shakoor H, Feehan J, Dhaheri A.S, et al. Immune-boosting role of vitamins D, C, E, zinc, selenium and omega-3 fatty acids: could they help against COVID-19? Maturitas. 10.1016/j.maturitas.2020.08.003

Shakoor H, Feehan J, Mikkelsen K, et al. Be well: a potential role for vitamin B in COVID-19. Maturitas. 10.1016/j.maturitas.2020.08.007

Derbyshire E, Delange J. COVID-19: is there a role for immunonutrition, particularly in the over 65s? BMJ Nutrition, Prevention & Health. 2020;3(1):100–105. doi: 10.1136/bmjnph-2020-000071.

Kumar P, Kumar M, Bedi O, et al. Role of vitamins and minerals as immunity boosters in COVID-19. Inflammopharmacology. 2021 Jun 10 : 1–16. doi: 10.1007/s10787-021-00826-7

Gombart AF, Pierre A, Maggini S. A review of micronutrients and the immune system–working in harmony to reduce the risk of infection. Nutrients. 10.3390/nu12010236

Magdalena P.A, Pop A, Iordache F, et al Antioxidant, anti-inflammatory and immunomodulatory roles of vitamins in COVID-19 therapy. Eur J Med Chem. 2022 Mar 15; 232: 114175. Published online 2022 Feb 4. doi: 10.1016/j.ejmech.2022.114175

Ng W.H, Tipih T, Makoah N.A, et al. Comorbidities in SARS-CoV-2 patients: a systematic review and meta-analysis. mBio. 2021;12 e03647-2

Loffredo L, Violi F. COVID-19 and cardiovascular injury: a role for oxidative stress and antioxidant treatment? Int. J. Cardiol. 2020;312:136.

Moldogazieva N.T, Mokhosoev I.M, Melnikova T.I, et al. Oxidative stress and advanced lipoxidation and glycation end products (ALEs and AGEs) in aging and age-related diseases. Oxid. Med. Cell. Longev. 2019:14. Article ID 3085756

Cheeseman K.H, Slater T.F. An introduction to free radical biochemistry. Br. Med. Bull. 1993;49:481–493.

Wang J.Z, Zhang R.Y, Bai J. An anti-oxidative therapy for ameliorating cardiac injuries of critically ill COVID-19-infected patients. Int. J. Cardiol. 2020;312:137–138.

Loffredo L, Martino F, Zicari A.M, et al. Enhanced NOX-2 derived oxidative stress in offspring of patients with early myocardial infarction. Int. J. Cardiol. 2019;293:56–59

Perrone L.A, Belser J.A, Wadford D.A, et al. Inducible nitric oxide contributes to viral pathogenesis following highly pathogenic influenza virus infection in mice. J. Infect. Dis. 2013;207 1576-158.

Abulmeaty M.M.A, Aljuraiban G.S, Shaikh S.M, et al. The efficacy of antioxidant oral supplements on the progression of COVID-19 in non-critically ill patients: a randomized controlled trial. Antioxidants (Basel) 2021;10:804.

Ntyonga P.M.P. COVID-19 infection and oxidative stress: an underexplored approach for prevention and tratament? Pan Afr. Med. J. 2020;35:12. doi: 10.11604/ pamj.2020.35.2.2287.

Merad M, Martin J.C. Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages. Nat. Rev. Immunol. 2020;20:355–362.

Ruan Q, Yang K, Wang W. Et al. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020;46:846–848. 1294-1297

Liu F, Zhu Y, Zhang J. et al. Intravenous high-dose vitamin C for the treatment of severe COVID-19: study protocol for a multicentre randomised controlled trial. BMJ Open. 2020;10

Pisoschi A.M, Pop A, Iordache F. et al. Oxidative stress mitigation by antioxidants-an overview on their chemistry and influences on health status. Eur. J. Med. Chem. 2021;209: 112891.

Johnson E.J, Russell R.M. In: Encyclopedia of Dietary Supplements. second ed. Coates P.M, et al. editors. Informa Healthcare; London, New York: 2010. Beta-carotene; pp. 115–120.

Ross A. In: Modern Nutrition in Health and Disease. tenth ed. Shils M., Shike M., Ross A., Caballero B., Cousins R., editors. Lippincott Williams & Wilkins; Baltimore: 2006. Vitamin A and carotenoids; pp. 351–375.

Ross C.A. In: Encyclopedia of Dietary Supplements. second ed. Coates P.M., Betz J.M., Blackman M.R., Cragg G.M., Levine M., Moss J., White J.D., editors. Informa Healthcare; London, New York: 2010. Vitamin A; pp. 778–791

Huang Z, Liu Y, Qi G, etal. Role of vitamin A in the immune system. J. Clin. Med. 2018;7:258. doi: 10.3390/jcm7090258. .

