Life-threatening course in coronavirus disease 2019 (COVID-19): Is there a link to methylenetetrahydrofolic acid reductase (MTHFR) polymorphism and hyperhomocysteinemia?

Karst, Matthias; Hollenhorst, Josef; Achenbach, Johannes

doi:10.1016/j.mehy.2020.110234

Cited by 34 publications

(35 citation statements)

References 26 publications

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“…15 Additionally, COVID-19 is not simply a disease of the upper respiratory tract, and some COVID-19 patients experience hypercoagulability which have been referred to as COVID-19-associated coagulopathy that appears to be caused by a SARS-CoV-2 induced local inflammatory response in small to mid-sized pulmonary arteries. 16 Also, a severe course of COVID-19 was found to be initiated by hyperhomocysteinmea (H-Hcy), which can be triggered by the presence of the 5, 10-methylenetetrahydrofolic acid reductase C677T polymorphism, 17 which is highly associated with thyroid disease. 18…”

Section: Discussionmentioning

confidence: 99%

Thyroid disease and covid‐19 infection: Case series

Allam

El‐Zawawy

Ahmed

et al. 2021

Clinical Case Reports

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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel RNA coronavirus responsible for the coronavirus disease-19 (COVID-19) pandemic. The clinical manifestations of COVID-19 are variable, ranging from asymptomatic cases to severe respiratory affection, and were found to cause thyroid dysfunction in some cases. Our case series aim to shed the light on the effect of SARS-COV-2 infection on thyroid function, thyroid gland size, and treatment of thyroid dysfunction. We demonstrated three cases indicating that COVID-19 infection can accentuate thyrotoxic state and Graves' ophthalmopathy, aggravate hypothyroidism, increase thyroid gland volume, and in euthyroid individuals can induce some sort of thyroiditis, characterized by hyperthyroidism followed by hypothyroidism which is eventually followed by euthyroidism. Furthermore, treatment of thyroid disease was found to be affected by COVID-19 infection.The novel coronavirus (SARS-COV-2) was first discovered at the end of the year 2019 in Wuhan, China. After which, it rapidly spread, causing an epidemic throughout China, which then spread across the entire world, resulting in coronavirus pandemic. In February 2020, the World Health Organization (WHO) designated the disease COVID-19, which stands for coronavirus disease 2019. 1 SARS-CoV-2-specific antibodies and cell-mediated responses are induced following infection. Preliminary evidence suggests that some of these responses are protective, but this remains to be definitively verified. Moreover, it is unknown whether all infected patients develop a protective immune response and how long a protective effect might last. 2 Data about the effect of SARS-COV-2 on the thyroid function are scarce; however, one study addressed this effect and demonstrated that, out of 287 patients with confirmed SARS-COV-2, 58 patients had hyperthyroidism and 15 patients had hypothyroidism. 3 Our case series aim to shed the light on the effect of SARS-COV-2 infection on thyroid function, which will ultimately influence thyroid disease sequelae and management in patients with COVID-19.

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Section: Discussionmentioning

confidence: 99%

Thyroid disease and covid‐19 infection: Case series

Allam

El‐Zawawy

Ahmed

et al. 2021

Clinical Case Reports

View full text Add to dashboard Cite

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“…31 Most interesting, the MTHFR C677T polymorphism has also previously been found to predispose to a more severe course of COVID-19, with vitamin supplementation recommended in individuals with this mutation. 32 In case 5, the patient had an underlying copper deficiency, likely resulting from zinc toxicity from supplementation. Although this may be considered a confounder for the patient's myelitis findings, clinical symptoms of rapid onset are in line with the other reported COVID-19-associated cases, and these symptoms did not improve with reversal of the copper deficiency.…”

Section: Discussionmentioning

confidence: 99%

COVID-19-Associated Myelitis Involving the Dorsal and Lateral White Matter Tracts: A Case Series and Review of the Literature

Huang

Shah

McNally

et al. 2021

AJNR Am J Neuroradiol

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“…It has been recently shown that SARS-CoV-2 remodels both the host folate and the one-carbon metabolism at the post-transcriptional level to meet the demand for viral subgenomic RNA replication, bypassing viral shutoff of host translation [47]. Since folate is depleted in SARS-CoV-2-infected cells [47], homocysteine levels should increase and eventually lead to hyper-homocysteinemia, a known risk factor for a variety of complex disorders including cardiovascular and neurological diseases [48], possibly contributing to a severe course of COVID-19 [49]. Interestingly, MTHFR variants and homocysteine levels have been suggested as modulators of the risk of COVID-19 incidence and severity [50,51].…”

Section: Discussionmentioning

confidence: 99%

MEDTEC Students against Coronavirus: Investigating the Role of Hemostatic Genes in the Predisposition to COVID-19 Severity

Cappadona

Paraboschi

Ziliotto

et al. 2021

JPM

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiologic agent of the coronavirus disease 2019 (COVID-19) pandemic. Besides virus intrinsic characteristics, the host genetic makeup is predicted to account for the extreme clinical heterogeneity of the disease, which is characterized, among other manifestations, by a derangement of hemostasis associated with thromboembolic events. To date, large-scale studies confirmed that genetic predisposition plays a role in COVID-19 severity, pinpointing several susceptibility genes, often characterized by immunologic functions. With these premises, we performed an association study of common variants in 32 hemostatic genes with COVID-19 severity. We investigated 49,845 single-nucleotide polymorphism in a cohort of 332 Italian severe COVID-19 patients and 1668 controls from the general population. The study was conducted engaging a class of students attending the second year of the MEDTEC school (a six-year program, held in collaboration between Humanitas University and the Politecnico of Milan, allowing students to gain an MD in Medicine and a Bachelor’s Degree in Biomedical Engineering). Thanks to their willingness to participate in the fight against the pandemic, we evidenced several suggestive hits (p < 0.001), involving the PROC, MTHFR, MTR, ADAMTS13, and THBS2 genes (top signal in PROC: chr2:127192625:G:A, OR = 2.23, 95%CI = 1.50–3.34, p = 8.77 × 10−5). The top signals in PROC, MTHFR, MTR, ADAMTS13 were instrumental for the construction of a polygenic risk score, whose distribution was significantly different between cases and controls (p = 1.62 × 10−8 for difference in median levels). Finally, a meta-analysis performed using data from the Regeneron database confirmed the contribution of the MTHFR variant chr1:11753033:G:A to the predisposition to severe COVID-19 (pooled OR = 1.21, 95%CI = 1.09–1.33, p = 4.34 × 10−14 in the weighted analysis).

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Life-threatening course in coronavirus disease 2019 (COVID-19): Is there a link to methylenetetrahydrofolic acid reductase (MTHFR) polymorphism and hyperhomocysteinemia?

Cited by 34 publications

References 26 publications

Thyroid disease and covid‐19 infection: Case series

Thyroid disease and covid‐19 infection: Case series

COVID-19-Associated Myelitis Involving the Dorsal and Lateral White Matter Tracts: A Case Series and Review of the Literature

MEDTEC Students against Coronavirus: Investigating the Role of Hemostatic Genes in the Predisposition to COVID-19 Severity

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