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REVIEW ARTICLE

Hyperhomocysteinemia and MTHFR C677T polymorphism in SARS-CoV-2 infection severity

Anurag Mishra1*
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1 Department of Biochemistry, Faculty of Science, Iswar Saran Degree College, University of Allahabad, Prayagraj, Uttar Pradesh, India
Global Translational Medicine, 025320059 https://doi.org/10.36922/GTM025320059
Received: 5 August 2025 | Revised: 11 February 2026 | Accepted: 12 February 2026 | Published online: 12 May 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

COVID-19 virus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) has imposed a huge burden of mortality, morbidity, and socio-economic issues worldwide. Dominating transmission efficacy and the surge in instant genetic mutations pose challenges to the overwhelmed healthcare system. In this study, we aim to explore the role of homocysteine (Hcy) as a biomarker in COVID-19 and to develop strategies to mitigate the severity of SARS-CoV-2 infection. We reviewed the biochemical, physiological, and genetic implications of COVID-19. Upon SARS-CoV-2 exposure, Hcy metabolism is disrupted, leading to hyperhomocysteinemia (HHcy) and inducing inflammatory markers, e.g., interleukins (IL-6 and IL-7), tumor necrosis factor, interferon-γ, and C-reactive protein, which are characterized as a cytokine storm. HHcy develops numerous complications, including cardiovascular disorders, neural problems, and musculoskeletal disorders. However, nutritional deficiencies, e.g., folic acid, vitamin B6, and vitamin B12, and elevated serum creatinine are the important determinants of Hcy concentrations in the body. Additionally, the MTHFR C677T polymorphism is also a key factor that modulates Hcy levels and increases the risk of viral incidence. Overall, the identification of biochemical, metabolic, and genetic biomarkers may improve risk stratification, inform COVID-19 management, and help identify potential therapeutic targets.

Keywords
SARS-CoV-2
Hyperhomocysteinemia
MTHFR C677T polymorphism
Folic acid
Vitamin B
Funding
None.
Conflict of interest
The author declares that he has no competing interests.
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Global Translational Medicine, Electronic ISSN: 2811-0021 Print ISSN: 3060-8600, Published by AccScience Publishing
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