Retinol|C20H30O—PubChem. [(accessed on 17 August 2020)]; Available online: https://pubchem.ncbi.nlm.nih.gov/compound/Retinol.

Lidén M, Eriksson U. Understanding retinol metabolism: Structure and function of retinol dehydrogenases. J. Biol. Chem. 2006;281:13001–13004. doi: 10.1074/jbc.R500027200

Lefebvre P, Martin P.J, Flajollet S, et al. Transcriptional Activities of Retinoic Acid Receptors. Vitam. Horm. 2005;70:199–264. doi: 10.1016/S0083-6729(05)70007-8.

Tanumihardjo SA. Vitamin A:Biomarkers of nutrition for development Am. J. Clin. Nutr. 2011;94:658S–65S. doi: 10.3945/ajcn. 110. 005777.

Tang G. Bioconversion of dietary provitamin A carotenoids to vitamin A in humans. Am. J. Clin. Nutr. 2010;91:1468S. doi: 10.3945/ajcn. 2010. 28674G.

Dao D.Q, Ngo T.C, Thong N.M, et al. Is vitamin A an antioxidant or a pro oxidant? J. Phys. Chem. B. 2017;121:9348–9357. doi: 10.1021/acs. jpcb.7b07065

Jørgensen M.J, Hein K.L, Hempel C, et al. The effect of vitamin A supplementation and diphtheria-tetanus-pertussis vaccination on parasitaemia in an experimental murine malaria model. Scand. J. Infect. Dis. 2011;43:296–303. doi: 10.3109/00365548.2010.535845.

Benn C.S. Combining vitamin A and vaccines: Convenience or conflict? Dan. Med. J. 2012;59:B4378.

Caccialanza R, Laviano A, Lobascio F, et al. Early nutritional supplementation in non-critically ill patients hospitalized for the 2019 novel coronavirus disease (COVID-19): Rationale and feasibility of a shared pragmatic protocol. Nutrition. 2020;74:110835. doi: 10.1016/j.nut. 2020. 110835.

Hashimoto S, Hayashi S, Yoshida S, et al. Retinoic acid differentially regulates interleukin-1β and interleukin-1 receptor antagonist production by human alveolar macrophages. Leuk. Res. 1998;22:1057–1061. doi: 10.1016/S0145-2126(98)00119-

Yang C, Yang X, Du J, et al. Retinoic acid promotes the endogenous repair of lung stem/progenitor cells in combined with simvastatin after acute lung injury: A stereological analysis. Respir. Res. 2015;16:140. doi: 10.1186/ s12931-015-0300-9.

Trottier C, Colombo M, Mann K.K, et al. Retinoids inhibit measles virus through a type I IFN-dependent bystander effect. FASEB J. 2009;23:3203–3212. doi: 10.1096/fj.09-129288.

Raverdeau M, Mills KHG. Modulation of T cell and innate immune responses by retinoic acid. J Immunol. 2014;192(7):2953–2958. doi: 10.4049 /jimmunol.1303245.

Matikainen S, Ronni T, Hurme M, et al. (1996) Retinoic acid activates interferon regulatory factor-1 gene expression in myeloid cells.

Angulo A, Chandraratna RA, LeBlanc JF, Ghazal P. Ligand induction of retinoic acid receptors alters an acute infection by murine cytomegalovirus. J Virol. 1998;72(6):4589–4600. doi: 10.1128/JVI.72.6. 4589-4600.1998.

Li B, Wang Y, Shen F, et al. Identification of retinoic acid receptor agonists as potent hepatitis B virus inhibitors via a drug repurposing screen. Antimicrob Agents Chemother. 10.1016/j.antiviral.2019.04.009

Gudas LJ Emerging roles for retinoids in regeneration and differentiation in normal and disease states. Biochim Biophys Acta (BBA)-Molecular Cell Biol Lipids. 1821(1):213–21. 10.1016/j.bbalip.2011.08.002.

Palace V.P, Khaper N, Qin Q, et al. Antioxidant potentials of vitamin A and carotenoids and their relevance to heart disease. Free Radical Biol. Med. 1999;26:746–761.

Dao D.Q, Ngo T.C, Thong N.M, et al. Is Vitamin A an antioxidant or a pro-oxidant? J. Phys. Chem. B. 2017;121:9348–9357.

Samad N, Dutta S, Sodunke T.E, et al. Fat-soluble vitamins and the current global pandemic of COVID-19: evidence-based efficacy from literature review. J. Inflamm. Res. 2021;14:2091–2110.

