Overview of the possible role of

vitamin C in management of COVID-19

[Epub ahead of print]

Anis Abobaker,Spire Fylde Coast Hospital,

St Walburgas road, Blackpool, FY3 8BP UK

Aboubaker Alzwi7th of October Hospital, Benghazi,

Libya

Alsalheen Hamed A. Alraied, Jomhorya Hospital,

Benghazi, Libya

Acknowledgement:

This article and Abstract

remain the property of

its authors

"Given the fact that vitamin C is cheap, available

and safe drug with beneficial effects in

management of viral infections and critically ill

patients reported in previous clinical trials, it is

sensible to add it to COVID-19 management

protocol particularly if the current ongoing

clinical trials testing the effect of vitamin C

in management of COVID-19 show positive results."

LINK TO THE STUDY - HERE

Please download a pdf copy of the study here -

OVERVIEW INFOGRAPHIC

REFERENCES:

1. Sanders J, Monogue M, Jodlowski T, Cutrell J. Pharmacologic treatments for coronavirus disease 2019 (COVID-19) JAMA. 2020 doi: 10.1001/jama.2020.6019. [PubMed] [CrossRef] [Google Scholar]

2. Bilbul M, Paparone P, Kim A, Mutalik S, Ernst C. Psychopharmacology of COVID-19. Psychosomatics. 2020 doi: 10.1016/j.psym.2020.05.006. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

3. Carr A, Rosengrave P, Bayer S, Chambers S, Mehrtens J, Shaw G. Hypovitaminosis C and vitamin C deficiency in critically ill patients despite recommended enteral and parenteral intakes. Crit Care. 2017 doi: 10.1186/s13054-017-1891-y. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

4. Earar K, Arbune M, Dorobat C, Rusu-Negraia M, Stefanescu V, Indrei L, et al. Biochemical effects and therapeutic application of vitamin C (C6H8O6) on COVID-19 infection. Rev Chim. 2020;71(5):473–478. doi: 10.37358/RC.20.5.8159. [CrossRef] [Google Scholar]

5. Bauer S, Kapoor A, Rath M, Thomas S. What is the role of supplementation with ascorbic acid, zinc, vitamin D, or N-acetylcysteine for prevention or treatment of COVID-19? Cleveland Clin J Med. 2020 doi: 10.3949/ccjm.87a.ccc046. [PubMed] [CrossRef] [Google Scholar]

6. Wang L, Wang Y, Ye D, Liu Q. Review of the 2019 novel coronavirus (SARS-CoV-2) based on current evidence. Int J Antimicrob Agents. 2020;55(6):105948. doi: 10.1016/j.ijantimicag.2020.105948. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

7. Wu J. Tackle the free radicals damage in COVID-19. Nitric Oxide. 2020;102:39–41. doi: 10.1016/j.niox.2020.06.002. [PubMed] [CrossRef] [Google Scholar]

8. Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020;323(11):1061. doi: 10.1001/jama.2020.1585. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

9. Kakodkar P, Kaka N, Baig M. A comprehensive literature review on the clinical presentation, and management of the pandemic coronavirus disease 2019 (COVID-19) Cureus. 2020 doi: 10.7759/cureus.7560. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

10. Colunga Biancatelli R, Berrill M, Marik P. The antiviral properties of vitamin C. Expert Rev Anti-infect Therapy. 2019;18(2):99–101. doi: 10.1080/14787210.2020.1706483. [PubMed] [CrossRef] [Google Scholar]

11. Gao Y, Lu B, Zhai J, Liu Y, Qi H, Yao Y, et al. The parenteral vitamin C improves sepsis and sepsis-induced multiple organ dysfunction syndrome via preventing cellular immunosuppression. Mediators Inflamm. 2017;2017:1–12. [PMC free article] [PubMed] [Google ScholarRetracted

