The Importance of Serum Homocysteine as a Biomarker in Diabetic and Obese COVID-19 Patients.

Homocysteine is a possible risk marker in hematological complications of COVID-19 infection. This study aimed to elucidate the significance of homocysteine as a biomarker for COVID-19 infection, and the relation of homocysteine with COVID-19 severity in obese people and diabetic patients.  The study groups were 1- COVID-19 patients + Diabetic + Obese (CDO), 2- COVID-19 patients + Diabetic (CD), 3- COVID-19 patients + Obese (CO), 4- Healthy Group (HG). Serum levels of homocysteine, IL-6, D-dimer, vitamin B12, and folate were measured by a fully automated biochemistry device Cobas 6000 analyzer series. The mean serum concentration of homocysteine in the COD, CD, CO and H groups were 32.0114, 23.604, 19.4154, and 9.3206 umol/l respectively. The mean concentration of homocysteine levels between every two groups was statistically significant differences (P<0.05) except for the CD and the CO group (P=0.957). In the CDO group, the males have higher mean concentrations than females (P<0.05). The means of homocysteine concentrations in the CDO group among different age groups were different (P <0.001). The serum homocysteine level in the CDO group has a strong positive correlation (R=0.748) with D-dimer and a strong negative correlation (R= - 0.788) with serum folate, while its correlation with serum vitamin B12 is moderate negative (-0.499) and its correlation with serum IL-6 is weakly positive (R=0.376). The AUC value for homocysteine in predicting COVID-19 in the CDO group was 0.843, while 0.714 for the CD group, and 0.728 for the CO group. The serum homocysteine concentration test for all study groups was compared to the serum IL-6 test and the sensitivity was equal to 95% and its specificity was 67.5%. Serum homocysteine has potential predictive power in COVID-19 patients, and the severity of COVID-19 infection and the type of comorbidity is associated with higher sensitivity and specificity of homocysteine serological tests.

The Prophylactic Effect of Vitamin C and Vitamin B12 against Ultraviolet-C-Induced Hepatotoxicity in Male Rats.

Ultraviolet C (UVC) devices are an effective means of disinfecting surfaces and protecting medical tools against various microbes, including coronavirus. Overexposure to UVC can induce oxidative stress, damage the genetic material, and harm biological systems. This study investigated the prophylactic efficacy of vitamin C and B12 against hepatotoxicity in UVC-intoxicated rats. Rats were irradiated with UVC (725.76, 967.68, and 1048.36 J/cm2) for 2 weeks. The rats were pretreated with the aforementioned antioxidants for two months before UVC irradiation. The prophylactic effect of vitamins against UVC hepatotoxicity was evaluated by monitoring the alteration of liver enzyme activities, antioxidant status, apoptotic and inflammatory markers, DNA fragmentation, and histological and ultrastructural alterations. Rats exposed to UVC showed a significant increase in liver enzymes, oxidant-antioxidant balance disruption, and increased hepatic inflammatory markers (TNF-α, IL-1ß, iNOS, and IDO-1). Additionally, obvious over-expression of activated caspase-3 protein and DNA fragmentation were detected. Histological and ultrastructural examinations verified the biochemical findings. Co-treatment with vitamins ameliorated the deviated parameters to variable degrees. In conclusion, vitamin C could alleviate UVC-induced hepatotoxicity more than vitamin B12 by diminishing oxidative stress, inflammation, and DNA damage. This study could provide a reference for the clinical practice of vitamin C and B12 as radioprotective for workers in UVC disinfectant areas.

Nitrous oxide misuse: a clue not to be missed in young patients with venous thromboembolism.

