Pregnancy Outcomes in Women with Sickle Cell Disease in Ireland: A Retrospective Review

Background: Sickle cell disease (SCD) is one of the most common single gene disorders worldwide and is characterised by significant morbidity and early mortality.[1] Pregnancy in SCD is associated with an increased risk of maternal and foetal complications.[2,3] The 2011 RCOG and the 2021 BSH guidelines[5,6] on the management of pregnancy in SCD have provided the basis for best practice care in the UK over the past decade and is the guidance which we follow in Ireland. To date, there is no published data on outcomes for pregnant women with SCD in Ireland. The number of Irish patients with SCD has risen over the past 20 years. Without a national database, the exact prevalence is not known but currently there are at least 600 adults and children with SCD in Ireland, whose population is just over 5 million.[4] Aims: Our study assesses outcomes of pregnant patients with SCD from 2015 to 2022. Our aims were to: * Assess adherence to current guidelines * Assess pregnancy outcomes and maternal complications * Assess transfusion rates amongst our patient cohort. Method(s): This is a retrospective cohort study. We do not have a directly matched cohort, but have compared our findings to published data on Irish pregnancy outcomes from the Irish Maternity Indicator System National Report and have correlated our findings with studies of women with SCD who were managed in UK centres.[8,9,10] Results: We reviewed outcomes of 29 pregnancies in 19 women over a 7-year period. The median age was 29 (range 20-41) and the predominant maternal sickle genotype was HbSS (65.5%). Before conception, 55.2% of cases had pre-existing complications of SCD, including acute chest syndrome (ACS), pulmonary hypertension (PHTN) and prior stroke. In accordance with current guidelines, 100% of women (n=29) were prescribed folic acid, penicillin, and aspirin prophylaxis. 51.7% (n=15) of women had documented maternal complications during pregnancy, including ACS (34%), vaso-occlusive crisis (34%), gestational diabetes (10%), VTE (3%) and UTI (3%). Two women (7%) developed Covid-19 pneumonitis despite vaccination. There was one case of maternal bacteraemia (3%). 65.5% of cases (n=19) required blood transfusion during pregnancy. One woman was already on a blood transfusion programme for disease modification prior to pregnancy. In 6 cases (20.6%), a transfusion programme was commenced during pregnancy due to prior pregnancy complications or intrauterine growth restriction. During pregnancy, 27.6% (n=8) of women required emergency red cell exchange for ACS. Prior studies have suggested that between 30% and 70% of pregnant women with SCD require at least one blood transfusion during pregnancy.[8,9,10] By comparison, only 2.6% of the Irish general obstetric population required transfusion during pregnancy.[7] 20.6% (n=6) of births were preterm at <37 weeks' gestation. There was one live preterm birth (3%) at <34 weeks and one intrauterine death (3%) at 23 weeks' gestation. Similar to UK data[9], 31% of women required critical care stay (n=9) during pregnancy, in comparison with 1.44% nationwide in 2020.[7] Conclusion(s): It is well established that pregnancy in SCD is high risk, and despite adherence to current guidelines, we have shown very high rates of critical care admission, significant transfusion requirement and hospital admissions. Our findings are comparable to published UK outcomes and they further support the need for a comprehensive specialist care setting for this patient cohort.

