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.

Auditory function assessment in patients with chronic obstructive pulmonary disease.

Background: Chronic obstructive pulmonary disease is a multisystem disease with multiple comorbidities. Hearing is dependent on the cochlear functions that may be affected by oxygenation. Affection of hearing is problematic and represents a major concern that should be seriously investigated as an important comorbidity in chronic obstructive pulmonary disease patients. Objective: To assess auditory status among chronic obstructive pulmonary disease patients. Methodology: The current study was carried out at Al-Azhar University Hospitals, Cairo, from 1 August 2021 to 2022, including 120 participants. In addition to the control group (60 healthy participants), there were two study groups: chronic obstructive pulmonary disease patients with respiratory failure group (30 patients) and non-respiratory failure group (30 patients). Hearing functions were studied using pure tone audiometry, and auditory brain stem response. Results: There was statistically significant hearing impairment in chronic obstructive pulmonary disease patients in comparison to control group. The hearing impairment was more significant in chronic obstructive pulmonary disease with respiratory failure group in comparison to chronic obstructive pulmonary disease without respiratory failure group. The auditory impairment shows a negative interrelationship with oxygen tension (PaO2) and a positive interrelationship with the smoking index. Conclusion: Hearing affection was meaningfully higher among chronic obstructive pulmonary disease patients and more prominent in patients with respiratory failure. Hypoxia results in deterioration of pure tone audiometry and increased absolute and interpeak latencies in auditory brain stem response. At every frequency, the mean pure tone audiometry thresholds were higher for chronic obstructive pulmonary disease groups than control group albeit remaining in the mild to moderate area of hearing loss. Retro-cochlear affection was suggested among patients with chronic obstructive pulmonary disease as evidenced with the prolongation of auditory brain stem response waves latencies.

The association of IL-17A rs2275913 single nucleotide polymorphism with anti-tuberculous drug resistance in patients with pulmonary tuberculosis.

BACKGROUND: Drug-resistant  Tuberculosis (DR-TB) is a global health burden with high morbidity and mortality in developing countries including Egypt. The susceptibility to infection with DR-TB strains may be genetically determined. Several interleukin gene polymorphisms were investigated as risk factors for tuberculosis infection but focusing on their association with DR-TB was limited. Therefore, the objective of this study is to assess the association of IL 17 - 197 G > A (rs2275913) single nucleotide polymorphism (SNP) with susceptibility to DR-TB strains in comparison to drug-sensitive tuberculosis (DS-TB) strains in Egyptian patients with pulmonary TB. This cross-sectional study was conducted on 80 patients with DR-TB strains and 80 with DS-TB strains as a control group. Both age and sex were comparable among the study's groups. IL-17 - 197 G > A (rs2275913) SNP was genotyped by real-time PCR, and IL-17 serum concentration was measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The GA and AA genotype frequencies of IL 17 - 197 G > A (rs2275913) SNP were significantly higher in patients with DR-TB strains than those with DS-TB strains (p < 0.001). The frequency of the A allele was significantly (p < 0.001) higher in patients with DR-TB group (32.5%) compared to the control group (13.8%). Substantial higher serum levels of IL-17 were detected in the DR-TB group with significant association with AA and AG genotypes. CONCLUSION: Polymorphism in IL-17 -197 G > A (rs2275913) resulted in higher serum levels of IL-17 and Egyptian patients with such polymorphism are three times at risk of infection with DR-TB strains than patients with wild type.

Functional outcomes in post Covid-19 patients with persistent dyspnea: multidisciplinary approach.

BACKGROUND: Post-acute sequelae of SARS-CoV-2 (PASC) have emerged as a major health issue in patients who have previously been infected with Covid-19 virus. PURPOSE: we aimed at the assessment of functional outcomes in post Covid-19 patients with persistent dyspnea using a multidisciplinary approach including clinical assessment, laboratory investigations, exercise ECG, and different echo-Doppler modalities, including left atrial functions. METHODS: The current observational randomized controlled study conducted on 60- patients one month after recovery from Covid-19 infection presented with persistent dyspnea compared to 30 healthy volunteers. All participants were subjected to evaluation of dyspnea by different scores, laboratory investigations, stress ECG, and echo-Doppler examination to measure LV dimensions, volumes, systolic and diastolic functions by M-mode, 2D, and tissue Doppler imaging in addition to 2-D speckle tacking LA strain. RESULTS: Post Covid-19 patients had persistent elevation of inflammatory markers, low functional capacity (evidenced by a higher NYHA class, m MRC score, PCFS scale) and decreased METs by stress ECG compared to control group. Post Covid-19 patients showed LV diastolic dysfunction and impairment of 2D-STE LA functions compared to control group. We found negative correlations between LA strain with NYHA class, mMRC scale, LAVI, ESR and CRP; meanwhile, there were significant positive correlations between LA strain with exercise duration and METs. CONCLUSION: post Covid patients presented with persistent dyspnea demonstrated low functional capacity evidenced by different scores and stress ECG. Moreover, patients with post Covid syndrome showed elevated inflammatory biomarkers, LV diastolic dysfunction in addition to impaired LA strain functions. Impairment of LA strain was closely correlated to different functional scores, inflammatory biomarkers, exercise duration, and METs suggesting that these could to be the possible etiologies for the persistence of post Covid symptoms.

