A review on the association between inflammatory markers and micronutrients in Covid-19 Patients with infection severity and T2DM
Inflammatory markers in Covid-19 Patients
Abstract
The management of treatment strategies in COVID-19 is critical, especially in patients with type 2 diabetes. Non-enzymatic glycation of transmembrane protease serine 2 and angiotensin-converting enzyme 2 during COVID-19 in patients with diabetes may exacerbate immune dysregulation and inflammation. Elevated inflammatory cytokines such as IL-1, IL-2, IL-6, IL-7, and IL-10, tumor necrosis factor-α, interferon-γ, granulocyte-macrophage colony-stimulating factor, and monocyte chemoattractant protein-1 have been observed in COVID-19 patients. This review aims to assess the relationship between inflammatory markers, including C-reactive protein, and micronutrients (vitamins D and C, zinc, and copper) with the severity of COVID-19 infection in patients with type 2 diabetes. A narrative review was conducted through a comprehensive literature search of English-language articles published between 2000 and 2025. The databases searched included PubMed, Scopus, the ISI Web of Science, Cochrane, and Embase. Search terms included COVID-19, infections, type 2 diabetes mellitus, interleukins, and micronutrients. English-language scientific articles, systematic reviews, and meta-analyses were included, while studies lacking sufficient information, letters, comments, and editorials were excluded. Evidence suggests that immune-boosting components such as proteins, vitamins, and minerals can enhance immunity to infections. Vitamins D and C, zinc, and copper play supportive roles in immune function, potentially modulating the inflammatory response in COVID-19 patients with type 2 diabetes. High levels of inflammatory cytokines correlate with increased disease severity in this population. Understanding the interplay between inflammatory markers and micronutrients may guide improved therapeutic strategies for managing COVID-19 in diabetic patients. Further research is warranted to clarify these relationships and optimize clinical outcomes.
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3. Hashemi B, Akram FA, Amirazad H, Dadashpour M, Sheervalilou M, Nasrabadi D, et al. Emerging importance of nanotechnology-based approaches to control the COVID-19 pandemic. J Drug Deliv Sci Technol. 2022;67:102967.
4. Pal A, Squitti R, Picozza M, Pawar A, Rongioletti M, Dutta AK, et al. Zinc and COVID-19: basis of current clinical trials. Biol Trace Elem Res. 2021;199(8):2882-92.
5. Mortaz E, Tabarsi P, Varahram M, Folkerts G, Adcock IM. The immune response and immunopathology of COVID-19. Front Immunol. 2020;11:2037.
6. Zemlin AE, Wiese OJ. Coronavirus disease 2019 and the renin-angiotensin system: a closer look at ACE2. Ann Clin Biochem. 2020;57(5):339-50.
7. Memon B, Abdelalim EM. ACE2 function in pancreatic islet: implications for relationship between SARS-CoV-2 and diabetes. Acta Physiol (Oxf). 2021;233:e13733.
8. Lontchi-Yimagou E, Sobngwi E, Matsha TE, Kengne AP. Diabetes mellitus and inflammation. Curr Diab Rep. 2013;13(3):435-44.
9. Maddaloni E, Buzzetti R. COVID-19 and diabetes mellitus. Diabetes Metab Res Rev. 2020;36(7):e33213321.
10. Chen Y, Yang D, Cheng B, Chen J, Peng A, Yang C, et al. Clinical characteristics and outcomes of patients with diabetes and COVID-19. Diabetes Care. 2020;43(7):1399-407.
11. Cefalu WT, Rodgers GP. COVID-19 and metabolic diseases. Cell Metab. 2021;33(3):563-73.
12. D’Onofrio N, Scisciola L, Sardu C, Trotta MC, De Feo M, Maiello C, et al. Glycated ACE2 receptor in diabetes. Cardiovasc Diabetol. 2021;20(1):99.
13. Chalmers S, Khawaja A, Wieruszewski PM, Gajic O, Odeyemi Y. Diagnosis and treatment of acute pulmonary inflammation. World J Crit Care Med. 2019;8(5):59-69.
14. Wang L. C-reactive protein levels in the early stage of COVID-19. Med Mal Infect. 2020;50(4):332-34.
15. Tan C, Huang Y, Shi F, Tan K, Ma Q, Chen Y, et al. C-reactive protein predicts severe COVID-19 early. J Med Virol. 2020;92(7):856-62.
16. Linkins LA, Takach Lapner S. Review of D-dimer testing. Int J Lab Hematol. 2017;39(Suppl 1):98-103.
17. Lippi G, Bonfanti L, Saccenti C, Cervellin G. Causes of elevated D-dimer. Eur J Intern Med. 2014;25(1):45-8.
18. Liu B, Li M, Zhou Z, Guan X, Xiang Y. IL-6 blockade for COVID-19-induced CRS. J Autoimmun. 2020;111:102452.
19. Fathalizadeh A, Rezabakhsh A, Tahmasbi F, Zoghi JFN, Safari P, Vahdati SS. Hematologic prognostic factors in COVID-19. J Res Clin Med. 2024;12(1):18-25.
20. Dolhnikoff M, Duarte-Neto AN, de Almeida Monteiro RA, da Silva LFF, de Oliveira EP, Saldiva PHN, et al. Pulmonary thrombotic phenomena in severe COVID-19. J Thromb Haemost. 2020;18(6):1517-9.
21. Paliogiannis P, Mangoni AA, Dettori P, Nasrallah GK, Pintus G, Zinellu A. D-dimer and COVID-19 severity. Front Public Health. 2020;8:432.
22. Rifai N. Tietz textbook of clinical chemistry and molecular diagnostics. 6th ed. Elsevier; 2017.
23. Jurisic V, Radenkovic S, Konjevic G. Role of LDH as tumor marker. Adv Cancer Biomark. 2015:115-24.
24. Serrano-Lorenzo P, Coya ON, López-Jimenez A, Blázquez A, Delmiro A, Lucia A, et al. Plasma LDH in COVID-19. Pract Lab Med. 2021;25:e00226.
25. Martha JW, Wibowo A, Pranata R. Prognostic value of LDH in COVID-19. Postgrad Med J. 2021;97:1-6.
26. Mo P, Xing Y, Xiao Y, Deng L, Zhao Q, Wang H, et al. Refractory COVID-19 pneumonia. Clin Infect Dis. 2020;72(11):e587-9.
27. Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical characteristics of hospitalized COVID-19 patients. JAMA. 2020;323(11):1061-9.
28. Zhang J, Wang X, Jia X, Li J, Hu K, Chen G, et al. Risk factors for COVID-19 severity. Clin Microbiol Infect. 2020;26(6):767-72.
29. Ahmed S, Siddiqui I, Jafri L, Hashmi M, Khan AH, Ghani F. Procalcitonin in suspected sepsis. Ann Med Surg (Lond). 2018;35:180-84.
30. Albrich WC, Harbarth S. Biomarkers vs clinical decisions for antibiotics. Intensive Care Med. 2015;41(10):1739-51.
31. Bhandari S, Bhargava A, Sharma S, Keshwani P, Sharma R, Banerjee S. Clinical profile of COVID-19 in India. J Assoc Physicians India. 2020;68(5):13-7.
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| Issue | Articles in Press | |
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| Keywords | ||
| Coronavirus disease Infections Interleukins Micronutrients Type 2 diabetes mellitus | ||
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Sowti R, Najafipour F, Ghaffarzadeh Rad S, Ghorbani H, Amirazad H. A review on the association between inflammatory markers and micronutrients in Covid-19 Patients with infection severity and T2DM. Iran J Allergy Asthma Immunol. 2026;:1-16.
