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.

Maintenance of Antibody Response in Egyptian Healthcare Workers Vaccinated with ChAdOx1 nCoV-19 Vaccine during Delta and Omicron Variants Pandemic: A Prospective Study.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a constantly evolving virus, resulting in an increased burden on the existing COVID-19 vaccines. Healthcare workers (HCWs) are the first line of defense against the coronavirus disease 2019 (COVID-19) pandemic and have been prioritized among the risk categories receiving the COVID-19 vaccine. This work aimed to investigate the maintenance of antibody response of the Oxford−AstraZeneca vaccine (ChAdOx1/nCoV-19). Methods: Anti-spike immunoglobulin G (IgG) was measured at baseline point (immediately prior to vaccination) and 12- and 24-week (w) points following vaccination. Adverse reactions to the vaccine were reported. Participants were followed up for the incidence of COVID-19 during the 12 w interval between vaccination doses for 24 w after the second dose. Results: A total of 255 HCWs participated in the study. Prior to vaccination, 54.1% experienced COVID-19, 88.2% were seropositive after the first dose, while seropositivity reached 95.7% after the second dose. Following the first and second doses, the anti-spike IgG serum level was significantly higher in subjects with past COVID-19 than in others (p < 0.001 and =0.001, respectively). Conclusions: The Oxford−AstraZeneca vaccine is generally safe and provides a highly effective long-term humoral immune response against the Delta and Omicron variants of SARS-CoV-2.

Susceptibility of carbapenem-resistant Enterobacterales isolates to new antibiotics from a tertiary care hospital, Egypt: A matter of hope.

INTRODUCTION: Carbapenem-resistant Enterobacterales (CRE) are particularly worrisome pathogens because of their resistance to last-resort antibiotics, significant morbidity, and mortality. With limited treatment options, new therapeutic choices have become available for the management of CRE infections. Data regarding the efficacy of these novel agents are still limited particularly in a low-middle-income country like Egypt. This study aims to assess the prevalence of different carbapenemase genes among CRE isolates and the susceptibility of these isolates to novel antibiotics for improving antibiotic policy and infection control strategies in Egypt. METHODOLOGY: In this cross-sectional study, 260 Enterobacterales were recovered from patients admitted to intensive care units between January and June 2021. Susceptibility testing was conducted using Kirby-Bauer method. Molecular detection of five carbapenemase genes, namely blaKPC, blaIMP, blaVIM, blaNDM, blaOXA-48 was done using polymerase chain reaction (PCR). RESULTS: Of the 260 Enterobacterales, 34.6% were found to be carbapenems resistant. All of the CRE isolates were multi-drug resistant exhibiting resistance to most antibiotics. All isolates harbored one or more carbapenemases genes. The most prevalent was blaNDM (84.4%), followed by blaOXA-48 (73.3%), blaKPC (13.3%), blaIMP (2.2%), while blaVIM gene wasn't detected. Among 62.2% of the CRE isolates, two or more carbapenemase genes co-existed. For the new antibiotics tested, 100% of CRE resisted ceftolozane/tazobactam, 86.7% resisted ceftazidime/avibactam, 51.1% were resistant to eravacyclin, and 42.2% were resistant to cefiderocol. CONCLUSIONS: A high percentage of resistance to carbapenems among Enterobacterales isolates was revealed. blaNDM was found to be the most predominant carbapenemase gene. A high rate of CRE resistance to novel agents signifies a major threat.

Ficolin-1 gene (FCN1) -144 C/A polymorphism is associated with adverse outcome of severe pneumonia in the under-five Egyptian children: A multicenter study.