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.

Clinical and Prognostic Significance of Baseline Serum Vitamin D Levels in Hospitalized Egyptian Covid-19 Patients.

Background and Aim: Vitamin D is a hormone with essential roles in both cellular metabolism and immunity. It controls calcium homeostasis and modulates innate and adaptive immune system responses. Many studies suggested an association between vitamin D deficiency and clinical outcomes of covid-19 infection, while others failed to document such a relation. The present study aimed to evaluate the clinical and prognostic significance of baseline vitamin D levels in hospitalized Egyptian covid-19 patients. Patients and Methods: The present retrospective study included 300 hospitalized covid-19 patients. Patients were submitted to standard clinical, laboratory, and radiological assessment. According to vitamin D levels, patients were classified to have normal levels (≥30), insufficient levels (20-29) or deficient levels (<20). Results: According to their vitamin D levels, patients were classified into those with normal vitamin D (n=135), others with vitamin D insufficiency (n=114), and a third group with vitamin D deficiency (n=51). Patients with normal vitamin D levels and vitamin D insufficiency are significantly younger [median (IQR): 49.0 (39.0-57.0) versus 51.0 (40.0-61.0) and 55.0 (43.0-62.0) years, respectively, p=0.012] and had less frequency of severe disease (24.4% versus 40.4% and 51.0%, respectively) when compared with those with vitamin D deficiency. Moreover, they had significantly lower levels of D dimer [median (IQR): 1.5 (0.9-2.5) versus 1.8 (0.9-3.1) and 2.0 (1.0-3.2)], CRP [median (IQR): 58.0 (30.0-120.0) versus 76.0 (42.5-160.0) and 105.0 (74.0-208.0), respectively, p<0.001], ferritin [median (IQR): 458.0 (240.0-759.0) versus 606.0 (433.8-897.8) and 820.0 (552.0-1087.0), respectively, p<0.001], and procalcitonin [median (IQR): 290.0 (152.0-394.0) versus 372.5 (227.0-530.5) and 443.0 (272.0-575.0), respectively, p<0.001]. Only lower vitamin D levels were significant predictors of mortality in multivariate analysis [OR (95% CI): 0.88 (0.84-0.92), p<0.001]. Conclusion: Low vitamin D levels are related to exaggerated inflammatory response, disease severity, and poor clinical outcome in hospitalized covid-19 patients.

Prognostic Significance of Platelet Activation Marker CD62P in Hospitalized Covid-19 Patients.

BACKGROUND: CD62P is a surface marker for platelet activation. Platelet dysfunction contributes to disproportionate intravascular microthrombosis in SARS-CoV-2. We aimed to assess the clinical significance of CD62P as a biomarker of platelet activation and its correlation to the clinical severity and outcome of COVID-19 infections. METHODS: The study included 80 COVID-19 patients and, in addition, there were 20 age and gender-matched healthy controls. Laboratory measurements included CBC, serum ferritin, LDH, CRP, D-dimer and flow cytometric assessments of the platelet markers CD42b and CD62P. The primary study outcome was patients' survival at the end of study. RESULTS: Among the studied patients, 24 patients (30.0%) died by the end of the study. Survivors had significantly lower CD62P values when compared with non-survivors [median (IQR): 75.5 (73.0 - 91.0) versus 96.0 (93.5 - 97.8), p < 0.001]. Patients with severe disease had significantly higher levels of CD62P levels [median (IQR): 95.5 (92.0 - 97.8) versus 75.0 (72.0 - 76.8), p < 0.001]. Logistic regression analysis identified D-dimer levels [OR (95% CI): 0.14 (0.03 - 0.74) and CD62P levels: OR (95% CI): 0.4 (0.17 - 0.94)] as significant predictors of mortality in multivariate analysis. CONCLUSIONS: CD62P expression on admission may be a useful prognostic maker in hospitalized Covid-19 patients. Its expression is related to other markers of inflammation and coagulopathy.

Diaphragmatic excursion by ultrasound: reference values for the normal population; a cross-sectional study in Egypt.