Jovic T.H, Ali S.R, Ibrahim N, et al. Could vitamins help in the fight against COVID-19? Nutrients. 2020;12:2550.

Ye Q, Wang B, Mao J. The pathogenesis and treatment of the “Cytokine storm” in COVID-19. J. Infect. 2020;80:607–613.

Al-Sumiadai M.M, Ghazzay H, Al-Dulaimy W.Z.S. Therapeutic effect of Vitamin A on severe COVID-19 patients. EurAsia J. BioSci. 2020;14:7347–7350.

Stephensen C.B, Lietz G. Vitamin A in resistance to and recovery from infection: relevance to SARS-CoV2. Br. J. Nutr. 2021;126:1663–1672.

Li R, Wu K, Li Y, et al. Revealing the targets and mechanisms of vitamin A in the treatment of COVID-19. Aging-US. 2020;12:15784–15796

U. Gröber, M.F. Holick, The coronavirus disease (COVID-19) - a supportive approach with selected micronutrients, Int. J. Vitam. Nutr. Res. DOI:10.1024/0300-9831/a000693.

Fiorino S, Gallo C, Zippi M, et al. Cytokine storm in aged people with CoV-2: possible role of vitamins as therapy or preventive strategy. Aging Clin. Exp. Res.2020;32: 2115–2

WHO I.M.A.I. Vol. 1. WHO; Geneva: 2012. https://apps.who .int/iris/handle/ 10665/77751 (District Clinician Manual: Hospital Care for Adolescents and Adults: Guidelines for the Management of Common Illnesses with Limited Resources).

Sarohan A.R. COVID-19: endogenous retinoic acid theory and retinoic acid depletion syndrome. Med. Hypotheses. 2020;144:110250

Thirumdas R, Kothakota A. Pandiselvam R, ET AL. Role of food nutrients and supplementation in fighting against viral infections and boosting immunity: a review. Trends Food Sci. Technol. 2021;110:66–77.

Timoneda J, Rodríguez-F.L, Zaragozá R, ET AL. Vitamin A deficiency and the lung. Nutrients. 2018;10:1132.

Spinas E, Saggini A, Kritas S.K, et al. Crosstalk Between Vitamin B and Immunity. J. Biol. Regul. Homeost. Agents. 2015;29:283–288.

European Union EU Register on Nutrition and Health Claims. [(accessed on 21 August 2020)]; Available online: https://ec.europa.eu/food/safety/ labelling nutrition/claims/ register/public

Calder P.C, Carr A.C, Gombart A.F., et al. Optimal nutritional status for a well-functioning immune system is an important factor to protect against viral infections. Nutrients. 2020;12:1181. doi: 10.3390/nu12041181.

Kandeel M, Al-Nazawi M. Virtual screening and repurposing of FDA approved drugs against COVID-19 main protease. Life Sci. 2020;251:15. doi: 10.1016/j.lfs.2020.117627.

Jin Z, Du X, Xu Y, et al. Structure of Mpro from COVID-19 virus and discovery of its inhibitors. Nature. 2020;582:289–293. doi: 10.1038/s 41586-020-2223-y.

Serseg T, Benarous K, Yousfi M. Hispidin and lepidine E: Two natural compounds and folic acid as potential inhibitors of 2019-novel coronavirus Main Protease (2019-nCoVMpro), molecular docking and SAR study. Curr. Comput. Aided. Drug Des. 2020 doi: 10.2174/157340991 6666200422075440.

Jovic T.H, Stephen R.A,Nader I, et al. Could Vitamins Help in the Fight Against COVID-19? Nutrients. 2020 Sep; 12(9): 2550. Published online 2020 Aug 23. doi:10.3390/ nu12092550

Lindschinger M, Tatzber F, Schimetta W, et al. Randomized pilot trial to evaluate the bioavailability of natural versus synthetic Vitamin B complexes in healthy humans and their effects on homocysteine, oxidative stress, and antioxidant levels. Oxid Med Cell Longev. 2019 doi: 10.1155/2019/6082613.

Calder PC et al (2020) Optimal nutritional status for a well-functioning immune system is an important factor to protect against viral infections. Nutrients. 10.3390/nu12041181

Shakoor H, Feehan J, Mikkelsen K, et al. Be well: a potential role for vitamin B in COVID-19. Maturitas. 2021;144:108–111.

Ozdemir Z.O, Senturk M, Ekinci D. Inhibition of mammalian carbonic anhydrase isoforms I, II and VI with thiamine and thiamine-like molecules. J. Enzym. Inhib. Med. Chem. 2013;28:316–319.

Kumar P, Kumar M, Bedi O, et al. Role of vitamins and minerals as immunity boosters in COVID-19. Infammopharmacology. 2021;29:1001–1016.