12. Boretti A, Banik B. Intravenous vitamin C for reduction of cytokines storm in acute respiratory distress syndrome. PharmaNutrition. 2020;12:100190. doi: 10.1016/j.phanu.2020.100190. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

13. White L, Freeman C, Forrester B, Chappell W. In vitro effect of ascorbic acid on infectivity of herpesviruses and paramyxoviruses. J Clin Microbiol. 1986;24(4):527–531. doi: 10.1128/JCM.24.4.527-531.1986. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

14. Uesato S, Kitagawa Y, Kaijima T, Tokuda H, Okuda M, Mou X, et al. Inhibitory effects of 6-O-acylated l-ascorbic acids possessing a straight- or branched-acyl chain on Epstein-Barr virus activation. Cancer Lett. 2001;166(2):143–146. doi: 10.1016/S0304-3835(01)00444-X. [PubMed] [CrossRef] [Google Scholar]

15. Cinatl J, Cinatl J, Weber B, Rabenau H, Gumbel H, Chenot J, et al. In vitro inhibition of human cytomegalovirus replication in human foreskin fibroblasts and endothelial cells by ascorbic acid 2-phosphate. Antiviral Res. 1995;27(4):405–418. doi: 10.1016/0166-3542(95)00024-G. [PubMed] [CrossRef] [Google Scholar]

16. Koyama A, Uozaki M, Yamasaki H, Arakawa T, Arita M, Koyama A. Antiviral effects of ascorbic and dehydroascorbic acids in vitro. Int J Mol Med. 1998;22(4):541–545. doi: 10.3892/ijmm_00000053. [PubMed] [CrossRef] [Google Scholar]

17. Schwerdt P, Schwerdt C. Effect of ascorbic acid on rhinovirus replication in WI-38 cells. Exp Biol Med. 1975;148(4):1237–1243. doi: 10.3181/00379727-148-38724. [PubMed] [CrossRef] [Google Scholar]

18. Jariwalla R, Roomi M, Gangapurkar B, Kalinovsky T, Niedzwiecki A, Rath M. Suppression of influenza A virus nuclear antigen production and neuraminidase activity by a nutrient mixture containing ascorbic acid, green tea extract and amino acids. BioFactors. 2007;31(1):1–15. doi: 10.1002/biof.5520310101. [PubMed] [CrossRef] [Google Scholar]

19. Atherton J, Kratzing C, Fisher A. The effect of ascorbic acid on infection of chick-embryo ciliated tracheal organ cultures by coronavirus. Adv Virol. 1978;56(3):195–199. [PMC free article] [PubMed] [Google Scholar]

20. Davelaar F, van den Bos J. Ascorbic acid and infectious bronchitis infections in broilers. Avian Pathol. 1992;21(4):581–589. doi: 10.1080/03079459208418879. [PubMed] [CrossRef] [Google Scholar]

21. Kim Y, Kim H, Bae S, Choi J, Lim S, Lee N, et al. Vitamin C is an essential factor on the anti-viral immune responses through the production of interferon-α/β at the initial stage of influenza A virus (H3N2) infection. Immune Netw. 2013;13(2):70. doi: 10.4110/in.2013.13.2.70. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

22. Jungeblut C. Further observations on vitamin C therapy in experimental poliomyelitis. J Exp Med. 1937;66(4):459–477. doi: 10.1084/jem.66.4.459. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

23. Chen J, Chang C, Feng P, Chu C, So E, Hu M. Plasma vitamin C is lower in postherpetic neuralgia patients and administration of vitamin C reduces spontaneous pain but not brush-evoked pain. Clin J Pain. 2009;25(7):562–569. doi: 10.1097/AJP.0b013e318193cf32. [PubMed] [CrossRef] [Google Scholar]

24. Kim M, Kim D, Na C, Shin B. A study of intravenous administration of vitamin C in the Treatment of acute herpetic pain and postherpetic neuralgia. Ann Dermatol. 2016;28(6):677. doi: 10.5021/ad.2016.28.6.677. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

