Baseline serum vitamin A and vitamin C levels and their association with disease severity in COVID-19 patients: Serum Vitamin A and C levels and COVID-19 severity

Gulseren Yilmaz; Huri Bulut; Derya Ozden Omaygenc; Aysu Akca; Esra Can; Nevin Tuten; Aysegul Bestel; Baki Erdem; Uygar Ozan Atmaca; Yasin Kara; Ebru Kaya; Murat Unsel; Ayca Sultan Sahin; Ziya Salihoglu

doi:10.23750/abm.v94i1.13655

Baseline serum vitamin A and vitamin C levels and their association with disease severity in COVID-19 patients

Serum Vitamin A and C levels and COVID-19 severity

Authors

Gulseren Yilmaz Kanuni Sultan Suleyman Training & Research Hospital, Department of Anesthesiology, Istanbul, Turkey https://orcid.org/0000-0003-2984-156X
Huri Bulut Istinye University, Faculty of Medicine, Department of Biochemistry, Istanbul, Turkey https://orcid.org/0000-0003-2706-9625
Derya Ozden Omaygenc Istanbul Haseki Training and Research Hospital https://orcid.org/0000-0003-1037-8915
Aysu Akca Kanuni Sultan Suleyman Training & Research Hospital, Department of Obstetrics and Gynecology, Istanbul, Turkey https://orcid.org/0000-0002-8644-7908
Esra Can Kanuni Sultan Suleyman Training & Research Hospital, Department of Obstetrics and Gynecology, Istanbul, Turkey https://orcid.org/0000-0001-7851-4026
Nevin Tuten Kanuni Sultan Suleyman Training & Research Hospital, Department of Obstetrics and Gynecology, Istanbul, Turkey https://orcid.org/0000-0001-8609-4770
Aysegul Bestel Kanuni Sultan Suleyman Training & Research Hospital, Department of Obstetrics and Gynecology, Istanbul, Turkey https://orcid.org/0000-0002-0700-6400
Baki Erdem Acıbadem University, Faculty of Medicine, Department of Gynecologic Oncology, Istanbul, Turkey https://orcid.org/0000-0002-6407-8718
Uygar Ozan Atmaca Kanuni Sultan Suleyman Training & Research Hospital, Department of Anesthesiology, Istanbul, Turkey https://orcid.org/0000-0002-7823-4400
Yasin Kara Kanuni Sultan Suleyman Training & Research Hospital, Department of General Surgery, Istanbul, Turkey https://orcid.org/0000-0002-9723-1774
Ebru Kaya Kanuni Sultan Suleyman Training & Research Hospital, Department of Critical Care, Istanbul, Turkey https://orcid.org/0000-0002-9506-0756
Murat Unsel Basaksehir Cam ve Sakura City Hospital, Department of Anesthesiology and Critical Care, Istanbul, Turkey https://orcid.org/0000-0002-2786-6811
Ayca Sultan Sahin Kanuni Sultan Suleyman Training & Research Hospital, Department of Anesthesiology, Istanbul, Turkey https://orcid.org/0000-0002-7765-5297
Ziya Salihoglu Istanbul University – Cerrahpasa, Faculty of Medicine, Department of Anesthesiology, Istanbul, Turkey https://orcid.org/0000-0002-6905-2664

Keywords:

Ascorbic acid, COVID-19, Hospital stay, Pulmonary disease, Vitamin A

Abstract

Aim: We aimed to investigate the association between the serum concentrations of Vitamin A and Vitamin C and the severity of the COVID-19.

Methods: Fifty-three consecutive PCR (+) COVID-19 patients admitted to a dedicated ward were enrolled in this study. Blood samples for serum Vitamin A and C measurements were drawn from all participants upon admission. All subjects underwent thoracic CT imaging prior to hospitalization. CT severity score (CT-SS) was then calculated for determining the extent of pulmonary involvement. A group of healthy volunteers, in whom COVID-19 was ruled out, were assigned to the control group (n=26). These groups were compared by demographic features and serum vitamin A and C levels. The relationship between serum concentrations of these vitamins and pre-defined outcome measures, CT-SS and length of hospitalization (LOH), was also assessed.

