Vitamin D deficiency and vitamin D receptor FokI polymorphism as risk factors for COVID-19.

BACKGROUND: Given the sparse data on vitamin D status in pediatric COVID-19, we investigated whether vitamin D deficiency could be a risk factor for susceptibility to COVID-19 in Egyptian children and adolescents. We also investigated whether vitamin D receptor (VDR) FokI polymorphism could be a genetic marker for COVID-19 susceptibility. METHODS: One hundred and eighty patients diagnosed to have COVID-19 and 200 matched control children and adolescents were recruited. Patients were laboratory confirmed as SARS-CoV-2 positive by real-time RT-PCR. All participants were genotyped for VDR Fok1 polymorphism by RT-PCR. Vitamin D status was defined as sufficient for serum 25(OH) D at least 30 ng/mL, insufficient at 21-29 ng/mL, deficient at <20 ng/mL. RESULTS: Ninety-four patients (52%) had low vitamin D levels with 74 (41%) being deficient and 20 (11%) had vitamin D insufficiency. Vitamin D deficiency was associated with 2.6-fold increased risk for COVID-19 (OR = 2.6; [95% CI 1.96-4.9]; P = 0.002. The FokI FF genotype was significantly more represented in patients compared to control group (OR = 4.05; [95% CI: 1.95-8.55]; P < 0.001). CONCLUSIONS: Vitamin D deficiency and VDR Fok I polymorphism may constitute independent risk factors for susceptibility to COVID-19 in Egyptian children and adolescents. IMPACT: Vitamin D deficiency could be a modifiable risk factor for COVID-19 in children and adolescents because of its immune-modulatory action. To our knowledge, ours is the first such study to investigate the VDR Fok I polymorphism in Caucasian children and adolescents with COVID-19. Vitamin D deficiency and the VDR Fok I polymorphism may constitute independent risk factors for susceptibility to COVID-19 in Egyptian children and adolescents. Clinical trials should be urgently conducted to test for causality and to evaluate the efficacy of vitamin D supplementation for prophylaxis and treatment of COVID-19 taking into account the VDR polymorphisms.

Detection of Chromosomal and Plasmid-Mediated Quinolone Resistance Among Escherichia coli Isolated from Urinary Tract Infection Cases; Zagazig University Hospitals, Egypt.

INTRODUCTION: Resistance to fluoroquinolones (FQ) in uropathogenic Escherichia coli (UPEC) has emerged as a growing problem. Chromosomal mutations and plasmid-mediated quinolone resistance (PMQR) determinants have been implicated. Data concerning the prevalence of these determinants in UPEC in our hospital are quite limited. PURPOSE: To investigate the occurrence and genetic determinants of FQ resistance in UPEC isolated from urinary tract infection (UTI) cases in Zagazig University Hospitals. PATIENTS AND METHODS: Following their isolation, the identification and susceptibility of UPEC isolates were performed by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometer (MALDI-TOF MS). FQ resistance was detected by the disc diffusion method. Ciprofloxacin minimal inhibitory concentration (MIC) was determined using E-test. Chromosomal mutations in the gyrA gene were detected using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and for detection of PMQR, a couple of multiplex PCR reactions were used. RESULTS: Among a total of 192 UPEC isolates, 46.9% (n=90) were FQ resistant. More than half of the isolates (57.8%) exhibited high-level ciprofloxacin resistance (MIC > 32 µg/mL). Mutations in gyrA were detected in 76.7% of isolates, with 34.4% having mutations at more than one site. PMQR determinants were detected in 80.1% of UPEC isolates, with aac(6')-Ib-cr gene being the most frequent found in 61.1% of isolates. CONCLUSION: There is a high prevalence of both gyrA mutations and PMQR determinants among UPEC isolates in our hospital which contribute to high-level ciprofloxacin resistance, a finding that may require the revision of the antibiotics used for empirical treatment of UTI.

Association of serum podocalyxin levels with peripheral arterial disease in patients with type 2 diabetes.

OBJECTIVE: Renal podocalyxin is a marker for kidney diseases. Previous studies have shown the expression of serum podocalyxin (s-Podxl) in the endothelial cells of blood vessels. We aimed to investigate the association between s-podxl levels and peripheral arterial disease (PAD) in subjects with type 2 diabetes (T2DM). SUBJECTS AND METHODS: Serum Podxl levels were analyzed in 69 subjects with normal glucose tolerance and PAD (NGT-PAD), 120 subjects with T2DM and PAD (D-PAD) and 36 subjects with T2DM without PAD (D-NPAD). RESULTS: In D-PAD Patients, s-Podxl was significantly higher (17.67 ±â€¯20.7 ng/mL) than in D-NPAD subjects (9.97 ±â€¯5.34 ng/mL; P < 0.001). Subjects with NGT-PAD had significantly higher s-Podxl levels (15.34 ±â€¯18.21 ng/mL), than D-NPAD patients (P < 0.001). Subjects with D-PAD and medial calcific sclerosis (MCS) had significantly higher s-Podxl levels compared to the same group but without MCS (P < 0.02). In D-PAD patients, MCS (P = 0.003) and glycosylated hemoglobin (P < 0.001) were the two variables that had the strongest prediction for s-Podxl as revealed by regression analysis. Multivariate regression showed that an increase of one standard deviation in s-Podxl was associated with an odds ratio of 3.4 (95% confidence interval = 2.2-4.6, P < 0.001) for the prevalence of PAD. CONCLUSIONS: This is the first study showing an association between s-Podxl and PAD in patients with T2DM. S-Podxl was higher in D-PAD patients than in D-NPAD subjects. In NGT-PAD patients, s-Podxl was also higher than in D-NPAD patients. In patients with D-PAD, s-Podxl was positively associated with MCS.

Association of low serum Meteorin like (Metrnl) concentrations with worsening of glucose tolerance, impaired endothelial function and atherosclerosis.

OBJECTIVE: Meteorin-like (Metrnl) is a novel secreted protein that has a beneficial effect on glucose homeostasis with anti-inflammatory properties. Our goal is to determine whether low serum Metrnl levels are associated with worsening of glucose tolerance, impaired endothelial function, and atherosclerosis. METHODS: This study included 260 adults, 89 of whom had normal oral glucose tolerance (nOGT), 77 with glucose tolerance impairment (GTI) and 94 with type 2 diabetes (T2DM). Insulin resistance was assessed by evaluating the homeostasis model assessment of insulin resistance (HOMA-IR). Serum Metrnl level, proinflammatory, biochemical, endothelial and atherosclerosis parameters were measured. RESULTS: Serum Metrnl levels decreased significantly in patients with T2DM versus subjects with nOGT (P < 0.001). Metrnl levels were negatively correlated with fasting blood glucose, 2-h postload glucose (2 h-PLG), fasting insulin, HOMA-IR, HbA1c, high-sensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), Carotid intima media thickness (CIMT), brachial-ankle pulse wave velocity (baPWV), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin. High serum Metrnl level was significantly correlated with reduced risk of T2DM as revealed by multivariate logistic regression analysis after control of potential risk factors for diabetes. Furthermore, the association remains significant after further adjustment for IL-6, TNF-α, hs-CRP, CIMT, baPWV, ICAM-1, VCAM-1 and E-selectin. CONCLUSIONS: Low Serum Metrnl may be associated with worsening of glucose tolerance, impaired endothelial function and atherosclerosis. It may also be considered a possible surrogate marker of endothelial dysfunction, and atherosclerosis and an independent risk factor of T2DM.