Background: Measurement of diaphragmatic motion by ultrasound is being utilized in different aspects of clinical practice. Defining reference values of the diaphragmatic excursion is important to identify those with diaphragmatic motion abnormalities. This study aimed to define the normal range of diaphragmatic motion (reference values) by Mmode ultrasound for the normal population. Methods: Healthy volunteers were included in this study. Those with comorbidities, skeletal deformity, acute or chronic respiratory illness were excluded. Diaphragmatic ultrasound in the supine position was performed using a lowfrequency probe. The B-mode was applied for diaphragmatic identification, and the M-mode was employed for the recording of the amplitude of diaphragm contraction during quiet breathing, deep breathing and sniffing. Results: The study included 757 healthy subjects [478 men (63.14%) and 279 women (36.86%)] with normal spirometry and negative history of previous or current respiratory illness. Their mean age and BMI were 45.17 ±14.84 years and 29.36±19.68 (kg/m2). The mean right hemidiaphragmatic excursion was 2.32±0.54, 5.54±1.26 and 2.90±0.63 for quiet breathing, deep breathing and sniffing, respectively, while the left hemidiaphragmatic excursion was 2.35±0.54, 5.30±1.21 and 2.97±0.56 cm for quiet breathing, deep breathing and sniffing, respectively. There was a statistically significant difference between right and left diaphragmatic excursion among all studied subjects. The ratio of right to left diaphragmatic excursion during quiet breathing was (1.009±0.19); maximum 181% and minimum 28%. Only 19 cases showed a right to left ratio of less than 50% (5 men and 14 women). The diaphragmatic excursion was higher in males than females. There was a significant difference in diaphragmatic excursion among age groups. Age, sex and BMI significantly affected the diaphragmatic motion. Conclusions: Diaphragmatic excursion values presented in this study can be used as reference values to detect diaphragmatic dysfunction in clinical practice. Diaphragmatic motion is affected by several factors including age, sex and body mass index.

Admission Levels of Serum P-Selectin and IL-6 Can Predict Development of Deep Venous Thrombosis in Hospitalized Covid-19 Patients.

Background and Aim: Deep venous thrombosis (DVT) of the lower extremities is common in Covid-19 patients. Interleukin (IL)-6 and P-selectin were found to be elevated in Covid-19 patients. The current study aimed to evaluate P-selectin and IL6 in Covid-19 patients with DVT and to explore its relation to clinical and laboratory parameters in those patients. Patients and methods: The present retrospective study included 150 hospitalized COVID-19 patients diagnosed on the basis of a positive result of reverse-transcriptase polymerase chain reaction (RT-PCR) test. Laboratory assessments were included for IL-6 and P selectin assessments via enzyme-linked immunosorbent assay. The primary outcome of the present study was the development of DVT detected by Doppler ultrasound (DU) evaluation of the lower extremities during the admission. Results: The present study included 150 hospitalized Covid-19 patients. DVT was developed in 59 patients (39.3%). DVP patients had significantly higher levels of P selectin [76.0 (63.0-87.0) versus 63.0 (54.3-75.0), p < 0.001] and IL-6 [37.0 (27.0-49.0) versus 18.5 (13.5-31.5), p < 0.001]. ROC curve analysis revealed good performance of P selectin [AUC (95% CI): 0.72 (0.64-0.81)] and IL-6 [AUC (95% CI): 0.79 (0.71-0.86)] in identification of DVT. Logistic regression analysis identified the presence of severe disease [OR (95% CI): 9.016 (3.61-22.49), p < 0.001], elevated P selectin [OR (95% CI): 1.032 (1.005-1.059), p = 0.018] and elevated IL-6 [OR (95% CI): 1.062 (1.033-1.091), p < 0.001] as significant predictors of DVT development in multivariate analysis. Conclusion: The present study identified a probable role of elevated P-selectin and IL-6 levels in the DVT development in hospitalized Covid-19 patients.

Copeptin: a neuroendocrine biomarker of COVID-19 severity.

Aim: To investigate the change in a serum level of copeptin, a neuroendocrine biomarker, in differentiating grades of COVID-19 severity on admission time and to find its diagnostic potential. Materials & Methods: 160 COVID-19 patients were classified according to disease severity into 80 mild to moderate and 80 severe patients. Serum copeptin level was assessed by ELISA on their admission time. Besides, serum CRP, ferritin and D-dimer were estimated. Results: Severe COVID-19 patients showed higher serum copeptin level in comparison to mild to moderate cases, with diagnostic potential to distinguish disease severity with 93.33% sensitivity and 100% specificity at cutoff value >18.5 Pmol/l. Conclusion: Serum copeptin was remarkably increased with COVID-19 severity with reasonable differentiation potential for recently admitted patients.