A 27-year-old man presented with altered mental status and unilateral right lower limb swelling. Brain imaging and cerebrospinal fluid analysis were unremarkable. He reported history of nitrous oxide misuse after he recovered from his delirium. The diagnosis of drug induced psychosis was made. The right lower limb swelling was found to be due to extensive deep vein thrombosis. In another case, a 21-year-old woman presented with headache, vomiting and dipoplia. Brain imaging showed extensive cerebral venous sinus thrombosis. She also misused nitrous oxide. Both cases had low-normal vitamin B12 and elevated methylmalonic acid, consistent with nitrous oxide misuse. The woman was found to have elevated homocysteine because of functional vitamin B12 deficiency. Homocysteine was not measured in the man. Raised homocysteine is associated with increased thrombosis risk. Fourteen cases of nitrous oxide misuse associated arterial and venous thrombosis have been reported. These two cases highlighted the importance of inquiring about recreational drug use in young patients who presented with apparently unprovoked venous thromboembolism.

Patient safety, self-injection, and B12 deficiency: a UK cross-sectional survey.

BACKGROUND: Individuals with vitamin B12 deficiency (including pernicious anaemia) often report being 'let down' or stigmatised by general practice systems and policy, and choose instead to self-medicate via injection; the association between this and perceptions of safe primary care in this group of people is unknown. AIM: To examine the association between self-medication for vitamin B12 deficiency and patient-reported safety in primary care. DESIGN AND SETTING: A UK cross-sectional online survey. METHOD: The survey consisted of the three components: demographics; the validated Primary Care Patient Measure of Safety; and questions about self-medication for vitamin B12 deficiency. Multivariable logistic regression analyses and thematic synthesis were undertaken. RESULTS: Responses from 1297 participants indicated 508 (39.2%) self-medicated via injection. Perceived primary care safety was low. Those who self-medicated via injection reported a significantly lower level of patient safety in primary care including adverse patient-related factors (odds ratio 0.82, 95% confidence interval = 0.73 to 0.92), and patients >34 years of age were significantly more likely to self-medicate via injection. Many reported that treatment under the guidance of a clinician was preferable to self-medication, but felt they had no other choice to regain quality of life. Almost half felt that the doctor did not always consider what they wanted for their care. CONCLUSION: To the authors' knowledge, this is the largest study to date examining patient safety and vitamin B12 deficiency. It found that four out of 10 patients with B12 deficiency self-medicate via injection. Patients who self-medicated perceived primary care as less safe. Providing patient-centred care and treating these patients with dignity and respect is a policy priority to reduce unsafe health behaviours.

Determination of B Vitamins by Double-Vortex-Ultrasonic Assisted Dispersive Liquid-Liquid Microextraction and Evaluation of their Possible Roles in Susceptibility to COVID-19 Infection: Hybrid Box-Behnken Design and Genetic Algorithm.

OBJECTIVES: In this study, double-vortex-ultrasonic assisted dispersive liquid-liquid microextraction (DVUDLLME) was applied to determine the concentration of vitamin B9, 5-methyl tetrahydrofolate (5-MeTHF) and vitamin B12 in human serum samples. METHODS: High-performance liquid chromatography (HPLC) coupled with DVUDLLME was applied to analyze vitamins B in patients with Coronavirus disease (COVID-19). Then, significant variables were chosen and optimized using the hybrid Box-Behnken design and genetic algorithm. RESULTS: The detection limits of DVUDLLME-HPLC were 0.21 ng mL-1, 0.18 ng mL-1 and 55 pgmL-1 for vitamin B9, 5-MeTHF and vitamin B12, respectively. Subsequently, DVUDLLME-HPLC was applied to measure B vitamins and investigated their possible roles in susceptibility to COVID-19 infection. Fifty-seven percent of the patients without an underlying disease have significantly lower serum vitamin B12 levels in comparison to controls. CONCLUSIONS: The advantages of this method are low detection limit, simple preparation, low retention time and the use of a cheaper technique instead of expensive mass detectors. The results suggest that vitamin B12 deficiency may decrease the immune system defenses against COVID-19 patients without an underlying disease and cause the disease to become severe. However, these works need a large population and further research, such as a randomized trial and a cohort study.