TESTING A NEW FATIGUE CHECKLIST IN SLE PATIENTS FOR EVERYDAY CLINICAL PRACTICE - AN INTERIM ANALYSIS

BackgroundFatigue is a difficult subject for both physicians and patients. It is barely addressed during consultations and can therefore burden patient-physician-relations. To improve communication regarding fatigue, we developed a checklist that includes suggestions for evaluating possible causes for fatigue. In this analysis, we describe our study population and report first results 3 and 6 months after using the checklist.ObjectivesThe aims of our study are to validate the use of our newly developed fatigue checklist and to demonstrate that addressing fatigue in daily clinical practice and offering possible interventions can improve fatigue.MethodsWe recruited n=110 SLE patients with fatigue from our university hospital-based lupus reference centre in Duesseldorf. Fatigue was measured using the FSS (Fatigue Severity Scale). Our checklist included signs of depression and anxiety using the PHQ-4 (Patient Health Questionnaire), BMI (body mass index), physical activity, anemia, hypothyroidism and vitamin D deficiency. For each applicable cause, we listed possible interventions for free selection by the treating physician, such as replacement therapy (vitamin D, vitamin B12, iron, folic acid, erythropoietin), physical activity programs and psychosomatic consultations that were discussed with the patients. We re-evaluated our patients after 3 (T1) and 6 months (T2).ResultsBaseline characteristics of patients are summarized in Table 1.Table 1.BMI=body mass index, TSH=thyroidea stimulating hormone, PHQ4=patient health questionnaire (cut-off >3 points), HAQ=health assessment questionnaire, IMET= Index for measuring restrictions on social participation (higher scores point towards more restrictions on social participation), FSS=fatigue severity scale (≥4 points equal severe fatigue)N = 110n (%)Mean (SD)Age (years)49.0 (12.34)Female sex99.0 (90.0)BMI (kg/m2)25.9 (5.55)Disease duration (years)19.1 (10.05)TSH (µIU/ml)1.5 (1.05)25-OH-Vitamin D (ng/ml)39.5 (15.35)Haemoglobin (g/dl)13.0 (1.64)Sports activities>4h/week6.0 (5.5)2-4h/week18.0 (16.4)1-2h/week16.0 (14.5)<1h/week28.0 (25.5)No sport42.0 (38.2)Depression (PHQ4 score)2.3 (1.63)Anxiety (PHQ4 score)2.0 (1.71)Functional status (HAQ score)0.8 (0.49)Participation (IMET score)2.8 (2.31)Fatigue (FSS score)5.3 (1.35)After 3 and 6 months, we re-evaluated 83 patients and saw a significant reduction in fatigue measured by the FSS score (T1: mean difference estimate 0.367 and p-value <0.001;T2: mean difference estimate 0.305;p-value <0.005).Figure 1.Comparing FSS-Scores from T0, T1 and T2[Figure omitted. See PDF]ConclusionThe preliminary analysis of our study shows for the first time that incorporation of a checklist procedure into the management of patients with fatigue may improve short-term outcome after 3 and 6 months of observation. The improvement of symptoms documented in our study occurred even though the suggested exercise program and psychosomatic counseling sessions were not available for use during the current observation period because of the COVID-19 pandemic. At present, the mechanisms behind the observed effect remain unclear. Our ongoing analysis will clarify whether an additional effect on fatigue will occur after all suggested interventions resulting from the use of the checklist have been executed. Finally, it will demonstrate whether the incorporation of our checklist into routine clinical practice is capable to reduce fatigue over a prolonged time period.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Health is complex, the solutions are long term

The debate on folic acid fortification of food to prevent neural tube defects in babies, for example, hasn't progressed in more than two decades (doi:10.1136/bmj.p1158).8 The worrying rise in perinatal suicides requires better funded services and support for women and young families to prevent deaths (doi:10.1136/bmj-2023-075414).9 And are the mandatory school inspections that harm the mental health of teaching staff even necessary (doi:10.1136/bmj.p1147)?10 The same applies to overzealous and discriminatory processes implemented by medical regulatory bodies such as the General Medical Council, despite claims of improvement by its chief executive (doi:10.1136/bmj.p1295 doi:10.1136/bmj.p1252).1112 The prevention principle would urge us to support a ban on vaping (doi:10.1136/bmj.p1266) and consider new options for reducing the number of days people experience migraines (doi:10.1136/bmj.p1249).1314 It would also induce bewilderment at the decision to wind down the UK's world leading covid surveillance network when covid-19 is still with us and future pandemics are inevitable (doi:10.1136/bmj.p1157).15 It would not, however, lend support to a non-evidence based screening programme for haemochromatosis (doi:10.1136/bmj.p1264).16 The first steps of an "avoid, reduce, reuse, recycle, research, rethink” framework (doi:10.1136/bmj-2021-069044) focus on better clinical practice that avoids low value care and inappropriate admissions and minimises blood tests and other interventions.17 This latest article in our series on achieving net zero and environmental sustainability in clinical practice examines critical care. The challenge isn't entirely a clinical one, because achieving net zero will depend on commitment across healthcare professions, engineering, waste management, hospital leadership, and beyond. A research paper assessing the value of routine monitoring of people being treated with methotrexate finds that frequency of monitoring should be adjusted according to risk, reducing the burden of work on clinical staff and making life more manageable for patients (doi:10.1136/bmj-2022-074678 doi:10.1136/bmj.p1120).1819 The difficulty here is one of getting research into practice, a timescale of 17 years by some estimates.

