Abstract

Aim: The COVID-19 pandemic is an emergent viral respiratory disease characterized by high fever and shortness of breath, and it was declared a pandemic by the World Health Organization in March 2020. Early assessment of patients’ biochemical tests is important for accelerating diagnosis, allowing effective treatment, and controlling the further spread of the disease. The present study aimed to investigate the association between the disease, trace elements -including copper (Cu), zinc (Zn), selenium (Se), manganese (Mn), and cobalt (Co) vitamin D, Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) biochemical levels, and the correlation between the parameters tested in patients with COVID-19.

Methods: In our study, 40 patients (case group) who were hospitalized with a diagnosis of COVID-19 based on chest X-ray images and RT-PCR results evaluated by an infectious diseases specialist were included, along with 40 healthy individuals (control group) over the age of 18 who had no prior symptoms of COVID-19, no visits to a medical doctor for COVID-19, and no history of hospitalization due to the disease. Beckman Coulter AU5800 (Beckman Coulter, Brea, CA, USA) autoanalyzer was used for spectrophotometric analyses of clinical biochemistry tests, and vitamin D levels were examined using the HPLC method with the Shimadzu SIL-20A HT autosampler. Levels of trace elements-including Cu, Zn, Se, Mn, and Co-were measured by inductively coupled plasma mass spectrometry (ICP-MS) on an ICP-MS Bruker Aurora M90 analytical complex. The normal distribution hypothesis for the variables in question was tested using the Kolmogorov–Smirnov test. Student’s t-test was used for intergroup comparisons of variables meeting the normal distribution hypothesis, whereas Mann–Whitney U test was used for variables that did not meet the hypothesis.

Results: Vitamin D levels were much lower in the case group (12.05 ng/mL ± 6.27) compared to the control group (23.54 ng/mL ± 10.54), and the difference was statistically significant (p < 0.001). Serum Cu, Zn, Se, Mn, and Co levels in the control group were higher compared to the COVID-19 group, yet only the differences in Zn, Se, and Mn levels were statistically significant (p <0.05, p <0.001, p <0.05, respectively).

Conclusion: Decreased levels of vitamin D and trace elements (Se, Zn, Mg and Cu) are associated with the development of viral pathogens, including COVID-19, as well as increased ALT and AST parameters. It was concluded that a diet rich in vitamins and trace elements would strengthen the immune system, reduce the rate of virus spread, and slow down the disease aggravation.

Keywords: Clinical chemistry tests, COVID-19, vitamin D, trace elements

Copyright and license

Copyright © 2025 The Author(s). This is an open-access article published by Bolu İzzet Baysal Training and Research Hospital under the terms of the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium or format, provided the original work is properly cited.

How to cite

1.
Sabancılar İ, Unsal V, Özbek E, Canpolat Erkan RE, Mermutluoğlu Ç, Temiz H. An investigation of the role of trace elements and biochemical parameters in patients with COVID-19. Northwestern Med J. 2025;5(3):169-76. https://doi.org/10.54307/2025.NWMJ.141