Results: In COVID-19 patients, serum Vitamin A (ng/ml, 494±96 vs. 698±93; p<0.001) and Vitamin C (ng/ml, 2961 [1991-31718] vs. 3953 [1385-8779]; p=0.007) levels were significantly lower with respect to healthy controls. According to the results of correlation analyses, there was a significant negative association between Vitamin A level and outcome measures (LOH, r=-0.293; p=0.009 and CT-SS, r=-0.289; p=0.010). The negative correlations between Vitamin C level and those measures were even more prominent (LOH, r=-0.478; p<0.001 and CT-SS, r=-0.734: p<0.001).

Conclusion: COVID-19 patients had lower baseline serum Vitamin A and Vitamin C levels as compared to healthy controls. In subjects with COVID-19, Vitamin A and Vitamin C levels were negatively correlated with CT-SS and LOH.

References

Jamal M, Bangash HI, Habiba M, et al. Immune dysregulation and system pathology in COVID-19. Virulence. 2021; 12(1):918-36. doi: 10.1080/21505594.2021.1898790.

Odegaard JI, Chawla A. Connecting type 1 and type 2 diabetes through innate immunity. Cold Spring Harb Perspect Med. 2012; 2(3):a007724. doi: 10.1101/cshperspect.a007724.

Tay MZ, Poh CM, Rénia L, MacAry PA, Ng LFP. The trinity of COVID-19: immunity, inflammation and intervention. Nat Rev Immunol. 2020; 20(6):363-74. doi: 10.1038/s41577-020-0311-8.

Farjana M, Moni A, Sohag AAM, et al. Repositioning Vitamin C as a Promising Option to Alleviate Complications associated with COVID-19. Infect Chemother. 2020 Dec;52(4):461-77. doi: 10.3947/ic.2020.52.4.461.

Murni IK, Prawirohartono EP, Triasih R. Potential Role of Vitamins and Zinc on Acute Respiratory Infections Including Covid-19. Glob Pediatr Health. 2021; 8:2333794X211021739. doi: 10.1177/2333794X211021739.

Yang R, Li X, Liu H, Zhen Y, Zhang X, Xiong Q, et al. Chest CT Severity Score: An Imaging Tool for Assessing Severe COVID-19. Radiol Cardiothorac Imaging. 2020; 2(2):e200047. doi: 10.1148/ryct.2020200047.

Tian J, Yuan X, Xiao J, et al. Clinical characteristics and risk factors associated with COVID-19 disease severity in patients with cancer in Wuhan, China: a multicentre, retrospective, cohort study. Lancet Oncol. 2020; 21(7):893-903. doi: 10.1016/S1470-2045(20)30309-0.

Pereira MR, Mohan S, Cohen DJ, et al. COVID-19 in solid organ transplant recipients: Initial report from the US epicenter. Am J Transplant. 2020; 20(7):1800-8. doi: 10.1111/ajt.15941.

Pecoraro A, Crescenzi L, Galdiero MR, et al. Immunosuppressive therapy with rituximab in common variable immunodeficiency. Clin Mol Allergy. 2019; 17:9. doi: 10.1186/s12948-019-0113-3.

Shiau S, Krause KD, Valera P, Swaminathan S, Halkitis PN. The Burden of COVID-19 in People Living with HIV: A Syndemic Perspective. AIDS Behav. 2020; 24(8):2244-9. doi: 10.1007/s10461-020-02871-9.

Riva A, Conti F, Bernacchia D, et al. Darunavir does not prevent SARS-CoV-2 infection in HIV patients. Pharmacol Res. 2020; 157:104826. doi: 10.1016/j.phrs.2020.104826.

McCullough FS, Northrop-Clewes CA, Thurnham DI. The effect of vitamin A on epithelial integrity. Proc Nutr Soc. 1999; 58(2):289-93. doi: 10.1017/s0029665199000403.

Wang JL, Swartz-Basile DA, Rubin DC, Levin MS. Retinoic acid stimulates early cellular proliferation in the adapting remnant rat small intestine after partial resection. J Nutr. 1997; 127(7):1297-303. doi: 10.1093/jn/127.7.1297.