Vitamin B12 attenuates leukocyte inflammatory signature in COVID-19 via methyl-dependent changes in epigenetic markings.

COVID-19 induces chromatin remodeling in host immune cells, and it had previously been shown that vitamin B12 downregulates some inflammatory genes via methyl-dependent epigenetic mechanisms. In this work, whole blood cultures from moderate or severe COVID-19 patients were used to assess the potential of B12 as adjuvant drug. The vitamin normalized the expression of a panel of inflammatory genes still dysregulated in the leukocytes despite glucocorticoid therapy during hospitalization. B12 also increased the flux of the sulfur amino acid pathway, that regulates the bioavailability of methyl. Accordingly, B12-induced downregulation of CCL3 strongly and negatively correlated with the hypermethylation of CpGs in its regulatory regions. Transcriptome analysis revealed that B12 attenuates the effects of COVID-19 on most inflammation-related pathways affected by the disease. As far as we are aware, this is the first study to demonstrate that pharmacological modulation of epigenetic markings in leukocytes favorably regulates central components of COVID-19 physiopathology.

Drug repurposing based on a quantum-inspired method versus classical fingerprinting uncovers potential antivirals against SARS-CoV-2.

The COVID-19 pandemic has accelerated the need to identify new antiviral therapeutics at pace, including through drug repurposing. We employed a Quadratic Unbounded Binary Optimization (QUBO) model, to search for compounds similar to Remdesivir, the first antiviral against SARS-CoV-2 approved for human use, using a quantum-inspired device. We modelled Remdesivir and compounds present in the DrugBank database as graphs, established the optimal parameters in our algorithm and resolved the Maximum Weighted Independent Set problem within the conflict graph generated. We also employed a traditional Tanimoto fingerprint model. The two methods yielded different lists of lead compounds, with some overlap. While GS-6620 was the top compound predicted by both models, the QUBO model predicted BMS-986094 as second best. The Tanimoto model predicted different forms of cobalamin, also known as vitamin B12. We then determined the half maximal inhibitory concentration (IC50) values in cell culture models of SARS-CoV-2 infection and assessed cytotoxicity. We also demonstrated efficacy against several variants including SARS-CoV-2 Strain England 2 (England 02/2020/407073), B.1.1.7 (Alpha), B.1.351 (Beta) and B.1.617.2 (Delta). Lastly, we employed an in vitro polymerization assay to demonstrate that these compounds directly inhibit the RNA-dependent RNA polymerase (RdRP) of SARS-CoV-2. Together, our data reveal that our QUBO model performs accurate comparisons (BMS-986094) that differed from those predicted by Tanimoto (different forms of vitamin B12); all compounds inhibited replication of SARS-CoV-2 via direct action on RdRP, with both models being useful. While Tanimoto may be employed when performing relatively small comparisons, QUBO is also accurate and may be well suited for very complex problems where computational resources may limit the number and/or complexity of possible combinations to evaluate. Our quantum-inspired screening method can therefore be employed in future searches for novel pharmacologic inhibitors, thus providing an approach for accelerating drug deployment.

Neurological and Psychological Characteristics of Young Nitrous Oxide Abusers and Its Underlying Causes During the COVID-19 Lockdown.