Vitamin D deficiency promoting non-24 h sleep-wake disorder: a case report.

We report a case of an emmetropic woman with excessive daytime sleepiness in alternation with insomnia consistent with the diagnosis criteria of a non-24 h sleep-wake disorder. After being refractory to the usual non-pharmacologic and pharmacologic treatment, we detected a deficiency of vitamin B12, vitamin D3, and folic acid. Substitution of these treatments led to a return of a 24 h sleep-wake rhythm though this remained independent from the external light-dark cycle. The question arises whether the vitamin D deficiency could be regarded as an epiphenomenon or whether there is an up-to-date unknown connection to the inner zeitgeber.

Folic acid - importance for human health and its role in COVID-19 therapy.

Folic acid (folacin, B9) is a vitamin that performs many very important functions in the human body, and its inadequate level - deficiency as well as excess, may contribute to an increased risk of developing many disease processes. The aim of this study was to analyze the available scientific literature on folic acid and its impact on human health. A systematic review of the studies, published until November 2022, was made on the basis of searching bibliographic databases such as: PubMed, Elsevier and Google Scholar. The following keywords and combinations were used: folic acid, folate, folic acid supplementation, folate deficiency. Folic acid, thanks to its high biological activity, has a direct and indirect effect on the metabolism of the human body cells. It plays a very important role, among others in the prevention of neural tube defects and megaloblastic anemia, the proper functioning of the nervous system, as well as reducing the risk of developing certain cancers. Currently, the important role of folic acid in maintaining the proper functioning of the immune system is also emphasized, which is of particular importance both in the prevention and in the situation of SARS-CoV-2 (COVID-19) infection. The effects of deficiency and excess of vitamin B9 may turn out to be dangerous to health and even life. There is a need for nutritional and health education of the society regarding the importance of folic acid for human health, due to the presence of large deficiencies in the population, which is particularly important for some social groups, such as, for example, women of procreation age, pregnant or breastfeeding, people with a nutrient malabsorption, and people who smoke or abuse alcohol.

Effect of folic acid in patients with lung damage caused by coronavirus SARS-CoV-2

Aim of study. To evaluate the influence exerted by additional use of a fixed combination of folic acid with pyridoxine hydrochloride and cyanocobalamin in complex therapy for hospitalised patients with COVID-19-associated lung damage on parameters of inflammation and clinical outcomes. Material and methods. A comparative prospective interventional study included 117 patients with a lung lesion volume caused by the SARS-CoV-2 coronavi-rus corresponding to CT-1 and CT-2. The study group included 78 patients who additionally received a fixed combination of 5mg folic acid, 4mg pyridoxine hydrochloride, and 6mug cyanocobalamin three times a day in combination with standard therapy. The comparison group included 39 patients. Results. By days 14-21 of hospitalisation, the main group showed a decrease in the proportion of patients with CT symptoms of "cobblestone appearance" by 26% (p = 0.005) and an increase in the proportion of patients with transformation of viral lung lesions into areas of consolidation of the pulmonary parenchyma by 23% (p <0.001). The effect of a fixed combination of folic acid with vitamins B6, B12 on the achievement of the level of C-reactive protein <20 mg / l by day 7 depending on the red blood parameters and the number of platelets was established (likelihood ratio test in the logistic regression model: 13.925;P = 0.084) as well as the shortening of the time period required to reach the first negative result of the SARS-CoV-2 RNA test (in the linear regression model, R = 0.437;R2 = 0.191;F = 4.552;p = 0.006). Conclusion. The use of a fixed combination of folic acid with vitamins B6, B12 for patients with COVID-19 is associated with earlier achievement of positive dynamics in CT symptoms of lung damage. The additional use of these micronutrients in combination with restoration of red blood count and platelet count improves the odds ratio of an early decrease in serum C-reactive protein, negative result of the SARS-CoV-2 RNA test.Copyright © 2021, Krasnoyarsk State Medical University. All rights reserved.