Nagai A, Matsumiya H, Hayashi M, et al. Effects of nicotinamide and niacin on bleomycin-induced acute injury and subsequent fibrosis in hamster lungs. Experimentallungresearch. 1994;20(4):263–281. doi: 10.3109/01902149409064387.

Mehmel M, Jovanović N, Spitz U. Nicotinamide riboside the current state of research and therapeutic uses. Nutrients. 2020;12(6):1616. doi: 10.3390/nu12061616.

Liu B, Li M, Zhou Z, et al. Can we use interleukin-6 blockade for coronavirus disease 2019 (COVID-19)-induced cytokine release syndrome. J Autoimmunity. https://doi.org/10.1016/j.jaut.2020.102452

Zhang L, Liu Y. Potential interventions for novel coronavirus in China: a systematic review. J. Med. Virol. 2020;92:479–490.

Peterson C.T, Rodionov D.A, Osterman A.L, et al. Vitamins and their role in immune regulation and cancer. Nutrients. 2020;12:3380

Parra M, Stahl S, Hellmann H. Vitamin B6 and its role in cell metabolism and physiology. Cells. 2018;7(7):84. doi: 10.3390/cells7070084.

Desbarats J. Pyridoxal 5’-phosphate to mitigate immune dysregulation and coagulopathy in COVID-19, Preprints 2020, 2020050144, DOI:10.20944/preprints 202005. 0144.v1.

Van W.V, Luus H.G, Heyns AdP. The in vivo effect in humans of pyridoxal-5′- phosphate on platelet function and blood coagulation. Thromb. Res. 1992;66:657–668.

Kumar V, Jena M In silico virtual screening-based study of nutraceuticals predicts the therapeutic potentials of folic acid and its derivatives against COVID-19. 10.1007/ 13337-020-00643-6.

Sheybani Z, Dokoohaki M.H, Negahdaripour M, et al. The role of folic acid in the management of respiratory disease caused by COVID-19. ChemRxiv. 2020 doi: 10.26434/chemrxiv.12034980.v1.

Kumar V, Kancharla S, Jena M.K. In silico virtual screening-based study of nutraceuticals predicts the therapeutic potentials of folic acid and its derivatives against COVID-19. Virusdisease. 2021;32:29–37.

Chalupsky K, Kračun D, Kanchev I, et al Folic acid promotes recycling of tetrahydrobiopterin and protects against hypoxia-induced pulmonary hypertension by recoupling endothelial nitric oxide synthase. Antioxidants Redox Signal. 2015;23:1076–1

Wiltshire E, Peña A.S, MacKenzie K, et al. High dose folic acid is a potential treatment for pulmonary hypertension, including when associated with COVID-19 pneumonia. Med. Hypotheses. 2020;143:110142.

Meisel E, Efros O, Bleier J, et al. Folate levels in patients hospitalized with coronavirus disease 2019. Nutrients. 2021;13:812.

Zhang Y, Guo R, Kim S.H, et al. SARS-CoV-2 hijacks folate and one-carbon metabolism for viral replication. Nat. Commun. 2021;12:1676.

Mikkelsen K, Stojanovska L, Prakash M, et al. The effects of vitamin B on the immune/cytokine network and their involvement in depression. Maturitas. 2017;96:58–7

Nemazannikova N, Mikkelsen K, Stojanovska L, et al. Is there -a link between vitamin B and multiple sclerosis? Med. Chem. 2018;14:170–180.

Sabry W, Elemary M, Burnouf T, et al. Vitamin B12 deficiency and metabolism-mediated thrombotic microangiopathy (MM-TMA) Transfus. Apher. Sci. 2020;59: 1027

Stipp M.M. SARS-CoV-2: micronutrient optimization in supporting host immunocompetence. Int. J. Clin.Case Rep. Rev. 2020;2(2) doi: 10.31579/2690-4861/024.

Wolffenbuttel B.H.R, Wouters H.J.C.M, HeinerFokkema M.R, et al The many faces of cobalamin (vitamin B12) deficiency. Mayo Clin. Proc.:Innov. Quality Outcomes. 2019;3:200–214.

Grangé S, Bekri S, Artaud M. E, et al. Adult-onset renal thrombotic microangiopathy and pulmonary arterial hypertension in cobalamin C deficiency. Lancet. 2015;386(9997):1011

Calder P.C, Carr A.C, Gombart A.F, et al. Optimal nutritional status for a well-functioning immune system is an important factor to protect against viral infections. Nutrients. 2020;12:1181.

Manzanares W, Hardy G. Vitamin B12 pharmaconutrition for COVID-19. Rev. Nutr. Clin. Metab. 2021;4:65–69.