Background: The COVID-19 pandemic has a serious impact on the mental health of the public due to its economic and social impact. And psychological effects have led to drug and alcohol abuse. After the city lifted the lockdown, we consecutively encountered several young nitrous oxide abusers admitted to hospital for neurological treatment. Purpose: To inform physician decisions and social intervention, this observational study aimed at investigating the neurological and psychological characteristics of nitrous oxide abusers and its underlying causes during the COVID-19 lockdown. Methods: The nitrous oxide abusers who sought neurological treatment at our hospital between May 2020 and June 2020 were enrolled. Clinical data including socio-demographic, physical examination, laboratory examination, electromyography and neuroimaging were collected. Their motivations for inhaling nitrous oxide, knowledge about the nitrous oxide abuse and the accompanying of family were investigated face to face. Psychological status was assessed by the Symptom Checklist 90 (SCL-90) psychological evaluation. Results: Six nitrous oxide abusers were enrolled and the age was 22 ± 4.3. Clinical presentations included varying degrees of limb numbness and an ataxic gait. Laboratory examination revealed that all the patients did not have pernicious anemia, 4 patients had decreased vitamin B12 while 3 patients exhibited elevated homocysteine levels. MR of the spinal cord revealed that 4 patients had abnormal signals in the cervical spinal cord of high symmetry with splayed or inverted V sign after T2WI. Electromyogram (EMG) test showed 5 patients had peripheral nerve damage. The SCL-90 psychological evaluation results indicated that all patients had severe anxiety, depression and psychosis and they had severer psychological problems than ordinary citizens. Their motives for inhaling nitrous oxide are to relieve boredom, curiosity and buddy pressure. Their family spent <1 day per week to stay with them during city lockdown. Conclusion: The enrolled patients caused by abuse of nitrous oxide presented with symptoms of subacute combined with spinal degeneration. They had more serious psychological problems related to the COVID-19 pandemic. These cases make us value the psychological problems of young people under the outbreak and take multi-layered measures from families, schools (companies), hospitals, and governments to address it.

Combined action of SAMe, Folate, and Vitamin B12 in the treatment of mood disorders: a review.

Mood disorders affect more than 500 million people around the world. In the last decade, their prevalence has increased, and many people suffer from nervousness, anxiety, and stress at least once in their lives. The incidence of mood disorders and anxiety increases during perimenopause or under stressful conditions. The social restrictions introduced during the COVID-19 pandemic have significantly increased the normal burden of psychological and psychic disorders. In moderate to severe cases, pharmacological treatment is currently recommended, while in mild disorders, especially in the initial phase, psychological therapy is preferable. It is known that several nutrients are crucial for brain function. Among them, folate (vitamin B9), cyanocobalamin (vitamin B12), and S-adenosyl-L-methionine (SAMe) have been shown to influence various neurobiological processes. Overall, the available evidence suggests that dietary supplementation with folic acid, vitamin B12, and SAMe can be beneficial for people with mild mood disorders.

Associations of depression and intake of antioxidants and vitamin B complex: Results of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

BACKGROUND: Optimum functioning of the central nervous system is dependent on a wide range of nutrients, so mental illness can be impacted by diet via several mechanisms. We aimed to investigate the associations of antioxidants (vitamin A, C and E, and selenium and zinc) and vitamin B complex (B6, folate and B12) intake with depression in 14,737 subjects of the Brazilian Longitudinal Study of Adult Health. METHODS: Baseline cross-sectional data was analyzed. Micronutrients intake was measured using the Food Frequency Questionnaire, and depression was assessed using the Clinical Interview Schedule Revised. Logistic regression models were built using daily intake quintiles of micronutrients. RESULTS: A significant inverse relationship was observed between depression and higher intake of selenium, zinc, vitamins B6 and B12 for the total sample. Among women, a similar pattern of associations was observed, in addition to the higher intake of vitamins A and C. Among men, a significant inverse relationship between depression was observed only with the intake of vitamins B12 and B6. Higher total antioxidant intake was significantly associated with lower odds of depression and an inverse dose-response effect between total antioxidant intake and clinical severity of depression was observed among women, in adjusted models. LIMITATIONS: Recall bias in assessing diet. Misclassification bias regarding current depression. CONCLUSIONS: Depression is associated with lower intake of antioxidants and B vitamins. Higher intake of selected micronutrients may contribute to reduce depression occurrence and severity.

COVID-19 and One-Carbon Metabolism.

