Efficacy and Safety of Remdesivir in Hospitalized Pediatric COVID-19: A Retrospective Case-Controlled Study.

Introduction: While most children experience mild coronavirus disease 2019 (COVID-19) infections, a minority of cases progress to severe or critical illness. This study aimed to assess the efficacy and safety of Remdesivir (RDV) therapy in children with moderate to severe COVID-19, enhancing clinical decision-making and expanding our understanding of antiviral treatments for pediatric patients. Methods: The study included 60 patients, 38 receiving RDV treatment and 22 serving as the control group. Data was collected retrospectively from January 2021 to January 2022 through electronic hospital records. Results: Regarding the main clinical symptoms reported, most patients experienced Upper Respiratory Tract Infections (93.3%), indicating respiratory involvement. Additional symptoms included Central Nervous System (11.7%) and Gastrointestinal (10.0%). Among the 38 cases in the RDV group included in the study, the adverse effects associated with using RDV: Hypoalbuminemia in 19 cases (50.0%) and anemia in 18 cases (47.4%), making them the most common adverse effects. Only one case in the RDV group experienced non-RDV-related death with a different clinical diagnosis. The results showed that RDV treatment was well-tolerated in pediatric patients, with no significant differences in hospital stay and oxygen treatment compared to the control group with P values (0.2, 0.18), respectively. Conclusion: The outcomes indicate that Remdesivir may represent a safe and therapeutic choice for children with coronavirus disease 2019 (COVID-19).

Fecal Carriage and Molecular Characterization of Carbapenemase-Producing Enterobacterales in the Pediatric Population in Qatar.

Whole-genome sequencing was used to characterize carbapenemase-producing Enterobacterales (CPE) strains recovered from rectal screening swab samples obtained from children at a tertiary-care pediatric hospital in Qatar during a 3-year period. A total of 72 CPE isolates recovered from 61 fecal carriers were characterized. Escherichia coli (47 isolates [65.3%]) and Klebsiella pneumoniae (22 isolates [30.6%]) were the most common species identified. High levels of genetic diversity were observed for both species. These 72 isolates produced 78 carbapenemases, characterized as either NDM-type (41 enzymes [52.6%]) or OXA-48-type (37 enzymes [47.4%]). NDM-5 (24 enzymes [30.8%]), NDM-1 (15 enzymes [19.2%]), and OXA-181 (15 enzymes [19.2%]) were the most common variants detected within each type. Twenty-three NDM producers exhibited difficult-to-treat resistance, compared with only 2 of the OXA-48 producers. Multiple comorbidities were identified in 88.5% of the patients, whereas recent travel history to countries in which CPE are endemic was documented for 57.4% of the patients. All 9 blaOXA-48-type-gene-containing E. coli sequence type 38 (ST38) strains were isolated from patients without international travel history. The mean quarterly incidence of fecal carriage decreased more than 6-fold after the implementation of coronavirus disease 2019 (COVID-19)-related international travel restrictions in Qatar in mid-March 2020. Our data suggest that NDM-type and OXA-48-type carbapenemases expressed by a large diversity of E. coli and K. pneumoniae genotypes are largely dominant in the pediatric population of Qatar. Although our data indicate successful local expansion of E. coli ST38 strains harboring blaOXA-244 genes, at least within health care settings, blaOXA-48-type and blaNDM-type genes appear to have been mainly introduced sporadically by asymptomatic carriers who visited or received health care in some nearby countries in which the genes are endemic. IMPORTANCE To the best of our knowledge, this is the first study addressing the molecular characteristics of CPE in a pediatric population in Qatar using whole-genome sequencing. Since several countries in the Arabian Peninsula share relatively similar demographic patterns and international links, it is plausible that the molecular characteristics of CPE in children, at least in the middle and eastern parts of the region, are similar to those observed in our study.

A Novel STK4 Mutation Impairs T Cell Immunity Through Dysregulation of Cytokine-Induced Adhesion and Chemotaxis Genes.

PURPOSE: Human serine/threonine kinase 4 (STK4) deficiency is a rare, autosomal recessive genetic disorder leading to combined immunodeficiency; however, the extent to which immune signaling and host defense are impaired is unclear. We assessed the functional consequences of a novel, homozygous nonsense STK4 mutation (NM_006282.2:c.871C > T, p.Arg291*) identified in a pediatric patient by comparing his innate and adaptive cell-mediated and humoral immune responses with those of three heterozygous relatives and unrelated controls. METHODS: The genetic etiology was verified by whole genome and Sanger sequencing. STK4 gene and protein expression was measured by quantitative RT-PCR and immunoblotting, respectively. Cellular abnormalities were assessed by high-throughput RT-RCR, RNA-Seq, ELISA, and flow cytometry. Antibody responses were assessed by ELISA and phage immunoprecipitation-sequencing. RESULTS: The patient exhibited partial loss of STK4 expression and complete loss of STK4 function combined with recurrent viral and bacterial infections, notably persistent Epstein-Barr virus viremia and pulmonary tuberculosis. Cellular and molecular analyses revealed abnormal fractions of T cell subsets, plasmacytoid dendritic cells, and NK cells. The transcriptional responses of the patient's whole blood and PBMC samples indicated dysregulated interferon signaling, impaired T cell immunity, and increased T cell apoptosis as well as impaired regulation of cytokine-induced adhesion and leukocyte chemotaxis genes. Nonetheless, the patient had detectable vaccine-specific antibodies and IgG responses to various pathogens, consistent with a normal CD19 + B cell fraction, albeit with a distinctive antibody repertoire, largely driven by herpes virus antigens. CONCLUSION: Patients with STK4 deficiency can exhibit broad impairment of immune function extending beyond lymphoid cells.