Dos Santos L.M.J. Can vitamin B12 be an adjuvant to COVID-19 treatment? GSC Biol. Pharm. Sci. 2020;11:1–5.

Manzanares W, Hardy G. Vitamin B12: the forgotten micronutrient for critical care. Curr. Opin. Clin. Nutr. Metab. Care. 2010;13:662–668.

Tan C.W, Ho L.P, Kalimuddin S, et al. A cohort study to evaluate the effect of combination vitamin D, magnesium and vitamin B12 (DMB) on progression to severe outcome in older COVID-19 patients. Nutrition. 2020;79–80:111017.

Padayatty S.J, Levine M. Vitamin C: The known and the unknown and Goldilocks. Oral Dis. 2016;22:463–493. doi: 10.1111/odi.12446. [

Wang Y, Russo T.A, Kwon O, et al. Ascorbate recycling in human neutrophils: Induction by bacteria. Proc. Natl. Acad. Sci. USA. 1997;94:13816–13819. doi: 10.1073/pnas.94.25.13816

Nualart F.J, Rivas C.I, Montecinos V.P, et al. Recycling of vitamin C by a bystander effect. J. Biol. Chem. 2003;278:10128–10133. doi: 10.1074/jbc. M210686200.

Thomas W.R, Holt P.G. Vitamin C and immunity: An assessment of the evidence. Clin. Exp. Immunol. 1978;32:370–379.

Webb A.L., Villamor E. Update: Effects of antioxidant and non-antioxidant vitamin supplementation on immune function. Nutr. Rev. 2007;65:181–217. doi: 10.1111/j.1753-4887.2007.tb00298.x.

Hemilä H. Vitamin C. Springer; Milano, Italy: 1998. Vitamin C and infectious diseases; pp. 73–85.

Goode H.F., Webster N.R. Free radicals and antioxidants in sepsis. Crit. Care Med. 1993;21:1770–1776. doi: 10.1097/00003246-199311000-00029.

Akaike T, Suga M, Maeda H. Free radicals in viral pathogenesis: Molecular mechanisms involving superoxide and NO. Proc. Soc. Exp. Biol. Med. 1998;217 doi: 10.3181/00379727-217-44206.

Peterhans E. Oxidants and antioxidants in viral diseases: Disease mechanisms and metabolic regulation. J. Nutr. 1997;127:962S–965S. doi: 10.1093/jn/127.5.962S.

Hemilä H. Doctoral Thesis. University of Helsinki; Helsinki, Iceland: 2006. Do Vitamins C and E Affect Respiratory Infections?

Chen Y., Luo G., Yuan J., et al. Vitamin C mitigates oxidative stress and tumor necrosis factor-alpha in severe community-acquired pneumonia and LPS-induced macrophages. Mediat. Inflamm. 2014;2014:426740. doi: 10.1155/2014/426740.

Carr AC, Maggini S. Vitamin C, and immune function. Nutrients. 2017;9 (11):1211. doi: 10.3390/nu9111211.

Hemilä H, Chalker E. Vitamin C can shorten the length of stay in the ICU: a meta-analysis. Nutrients.2019;11(4):708. doi:10.1002/14651858. pub4.

Hemilä H, Chalker E (2013) Vitamin C for preventing and treating the common cold. Cochrane database Syst Rev.10.1002/14651858.CD0009 80. pub4

Kashiouris M.G, L’Heureux M, Cable C.A, et al. The emerging role of vitamin C as a treatment for sepsis. Nutrients. 2020;12(2):292. doi: 10.3390/nu12020292.

Baladia E, Pizarro AB, Rada G Vitamin C for the treatment of COVID-19: a living systematic review. medRxiv. 10.1101/2020.04.28. 20083360

Bae M, Kim H. The role of vitamin C, vitamin D, and Selenium in immune system against COVID-19. Molecules. 2020;25:5346.

Hoang B.X, Shaw G, Fang W, et al. Possible application of high-dose vitamin C in the prevention and therapy of coronavirus infection. J. Glob. Antimicrob. Resist. 2020; 23:256–26

Kornberg M.D, Bhargava P, Kim P.M, et al. Dimethyl fumarate targets GAPDH and aerobic glycolysis to modulate immunity. Science. 2018;360: 449 453.

Lips P, Van Schoor N.M. The effect of vitamin D on bone and osteoporosis. Best Pract. Res. Clin. Endocrinol. Metab. 2011;25:585–591. doi: 10.1016/j. beem.2011.05.002

Carpagnano G.E, Di Lecce V, Quaranta V.N, et al. Vitamin D deficiency as a predictor of poor prognosis in patients with acute respiratory failure due to COVID-19. J. Endocrinol. Invest. 2021;44:765–771.