PORTAL VEIN THROMBOSIS WHILE TAKING A COMBINED ORAL CONTRACEPTIVE AFTER EXPERIENCED CORONAVIRUS INFECTION.

Background: Contraceptives are an important component of women's reproductive health care, as they not only reduce the number of unwanted pregnancies, but also improve reproductive function. However, oral contraceptives are known to increase the risk of venous thromboembolism. This risk is increased by infection with the COVID-19 virus that predisposes patients to both venous and arterial thrombosis as a result of excessive inflammation, platelet activation, aggravated endothelial dysfunction, and congestive events. If these patients have hereditary thrombophilia, the risk of venous thromboembolism becomes fatal. Case report: The paper describes a clinical case of a patient with total portal vein thrombosis, who have been taking oral contraceptives for a long time and recovering from the novel coronavirus infection. Studying the blood coagulation system and folate cycle genes, by using PCR, has revealed a gene mutation in the plasminogen activator inhibitor (serpine). The authors demonstrate the data of spiral computed tomography of the abdominal organs, as well as changes in laboratory parameters. Conclusion(s): A balanced approach is required when prescribing combined oral contraceptives during the COVID-19 pandemic, especially in women with prothrombotic mutations.Copyright © A group of authors, 2023.

The use of folic acid as a prophylaxis against COVID-19 among healthcare workers

Background: Vaccines may be thought of as a reliable intervention to prevent SARS-CoV-2 infection. Prophylactic drugs may be a sound alternative. We aimed to assess the use of folic acid to protect against COVID-19 infection. Methods: This randomized controlled study was conducted in an isolation hospital at Cairo University Hospitals on three groups of nurses caring for COVID-19 patients: group I;the control group, group II whose participants received 500 micrograms of folic acid daily, and group III whose participants received 1000 micrograms daily. PCR conversion was tested for the three groups as a primary endpoint. Results: In total, 526 nurse were included. Group I comprised 139 nurse, group II comprised 163 nurse, and group III comprised 224 nurses. The rates of PCR conversion from negative to positive were 4.9% (8/163) in group II and 1.8% in group III (4/224) compared with 14.4% in the control group I (20/139). Statistically significant (p<0.005) and highly statistically significant (p<0.001) differences respectively were found. Conclusions: Prescribing folic acid daily may significantly decrease the risk of COVID-19 infection among exposed healthcare workers. © 2020 The author (s).

Notes from the 2022 Folate, Vitamin B12, and One-Carbon Metabolism Conference.

Here, we present notes from the Folate, Vitamin B12, and One-Carbon Metabolism Conference organized by The Federation of American Societies for Experimental Biology (FASEB), held in Asheville, North Carolina, USA, 14-19 August 2022. We aim to share the most recent findings in the field with members of our scientific community who did not attend the meeting and who are interested in the research that was presented. The research described includes discussions of one-carbon metabolism at the biochemical and physiological levels and studies of the role of folate and B12 in development and in the adult, and from bacteria to mammals. Furthermore, the summarized studies address the role of one-carbon metabolism in disease, including COVID-19, neurodegeneration, and cancer.