25. Kim G, Yoo W, Park M, Chung J, Han Y, Chung I, et al. Clinical features of herpes simplex keratitis in a Korean tertiary referral center: efficacy of oral antiviral and ascorbic acid on recurrence. Korean J Ophthalmol. 2018;32(5):353. doi: 10.3341/kjo.2017.0131. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

26. Simonson W. Vitamin C and coronavirus. Geriatr Nurs. 2020;41(3):331–332. doi: 10.1016/j.gerinurse.2020.05.002. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

27. Zabetakis I, Lordan R, Norton C, Tsoupras A. COVID-19: the inflammation link and the role of nutrition in potential mitigation. Nutrients. 2020;12(5):1466. doi: 10.3390/nu12051466. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

28. Banerjee D, Kaul D. Combined inhalational and oral supplementation of ascorbic acid may prevent influenza pandemic emergency: A hypothesis. Nutrition. 2010;26(1):128–132. doi: 10.1016/j.nut.2009.09.015. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

29. Wintergerst E, Maggini S, Hornig D. Immune-enhancing role of vitamin C and zinc and effect on clinical conditions. Ann Nutr Metab. 2006;50(2):85–94. doi: 10.1159/000090495. [PubMed] [CrossRef] [Google Scholar]

30. Anderson T, Reid D, Beaton G. Vitamin C and the common cold: a double-blind trial. Can Med Assoc J. 1972;107(6):503–508. [PMC free article] [PubMed] [Google Scholar]

31. Vorilhon P, Arpajou B, Vaillant Roussel H, Merlin É, Pereira B, Cabaillot A. Efficacy of vitamin C for the prevention and treatment of upper respiratory tract infection. A meta-analysis in children. Eur J Clin Pharmacol. 2018;75(3):303–311. doi: 10.1007/s00228-018-2601-7. [PubMed] [CrossRef] [Google Scholar]

32. Hemilä H, Chalker E. Vitamin C for preventing and treating the common cold. Cochrane Database Syst Rev. 2013 doi: 10.1002/14651858.CD000980. [PubMed] [CrossRef] [Google Scholar]

33. Gorton H, Jarvis K. The effectiveness of vitamin C in preventing and relieving the symptoms of virus-induced respiratory infections. J Manipulative Physiol Ther. 1999;22(8):530–533. doi: 10.1016/S0161-4754(99)70005-9. [PubMed] [CrossRef] [Google Scholar]

34. Ran L, Zhao W, Wang J, Wang H, Zhao Y, Tseng Y, et al. Extra dose of vitamin C based on a daily supplementation shortens the common cold: a meta-analysis of 9 randomized controlled trials. Biomed Res Int. 2018;2018:1–12. doi: 10.1155/2018/1837634. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

35. Cathcart R. Vitamin C in the treatment of acquired immune deficiency syndrome (AIDS) Med Hypotheses. 1984;14(4):423–433. doi: 10.1016/0306-9877(84)90149-X. [PubMed] [CrossRef] [Google Scholar]

36. Calder P, Carr A, Gombart A, Eggersdorfer M. Optimal nutritional status for a well-functioning immune system is an important factor to protect against viral infections. Nutrients. 2020;12(4):1181. doi: 10.3390/nu12041181. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

37. Carr A, Maggini S. Vitamin C and immune function. Nutrients. 2017;9(11):1211. doi: 10.3390/nu9111211. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

38. Heuser G, Vojdani A. Enhancement of natural killer cell activity and T and B cell function by buffered vitamin C in patients exposed to toxic chemicals: the role of protein kinase-C. Immunopharmacol Immunotoxicol. 1997;19(3):291–312. doi: 10.3109/08923979709046977. [PubMed] [CrossRef] [Google Scholar]

39. Liugan M, Carr A. Vitamin C and neutrophil function: findings from randomized controlled trials. Nutrients. 2019;11(9):2102. doi: 10.3390/nu11092102. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