Mendy A, Apewokin S, Wells A.A, et al. Factors associated with hospitalization and disease severity in a racially and ethnically diverse population of COVID-19 patients. medRxiv. 2020;6:20137323. doi: 10.1101/2020.06.25.20137323. 25.

Bassatne A, Basbous M, Chakhtoura M, et al. The link between COVID-19 and Vitamin D a systematic review and meta-analysis. Metab. Clin. Exp. 2020;119:154753

Di Filippo L, Formenti A.M, Rovere-Querini P, et al. Hypocalcemia is highly prevalent and predicts hospitalization in patients with COVID-19. Endocrine. 2020; 68:475-47

Liu J, Han P, Wu J, et al. Prevalence and predictive value of hypocalcemia in severe COVID-19 patients. J. Infect. Public Health. 2020;13:1224-1228

Nieto TJLE, Verdia BC, Jimenez GJM, et al. Severe acute respiratory syndrome coronavirus E protein transports calcium ions and activates the NLRP3 inflammasome. Virology. 2015;485:330–339.

Walls AC, Park YJ, Tortorici MA, et al. Structure, function and antigenici ty of the SARS-CoV-2 spike glycoprotein. Cell. 2020;181:281–292.

Ulivieri F.M, Banfi G, Camozzi V, et al. Vitamin D in the Covid-19 era: a review with recommendations from a G.I.O.S.E.G. expert panel. Endocrine. 2021;72:597–603

Jain S.K, Parsanathan R. Can Vitamin D and L-Cysteine co-supplementation reduce 25(OH)-Vitamin D deficiency and the mortality associated with COVID-19 in African Americans? J. Am. Coll. Nutr. 2020;39:694–699

Rondanelli M, Miccono A, Lamburghini S, et al. Self-care for common colds: The pivotal role of vitamin D, vitamin C, zinc, and echinacea in three main immune interactive clusters (physical barriers, innate and adaptive immunity) involved during an episode of common colds-Practical advice on dosages and on the time to take these nutrients/botanicals in order to prevent or treat common colds. Evid. Based Complement. Altern. Med. 2018;2018:5813095. doi: 10.1155/2018/5813095

Vankadari N, Wilce J.A. Emerging WuHan (COVID-19) coronavirus: Glycan shield and structure prediction of spike glycoprotein and its interaction with human CD26. Emerg. Microbes Infect. 2020;9:601–604. doi: 10.1080/22221751.2020.1739565

Skariyachan S, Challapilli S, Packirisamy S, et al. Recent aspects on the pathogenesis mechanism, animal models and novel therapeutic interventions for middle east respiratory syndrome coronavirus infections. Front. Microbiol. 2019;10:569. doi: 10.3389/ fmicb. 2019.00569

Liu P.T, Stenger S, Li H, et al. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science. 2006;311:1770-1773. doi: 10.1126/science. 1123933.

Adams J.S, Ren S, Liu P.T, et al. Vitamin D-directed rheostatic regulation of monocyte antibacterial responses. J. Immunol. 2009;182:4289–4295. doi: 10.4049/jimmunol.0803736

Martínez-M.J, Hernandez J.C, Urcuqui-I.S. Effect of high doses of vitamin D supplementation on dengue virus replication, toll-like receptor expression, and cytokine profiles on dendritic cells. Mol. Cell. Biochem. 2020;464:169–180. doi: 10.1007/ s11010-019-03658-w.

Maghbooli Z, Sahraian M.A, Ebrahimi M, et al. Vitamin D sufficiency, a serum 25-hydroxyvitamin D at least 30 ng/mL reduced risk for adverse clinical outcomes in patients with COVID-19 infection. PLoS One. 2020;15

Quesada-Gomez J.M, Entrenas-Castillo M, Bouillon R. Vitamin D receptor stimulation to reduce acute respiratory distress syndrome (ARDS) in patients with coronavirus SARS-CoV-2 infections. J. Steroid Biochem. Mol. Biol. 2020;202:10571

Bilezikian J.P, Bikle D, Hewison M, et al. Mechanisms in endocrinology: vitamin D and COVID-19. Eur. J. Endocrinol. 2020;185:R133–R147.

Greiller C.L, Martineau A.R. Modulation of the immune response to respiratory viruses by vitamin D. Nutrients. 2015;7:4240–4270.

A. Roth, S. Lütke, D. Meinberger, et al. LL-37 fights SARS-CoV-2: the Vitamin D-inducible peptide LL-37 inhibits binding of SARS-CoV-2 spike protein to its cellular receptor angiotensin converting enzyme 2 in vitro, bioRxiv, 10.1101/2020. 12.02. 408153.

