Homocysteine (Hcy) assessment to predict outcomes of hospitalized Covid-19 patients: a multicenter study on 313 Covid-19 patients

Ponti, Giovanni; Rovedatti, L.; Oliva, Gabriella; Manfredini, Marco; Trenti, Tommaso; Kaleci, Shaniko; Iannella, Raffaele; Balzano, Brigida; Coppola, Antonietta; Fiorentino, Giuseppe; Özben, Tomris; Paoli, Venere Delli; Debbia, Daria; Santis, Elena De; Pecoraro, Valentina; Melegari, Alessandra; Sansone, Monica Rosalia; Lugarà, Marina; Tomasi, Aldo

doi:10.1515/cclm-2021-0168

Cited by 29 publications

(26 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Furthermore, capillary changes have been observed more frequently in post-COVID-19 patients compared to healthy controls and the group of ASCVD including also a higher MES. Changes for most of the respective parameters have previously been described in patients mainly with acute COVID-19 while data about persistent changes after suffered COVID-19 are very limited (9,(35)(36)(37)(38)(39)(40). Pathophysiological mechanisms contributing to endothelial dysfunction in COVID-19 are largely unknown.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Endothelial Dysfunction and Inflammatory Vasculopathy After SARS-CoV-2 Infection—A Cross-Sectional Study

Jud

Gressenberger

Muster

et al. 2021

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

Background: Rising data suggest that COVID-19 affects vascular endothelium while the underlying mechanisms promoting COVID-19-associated endothelial dysfunction and inflammatory vasculopathy are largely unknown. The aim was to evaluate the contribution of COVID-19 to persisting vascular injury and to identify parameters linked to COVID-19-associated endothelial dysfunction and inflammatory vasculopathy.Methods: In a cross-sectional design, flow-mediated dilation (FMD), nitroglycerine-related dilation (NMD), pulse-wave velocity (PWV), augmentation index, intima-media thickness (IMT), compounds of the arginine and kynurenine metabolism, homocysteine, von Willebrand factor (vWF), endothelial microparticles (EMP), antiendothelial cell antibodies, inflammatory, and immunological parameters, as well as nailfold capillary morphology were measured in post-COVID-19 patients, patients with atherosclerotic cardiovascular diseases (ASCVD) and healthy controls without prior or recent SARS-CoV-2 infection.Results: Post-COVID-19 patients had higher values of PWV, augmentation index, IMT, asymmetric and symmetric dimethylarginine, vWF, homocysteine, CD31+/CD42b– EMP, C-reactive protein, erythrocyte sedimentation rate, interleukin-6, and β-2-glycoprotein antibodies as well as lower levels of homoarginine and tryptophan compared to healthy controls (all with p < 0.05). A higher total number of pathologically altered inflammatory conditions and higher rates of capillary ramifications, loss, caliber variability, elongations and bushy capillaries with an overall higher microangiopathy evolution score were also observed in post-COVID-19 patients (all with p < 0.05). Most parameters of endothelial dysfunction and inflammation were comparably altered in post-COVID-19 patients and patients with ASCVD, including FMD and NMD.Conclusion: COVID-19 may affect arterial stiffness, capillary morphology, EMP and selected parameters of arginine, kynurenine and homocysteine metabolism as well as of inflammation contributing to COVID-19-associated endothelial dysfunction and inflammatory vasculopathy.

show abstract

Section: Discussionmentioning

confidence: 99%

Evaluation of Endothelial Dysfunction and Inflammatory Vasculopathy After SARS-CoV-2 Infection—A Cross-Sectional Study

Jud

Gressenberger

Muster

et al. 2021

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

show abstract

“…Hyperhomocysteinemia leads to a reduction in endothelial nitric oxide (NO) bioavailability and induces inhibition of NO production in platelets, which might result in vasoconstriction and platelet aggregation (100,101) . Similar endothelial dysfunction, along with impairment in NO biosynthetic pathway and massive platelet activation has been observed in COVID-Recent studies have identified homocysteine as a potential predictive biomarker in COVID-19 patients with multiple comorbidities, in addition to already established biochemical and hematological biomarkers of progression, severity and mortality in COVID-19; however, further testing is needed to determine if this finding relates to all COVID-19 patients (103,104) . Although it seems likely that COVID-19 patients might benefit from folate/B6/B12 supplementation, randomized controlled trials are certainly needed to answer.…”

Section: Folate/vitamin B6/vitamin B12 and Hyperhomocysteinemia: Implications In Covid-19mentioning

confidence: 84%

Vitamins, microelements and the immune system: current standpoint in the fight against coronavirus disease 2019

et al. 2022

View full text Add to dashboard Cite

Coronavirus disease 2019 (COVID-19) is an acute respiratory disease associated with severe systemic inflammation. The optimal status of vitamins and microelements is considered crucial for the proper functioning of the immune system and necessary for successful recovery. Most patients with respiratory distress in COVID-19 are vitamin and microelement deficient, with vitamin D and selenium deficiency being the most common. Anyway, various micronutrient supplements are widely and arbitrarily used for prevention or in the treatment of COVID-19. We aimed to summarize current knowledge about molecular and physiological mechanisms of vitamins (D, A, C, B6, B9, B12) and microelements (selenium, zinc, copper, iron) involved in the immune system regulation in consideration with COVID-19 pathogenesis, as well as recent findings related to their usage and effects in the prevention and treatment of COVID-19. In the early course of the pandemic, several, mainly observational, studies reported an association of some micronutrients, such as vitamin C, D, and zinc, with severity reduction and survival improvement. Still, emerging randomized controlled trials showed no effect of vitamin D on hospitalization length and no effect of vitamin C and zinc on symptom reduction. Up to date, there is evidence neither for nor against the use of micronutrients in the treatment of COVID-19. The doses that exceed the recommended for the general population and age group should not be used, except in clinical trials. Benefits of supplementation are primarily expected in populations prone to micronutrient deficiencies, who are, as well, at a higher risk of worse outcomes in COVID-19.

show abstract

“…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]. Moreover, elevated homocysteine levels may in turn increase tissue factor activity [52,53], thus promoting a prothrombotic state.…”

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

View full text Add to dashboard Cite

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).

show abstract

Homocysteine (Hcy) assessment to predict outcomes of hospitalized Covid-19 patients: a multicenter study on 313 Covid-19 patients

Cited by 29 publications

References 10 publications

Evaluation of Endothelial Dysfunction and Inflammatory Vasculopathy After SARS-CoV-2 Infection—A Cross-Sectional Study

Evaluation of Endothelial Dysfunction and Inflammatory Vasculopathy After SARS-CoV-2 Infection—A Cross-Sectional Study

Vitamins, microelements and the immune system: current standpoint in the fight against coronavirus disease 2019

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

Contact Info

Product

Resources

About