40. Kennes B, Dumont I, Brohee D, Hubert C, Neve P. Effect of vitamin C supplements on cell-mediated immunity in old people. Gerontology. 1983;29(5):305–310. doi: 10.1159/000213131. [PubMed] [CrossRef] [Google Scholar]

41. Anderson R, Hay I, van Wyk H, Theron A. Ascorbic acid in bronchial asthma. S Afr Med J. 1983;63(17):649–652. [PubMed] [Google Scholar]

42. Anderson R, Oosthuizen R, Maritz R, Theron A, Van Rensburg A. The effects of increasing weekly doses of ascorbate on certain cellular and humoral immune functions in normal volunteers. Am J Clin Nutr. 1980;33(1):71–76. doi: 10.1093/ajcn/33.1.71. [PubMed] [CrossRef] [Google Scholar]

43. Jayachandran M, Rani P, Arivazhagan P, Panneerselvam C. Neutrophil phagocytic function and humoral immune response with reference to ascorbate supplementation in aging humans. J Anti-Aging Med. 2000;3(1):37–42. doi: 10.1089/rej.1.2000.3.37. [CrossRef] [Google Scholar]

44. De la Fuente M, Ferrández M, Burgos M, Soler A, Prieto A, Miquel J. Immune function in aged women is improved by ingestion of vitamins C and E. Can J Physiol Pharmacol. 1998;76(4):373–380. doi: 10.1139/y98-038. [PubMed] [CrossRef] [Google Scholar]

45. Shilotri P, Bhat K. Effect of mega doses of vitamin C on bactericidal ativity of leukocytes. Am J Clin Nutr. 1977;30(7):1077–1081. doi: 10.1093/ajcn/30.7.1077. [PubMed] [CrossRef] [Google Scholar]

46. Ferrón-Celma I, Mansilla A, Hassan L, Garcia-Navarro A, Comino A, Bueno P, et al. Effect of vitamin C administration on neutrophil apoptosis in septic patients after abdominal surgery. J Surg Res. 2009;153(2):224–230. doi: 10.1016/j.jss.2008.04.024. [PubMed] [CrossRef] [Google Scholar]

47. Mousavi S, Bereswill S, Heimesaat M. Immunomodulatory and antimicrobial effects of vitamin C. Eur J Microbiol Immunol. 2019;9(3):73–79. doi: 10.1556/1886.2019.00016. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

48. Manning J, Mitchell B, Appadurai D, Shakya A, Pierce L, Wang H, et al. Vitamin C promotes maturation of T-cells. Antioxid Redox Signal. 2013;19(17):2054–2067. doi: 10.1089/ars.2012.4988. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

49. Delafuente J, Prendergast J, Modigh A. Immunologic modulation by vitamin C in the elderly. Int J Immunopharmacol. 1986;8(2):205–211. doi: 10.1016/0192-0561(86)90060-3. [PubMed] [CrossRef] [Google Scholar]

50. Brennan L, Morris G, Wasson G, Hannigan B, Barnett Y. The effect of vitamin C or vitamin E supplementation on basal and H2O2-induced DNA damage in human lymphocytes. Br J Nutr. 2000;84(2):195–202. doi: 10.1017/S0007114500001422. [PubMed] [CrossRef] [Google Scholar]

51. Tanaka M, Muto N, Gohda E, Yamamoto I. Enhancement by ascorbic acid 2-glucoside or repeated additions of ascorbate of mitogen-induced IgM and IgG productions by human peripheral blood lymphocytes. Jpn J Pharmacol. 1994;66(4):451–456. doi: 10.1254/jjp.66.451. [PubMed] [CrossRef] [Google Scholar]

52. Siegel B, Morton J. Vitamin C and the immune response. Experientia. 1977;33(3):393–395. doi: 10.1007/BF02002847. [PubMed] [CrossRef] [Google Scholar]