Shiozawa K, Shiozawa S, Shimizu S, et al. 1 alpha, 25-dihydroxyvitamin D3 inhibits pokeweed mitogen-stimulated human B-cell activation: an analysis using serum-free culture conditions. Immunology. 1985;56:161

Bruce D, Ooi J.H, Yu S, et al. Vitamin D and host resistance to infection? Putting the cart in front of the horse. Exp. Biol. Med. 2010;235:921–927.

Xu Y, Baylink D.J, Chen C.S, et al. The importance of vitamin D metabolism as a potential prophylactic, immunoregulatory and neuroprotective treatment for COVID-19. J. Transl. Med. 2020;18:322.

Teymoori-Rad M, Shokri F, Salimi V, Marashi S.M. The interplay between vitamin D and viral infections. Rev. Med. Virol. 2019;29

Gruber-Bzura B.M. Vitamin D and influenza-prevention or therapy? Int. J. Mol. Sci. 2018;19:2419

Yaqinuddin A, Ambia A.R, Alaujan R.A. Immunomodulatory effects of Vitamin D and Vitamin C to improve immunity in COVID-19 patients. J. Health Allied Sci. 2022;12:1–6.

Cantorna M.T, Snyder L, Lin Y.D, et al. Vitamin D and 1,25(OH) 2D regulation of T cells. Nutrients. 2015;7:3011–3021. [

Xiao D, Li X, Su X, et al. Could SARS-CoV-2-induced lung injury be attenuated by vitamin D? Int. J. Infect. Dis. 2021;102:196–202.

Sassi F, Tamone C, D'Amelio P. Vitamin D: nutrient, hormone, and immunomodulator. Nutrients. 2018;10:1656.

Sloka S, Silva C, Wang J, et al. Predominance of Th2 polarization by vitamin D through a STAT6-dependent mechanism. J. Neuro inflam mation. 2011;8:56.

Kaiko G.E, Horvat J.C, Beagley K.W, et al. Immunological decision-making: how does the immune system decide to mount a helper T-cell response? Immunology.2008; 123:326–338.

Chen Y, Zhang J, Ge X, et al. Vitamin D receptor inhibits nuclear factor κB activation by interacting with IκB kinase β protein. J. Biol. Chem. 2013;288:19450–19458.

Silberstein M. COVID-19 and IL-6: why vitamin D (probably) helps but tocilizumab might not. Eur. J. Pharmacol. 2021;899:174031.

Xu J, Yang J, Chen J, et al. Vitamin D alleviates lipopolysaccharide-induced acute lung injury via regulation of the renin-angiotensin system. Mol. Med. Rep. 2017;16:7432–7438.

Verdecchia P, Cavallini C, Spanevello A, et al. The pivotal link between ACE2 deficiency and SARS-CoV-2 infection. Eur. J. Intern. Med. 2020;76:14–20.

Wösten V.A.R.M, Lutter R, Specht P.A, et al. Acute respiratory distress syndrome leads to reduced ratio of ACE/ACE2 activities and is prevented by angiotensin-(1-7) or an angiotensin II receptor antagonist. J. Pathol. 2011;225:618–627

Hansdottir S, Monick M.M. Vitamin D effects on lung immunity and respiratory diseases. Vitam. Horm. 2011;86:217–237.

Han J.E, Jones J.L, Tangpricha V, et al. High dose vitamin D administration in ventilated intensive care unit patients: a pilot double blind randomized controlled trial. J. Clin. Transl. Endocrinol. 2016;4:59

Meydani S.N, Leka L.S, Fine B.C, et al. Vitamin E and respiratory tract infections in elderly nursing home residents: A randomized controlled trial. J. Am. Med. Assoc.2004;292:828–836. doi:10.1001/ jama.292.7.828

Meydani S.N. Vitamin E supplementation and in vivo immune response in healthy elderly subjects. JAMA. 1997;277:1380–1386. doi: 10.1001/jama. 1997.035404100580

Tian S, Hu W, Niu L, et al. Pulmonary pathology of early-phase 2019 novel coronavirus (COVID-19) pneumonia in two patients with lung cancer. J. Thorac. Oncol. 2020;15:700–704. doi: 10.1016/j.jtho.2020.02.010.

Xu Z, Shi L, Wang Y, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir. Med. 2020;8: 420-422. doi: 10.1016/S2213-2600(20)30076-X.

Beck M.A, Handy J, Levander O.A. Host nutritional status: The neglected virulence factor. Trends Microbiol. 2004;12:417–423. doi: 10.1016/j.tim. 2004.07.007.

Tavakol S, Seifalian A.M, Vitamin E at a high dose as an anti-ferroptosis drug and not just a supplement for COVID-19 treatment, Biotechnol. Appl. Biochem. 10.1002/bab.2176.

