SARS-CoV-2 Infection: What Is Currently Known about Homocysteine Involvement?
Abstract
:1. Introduction
2. Homocysteine Metabolism
3. Hyperhomocysteinemia and Vascular Damage
3.1. Overview of Hyperhomocysteinemia
3.2. Hyperhomocysteinemia and Endothelial Dysfunction
3.3. Hyperhomocysteinemia and Cardiovascular Disease
4. Homocysteine: A Closer Look at the Correlation with SARS-CoV-2 Infection
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Factors | Comments | References |
---|---|---|
Genetic abnormalities | ||
MTHFR deficiency | Homozygous with thermolabile C677T mutation NM_005957.4(MTHFR): c.665C > T (p. Ala222Val) tend to have higher homocysteine levels. | [57,58,59] |
MTHFR defect | Homozygous thermostable mutations, rare in population. | [46,60,61,62] |
CBS deficiency | Heterozygosity led to higher homocysteine levels following methionine loading. | [63,64,65] |
CBS defect | Homozygotes (rare) tend to develop severe basal hyperhomocysteinemia. | [46,60] |
Methionine synthase deficiency | Caused by biallelic defects in the MTR (5-Methyltetrahydrofolate-Homocysteine Methyltransferase) gene is a rare inborn error of metabolism affecting the homocysteine remethylation pathway, leading to intermediate or severe hyperhomocysteinemia. | [45,66,67,68] |
Nutritional factors | ||
Vitamin B6 deficiency | Contribute to impaired transsulfuration and an abnormal methionine load test, which is associated with premature vascular disease. | [69,70] |
Vitamin B12 deficiency | Serum total homocysteine concentrations are markedly increased in most patients. | [69,71,72] |
Folate deficiency | Folate acts as a donor of methyl groups for the homocysteine and deficiency can cause moderate/intermediate hyperhomocysteinemia. | [46,73] |
Medications | ||
Methotrexate | Inhibits dihydrofolate reductase. | [46,74] |
Metformin | Inhibit the absorption of Vitamin B12. | [74,75] |
Oral contraceptive pills | Mechanism for how oral contraceptive pills increase the level of homocysteine is no known. The proposed mechanisms are: (a) synthesis of free radicals inside the body that directly increase homocysteine concentration and, (b) decreases of the bioavailability of cofactors utilized to degrade homocysteine. | [46,76] |
Colchicine | Inhibit Vitamin B12 absorption. | [77,78] |
Methylprednisolone | Reduces the concentration of Vitamin B6. | [74] |
Reference | Participants | Results |
---|---|---|
Yang et al., 2020 [122] | 273 patients with COVID-19 | Homocysteine was reported as predictive marker for imaging lung progression in patients with SARS-CoV-2 infection. |
Ponti et al., 2021 [123] | 304 patients hospitalized for COVID-19 | The authors report that homocysteine is a predictive marker for the outcome of patients infected with SARS-CoV-2. |
Smirnova et al., 2021 [124] | 104 patients with COVID-19 | Patients with COVID-19 presented a hypercoagulable state and homocysteine can be a diagnostic indicator for the outcome of the disease. |
Ali et al., 2021 [125] | 42 participants with COVD19, survival 19 patients and non-survival 23 patients | One week after starting medication, homocysteine concentration increased in the non-survival group and decreased in the survival group. |
Petelina et al., 2021 [126] | 65 patients after COVID-19-associated pneumonia | Elevated levels of homocysteine three months after COVID-19, endothelial dysfunction and thrombophilia are indicators of prolonged arterial inflammatory syndrome. |
Fouda et al., 2022 [127] | 80 participants, 40 children with COVID-19 and 40 healthy as control | In patients with COVID-19, the level of homocysteine showed a significant increase with an average value of 27.5 μmol/L, which suggests that it could be a marker for predicting the severity of the disease. |
Khalid et al., 2022 [128] | 90 participants, 45 hospitalized patients with COVID-19, and 45 healthy as control | Moderate correlation between hyperhomocysteinemia and the severity of SARS-CoV-2 infection. |
Khidoyatovna et al., 2022 [129] | 80 patients with COVID19 | Homocysteine was significantly higher in patients with the non-wild-type allele of the MTHFR gene polymorphisms 677 C > T and 1298 A > C compared to the control group. |
Keskin et al., 2022 [130] | 151 participants, 117 patients with COVID-19 and 34 healthy as control | Hyperhomocysteinemia can be considered a risk factor in patients with COVID-19 and can predict the severity of the disease. |
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Filip, N.; Cojocaru, E.; Badulescu, O.V.; Clim, A.; Pinzariu, A.C.; Bordeianu, G.; Jehac, A.E.; Iancu, C.E.; Filip, C.; Maranduca, M.A.; et al. SARS-CoV-2 Infection: What Is Currently Known about Homocysteine Involvement? Diagnostics 2023, 13, 10. https://doi.org/10.3390/diagnostics13010010
Filip N, Cojocaru E, Badulescu OV, Clim A, Pinzariu AC, Bordeianu G, Jehac AE, Iancu CE, Filip C, Maranduca MA, et al. SARS-CoV-2 Infection: What Is Currently Known about Homocysteine Involvement? Diagnostics. 2023; 13(1):10. https://doi.org/10.3390/diagnostics13010010
Chicago/Turabian StyleFilip, Nina, Elena Cojocaru, Oana Viola Badulescu, Andreea Clim, Alin Constantin Pinzariu, Gabriela Bordeianu, Alina Elena Jehac, Cristina Elena Iancu, Cristiana Filip, Minela Aida Maranduca, and et al. 2023. "SARS-CoV-2 Infection: What Is Currently Known about Homocysteine Involvement?" Diagnostics 13, no. 1: 10. https://doi.org/10.3390/diagnostics13010010