Association between low serum folic acid and vitamin B12 levels with COVID-19 prognosis

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Olgun Keskin
Ayşegül Seremet Keskin
Nilgün Seremet


COVID-19, Folic acid, Vitamin B12


Background and aim: It is important that the immune system is active and strong in protection from the COVID-19 pandemic. Folic acid and vitamin B12 involved in the initiation, maintenance and regulation of both innate and adaptive immune reactions of the host against the infections. In this study, it was aimed to investigate the relationship between serum folic acid and vitamin B12 levels of COVID-19 patients on the prognosis of the disease.

Methods: The sample of the study consists of 529 individuals hospitalized in the Pandemic Chest Diseases Intensive Care Unit. General characteristics of the individuals, biochemical parameters checked routinely (white blood cell (WBC), platelet (PLT), lymphocyte, Neutrophil/Lymphocyte (N/L) rate, C-reactive protein (CRP), oxygen (O2) saturation at the time of admission), serum vitamin B12 and folic acid levels, length of stay in intensive care unit (ICU) and hospitalization, and mortality were recorded.  

Results: The mean age of individuals was 62.8±15.12 years, and 50.9% were men and 49.1% women. The mean level of serum folic acid in the subjects was 9.1±4.91 (ng/mL), and 2.4% had folic acid deficiency and 28.4% had folic acid insufficiency. The mean serum vitamin B12 was 295.6±229.98 (pg/mL), and vitamin B12 deficiency was observed only in 14.4%. The increase in serum folic acid levels reduces the total length of hospitalization and the risk of mortality (p<0.05). On the other hand, no correlation was found between B12 levels and the length of stay in ICU, hospitalization and mortality. It was shown that WBC and N/L rate decreased as serum folic acid levels increased, and O2 saturation at the first hospital admission was higher.

Conclusions: Folate deficiency and insufficiency are common among hospitalized COVID-19 patients and cause progression to severe disease. Therefore, examining COVID-19 patients in terms of nutritional deficiencies is critical in monitoring the clinical outcomes of  disease

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1. Siordia JA. Epidemiology and clinical features of COVID-19: A review of current literature. J Clin Virol 2020; 127: 104357.
2. World Health Organization. WHO Coronavirus (COVID-19) Dashboard. 2022 [cited: 2022/06]; Available from:
3. Şenyiğit A. COVID-19 Pandemisi. Klinik, Tanı, Tedavi ve Korunma. Dicle Tip Derg 2021; 48: 176-86.
4. Jayawardena R, Sooriyaarachchi P, Chourdakis M, Jeewandara C, Ranasinghe PJD, Research MSC. Enhancing immunity in viral infections, with special emphasis on COVID-19: A review. Diabetes Metab Syndr 2020; 14(4):367-82.
5. Seremet Kürklü N, Seremet Keskin A, Türker M. Is High Body Mass Index a Risk Factor for COVID-19? Bezmialem Sci 2021; 9: 40-5.
6. Fedele D, De Francesco A, Riso S, Collo A. Obesity, malnutrition, and trace element deficiency in the coronavirus disease (COVID-19) pandemic: an overview. Nutr 2021; 81: 111016.
7. Gasmi A, Tippairote T, Mujawdiya PK, et al. Micronutrients as immunomodulatory tools for COVID-19 management. Clin Immunol 2020: 108545.
8. Hu B, Huang S, Yin L. The cytokine storm and COVID‐19. J Med Virol 2021; 93(1): 250-6.
9. Iddir M, Brito A, Dingeo G, et al. Strengthening the immune system and reducing inflammation and oxidative stress through diet and nutrition: considerations during the COVID-19 crisis. Nutrients 2020; 12(6): 1562.
10. Calder PC. Nutrition, immunity and COVID-19. BMJ Nutr Prev Health 2020; 3(1): 74.
11. Sheybani Z, Dokoohaki MH, Negahdaripour M, et al. The role of folic acid in the management of respiratory disease caused by COVID-19. ChemRxiv Preprint 2020.
12. Shakeri H, Azimian A, Ghasemzadeh‐Moghaddam H, et al. Evaluation of the relationship between serum levels of zinc, vitamin B12, vitamin D, and clinical outcomes in patients with COVID‐19. J Med Virol 2022; 94(1): 141-6.
13. Shakoor H, Feehan J, Mikkelsen K, et al. Be well: A potential role for vitamin B in COVID-19. Maturitas 2021; 144: 108-11.
14. Meisel E, Efros O, Bleier J, et al. Folate levels in patients hospitalized with coronavirus disease 2019. Nutrients 2021;13(3):812.
15. Ersöz A, Yılmaz TE. The association between micronutrient and hemogram values and prognostic factors in COVID‐19 patients: A single‐center experience from Turkey. Int J Clin Pract 2021; 75(6): e14078.
16. Tek NA, Koçak T. Koronavirüsle (Covid-19) Mücadelede Beslenmenin Bağişiklik Sisteminin Desteklenmesinde Rolü. Gazi Sağlık Bil Derg 2020; Özel Sayı: 18-45.
17. 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 2021; 17(3): 469-79.
18. Taheri M, Bahrami A, Habibi P, Nouri F. A review on the serum electrolytes and trace elements role in the pathophysiology of COVID-19. Biol Trace Elem Res 2021; 199(7): 2475-81.
19. Kumar V, Kancharla S, Jena MK. In silico virtual screening-based study of nutraceuticals predicts the therapeutic potentials of folic acid and its derivatives against COVID-19. Virusdisease 2021; 32(1): 29-37.
20. Ibrahimagić OĆ, Kunić S. Comment on an article:“High dose folic acid is a potential treatment for pulmonary hypertension, including when associated with COVID-19 pneumonia”. Med Hypotheses 2020; 145: 110338.
21. Wiltshire E, Peña AS, MacKenzie K, Shaw G, Couper J. High dose folic acid is a potential treatment for pulmonary hypertension, including when associated with COVID-19 pneumonia. Med Hypotheses 2020; 143: 110142.
22. Acosta-Elias J, Espinosa-Tanguma R. The folate concentration and/or folic acid metabolites in plasma as factor for COVID-19 infection. Front Pharmacol 2020; 11: 1062.
23. Itelman E, Wasserstrum Y, Segev A, et al. Clinical Characterization of 162 COVID-19 patients in Israel: Preliminary Report from a Large Tertiary Center. Isr Med Assoc J 2020: 271-4.
24. Dalbeni A, Bevilacqua M, Teani I, Normelli I, Mazzaferri F, Chiarioni G. Excessive vitamin B12 and poor outcome in COVID-19 pneumonia. Nutr Metab Cardiovasc Dis 2021; 31(3): 774-5.
25. Spence JD, Yi Q, Hankey GJ. B vitamins in stroke prevention: time to reconsider. Lancet Neurol 2017; 16(9): 750-60.
26. Wee AKH. COVID-19’s toll on the elderly and those with diabetes mellitus–is vitamin B12 deficiency an accomplice? Med Hypotheses 2021; 146: 110374.

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