Methodology, efficacy and safety of fecal microbiota transplantation in treating inflammatory bowel disease

Fecal microbiota transplantation (FMT), as an emerging therapy, can be used to treat microbiota related diseases. Progresses in donor screening, washed microbiota preparation, microbiota delivery routes, clinical administrative strategies, and long-term safety are moving FMT forward. Increasing clinical studies, especially those randomized controlled trials about ulcerative colitis and pilot real-word studies about serious inflammatory bowel disease (IBD), have been conducted. This review presents the latest findings about the efficacy, safety and methodology of FMT in treating IBD.Copyright © 2020 The Authors

Design and Synthesis of Vitamin Drug Conjugate for its Probable Potential against SARS-COV-2 Infections

The novel corona virus infection had become a global epidemic due to its rapid spread. So, there is an urgent need to treat COVID-19 patients. The aim of this research was to hypothesize and examine vitamin drug conjugate as targeted moiety. The present scaffold may have potential role to fight against COVID-19 infection due to its antimicrobial, antioxidants and immunomodulatory activities. Here, we've highlighted the term Vitamin Drug Conjugate as possible therapy approach for SARS-COV-2 infection. As a result, we synthesize, characterized, and evaluated a Hydroxychloroquine — Folic Acid conjugate (HCQ-FA) by esterification mechanism to provide effective treatment against SARS-CoV-2 infection by enhancing therapeutic effect through synergistic mechanism, masking undesired side effects, and improving cellular internalization. By using prodrug, the efficacy and bioavailability of existing antiviral drugs could be improved. The structure of the conjugate was determined by spectroscopic data like IR, NMR, and mass spectra, which indicates that HCQ-FA conjugate formed by esteric conjugation. Molecular docking studies revealed that HCQ-FA conjugate shows good level of docking as well as binding interaction with main protease moiety. Molecular dynamic stimulation revealed that this conjugate shows good stability at the binding site of SARS main protease moiety and exhibits inhibitory activity against COVID-19 infection. © 2022 The Authors.

Role of vitamin D, folic acid, ferritin, inflammation and oxidative stress in the pathogenesis of COVID-19

The COVID-19 pandemic is one of the most devastating and significant events of recent times. COVID-19 has so far become one of the worst infectious disease outbreaks of recent times, with more than 635 million cases and more than 6.6 million deaths. Viruses cause an explosion of inflammatory cytokines and reactive oxygen types. Oxidative stress is thought to have a key role in COVID-19. vitamin D, folic acid, calcium (Ca), magnesium (Mg) and ferritin levels are thought to be associated with COVID-19. This study aims to investigate the role of oxidative stress, inflammation, vitamin D and folic acid, ferritin, Ca and Mg in the pathogenesis of COVID-19. Material(s) and Method(s): 45 patients diagnosed with COVID-19 and 45 healthy persons (control group) were included in the study. Vitamin D, ferritin, folic acid, CRP, Ca, Mg and Phosphorus were measured in an autoanalyzer, and SOD, GSH-Px and MDA were spectrophotometrically measured in the serum of the participants. TNF-alpha, IL-1beta and IL6 levels were studied by the ELISA method. Result(s): The activity of SOD, GSH-px, antioxidant enzymes, Serum vitamin D, folic acid, Ca and Mg of the COVID-19 group was found to be significantly lower than the control group (p<0.05). Conclusion(s): Again, the levels of MDA, TNF-alpha, IL-1beta, IL-6, CRP and ferritin in the Covid-19 group were found to be significantly higher than in the control group (p<0.05).Antioxidant enzyme activities were low and oxidative stress was high in patients with COVID-19. At the same time, the levels of serum ferritin, CRP, TNF-alpha, IL-1beta and IL6 were high, and levels of Ca and Mg were low in patients with COVID-19.According to these results, we hypothesize think that the level of oxidative stress, inflammation, vitamin D, and serum ferritin, Ca, and Mg levels play a role in the pathogenesis of COVID-19. Future clinical trials should be conducted to further clarify the pathogenesis in patients with COVID-19.Copyright © 2022 Mattioli 1885. All rights reserved.

PORTAL VEIN THROMBOSIS WHILE TAKING A COMBINED ORAL CONTRACEPTIVE AFTER EXPERIENCED CORONAVIRUS INFECTION.

