Genomic characterization of SARS-CoV-2 in Egypt: insights into spike protein thermodynamic stability.

The overall pattern of the SARS-CoV-2 pandemic so far has been a series of waves; surges in new cases followed by declines. The appearance of novel mutations and variants underlie the rises in infections, making surveillance of SARS-CoV-2 mutations and prediction of variant evolution of utmost importance. In this study, we sequenced 320 SARS-CoV-2 viral genomes isolated from patients from the outpatient COVID-19 clinic in the Children's Cancer Hospital Egypt 57357 (CCHE 57357) and the Egypt Center for Research and Regenerative Medicine (ECRRM). The samples were collected between March and December 2021, covering the third and fourth waves of the pandemic. The third wave was found to be dominated by Nextclade 20D in our samples, with a small number of alpha variants. The delta variant was found to dominate the fourth wave samples, with the appearance of omicron variants late in 2021. Phylogenetic analysis reveals that the omicron variants are closest genetically to early pandemic variants. Mutation analysis shows SNPs, stop codon mutation gain, and deletion/insertion mutations, with distinct patterns of mutations governed by Nextclade or WHO variant. Finally, we observed a large number of highly correlated mutations, and some negatively correlated mutations, and identified a general inclination toward mutations that lead to enhanced thermodynamic stability of the spike protein. Overall, this study contributes genetic and phylogenetic data, as well as provides insights into SARS-CoV-2 viral evolution that may eventually help in the prediction of evolving mutations for better vaccine development and drug targets.

Routine laboratory testing in hemodialysis: how frequently is it needed?

BACKGROUND: Hemodialysis patients are followed by routine laboratory testing. There is uncertainty whether these tests always lead to a change in decision-making. This study aims to discover the number of yearly interventions/changes in prescription based on these tests and depict the group of patients who would benefit from reduced or increased laboratory blood tests. METHODS: This is a multi-center retrospective study that included patients on hemodialysis for more than one year. Laboratory data collected included yearly average of hemoglobin, urea reduction ratio (URR), serum phosphate, calcium, potassium, parathormone (PTH), ferritin and transferrin saturation (TSAT); changes in prescription of erythropoietin-stimulating agents (ESAs), intravenous (IV) iron, alfacalcidol, phosphate binders and dialysis parameters were retrieved from medical records. A multivariate regression analysis assessed factors associated with high number of interventions. RESULTS: A total of 210 hemodialysis patients were included: 62.4% males, 47.1% diabetics. Their median age was 72 (62,78.5) years. Their laboratory parameters were within KDIGO targets. The median number of yearly interventions was 5 (3,7) for ESAs, 4 (2,6) for IV iron, 1 (0,2.25) for phosphate binders, 0 (0,1) for alfacalcidol. Based on the multivariate analysis, patients with higher ferritin, frequent changes in ESA, more changes in alfacalcidol and higher PTH had higher number of prescription's changes in ESA, IV iron, phosphate binders and alfacalcidol respectively. CONCLUSION: While maintaining KDIGO targets, therapeutic interventions following routine laboratory testing did not exceed six times yearly for all parameters. This suggests that a reduced testing frequency in hemodialysis patients is possible without any impact on quality of care. A personalized approach remains safe for hemodialysis patients while reducing the cost. This is very relevant in low-resource settings and during economic crises and needs to be evaluated in prospective studies.

COVID-19-Associated Pulmonary Fungal Infection among Pediatric Cancer Patients, a Single Center Experience.

Patients with COVID-19 are at risk of developing secondary complications such as invasive pulmonary aspergillosis and mucormycosis. This is a retrospective study including all cancer children diagnosed with COVID-19-associated pulmonary fungal infection (CAPFI) during the period 2020-2021. A total of 200 patients were diagnosed with COVID-19, out of which 21 (10%) patients were diagnosed with CAPFI, 19 patients (90%) with COVID-aspergillosis (CAPA), and 2 (10%) patients with COVID-mucormycosis (CAM). Patients with CAPFI were classified using the "2020 ECMM/ISHAM consensus criteria"; proven in 2 (10%) patients, probable in 12 (57%), and possible in 7 (33%) patients. Although the hematological malignancy patients were already on antifungal prophylaxis, breakthrough fungal infection was reported in 16/21 (75%), 14 (65%) patients had CAPA while on echinocandin prophylaxis, while 2 (10%) patients had CAM while on voriconazole prophylaxis. Overall mortality was reported in 8 patients (38%) while CAPFI-attributable mortality was reported in 4 patients (20%). In conclusion, clinicians caring for pediatric cancer patients with COVID-19 should consider invasive pulmonary fungal infection, even if they are on antifungal prophylaxis, especially with worsening of the clinical chest condition. A better understanding of risk factors for adverse outcomes may improve clinical management in these patients.

SARS-CoV-2 genome variations and evolution patterns in Egypt: a multi-center study.