References

  1. Al-Saleh I, Alrushud N, Alnuwaysir H, et al. Essential metals, vitamins and antioxidant enzyme activities in COVID-19 patients and their potential associations with the disease severity. Biometals. 2022; 35(1): 125-45. https://doi.org/10.1007/s10534-021-00355-4
  2. Doğan S, Bal T, Çabalak M, Dikmen N, Yaqoobi H, Ozcan O. Oxidative stress index can be a new marker related to disease severity in COVID-19. Turkish Journal of Biochemistry. 2021; 46: 349-57. https://doi.org/10.1515/tjb-2021-0013
  3. World Health Organization (WHO). COVID-19 cases | WHO COVID-19 dashboard. Available at: https://data.who.int/dashboards/covid19/cases
  4. Saja RK, Al-Mamouri Ali MA, Al-Kufaishi. Evaluation of total antioxidant capacity and total oxidant status in patients with COVID-19. J Pharm Negat Results. 2022; 13(4): 125-9. https://doi.org/10.47750/pnr.2022.13.04.016
  5. Karkhanei B, Talebi Ghane E, Mehri F. Evaluation of oxidative stress level: total antioxidant capacity, total oxidant status and glutathione activity in patients with COVID-19. New Microbes New Infect. 2021; 42: 100897. https://doi.org/10.1016/j.nmni.2021.100897
  6. Shakoor H, Feehan J, Al Dhaheri AS, et al. Immune-boosting role of vitamins D, C, E, zinc, selenium and omega-3 fatty acids: Could they help against COVID-19? Maturitas. 2021; 143: 1-9. https://doi.org/10.1016/j.maturitas.2020.08.003
  7. Andreou A, Trantza S, Filippou D, Sipsas N, Tsiodras S. COVID-19: the potential role of copper and N-acetylcysteine (NAC) in a combination of candidate antiviral treatments against SARS-CoV-2. In Vivo. 2020; 34(Suppl 3): 1567-88. https://doi.org/10.21873/invivo.11946
  8. Ntyonga-Pono MP. COVID-19 infection and oxidative stress: an under-explored approach for prevention and treatment? Pan Afr Med J. 2020; 35(Suppl 2): 12. https://doi.org/10.11604/pamj.2020.35.2.22877
  9. Bagher Pour O, Yahyavi Y, Karimi A, et al. Serum trace elements levels and clinical outcomes among Iranian COVID-19 patients. Int J Infect Dis. 2021; 111: 164-8. https://doi.org/10.1016/j.ijid.2021.08.053
  10. Bayraktar N, Bayraktar M, Ozturk A, Ibrahim B. Evaluation of the relationship between aquaporin-1, hepcidin, zinc, copper, and iron levels and oxidative stress in the serum of critically ill patients with COVID-19. Biol Trace Elem Res. 2022; 200(12): 5013-21. https://doi.org/10.1007/s12011-022-03400-6
  11. Martín-Fernández M, Aller R, Heredia-Rodríguez M, et al. Lipid peroxidation as a hallmark of severity in COVID-19 patients. Redox Biol. 2021; 48: 102181. https://doi.org/10.1016/j.redox.2021.102181
  12. Moghaddam A, Heller RA, Sun Q, et al. Selenium deficiency is associated with mortality risk from COVID-19. Nutrients. 2020; 12(7): 2098. https://doi.org/10.3390/nu12072098
  13. Nedjimi B. Can trace element supplementations (Cu, Se, and Zn) enhance human immunity against COVID-19 and its new variants? Beni Suef Univ J Basic Appl Sci. 2021; 10(1): 33. https://doi.org/10.1186/s43088-021-00123-w
  14. Joachimiak MP. Zinc against COVID-19? Symptom surveillance and deficiency risk groups. PLoS Negl Trop Dis. 2021; 15(1): e0008895. https://doi.org/10.1371/journal.pntd.0008895
  15. Skalny AV, Timashev PS, Aschner M, et al. Serum zinc, copper, and other biometals are associated with COVID-19 severity markers. Metabolites. 2021; 11(4): 244. https://doi.org/10.3390/metabo11040244
  16. Alexander J, Tinkov A, Strand TA, Alehagen U, Skalny A, Aaseth J. Early nutritional interventions with zinc, selenium and vitamin d for raising anti-viral resistance against progressive COVID-19. Nutrients. 2020; 12(8): 2358. https://doi.org/10.3390/nu12082358
  17. Tek NA, Koçak T. Koronavirüsle (COVID-19) mücadelede beslenmenin bağışıklık sisteminin desteklenmesinde rolü. Gazi Sağlık Bilimleri Dergisi. 2020; Özel Sayı: 18-45.
  18. Povaliaeva A, Bogdanov V, Pigarova E, et al. Impaired vitamin D metabolism in hospitalized COVID-19 patients. Pharmaceuticals (Basel). 2022; 15(8): 906. https://doi.org/10.3390/ph15080906
  19. Davoudi A, Najafi N, Aarabi M, et al. Lack of association between vitamin D insufficiency and clinical outcomes of patients with COVID-19 infection. BMC Infect Dis. 2021; 21(1): 450. https://doi.org/10.1186/s12879-021-06168-7