We conducted a biochemical study on the role of copeptin ­ a biomarker of acute stress due to COVID-19 infection ­ in classification of COVID-19 severity on admission over 160 adult patients. Copeptin was highly elevated in severe cases more than the mild to moderate ones. So, it may be an early marker in admission departments to ease early clinical decisions and medical intervention.

Cytokine profile in Egyptian children and adolescents with COVID-19 pneumonia: A multicenter study.

BACKGROUND: To date, the cytokine profile in children and adolescent with novel coronavirus disease 2019 (COVID-19) has not been reported. OBJECTIVES: We investigated serum levels of a panel of key cytokines in children and adolescent with COVID-19 pneumonia with a primary focus on "cytokine storm" cytokines such as interleukin (IL)-1ß, IL-6, IL-17, IL-2, IL-4, IL-10, interferon (IFN-γ), tumor necrosis factor (TNF)-α, and two chemokines interferon-inducible protein-10 (IP-10) and IL-8. We also studied whether these cytokines could be potential markers for illness severity in COVID-19 pneumonia. METHODS: Ninety-two symptomatic patients aged less than 18 years with confirmed COVID-19 pneumonia and 100 well-matched healthy controls were included in this multi-center study. For all patients, the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in respiratory fluid specimens was detected by real-time reverse-transcriptase polymerase chain reaction. We measured serum concentrations of studied cytokines by using flow cytometry. RESULTS: Patients with COVID-19 had significantly higher median IL-1ß, IL-6, IL-8, IL-10, IL-17, TNF-α, and IP-10 serum levels than did control children (all p < 0.01). Patients with severe COVID-19 pneumonia had significantly higher median IL-1ß, IL-6, and IP-10 serum levels as compared with those with moderate COVID-19 pneumonia; all p < 0.01. ROC analysis revealed that three of the studied markers (IL-6, IL-1ß, and IP-10) could predict severe COVID-19 pneumonia cases with the largest AUC for IL-6 of 0.893 (95% confidence interval: 0.84-0.98; p < 0.01). CONCLUSION: Our study shows that pediatric patients with COVID-19 pneumonia have markedly elevated serum IL-1ß, IL-6, IL-8, IL-10, IL-17, TNF-α, and IP-10 levels at the initial phase of the illness indicating a cytokine storm following SARS-CoV-2 infection. Moreover, serum IL-6, IL-1ß, and IP-10 concentrations were independent predictors for severe COVID-19 pneumonia.

Yoga in Burn: Role of pranayama breathing exercise on pulmonary function, respiratory muscle activity and exercise tolerance in full-thickness circumferential burns of the chest.

BACKGROUND: Circumferential burn of chest (CBC) is a significant type of burn and considers as a major cause of restrictive lung disease (RLD). Patient who has CBC with RLD leads to respiratory symptoms such as breathing difficulty, airway obstruction, reduced exercise capacity and altered pulmonary functions. However, studies examining the role of pranayama breathing exercise on pulmonary function, respiratory muscle activity and exercise tolerance in full thickness circumferential burn of chest are lacking. OBJECTIVE: To find the short term effects of pranayama breathing exercise on pulmonary function, respiratory muscle activity and exercise tolerance in full thickness circumferential burns of chest. METHODS: Through simple random sampling method thirty subjects (N = 30) with RLD following CBC were allocated to pranayama breathing exercise group (PBE-G; n = 15) and conventional breathing exercise group (CBE-G; n = 15). They received pranayama breathing exercise and conventional breathing exercise for 4 weeks respectively. All the subjects received chest mobility exercise as common treatment. Primary (Numeric Pain Rating Scale - NPRS, forced expiratory volume (FEV1), forced vital capacity (FVC) and maximum voluntary ventilation (MVV) and secondary (Electromyogram of sternocleidomastoid, scalene, external intercostal and diaphragm muscle, 6 min walk test & Global Rating of Change - GRC) outcome measures were measured at baseline, after four weeks and after three months follow up. RESULTS: Baseline demographic and clinical variables show homogenous distribution between the groups (p > 0.05). Four weeks following different breathing exercises, PBE-G group shows more significant changes in pain intensity, pulmonary function, respiratory muscle activity, exercise tolerance and global rating of change than CBE-G group (p ≤ 0.05) at four weeks and three months follow up. CONCLUSION: Both groups showed improvement over time. However, differences between the groups were noticed small. Still physiotherapy management, which included pranayama breathing exercises with chest mobilization program, had an effective strategy in the treatment of restrictive lung disease following circumferential burn of chest.