53. Stipp M. SARS-CoV-2: micronutrient optimization in supporting host immunocompetence. Int J Clin Case Rep Rev. 2020;2(2):01–10. [Google Scholar]

54. Kim H, Jang M, Kim Y, Choi J, Jeon J, Kim J, et al. Red ginseng and vitamin C increase immune cell activity and decrease lung inflammation induced by influenza A virus/H1N1 infection. J Pharm Pharmacol. 2016;68(3):406–420. doi: 10.1111/jphp.12529. [PubMed] [CrossRef] [Google Scholar]

55. Jacob R. The integrated antioxidant system. Nutr Res. 1995;15(5):755–766. doi: 10.1016/0271-5317(95)00041-G. [CrossRef] [Google Scholar]

56. Horowitz R, Freeman P. Three novel prevention, diagnostic, and treatment options for COVID-19 urgently necessitating controlled randomized trials. Med Hypotheses. 2020;143:109851. doi: 10.1016/j.mehy.2020.109851. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

57. Peters E, Goetzsche J, Grobbelaar B, Noakes T. Vitamin C supplementation reduces the incidence of postrace symptoms of upper-respiratory-tract infection in ultramarathon runners. Am J Clin Nutr. 1993;57(2):170–174. doi: 10.1093/ajcn/57.2.170. [PubMed] [CrossRef] [Google Scholar]

58. Rodrigues da Silva M, Schapochnik A, Peres Leal M, Esteves J, Bichels Hebeda C, Sandri S, et al. Beneficial effects of ascorbic acid to treat lung fibrosis induced by paraquat. PLoS ONE. 2018;13(11):e0205535. doi: 10.1371/journal.pone.0205535. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

59. Calder P. Nutrition, immunity and COVID-19. BMJ Nutr Prevent Health. 2020;3(1):74–92. doi: 10.1136/bmjnph-2020-000085. [CrossRef] [Google Scholar]

60. Castro S, Guerrero-Plata A, Suarez-Real G, Adegboyega P, Colasurdo G, Khan A, et al. Antioxidant treatment ameliorates respiratory syncytial virus–induced disease and lung inflammation. Am J Respir Crit Care Med. 2006;174(12):1361–1369. doi: 10.1164/rccm.200603-319OC. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

61. Infusino F, Marazzato M, Mancone M, Fedele F, Mastroianni C, Severino P, et al. Diet Supplementation, probiotics, and nutraceuticals in SARS-CoV-2 infection: a scoping review. Nutrients. 2020;12(6):1718. doi: 10.3390/nu12061718. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

62. Carr A, Spencer E, Dixon L, Chambers S. Patients with community acquired pneumonia exhibit depleted vitamin C status and elevated oxidative stress. Nutrients. 2020;12(5):1318. doi: 10.3390/nu12051318. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

63. Hunt C, Chakravorty N, Annan G, Habibzadeh N, Schorah C. The clinical effects of vitamin C supplementation in elderly hospitalised patients with acute respiratory infections. Int J Vitam Nutr Res. 1994;64(3):212–219. [PubMed] [Google Scholar]

64. Hemilä H. Vitamin C and Infections. Nutrients. 2017;9(4):339. doi: 10.3390/nu9040339. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

65. Khan I, Shabbier A, Naeemullah S, Siddiqui F, Rabia M, Khan S, et al. Efficacy of vitamin C in reducing duration of severe pneumonia in children. J Rawalpindi Med Coll. 2014;18(1):55–57. [Google Scholar]

66. Hemilä H, Louhiala P. Vitamin C for preventing and treating pneumonia. Cochrane Database Syst Rev. 2013;8:CD05532. doi: 10.1002/14651858.CD005532.pub3. [PubMed] [CrossRef] [Google Scholar]

67. Brant E, Angus D. Is high-dose vitamin C beneficial for patients with sepsis? JAMA. 2019;322(13):1257. doi: 10.1001/jama.2019.11643. [PubMed] [CrossRef] [Google Scholar]