Background: Contraceptives are an important component of women's reproductive health care, as they not only reduce the number of unwanted pregnancies, but also improve reproductive function. However, oral contraceptives are known to increase the risk of venous thromboembolism. This risk is increased by infection with the COVID-19 virus that predisposes patients to both venous and arterial thrombosis as a result of excessive inflammation, platelet activation, aggravated endothelial dysfunction, and congestive events. If these patients have hereditary thrombophilia, the risk of venous thromboembolism becomes fatal. Case report: The paper describes a clinical case of a patient with total portal vein thrombosis, who have been taking oral contraceptives for a long time and recovering from the novel coronavirus infection. Studying the blood coagulation system and folate cycle genes, by using PCR, has revealed a gene mutation in the plasminogen activator inhibitor (serpine). The authors demonstrate the data of spiral computed tomography of the abdominal organs, as well as changes in laboratory parameters. Conclusion(s): A balanced approach is required when prescribing combined oral contraceptives during the COVID-19 pandemic, especially in women with prothrombotic mutations.Copyright © A group of authors, 2023.

PORTAL VEIN THROMBOSIS WHILE TAKING A COMBINED ORAL CONTRACEPTIVE AFTER EXPERIENCED CORONAVIRUS INFECTION.

Background: Contraceptives are an important component of women's reproductive health care, as they not only reduce the number of unwanted pregnancies, but also improve reproductive function. However, oral contraceptives are known to increase the risk of venous thromboembolism. This risk is increased by infection with the COVID-19 virus that predisposes patients to both venous and arterial thrombosis as a result of excessive inflammation, platelet activation, aggravated endothelial dysfunction, and congestive events. If these patients have hereditary thrombophilia, the risk of venous thromboembolism becomes fatal. Case report: The paper describes a clinical case of a patient with total portal vein thrombosis, who have been taking oral contraceptives for a long time and recovering from the novel coronavirus infection. Studying the blood coagulation system and folate cycle genes, by using PCR, has revealed a gene mutation in the plasminogen activator inhibitor (serpine). The authors demonstrate the data of spiral computed tomography of the abdominal organs, as well as changes in laboratory parameters. Conclusion(s): A balanced approach is required when prescribing combined oral contraceptives during the COVID-19 pandemic, especially in women with prothrombotic mutations.Copyright © A group of authors, 2023.

Male fertility: Review of the publications of April - June 2020.

The article provides an overview of the most significant publications on the topic of male infertility. The main selection criteria are the practical relevance of the article, as well as the impact factor of the journal in which it was published, according to the ScImago Journal Rank (SJR). as a result, a list of 10 works published in the II quarter (april - June) of 2020 was formed. The review includes articles on the following topics: the effect of asymptomatic genital tract infection on male fertility, methods of spermatogonia transplantation, the effect of alcohol on fertility, the role of folate status in male fertility, lumicrine regulation of spermatogenesis, oxidative-reductive balance in the male reproductive system, comparison of testicular sperm extraction (TESE) and micro-TESE results, natural conception and intrauterine insemination (IUI) at high MaR test values, and the first data on the effect of cOVID-19 on male fertility.Copyright © 2020 Rostovskii Gosudarstvennyi Meditsinskii Universitet. All rights reserved.

The Role of Folic Acid in SARS-CoV-2 Infection: An Intriguing Linkage under Investigation.

BACKGROUND: SARS-CoV-2 is a life-threatening RNA virus that may cause an acute respiratory syndrome associated with extremely high morbidity and mortality rates. Folic acid (FA), also known as folate, is an essential vitamin vital for human homeostasis, participating in many biochemical pathways, and its deficiency has been associated with viral infection vulnerability. In this review, we investigated the association between FA intake and SARS-CoV-2 infection, along with the existence of any potential impact of FA on the health outcome of patients suffering from this new viral infection. METHODS: Studies included were patients' and in silico and molecular docking studies. RESULTS: Data from in silico studies and molecular docking support that FA inhibits SARS-CoV-2 entry into the host and viral replication, binding at essential residues. Accordingly, in patients' studies, a protective role of FA supplementation against SARS-CoV-2 infection is indicated. However, contradictory data from observational studies indicate that FA supplementation, often linked to deficits during systemic inflammation due to SARS-CoV-2, increases the risk of post-infection mortality. CONCLUSIONS: Future randomized controlled trial studies, including the FA pharmacological group, are needed to better understand the role of FA as a potential protective or mortality risk indicator in COVID-19 patients.