Qi YJ, Niu QL, Zhu XL, Zhao XZ, Yang WW, Wang XJ. Relationship between deficiencies in vitamin A and E and occurrence of infectious diseases among children. Eur Rev Med Pharmacol Sci. 2016; 20(23):5009-12.

Kiss I, Rühl R, Szegezdi E, et al. Retinoid receptor-activating ligands are produced within the mouse thymus during postnatal development. Eur J Immunol. 2008; 38(1):147-55. doi: 10.1002/eji.200737342.

Kuwata T, Wang IM, Tamura T, et al. Vitamin A deficiency in mice causes a systemic expansion of myeloid cells. Blood. 2000; 95(11):3349-56.

van Bennekum AM, Wong Yen Kong LR, Gijbels MJ, et al. Mitogen response of B cells, but not T cells, is impaired in adult vitamin A-deficient rats. J Nutr. 1991; 121(12):1960-8. doi: 10.1093/jn/121.12.1960.

Mohammed BM, Fisher BJ, Kraskauskas D, et al. Vitamin C promotes wound healing through novel pleiotropic mechanisms. Int Wound J. 2016; 13(4):572-84. doi: 10.1111/iwj.12484.

Fisher BJ, Kraskauskas D, Martin EJ, et al. Mechanisms of attenuation of abdominal sepsis induced acute lung injury by ascorbic acid. Am J Physiol Lung Cell Mol Physiol. 2012; 303(1): L20-32. doi: 10.1152/ajplung.00300.2011.

Jimenez MF, Watson RW, Parodo J, et al. Dysregulated expression of neutrophil apoptosis in the systemic inflammatory response syndrome. Arch Surg. 1997; 132(12):1263-9; doi: 10.1001/archsurg.1997.01430360009002.

Demaret J, Venet F, Friggeri A, et al. Marked alterations of neutrophil functions during sepsis-induced immunosuppression. J Leukoc Biol. 2015; 98(6):1081-90. doi: 10.1189/jlb.4A0415-168RR.

Arraes SM, Freitas MS, da Silva SV, de Paula Neto HA, Alves-Filho JC, Auxiliadora Martins M, et al. Impaired neutrophil chemotaxis in sepsis associates with GRK expression and inhibition of actin assembly and tyrosine phosphorylation. Blood. 2006; 108(9):2906-13. doi: 10.1182/blood-2006-05-024638.

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.

Kim Y, Kim H, Bae S, 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):70-4. doi: 10.4110/in.2013.13.2.70.

Mochalkin NI. Askorbinovaia kislota v kompleksnoĭ terapii bol'nykh ostroĭ pnevmonieĭ [Ascorbic acid in the complex therapy of acute pneumonia]. Voen Med Zh. 1970; 9:17-21. Russian.

Hunt C, Chakravorty NK, Annan G, Habibzadeh N, Schorah CJ. The clinical effects of vitamin C supplementation in elderly hospitalised patients with acute respiratory infections. Int J Vitam Nutr Res. 1994; 64(3):212-9.

Li R, Wu K, Li Y, et al. Revealing the targets and mechanisms of vitamin A in the treatment of COVID-19. Aging (Albany NY). 2020; 12(15):15784-96. doi: 10.18632/aging.103888.

Stephensen CB, Lietz G. Vitamin A in resistance to and recovery from infection: relevance to SARS-CoV2. Br J Nutr. 2021; 126(11):1663-72. doi: 10.1017/S0007114521000246.

Coppock D, Violet PC, Vasquez G, et al. Pharmacologic Ascorbic Acid as Early Therapy for Hospitalized Patients with COVID-19: A Randomized Clinical Trial. Life (Basel). 2022; 12(3):453. doi: 10.3390/life12030453.

Al Sulaiman K, Aljuhani O, Saleh KB, et al. Ascorbic acid as an adjunctive therapy in critically ill patients with COVID-19: a propensity score matched study. Sci Rep. 2021; 11(1):17648. doi: 10.1038/s41598-021-96703-y.