Dysregulation of one-carbon metabolism affects a wide range of biological processes and is associated with a number of diseases, including cardiovascular disease, dementia, neural tube defects, and cancer. Accumulating evidence suggests that one-carbon metabolism plays an important role in COVID-19. The symptoms of long COVID-19 are similar to those presented by subjects suffering from vitamin B12 deficiency (pernicious anemia). The metabolism of a cell infected by the SARS-CoV-2 virus is reshaped to fulfill the need for massive viral RNA synthesis, which requires de novo purine biosynthesis involving folate and one-carbon metabolism. Many aspects of host sulfur amino acid metabolism, particularly glutathione metabolism underlying antioxidant defenses, are also taken over by the SARS-CoV-2 virus. The purpose of this review is to summarize recent findings related to one-carbon metabolism and sulfur metabolites in COVID-19 and discuss how they inform strategies to combat the disease.

The impact of vitamin and mineral supplements usage prior to COVID-19 infection on disease severity and hospitalization.

The COVID-19 pandemic has caused a global public health emergency. Nutritional status is suggested to be related to the severity of COVID-19 infection. Herein, we aimed to explore the impact of using vitamin and mineral supplements prior to COVID-19 infection on disease severity and hospitalization. In addition, the prior use of aspirin as an anticoagulant on the disease severity was investigated. A cross-sectional, self-administered survey was conducted between March and July 2021. Recovered COVID-19 individuals (age ≥ 18 years, n = 2148) were recruited in the study. A multivariate logistic regression was used to evaluate the associations of supplements and aspirin use with COVID-19 disease severity and hospitalization status. Among the participants, 12.1% reported symptoms consistent with severe COVID-19, and 10.2% were hospitalized due to COVID-19. After adjustment for confounding variables (age, gender, BMI, cigarette smoking status, and the number of comorbidities), the multivariate logistic regression model showed that the consumption of vitamin D supplements prior to COVID-19 infection was associated with a significant decrease in disease severity (OR = 0.68, 95% CI 0.50 - 0.92; P = 0.01), and a lower risk of hospitalization (OR = 0.64, 95% CI 0.45 - 0.89; P = 0.01). On the other hand, there were no significant differences in the frequencies of severe illness and hospitalizations with the consumption of vitamin A, folic acid, vitamin B12, vitamin B complex, vitamin C, zinc, iron, selenium, calcium, magnesium, omega 3, and aspirin before COVID-19 infection. Among the investigated nutrients, the use of vitamin D prior to COVID-19 infection was associated with reduced disease severity and hospitalization. However, more studies are required to confirm this finding.

Structure of a B12-dependent radical SAM enzyme in carbapenem biosynthesis.

Carbapenems are antibiotics of last resort in the clinic. Owing to their potency and broad-spectrum activity, they are an important part of the antibiotic arsenal. The vital role of carbapenems is exemplified by the approval acquired by Merck from the US Food and Drug Administration (FDA) for the use of an imipenem combination therapy to treat the increased levels of hospital-acquired and ventilator-associated bacterial pneumonia that have occurred during the COVID-19 pandemic1. The C6 hydroxyethyl side chain distinguishes the clinically used carbapenems from the other classes of ß-lactam antibiotics and is responsible for their low susceptibility to inactivation by occluding water from the ß-lactamase active site2. The construction of the C6 hydroxyethyl side chain is mediated by cobalamin- or B12-dependent radical S-adenosylmethionine (SAM) enzymes3. These radical SAM methylases (RSMTs) assemble the alkyl backbone by sequential methylation reactions, and thereby underlie the therapeutic usefulness of clinically used carbapenems. Here we present X-ray crystal structures of TokK, a B12-dependent RSMT that catalyses three-sequential methylations during the biosynthesis of asparenomycin A. These structures, which contain the two metallocofactors of the enzyme and were determined in the presence and absence of a carbapenam substrate, provide a visualization of a B12-dependent RSMT that uses the radical mechanism that is shared by most of these enzymes. The structures provide insight into the stereochemistry of initial C6 methylation and suggest that substrate positioning governs the rate of each methylation event.