Folic Acid and Leucovorin Have Potential to Prevent SARS-CoV-2-Virus Internalization by Interacting with S-Glycoprotein/Neuropilin-1 Receptor Complex.

The interaction of the SARS-CoV-2 spike (S) glycoprotein receptor-binding domain with the host-cell ACE2 receptor is a well-known step in virus infection. Neuropilin-1 (NRP-1) is another host factor involved in virus internalization. The interaction between S-glycoprotein and NRP-1 has been identified as a potential COVID-19 treatment target. Herein, the effectiveness of folic acid and leucovorin in preventing contact between S-glycoprotein and NRP-1 receptors was investigated using in silico studies and then confirmed in vitro. The results of a molecular docking study showed that leucovorin and folic acid had lower binding energies than EG01377, a well-known NRP-1 inhibitor, and lopinavir. Two hydrogen bonds with Asp 320 and Asn 300 residues stabilized the leucovorin, while interactions with Gly 318, Thr 349, and Tyr 353 residues stabilized the folic acid. The molecular dynamic simulation revealed that the folic acid and leucovorin created very stable complexes with the NRP-1. The in vitro studies showed that the leucovorin was the most active inhibitor of the S1-glycoprotein/NRP-1 complex formation, with an IC75 value of 185.95 µg/mL. The results of this study suggest that folic acid and leucovorin could be considered as potential inhibitors of the S-glycoprotein/NRP-1 complex and, thus, could prevent the SARS-CoV-2 virus' entry into host cells.

URINARY BIOMARKER ANALYSES ON JAPANESE, MEDITERRANEAN AND EURO-WESTERN POPULATIONS: WHICH IS BETTER FOR POSTPANDEMIC LONGEVITY?

Objective: Since nutrition could extend lifespan even in stroke-prone rats developing stroke genetically, our WHO-Collaborating Center for Primary Prevention of Cardio-vascular Diseases (CVD) started world-wide hearth examination to investigate nutrition good for healthy longevity by collecting 24-hour urine (24U) samples. Design: Urinary biomarkers of nutritions, sodium for salt, potassium (K) for vegetables and fruits, isoflavones(Is) for soy, taurine(Ta) for fish and magnesium (Mg) for beans and nuts were analyzed in 24U among 4211 participants (49.7% females(F)), aged 48-56 years in 50 populations from 22 countries according to WHO-CARDIAC(Cardiovascular Diseases and Alimentary Compression) Study Protocol, and studied comparatively in 6 Japanese(J), 6 Mediterranean(M) populations from Greece, Italy(2), Spain(2), Portugal and 6 Euro-Western(EW) populations from Sweden, Ireland, Scotland, Canada, Australia, New Zealand. Results with Discussion: The quintile analyses of Ta and Mg/creatine ratio in the world were inversely associated with CVD risks. The Odds ratios of obesity, hypercholesterolemia and hypertension in the lowest quintile of both Ta and Mg were 6.3, 4.6 and 1.8, respectively. J and M populations had significantly higher Ta and Mg therefore, lower CVD risks than EW, but J and M took more salt increasing the risk of stroke (Table 1). Despite the high salt intake, M had the merit of significantly high K intake to attenuate the adverse salt effect. J had a merit to take Is from soy containing Mg. Since Is intake was inversely associated with lower BMI in the world populations, high Japanese Mg intake was related to high Is intake which was inversely associated with obesity in Japan. In fact, the Japanese populations who took significantly higher T and Mg had lower BMI as well as higher HDL and folic acid in the blood, expected to prevent atherosclerosis and dementia. In contrast to M and EW, particularly severe obesity over BMI 30 was obviously less in J, ranking 182nd among 190 populations (WHO). The mortality rates of COVID-19 were significantly positively related to the ratio of severe obesity among 20 major countries in the world and this mortality was obviously lower in J, suggestive of the potential of J diet for post-pandemic longevity. Conclusion: 24U biomarker analyses indicated low-salted J and M diets are recommendable for CVD prevention. J diet is so far better than M diet because of lower CVD risks such as obesity and lipidemia, which were proven by urinary biomarkers to be related with traditional fish and soy intakes.