BACKGROUND: Pneumonia is the foremost cause of child death worldwide. M-ficolin is encoded by the FCN1 gene and represents a novel link between innate and adaptive immunity. OBJECTIVES: To investigate the FCN1 -144 C/A (rs10117466) polymorphism as a potential marker for pneumonia severity and adverse outcome namely complications or mortality in the under-five Egyptian children. METHODS: This was a prospective multicenter study that included 620 children hospitalized with World Health Organization-defined severe pneumonia and 620 matched healthy control children. Polymorphism rs10117466 of the FCN1 gene promoter was analyzed by PCR-SSP, while serum M-ficolin levels were assessed by ELISA. RESULTS: The FCN1 A/A genotype and A allele at the -144 position were more frequently observed in patients compared to the control children (43.4% vs 27.6%; odds ratio [OR]: 1.62; [95% confidence interval {CI}: 1.18-2.2]; for the A/A genotype) and (60.8% vs 52.5%; OR: 1.4; [95% CI: 1.19-1.65]; for the A allele); P < .01. The FCN1 -144 A/A homozygous patients had significantly higher serum M-ficolin concentrations (mean: 1844 ± 396 ng/mL) compared with those carrying the C/C or C/A genotype (mean: 857 ± 278 and 1073 ± 323 ng/mL, respectively; P = .002). FCN1 -144 A/A genotype was an independent risk factor for adverse outcomes in children with severe pneumonia (adjusted OR = 4.85, [95% CI: 2.96-10.25]; P = .01). CONCLUSION: The FCN1 A/A genotype at the -144 position was associated with high M-ficolin serum levels and possibly contributes to enhanced inflammatory response resulting in the adverse outcome of pneumonia in the under-five Egyptian children.

Healthcare Workers' Preparedness: An Exploratory Study for Measles Control in a Middle-Income Country.

BACKGROUND: Healthcare workers (HCWs) should have an active role in measles control. OBJECTIVE: This study aimed to assess the HCWs' measles immune status and its influencing factors; to measure their knowledge, attitude, and practice toward measles infection/vaccination; and to identify factors predicting their vaccination status. METHODS: Data were collected using a semi-tailored questionnaire. Immunoglobulin G against measles was measured. Regression analysis for measles vaccination was performed. RESULTS: Approximately 97 HCWs (93.3%) were seropositive, 79 (76.0%) were vaccinated, 18 (17.3%) were previously infected, and 9 (8.7%) were both vaccinated and previously infected. One previously vaccinated participant was seronegative. The immune status was associated with marital status, residence, work duration, infection control training, and wearing personal protective equipment. Positive attitudes and practices were reported. Marital status and infection control training were predictors for measles vaccination. CONCLUSION: HCWs showed readiness to control the spread of measles. National policies for compulsory HCWs' vaccination and immune status check before training and employment are required.

Occurrence of classes I and II integrons in Enterobacteriaceae collected from Zagazig University Hospitals, Egypt.

Integrons are genetic units characterized by the ability to capture and incorporate gene cassettes, thus can contribute to the emergence and transfer of antibiotic resistance. The objectives of this study were: (1) to investigate the presence and distribution of class I and class II integrons and the characteristics of the gene cassettes they carry in Enterobacteriaceae isolated from nosocomial infections at Zagzig University Hospital in Egypt, (2) to determine their impact on resistance, and (3) to identify risk factors for the existence of integrons. Relevant samples and full clinical history were collected from 118 inpatients. Samples were processed; isolated microbes were identified and tested for antibiotic susceptibilities. Integrons were detected by polymerase chain reaction (PCR) and were characterized into class I or II by restriction fragment length polymorphism (RFLP). Integron-positive isolates were subjected to another PCR to detect gene cassette, followed by gene cassette sequencing. Risk factors were analyzed by logistic regression analysis. Seventy-six Enterobacteriaceae isolates were recognized, 41 of them (53.9%) were integron-positive; 39 strains carried class I and 2 strains carried class II integrons. Integrons had gene cassettes encoding different combinations and types of resistance determinants. Interestingly, blaOXA129 gene was found and ereA gene was carried on class I integrons. The same determinants were carried within isolates of the same species as well as isolates of different species. The presence of integrons was significantly associated with multidrug resistance (MDR). No risk factors were associated for integron carriage. We conclude that integrons carrying gene cassettes encoding antibiotic resistance are significantly present among Enterobacteriaceae causing nosocomial infection in our hospital. Risk factors for acquisition remain to be identified.