A serious global public health emergency emerged late November 2019 in Wuhan City, China, by a new highly pathogenic virus, SARS-CoV-2. The virus evolution spread has been tracked by three developing databases: GISAID, Nextstrain and PANGO to understand its circulating variants. In this study, 110 diagnosed positive COVID-19 patient's samples, were collected from Kasr Al-Aini Hospital and the Children Cancer Hospital Egypt 57357 between May 2020 and January 2021, with clinical severity ranging from mild to severe. The viral genomes were sequenced by next generation sequencing, and phylogenetic analysis was performed to understand viral transmission dynamics. According to Nextstrain clades, most of our sequenced samples belonged to clades 20A and 20D, which in addition to clade 20B were present from the beginning of sample collection in May 2020. Clades 19A and 19B, on the other hand, appeared in the mid and late 2020 respectively, followed by the disappearance of clade 20B at the end of 2020. We identified a relatively high prevalence of the D614G spike protein variant and novel patterns of mutations associated together and with different clades. We also identified four mutations, spike H49Y, ORF3a H78Y, ORF8 E64stop and nucleocapsid E378V, associated with higher disease severity. Altogether, our study contributes genetic, phylogenetic, and clinical correlation data about the spread of the SARS-CoV-2 pandemic in Egypt.

Effects of dietary supplementation of chromium methionine chelate on growth performance, oxidative stress, hematological indices, and carcass traits of broiler chickens.

This study was conducted to evaluate the dietary effects of chromium methionine (Cr-Meth) chelate on growth performance, oxidative stress parameters, blood biochemistry, and carcass traits of broiler chickens. An experiment was conducted on 34,000 1-day-old straight-run broiler chicks (Indian River; 42.0 ± 0.03) at a commercial farm. The chicks were divided randomly into 3 groups; the first group contained 17,000 birds, which used as a control, whereas the second and third groups consisted of 7000 and 10,000 birds, respectively, with 5 replicates per group. A completely randomized design was used. The birds were fed the experimental diets containing graded levels of Cr-Meth chelate: 0 (control), 50, and 100 g/ton. This compound consisted of chromium (0.4%) chelated with methionine, and it supply the diets with 200 and 400 ppb Cr for the used levels of 50 and 100 g/ton feed, respectively. Growth performance indices (body weight, body weight gain, feed intake, and feed conversion ratio) were measured throughout the experiment. At the end of experiment, 10 birds per treatment were slaughtered, and the carcass yield with relative weight of the internal organs was determined. Also, blood samples were taken and analyzed for glutathione peroxidase activity, malondialdehyde, ALT, AST, total protein, albumin, glucose, urea, creatinine, triglycerides, and total cholesterol. It was found that Cr-Meth improved the body weight, weight gain, feed intake, and feed conversion ratio of broilers. Moreover, it reduced the mortality rate of birds. The chelated chromium can alleviate the oxidative status of birds by increasing the plasma glutathione peroxidase activity and reducing the serum malondialdehyde level. It was observed that the effects of 100 g/ton Cr-Meth chelate on performance indices, mortality rate, and oxidative stress parameters were better than that of 50 g/ton inclusion rate. Supplementation of Cr-Meth increased the total protein level, but reduced the glucose, total cholesterol, and triglyceride concentrations in the blood serum. In addition, it increased the carcass yield and reduced the abdominal fat percentage of the birds' carcass. Therefore, chromium can be included in diets of broilers at a rate of 200 to 400 ppb, and the higher concentration was more effective than the lower one. So, it can be recommended to use Cr-Meth chelate in broiler diets at 100 g/ton to improve the productive performance and reduce the oxidative stress of birds.

Management and Outcome of Coronavirus Disease 2019 (COVID-19) in Pediatric Cancer Patients: A Single Centre Experience from a Developing Country.

INTRODUCTION: Sufficient data pertaining to the impact of the Coronavirus disease 2019 (COVID-19) on pediatric cancer patients is still lacking. The aim of this prospective study was to describe clinical management and outcomes of COVID-19 in pediatric oncology patients. PATIENTS AND METHODS: Conducted between May 1, 2020 and November 30, 2020, this study included 76 pediatric oncology patients with confirmed COVID-19. Remdesivir (RDV) was the antiviral therapy used. RESULTS: The median age of patients was 9 years. Sixty patients were on first line treatment. Hematological malignancies constituted 86.8% of patients. Severe to critical infections were 35.4% of patients. The commonest symptom was fever (93.4%). Chemotherapy was delayed in 59.2% of patients and doses were modified in 30.2%. The 60-day overall survival (OS) stood at 86.8%, with mortalities occurring only among critical patients. Of sixteen acute leukemia patients in the first induction therapy, 13 survived and 10 achieved complete remission. A negative RT-PCR within 2 weeks and improvement of radiological findings were statistically related to disease severity (P = .008 and .002, respectively). Better OS was associated with regression of radiological findings after 30 days from infection (P = .002). Forty-five patients received RDV, 42.1% had severe and critical forms of infection compared to 25.7% in the No-RDV group and yet OS was comparable in both groups. CONCLUSION: Most pediatric cancer patients with COVID-19 should have good clinical outcomes except for patients with critical infections. Cancer patients can tolerate chemotherapy including induction phase, alongside COVID-19 treatment. In severe and critical COVID-19, RDV might have a potential benefit.