Evaluation of the relationship between serum levels of zinc, vitamin B12, vitamin D, and clinical outcomes in patients with COVID-19.

Due to the known anti-inflammatory and antiviral effects of zinc, 25(OH)D, and vitamin B12, in this study, we explored the association between serum levels of these micronutrients in coronavirus disease 2019 (COVID-19) patients at the time of admission and the clinical outcomes. This study was carried out on 293 patients with COVID-19, who were hospitalized at Imam Hassan hospital (Bojnourd, Iran). We collected demographic data, clinical characteristics, values of serum biochemical parameters in the first week of admission, and clinical outcomes from electronic medical records. We also measured serum levels of zinc, 25(OH)D, and vitamin B12 within 3 days of admission. Of the 293 hospitalized, the median age was 53 years, and 147 (50.17%) were female. Thirty-seven patients (12.62%) were admitted to the intensive care unit (ICU), and forty-two (14.32%) died. We found that the serum levels of zinc, vitamin B12, and 25(OH)D were lower in patients who died than those who were admitted to ICU or non-ICU and survived; however, these differences were not statistically significant for vitamin B12 and 25(OH)D (p > 0.05). The serum concentrations of zinc, vitamin B12, and 25(OH)D at the time of admission did not affect the length of hospital stay in patients with COVID-19. In general, it seems that serum levels of 25(OH)D, vitamin B12, and especially zinc at the time of admission can affect clinical outcomes in COVID-19 patients.

The role of vitamin B12 in viral infections: a comprehensive review of its relationship with the muscle-gut-brain axis and implications for SARS-CoV-2 infection.

This comprehensive review establishes the role of vitamin B12 as adjunct therapy for viral infections in the treatment and persistent symptoms of COVID-19, focusing on symptoms related to the muscle-gut-brain axis. Vitamin B12 can help balance immune responses to better fight viral infections. Furthermore, data from randomized clinical trials and meta-analysis indicate that vitamin B12 in the forms of methylcobalamin and cyanocobalamin may increase serum vitamin B12 levels, and resulted in decreased serum methylmalonic acid and homocysteine concentrations, and decreased pain intensity, memory loss, and impaired concentration. Among studies, there is much variation in vitamin B12 doses, chemical forms, supplementation time, and administration routes. Larger randomized clinical trials of vitamin B12 supplementation and analysis of markers such as total vitamin B12, holotranscobalamin, total homocysteine and methylmalonic acid, total folic acid, and, if possible, polymorphisms and methylation of genes need to be conducted with people with and without COVID-19 or who have had COVID-19 to facilitate the proper vitamin B12 form to be administered in individual treatment.

Neurological consequences of recreational nitrous oxide abuse during SARS-CoV-2 pandemic.

INTRODUCTION: Recreational use of nitrous oxide (N2O) is a growing practice in France and all around the world and is often associated with neurological complications. We report detailed clinical and paraclinical presentations of 12 patients with combined degeneration of the spinal cord and peripheral neuropathies in relation to N2O consumption, possibly favored by lockdowns due to SARS-CoV-2 pandemic. RESULTS: With variable levels of consumption, the 12 patients presented spinal cord and/or peripheral nerve damage, with mostly motor and ataxic symptoms, motor axonal nerve damage, and medullary T2-weighted hyperintensities on MRI. There was a clear improvement in symptoms after vitamin B12 substitution, although some sequelae remained, particularly sensory. DISCUSSION: We report detailed clinical, electrophysiological, radiological, and biological consequences of N2O abuse in 12 patients. Our data support the clinical and paraclinical observations reported in the literature. The mechanisms of neurological N2O toxicity are still debated. There is currently no precise recommendation on the therapeutic management. The clinical evolution after vitamin B12 substitution seems sufficient but could depend on early management. Effective messages targeting at risk population, but also the health professionals involved, seem crucial as does a better legal framework for this growing practice.