Murni I.K. Prawirohartono E.P.Triasih R. Potential role of Vitamins and Zinc on acute respiratory infections including Covid-19. Glob. Pediatr. Health.2021;8:18.

Maggini S, Maldonado P, Cardim P, et al. Vitamins C, D and zinc: synergistic roles in immune function and infections. Vitam. Miner. 2017;6:3.

Hakamifard A, Soltani R, Maghsoudi A, et al. The effect of vitamin E and vitamin C in patients with COVID-19 pneumonia; a randomized controlled clinical trial. Immunopathol. Persa. 2021;8:e08. doi: 10.34172/ipp.2022.08.

Hubicka U, Padiasek A, Żuromska W.B, et al. Determination of Vitamins K1, K2 MK-4, MK-7, MK-9 and D3 in pharmaceutical products and dietary supplements by TLC- Densitometry. Processes. 2020;8(7):870. doi: 10.1021/jf204194z.

Janssen R, Walk J. Vitamin K epoxide reductase complex subunit 1 (VKORC1) gene polymorphism as determinant of differences in Covid-19-related disease severity. Med Hypotheses. 2020;144:110218. doi: 10.1016/j.mehy.2020.110218.

Mccann JC, Ames BN (2020) Vitamin K, an example of triage theory: is micronutrient inadequacy linked to diseases of aging? 1–3. 10.3945/ajcn. 2009.27930

Klok FA, Kruip MJHA, Meer NJM et al., Arbous MS, Gommers DAMPJ, Kant KM, Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res. 2020;191:145. doi: 10.1016/j.thromres.2020.04.013.

Hodges S.J, Pitsillides A.A, Ytrebø L.M, et al. In: Vitamin K2: Vital for Health and Wellbeing. Gordeladze J, editor. IntechOpen; 2017. Anti-inflammatory actions of vitamin K. Chap. 8.

Janssen R, Visser M.P.J, Dofferhoff A.S.M, et al. Vitamin K metabolism as the potential missing link between lung damage and thromboembolism in Coronavirus disease 2019. Br. J. Nutr. 2021;126:191–198

Chakraverty R, Davidson S, Peggs K, et al. The incidence and cause of coagulopathies in an intensive care population. Br. J. Haematol. 1996;93:460–463.

Crowther M.A, McDonald E, Johnston M, et al. Vitamin K deficiency and D-dimer levels in the intensive care unit: a prospective cohort study. Blood Coagul. Fibrinolysis. 2002;13:49–52.

Becker R.C. COVID-19 update: COVID-19-associated coagulopathy. J. Thromb. Thrombolysis. 2020;50:54–67.

Dofferhoff A.S.M, Piscaer I, Schurgers L.J, et al. Reduced vitamin K status as a potentially modifiable risk factor of severe COVID-19. Clin. Infect. Dis. 2021;73:e4039

Piscaer I, van den Ouweland J.M.V, Vermeersch K, Low Vitamin K status is associated with increased elastin degradation in chronic obstructive pulmonary disease. J. Clin. Med. 2019;8:1116.

Riphagen I.J, Keyzer C.A, Drummen N.E.A, et al. Prevalence and effects of functional Vitamin K insufficiency: the PREVEND study. Nutrients. 2017;9:1334

Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497–506

Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054–1062

Klok F.A, Kruip M.J.H.A, van der Meer N.J.M, et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb. Res. 2020;191:145–147.

Reiffel J.A. An important indirect drug interaction between dronedarone and warfarin that may be extrapolated to other drugs that can alter gastrointestinal function. Am. Heart J. 2011;161:e5.

Ghobadi-M. H, Matin S, Nemati A, et al. The effects of conjugated linoleic acid supplementation on the serum levels of Interleukin-6 and Sirtuin-1 in COPD patients. Eur. Respir. J. 2019;54:OA3582

da Costa C.A.S. Likely positive effect of alpha-linolenic acid supplementation on the lung and the negative effect of it on the adipose tissue of COVID-19 patients. Nutr. Food Sci. 2020;51:878–882.

Ross A.C., Stephensen C.B. Vitamin A and retinoids in antiviral responses. Faseb. J. 1996;10:979–985

Lammi C., Arnold A. Food-derived antioxidants and COVID-19. J. Food Biochem. 2021;45

Irriguible T., Berrocal B. COVID 19: up to 82% critically ill patients had low Vitamin C value. Nutr. J. 2021;20:66

Bakaloudi D.R., Chourdakis M. A critical update on the role of mild and serious vitamin D deficiency prevalence and the COVID-19 epidemic in Europe. Nutrition. 2022;93:111441.