Association of ACE1 I/D polymorphism and susceptibility to COVID-19 in Egyptian children and adolescents.

BACKGROUND: Given the sparse data on the renin-angiotensin system (RAS) and its biological effector molecules ACE1 and ACE2 in pediatric COVID-19 cases, we investigated whether the ACE1 insertion/deletion (I/D) polymorphism could be a genetic marker for susceptibility to COVID-19 in Egyptian children and adolescents. METHODS: This was a case-control study included four hundred sixty patients diagnosed with COVID-19, and 460 well-matched healthy control children and adolescents. The I/D polymorphism (rs1799752) in the ACE1 gene was genotyped by polymerase chain reaction (PCR), meanwhile the ACE serum concentrations were assessed by ELISA. RESULTS: The ACE1 D/D genotype and Deletion allele were significantly more represented in patients with COVID-19 compared to the control group (55% vs. 28%; OR = 2.4; [95% CI: 1.46-3.95]; for the DD genotype; P = 0.002) and (68% vs. 52.5%; OR: 1.93; [95% CI: 1.49-2.5] for the D allele; P = 0.032). The presence of ACE1 D/D genotype was an independent risk factor for severe COVID-19 among studied patients (adjusted OR: 2.6; [95% CI: 1.6-9.7]; P < 0.001. CONCLUSIONS: The ACE1 insertion/deletion polymorphism may confer susceptibility to SARS-CoV-2 infection in Egyptian children and adolescents. IMPACT: Recent studies suggested a crucial role of renin-angiotensin system and its biological effector molecules ACE1 and ACE2 in the pathogenesis and progression of COVID-19. To our knowledge, ours is the first study to investigate the association of ACE1 I/D polymorphism and susceptibility to COVID-19 in Caucasian children and adolescents. The presence of the ACE1 D/D genotype or ACE1 Deletion allele may confer susceptibility to SARS-CoV-2 infection and being associated with higher ACE serum levels; may constitute independent risk factors for severe COVID-19. The ACE1 I/D genotyping help design further clinical trials reconsidering RAS-pathway antagonists to achieve more efficient targeted therapies.

Relationship between Subclinical Hypothyroidism and Uremic Pruritis in Hemodialysis Patients.

BACKGROUND AND AIM: Uremic pruritus (UP) is one of the most distressing symptoms in hemodialysis (HD) patients. Subclinical hypothyroidism (SCH) is a biochemical condition with high prevalence in HD patients. The present multicentric study aimed to assess the relationship between UP and SCH in HD patients. METHODS: The present cross-sectional study included 328 HD patients. All patients were submitted to careful history through clinical examination and standard laboratory assessment. Pruritis was evaluated using the pruritis visual analog scale (VAS). Patients were diagnosed with SCH if they had TSH levels above the upper limit of the normal reference range in association with normal free thyroxine (FT4) levels. RESULTS: Among the studied patients, there were 196 patients (59.8 %) with UP. Comparison between patients with UP and patients without revealed that patients in the former group had significantly longer HD duration (median (IQR): 47.5 (27.0-72.5) versus 36.0 (23.0-50.5) months, p < 0.001) and lower Kt/v (median (IQR): 1.4 (1.09-1.7) versus 1.54 (1.12-1.91), p = 0.009). Moreover, they had significantly higher ferritin (median (IQR): 653.0 (526.0-800.0) versus 628.0 (470.8- 716.0) ng/mL), hsCRP (median (IQR): 12.0 (8.0-14.0) versus 8.0 (6.0-9.0) mg/dL, p < 0.001) and TSH levels (median (IQR): 4.34 (1.98-5.2) versus 3.34 (1.9-4.85) µIU/ml) with a significantly higher frequency of SCH (45.9 % versus 28.8 %, p = 0.002). Logistic regression analysis identified hemodialysis duration (OR (95%) CI): 1.02 (1.009-1.028), p < 0.001), ferritin levels (OR (95% CI): 1.002 (1.001-1.003), p < 0.001), and SCH (OR (95% CI): 0.54 (0.32-0.89), p = 0.016) as significant predictors of UP. CONCLUSION: The present study suggested a possible link between SCH and the development of UP in HD patients.

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.