New onset clinically amyopathic dermatomyositis following SARS-CoV- 2 vaccine: A case report

Background: Amyopathic dermatomyositis is a rare autoimmune skin disease with similar cutaneous manifestations as classic dermatomyositis (CDM), but with absent or subclinical muscle involvement i.e. Clinically Amyopathic Dermatomyositis (CADM). Inciting agents including vaccines have been linked to CADM. We describe a case of new-onset CADM associated with COVID-19 vaccine. Objective(s): To illustrate the occurrence of new-onset CADM in a 27-year- old male following COVID-19 immunization. Case Summary: A previously well 27-year- old male developed joint and muscle aches accompanied by scattered erythematous patches on the face and both upper and lower extremities, a week after receiving first dose of viral vector SARS-CoV- 2 vaccine. He took an anti-histamine and paracetamol with some relief of pains and slight clearing of the rashes. He proceeded to receive a second dose of the same vaccine 2 months later. A few days following the second dose, there was exacerbation of the skin lesions and was referred to Rheumatology clinics. Physical exam disclosed an ambulatory well-built male with normal vital signs and no objective muscle weakness. Skin involvement included facial rash, and the characteristic Heliotrope rash, Gottron's papules, and Holster sign. Complete blood counts, chemistries and muscle enzymes were within normal. Antinuclear antibody (ANA), erythrocyte sedimentation rate (ESR) and Smith/ribonucleoprotein (Sm/RNP) antibody were positive. He was managed with tapering prednisone and maintained on methotrexate and folic acid with significant improvement at time of this report. Conclusion(s): This is the first reported case of adverse reaction to COVID-19 vaccine that had studied in detail the skin and systemic autoimmune reaction. Development of autoimmune reaction following SARS-CoV- 2 vaccine has been described extensively;however, evidence of autoimmunity following vaccination is still relatively scant. Our case suggests that in predisposed subjects' vaccination could trigger an autoimmune reaction similar to the natural infection.

Association Between Low Serum Folic Acid and Vitamin B12 Levels with Covid-19 Prognosis

Background and aim: It is important that the immune system is active and strong in protection from the COVID-19 pandemic. Folic acid and vitamin B12 are involved in the initiation, maintenance and regulation of both innate and adaptive immune reactions of the host against infections. In this study, it was aimed to investigate the relationship between serum folic acid and vitamin B12 levels of COVID-19 patients on the prognosis of the disease. Methods: The sample of the study consists of 529 individuals hospitalized in the Pandemic Chest Diseases Intensive Care Unit. General characteristics of the individuals, biochemical parameters checked routinely (white blood cell (WBC), platelet (PLT), lymphocyte, Neutrophil/Lympho-cyte (N/L) rate, C-reactive protein (CRP), oxygen (O2) saturation at the time of admission), serum vitamin B12 and folic acid levels, length of stay in intensive care units (ICUs) and hospitalization, and mortality were recorded. Results: The mean age of individuals was 62.8 +/- 15.12 years, and 50.9% were men and 49.1% were women. The mean level of serum folic acid in the subjects was 9.1 +/- 4.91 (ng/mL), and 2.4% had folic acid deficiency and 28.4% had folic acid insufficiency. The mean serum vitamin B12 was 295.6 +/- 229.98 (pg/mL), and vitamin B12 deficiency was observed only in 14.4%. The increase in serum folic acid levels reduces the total length of hospitalization and the risk of mortality (p<0.05). On the other hand, no correlation was found between B12 levels and the length of stay in ICU, hospitalization, and mortality. It was shown that WBC and N/L rates decreased as serum folic acid levels increased, and O2 saturation at the first hospital admission was higher. Conclusions: Folate deficiency and insufficiency are common among hospitalized COVID-19 patients and cause progression to severe disease. Therefore, examining COVID-19 patients in terms of nutritional deficiencies is critical in monitoring the clinical outcomes of the disease.