68. Carr A, Rosengrave P, Bayer S, Chambers S, Mehrtens J, Shaw G. Hypovitaminosis C and vitamin C deficiency in critically ill patients despite recommended enteral and parenteral intakes. Crit Care. 2017;21(1):1. doi: 10.1186/s13054-017-1891-y. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

69. Marik P. Hydrocortisone, ascorbic acid and thiamine (HAT Therapy) for the treatment of sepsis. Focus Ascorbic Acid Nutr. 2018;10(11):1762. [PMC free article] [PubMed] [Google Scholar]

70. Li R, Guo C, Li Y, Qin Z, Huang W. Therapeutic targets and signaling mechanisms of vitamin C activity against sepsis: a bioinformatics study. Brief Bioinform. 2020 doi: 10.1093/bib/bbaa079. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

71. Fowler A, Syed A, Knowlson S, Sculthorpe R, Farthing D, DeWilde C, et al. Phase I safety trial of intravenous ascorbic acid in patients with severe sepsis. J Transl Med. 2014;12(1):32. doi: 10.1186/1479-5876-12-32. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

72. Yoo J, Kim R, Ju S, Lee S, Cho Y, Jeong Y, et al. Clinical impact of supplementation of vitamins B1 and C on patients with sepsis-related acute respiratory distress syndrome. Tuberc Respir Dis. 2020;83(3):248–254. doi: 10.4046/trd.2020.0008. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

73. Fowler A, Truwit J, Hite R, Morris P, DeWilde C, Priday A, et al. Effect of vitamin C infusion on organ failure and biomarkers of inflammation and vascular injury in patients with sepsis and severe acute respiratory failure. JAMA. 2019;322(13):1261. doi: 10.1001/jama.2019.11825. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

74. Qiao X, Fisher B, Kashiouris M, Truwit J, Hite R, Morris P, et al. Effects of high dose intravenous vitamin C (IVC) on plasma cell-free DNA levels in patients with sepsis-associated ARDS. A60 lung injury, sepsis, and ARDS. Am Thorac Soc. 2019 doi: 10.1164/ajrccm-conference.2019.199.1_MeetingAbstracts.A2100. [CrossRef] [Google Scholar]

75. Fowler A, III, Kim C, Lepler L, Malhotra R, Debesa O, Natarajan R, et al. Intravenous vitamin C as adjunctive therapy for enterovirus/rhinovirus induced acute respiratory distress syndrome. World J Crit Care Med. 2017;6(1):85. doi: 10.5492/wjccm.v6.i1.85. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

76. Khalili H, Zabet M, Mohammadi M, Ramezani M. Effect of high-dose Ascorbic acid on vasopressor′s requirement in septic shock. J Res Pharm Pract. 2016;5(2):94. doi: 10.4103/2279-042X.179569. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

77. Patak P, Willenberg H, Bornstein S. Vitamin C is an important cofactor for both adrenal cortex and adrenal medulla. Endocr Res. 2004;30(4):871–875. doi: 10.1081/ERC-200044126. [PubMed] [CrossRef] [Google Scholar]

78. Nabil Habib T, Ahmed I. Early adjuvant intravenous vitamin C treatment in septic shock may resolve the vasopressor dependence. Int J Microbiol Adv Immunol. 2017;5:77–81. [Google Scholar]

79. Kim W, Jo E, Eom J, Mok J, Kim M, Kim K, et al. Combined vitamin C, hydrocortisone, and thiamine therapy for patients with severe pneumonia who were admitted to the intensive care unit: Propensity score-based analysis of a before-after cohort study. J Crit Care. 2018;47:211–218. doi: 10.1016/j.jcrc.2018.07.004. [PubMed] [CrossRef] [Google Scholar]

80. Marik P, Khangoora V, Rivera R, Hooper M, Catravas J. Hydrocortisone, vitamin C, and thiamine for the treatment of severe sepsis and septic shock. Chest. 2017;151(6):1229–1238. doi: 10.1016/j.chest.2016.11.036. [PubMed] [CrossRef] [Google Scholar]

