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.

Al-hijamah (the triple S treatment of prophetic medicine) significantly increases CD4/CD8 ratio in thalassemic patients via increasing TAC/MDA ratio: a clinical trial.

Beta thalassemia is associated with decreased immunity possibly due to iron overload. Al-hijamah (Hijamah) is wet cupping therapy (WCT) of prophetic medicine. Prophet Muhammad Peace be upon him said: "The best among your treatments is Al-hijamah". Al-hijamah is a promising excretory treatment to clear blood of causative pathological substances. Al-hijamah is a three-step technique (skin suction, scarification and suction) i.e. triple S technique). Recently, we introduced Al-hijamah as a novel iron excretion therapy (through pressure-dependent filtration then excretion via the skin dermal capillaries) that significantly decreased serum iron overload and related oxidative stress using a physiological excretory mechanism (Taibah mechanism). Iron overload was reported to impair both humoral immunity and cell mediated immunity in patients with beta thalassemia. In this study, twenty patients having ß-thalassemia major (maintained on iron chelation therapy) underwent a single session of Al-hijamah (30-60 minutes) using 4-5 sucking cups only. Another age and sex-matched control group of thalassemic patients received iron chelation therapy only. Al-hijamah enhanced the immunity of thalassemic patients in the form of increased CD4+ T cell count, from 124.10±36.98 to 326.20±57.94 cells/mm3, and an increased CD8+ T cell count from 100.30±36.98 to 272.40±46.37 cells/mm3. CD4/CD8 ratio significantly increased from 1.29 to 1.7 (P<0.001). There was a significant increase of ten times (P<0.001) in serum TAC/MDA ratio (reflects increased antioxidant capacity vs decreased oxidative load and stress) induced by Al-hijamah. After Al-hijamah, both CD4+ and CD8+ T cell counts significantly increased and positively correlated with TAC/MDA ratio (r = 0.246) and (r = 0.190), respectively. Moreover, CD4/CD8 ratio positively correlated with TAC/MDA after Al-hijamah (r = 0.285). In conclusion, Al-hijamah significantly increased CD4/CD8 ratio in thalassemic patients via increasing TAC/MDA ratio. Our study strongly recommends medical practice of Al-hijamah in hospitals for its immune potentiating effects in agreement with the evidence-based Taibah mechanism. Al-hijamah should be generalized for treating other immune-deficiency conditions. Al-hijamah-induced bloody excretion is so minimal and never aggravates the anaemic status.

Al-hijamah (wet cupping therapy of prophetic medicine) significantly and safely reduces iron overload and oxidative stress in thalassemic children: a novel pilot study.

BACKGROUND: Thalassemia is a major health problem due to iron overload, iron deposition and oxidative stress-induced tissue damage. Here, we introduce Al-hijamah (a minor surgical excretory procedure) as a novel percutaneous iron excretion therapy. Al-hijamah is a wet cupping therapy of prophetic medicine, and prophet Muhammad, peace be upon him, strongly recommended Al-hijamah, saying: "The best of your treatment is Al-hijamah". AIM OF THE STUDY: Our study aimed at investigating the safety, iron chelation, pharmacological potentiation and oxidant clearance effects exerted by Al-hijamah to thalassemic children. PATIENTS AND METHODS: Ethical committee's approval and patients' written agreement consents were obtained. We treated 20 thalassemic children (15 males and five females aged 9.07±4.26 years) with iron chelation therapy (ICT) plus Al-hijamah (using sterile disposable sets and in a complete aseptic environment) vs a control group treated with ICT only. This clinical trial was registered in the ClinicalTrial.gov registry under the name "Study of the Therapeutic Benefits of Al-hijamah in Children with Beta Thalassemia Major" (identifier no NCT 02761395) on 30 January 2016. RESULTS: Al-hijamah was quite simple, safe, effective, tolerable (with no side effects) and time-saving procedure (30-60 minutes). A single session of Al-hijamah significantly reduced iron overload (P<0.001) in all thalassemic children. Al-hijamah significantly decreased serum ferritin by 25.22% (from 3,778.350±551.633 ng/mL to 2,825.300±558.94 ng/mL), significantly decreased oxidative stress by 68.69% (P<0.05; serum malondialdehyde dropped from 42.155±12.42 to 13.195±0.68 nmol/L), exerted pharmacological potentiation to ICT and significantly increased total antioxidant capacity (P<0.001) by 260.95% (from 13.195±0.68 nmol/L to 42.86±12.40 nmol/L through excreting reactive oxygen species). Moreover, therapeutic indices for evaluating Al-hijamah were promising. CONCLUSION: Al-hijamah is a novel, safe, effective percutaneous iron excretion therapy through percutaneous iron excretion with minimal blood loss in agreement with the evidence-based Taibah mechanism. Al-hijamah is an effective outpatient hematological procedure that is safer than many pediatric procedures such as catheterization, hemofiltration and dialysis. Increasing the number of cups during Al-hijamah session or the number of sessions reduces iron overload more strongly. Medical practice of Al-hijamah is strongly recommended in hospitals.

Heat shock protein 60 as a biomarker for acute kidney injury secondary to septic shock in pediatric patients, Egyptian multicenter experience.

Acute kidney injury (AKI) is an independent predictor of morbidity and mortality for critically ill children at pediatric Intensive Care Units (PICU). It is proposed that heat shock protein 60 (HSP60) may be either a biomarker or a co-factor of survival in PICU. The aim of this work is to assess plasma levels of HSP60 in critically ill pediatric patients with AKI secondary to septic shock within the first 24 h of admission. This study was carried out on 120 pediatric patients admitted to PICUs of four university hospitals. They were divided into Group 1 included 60 patients meeting the criteria of AKI Network and septic shock, the second group included 60 critically ill patients without AKI or septic shock and the third group was 60 healthy children as controls. HSP60 levels were measured in the plasma using a commercially available ELISA and difference between groups were analyzed with a Kruskal-Wallis one-way ANOVA. P <0.05 was considered significant. There was highly significant increase in plasma levels of HSP60 in Group 1 (median 25.85 ng/mL) compared to both Group 2 (median 6.15 ng/mL) and healthy controls (median 4.35 ng/mL) (P <0.001). At a cut-off value ≥10 ng/mL, HSP60 sensitivity for prediction of cases with AKI secondary to septic shock was 96.67% with specificity 86.67%, positive predictive value 87.9%, negative predictive value 96.3%, AUC 0.993. HSP60 levels are significantly elevated in pediatric patients in Group 1 when compared to Groups 2 and 3. Hence, HSP60 may play a role in the pathogenesis of sepsis in pediatric patients.