  20. Tietz NW, Pruden EL, Siggaard-Anderson O. Electrolytes. In: Teitz NW, editor. Fundamentals of clinical chemistry. 3nd ed. Philadelphia: WB Saunders Company; 1987: 614-24.
  21. Jia KK, Zhang J. Evaluation of five routine glucose methods on an Olympus AU5400 analyzer using the CDC hexokinase reference method. Clin Chem Lab Med. 2010; 48(3): 361-4. https://doi.org/10.1515/cclm.2010.018
  22. Keyfi F, Nahid S, Mokhtariye A, Nayerabadi S, Alaei A, Varasteh A-R. Evaluation of 25-OH vitamin D by high performance liquid chromatography: validation and comparison with electrochemiluminescence. J Anal Sci Technol. 2018; 9: 25. https://doi.org/10.1186/s40543-018-0155-z
  23. Muhammad Y, Kani YA, Iliya S, et al. Deficiency of antioxidants and increased oxidative stress in COVID-19 patients: a cross-sectional comparative study in Jigawa, Northwestern Nigeria. SAGE Open Med. 2021; 9: 2050312121991246. https://doi.org/10.1177/2050312121991246
  24. Malavolta M, Piacenza F, Basso A, Giacconi R, Costarelli L, Mocchegiani E. Serum copper to zinc ratio: relationship with aging and health status. Mech Ageing Dev. 2015; 151: 93-100. https://doi.org/10.1016/j.mad.2015.01.004
  25. Bahi GA, Boyvin L, Méité S, et al. Assessments of serum copper and zinc concentration, and the Cu/Zn ratio determination in patients with multidrug resistant pulmonary tuberculosis (MDR-TB) in Côte d’Ivoire. BMC Infect Dis. 2017; 17(1): 257. https://doi.org/10.1186/s12879-017-2343-7
  26. Bae M, Kim H. Mini-review on the roles of vitamin C, vitamin D, and selenium in the immune system against COVID-19. Molecules. 2020; 25(22): 5346. https://doi.org/10.3390/molecules25225346
  27. Domingo JL, Marquès M. The effects of some essential and toxic metals/metalloids in COVID-19: a review. Food Chem Toxicol. 2021; 152: 112161. https://doi.org/10.1016/j.fct.2021.112161
  28. Im JH, Je YS, Baek J, Chung MH, Kwon HY, Lee JS. Nutritional status of patients with COVID-19. Int J Infect Dis. 2020; 100: 390-3. https://doi.org/10.1016/j.ijid.2020.08.018
  29. Zeng HL, Yang Q, Yuan P, Wang X, Cheng L. Associations of essential and toxic metals/metalloids in whole blood with both disease severity and mortality in patients with COVID-19. FASEB J. 2021; 35(3): e21392. https://doi.org/10.1096/fj.202002346RR
  30. Batyrova G, Tlegenova Z, Kononets V, et al. Content of essential trace elements in the hair of residents of the Caspian Region of the Republic of Kazakhstan who recovered from COVID-19. Diagnostics (Basel). 2022; 12(11): 2734. https://doi.org/10.3390/diagnostics12112734
  31. Yaghoubi N, Youssefi M, Jabbari Azad F, Farzad F, Yavari Z, Zahedi Avval F. Total antioxidant capacity as a marker of severity of COVID-19 infection: possible prognostic and therapeutic clinical application. J Med Virol. 2022; 94(4): 1558-65. https://doi.org/10.1002/jmv.27500
  32. Mehri F, Rahbar AH, Ghane ET, Souri B, Esfahani M. Changes in oxidative markers in COVID-19 patients. Arch Med Res. 2021; 52(8): 843-9. https://doi.org/10.1016/j.arcmed.2021.06.004
  33. Lambadiari V, Mitrakou A, Kountouri A, et al. Association of COVID-19 with impaired endothelial glycocalyx, vascular function and myocardial deformation 4 months after infection. Eur J Heart Fail. 2021; 23(11): 1916-26. https://doi.org/10.1002/ejhf.2326
  34. Watkins RR, Lemonovich TL, Salata RA. An update on the association of vitamin D deficiency with common infectious diseases. Can J Physiol Pharmacol. 2015; 93(5): 363-8. https://doi.org/10.1139/cjpp-2014-0352
  35. Kazemi A, Mohammadi V, Aghababaee SK, Golzarand M, Clark CCT, Babajafari S. Association of vitamin D status with SARS-CoV-2 infection or COVID-19 severity: a systematic review and meta-analysis. Adv Nutr. 2021; 12(5): 1636-58. https://doi.org/10.1093/advances/nmab012
  36. Merzon E, Tworowski D, Gorohovski A, et al. Low plasma 25(OH) vitamin D level is associated with increased risk of COVID-19 infection: an Israeli population-based study. FEBS J. 2020; 287(17): 3693-702. https://doi.org/10.1111/febs.15495