81. Fujii T, Luethi N, Young P, Frei D, Eastwood G, French C, et al. Effect of vitamin C, hydrocortisone, and thiamine vs hydrocortisone alone on time alive and free of vasopressor support among patients with septic shock. JAMA. 2020;323(5):423. doi: 10.1001/jama.2019.22176. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

82. Nathens A, Neff M, Jurkovich G, Klotz P, Farver K, Ruzinski J, et al. Randomized, prospective trial of antioxidant supplementation in critically Ill surgical patients. Ann Surg. 2002;236(6):814–822. doi: 10.1097/00000658-200212000-00014. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

83. Hemilä H, Chalker E. Vitamin C may reduce the duration of mechanical ventilation in critically ill patients: a meta-regression analysis. J Intensive Care. 2020;8(1):15. doi: 10.1186/s40560-020-0432-y. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

84. Hemilä H, Chalker E. Vitamin C can shorten the length of stay in the ICU: a meta-analysis. Nutrients. 2019;11(4):708. doi: 10.3390/nu11040708. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

85. Ahn J, Oh D, Huh J, Lim C, Koh Y, Hong S. Vitamin C alone does not improve treatment outcomes in mechanically ventilated patients with severe sepsis or septic shock: a retrospective cohort study. J Thorac Dis. 2019;11(4):1562–1570. doi: 10.21037/jtd.2019.03.03. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

86. Wang Y, Lin H, Lin B, Lin J. Effects of different ascorbic acid doses on the mortality of critically ill patients: a meta-analysis. Ann Intensive Care. 2019;9(1):58. doi: 10.1186/s13613-019-0532-9. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

87. Briguglio M, Pregliasco F, Lombardi G, Perazzo P, Banfi G. The malnutritional status of the host as a virulence factor for new coronavirus SARS-CoV-2. Front Med. 2020 doi: 10.3389/fmed.2020.00146. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

88. Chen L, Hu C, Hood M, Zhang X, Zhang L, Kan J, et al. A novel combination of vitamin C, curcumin and glycyrrhizic acid potentially regulates immune and inflammatory response associated with coronavirus infections: a perspective from system biology analysis. Nutrients. 2020;12(4):1193. doi: 10.3390/nu12041193. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

89. Ding H, Deng W, Ding L, Ye X, Yin S, Huang W. Glycyrrhetinic acid and its derivatives as potential alternative medicine to relieve symptoms in nonhospitalized COVID-19 patients. J Med Virol. 2020 doi: 10.1002/jmv.26064. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

90. Colunga Biancatelli R, Berrill M, Catravas J, Marik P. Quercetin and vitamin C: an experimental, synergistic therapy for the prevention and treatment of SARS-CoV-2 related disease (COVID-19) Front Immunol. 2020 doi: 10.3389/fimmu.2020.01451. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

91. Rizzo J, Rowan M, Driscoll I, Chung K, Friedman B. Vitamin C in burn resuscitation. Crit Care Clin. 2016;32(4):539–546. doi: 10.1016/j.ccc.2016.06.003. [PubMed] [CrossRef] [Google Scholar]

92. Pons S, Fodil S, Azoulay E, Zafrani L. The vascular endothelium: the cornerstone of organ dysfunction in severe SARS-CoV-2 infection. Crit Care. 2020 doi: 10.1186/s13054-020-03062-7. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

93. Hernández A, Papadakos P, Torres A, González D, Vives M, Ferrando C, et al. Two known therapies could be useful as adjuvant therapy in critical patients infected by COVID-19. Rev Esp Anestesiol Reanim. 2020;67(5):245–252. doi: 10.1016/j.redar.2020.03.004. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

94. Rozga M, Cheng F, Moloney L, Handu D. Effects of micronutrients or conditional amino acids on COVID-19-related outcomes: an evidence analysis center scoping review. J Acad Nutr Diet. 2020 doi: 10.1016/j.jand.2020.05.015. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

95. Anderson P. Intravenous ascorbic acid (IVAA) for COVID-19 supportive treatment in hospitalized COVID-19 patients (based on use in China and US settings) [Internet]. Cdn.ymaws.com. 2020. https://cdn.ymaws.com/naturopathic.org/resource/resmgr/documents/covid19/IVAA-COVID19-Hospital-Use-An.pdf. Accessed 11 Sept 2020

96. Cheng R. Hospital treatment of serious and critical COVID-19 infection with high-dose vitamin C. 2020. https://www.drwlc.com/blog/2020/03/18/hospital-treatment-of-serious-and-critical-covid-19-infection-with-high-dose-vitamin-c/. Accessed 2 Apr 2020.

97. Cheng R, Shi H, Yanagisawa A, Levy T, Saul A. Early large dose intravenous vitamin c is the treatment of choice for 2019-nCov pneumonia [Internet]. Orthomolecular.org. 2020. https://orthomolecular.org/resources/omns/v16n11.shtml?fbclid=IwAR10Ak6G9QQBrwOaQsan7g_avChvizqPYqEL5wJI2-iP_LPve6ZWTYNrD64. Accessed 11 Sept 2020.

98. Bakare TA, Soar JS. A cost-effective preventative approach to potentially save lives in the coronavirus pandemic, jointly using vitamin D, curcumin, and vitamin C, (with updated dosage parameters). 2020. 10.35543/osf.io/cq8sa.

99. Hemilä H, Louhiala P. Vitamin C may affect lung infections. J R Soc Med. 2007;100(11):495–498. doi: 10.1177/014107680710001109. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

100. Kim S, Yeom J. Reply: vitamin C as a possible therapy for COVID-19. Infect Chemother. 2020;52(2):224. doi: 10.3947/ic.2020.52.2.224. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

101. Nabzdyk C, Bittner E. Vitamin C in the critically ill—indications and controversies. World J Crit Care Med. 2018;7(5):52–61. doi: 10.5492/wjccm.v7.i5.52. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

102. Adams K, Baker W, Sobieraj D. Myth busters: dietary supplements and COVID-19. Ann Pharmacother. 2020;54(8):820–826. doi: 10.1177/1060028020928052. [PubMed] [CrossRef] [Google Scholar]

103. Massey L, Liebman M, Kynast-Gales S. Ascorbate increases human oxaluria and kidney stone risk. J Nutr. 2005;135(7):1673–1677. doi: 10.1093/jn/135.7.1673. [PubMed] [CrossRef] [Google Scholar]

104. Kashiouris M, L’Heureux M, Cable C, Fisher B, Leichtle S, Fowler A. The emerging role of vitamin C as a treatment for sepsis. Nutrients. 2020;12(2):292. doi: 10.3390/nu12020292. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

105. Kuhn S, Meissner K, Mayes L, Bartels K. Vitamin C in sepsis. Curr Opin Anaesthesiol. 2018;31(1):55–60. doi: 10.1097/ACO.0000000000000549. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

106. Hager D, Hinson J, Rothman R. Vitamin C for sepsis and acute respiratory failure. JAMA. 2020;323(8):791. doi: 10.1001/jama.2019.21984. [PubMed] [CrossRef] [Google Scholar]

107. Abat M, Larracas C, Cabaluna I. Should vitamin C/ascorbic acid infusion be used in the treatment of COVID-19? ACTA Medica Philippina. 2020;54:1–13. [Google Scholar]

108. Rees D, Kelsey H, Richards J. Acute haemolysis induced by high dose ascorbic acid in glucose-6-phosphate dehydrogenase deficiency. BMJ. 1993;306(6881):841–842. doi: 10.1136/bmj.306.6881.841. [PMC free article] [PubMed] [CrossRef] [Google Scholar]