COVID-19 related multisystem inflammatory syndrome in children (MIS-C): a case series from a tertiary care pediatric hospital in Qatar.

BACKGROUND: Multisystem Inflammatory Syndrome in Children (MIS-C) is a severe complication of coronavirus disease 2019 (COVID-19) in children, which is increasingly being reported worldwide. Here we report the first case series of 7 children diagnosed with MIS-C in Qatar. METHODS: Clinical features and outcomes of COVID-19 positive patients admitted to Sidra Medicine, Qatar from June to October 2020, who met the WHO case definition for MIS-C were reviewed. RESULTS: The mean age in our case series was 5.6 years, of which 71.4% were males. All patients were previously healthy but had a history of COVID-19 infection. Fever, rash, vomiting and abdominal pain were the most common symptoms (70-100%). The average hospitalization was 12.9 days with no case fatalities. Laboratory findings included lymphopenia and thrombocytopenia in most patients, as well as evidence of coagulopathy and elevated inflammatory markers such as C-reactive protein, ferritin and procalcitonin. Many patients (71.4%) required inotropic support in intensive care, while only one required respiratory support. Although all patients had elevated cardiac biomarkers, cardiovascular involvement was observed in 42.9% of patients with one patient developing a giant coronary aneurysm. All patients received intravenous immunoglobulin (IVIG) and 86% of patients received corticosteroids, with two patients requiring treatment with IL-1 inhibitors. CONCLUSIONS: Our report is one of the first reports on MIS-C from Asia. Although clinical features and outcomes are not significantly different from those reported elsewhere, lack of case fatalities in our cohort may indicate that early recognition and prompt medical attention is necessary for a favorable outcome in MIS-C.

Neonates and Young Infants With COVID-19 Presented With Sepsis-Like Syndrome: A Retrospective Case Controlled Study.

Objective: We aimed to describe the presentations and biochemical characteristics of sepsis-like syndrome (SLS) in infants aged <2 months who tested positive for SARS-CoV-2-in comparison to those in the same age group who were SARS-CoV-2-negative. Background: COVID-19 presents with a spectrum of manifestations, and children seem to have a favorable clinical course compared to other age groups. Limited data are available for symptomatic infants. Design: This was a case-controlled single-institution retrospective study on infants aged <2 months admitted with SLS between 1 April 2020 and 1 July 2020. These infants were divided into 2 groups: Group 1 (n = 41), infants with positive nasal/oropharyngeal swab polymerase chain reaction (PCR) results for SARS-CoV-2; and Group 2 (n = 40), infants with negative PCR results for SARS-CoV-2 (control group). Details between both groups were reviewed and analyzed. Outcome: The clinical and laboratory data for SARS-CoV-2 -positive infants who presented with SLS may differ from those for infants with SLS who tested negative for SARS-CoV-2. Results: Overall, 105 infants were admitted with clinical sepsis: 41 were SARS-CoV-2-positive, and 64 were negative. Fever was present in 90% of SARS-CoV-2-positive infants vs. 80% of the negative group. SARS-CoV-2-positive infants had a higher incidence of nasal congestion and cough (39 and 29%, respectively) compared to the SARS-CoV-2-negative group (20 and 3%, respectively) (P < 0.05). Poor feeding and hypoactivity occurred more frequently in the SARS-CoV-2-negative group (58 and 45%, respectively) than in the SARS-CoV-2-positive group (22 and 12%, respectively, P < 0.004). Sepsis workup, including lumbar puncture, was performed in 67% and partial septic workup was performed in 23% of the SARS-CoV-2-positive infants. Full sepsis workup was performed in 92% of the SARS-CoV-2-negative group. Cerebrospinal fluid (CSF) cultures were negative in 26/27SARS-CoV-2-positive infants (an infant had Klebsiella meningitis). All the SARS-CoV-2-negative infants had negative CSF cultures. Blood culture was negative in both groups. Urine culture showed bacterial growth in 9 infants with SARS-CoV-2-negative sepsis. Conclusions: Our study showed that respiratory symptoms (cough and nasal congestion) were more prominent in the SARS-CoV-2-positive group, while poor feeding and hypoactivity were reported more frequently in the negative group. However, the clinical differentiation between COVID-19 disease and sepsis in such age groups is difficult. Therefore, screening young infants with SLS for SARS-CoV-2- is necessary during this pandemic.

Molecular Characterization of Extended-Spectrum ß-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae Among the Pediatric Population in Qatar.

INTRODUCTION: Although extended-spectrum ß-lactamase (ESBL)-producing Enterobacterales are a public health problem in the Arabian Peninsula, data on the molecular characteristic of their antimicrobial resistance determinants in children is limited. AIM: To determine the molecular characteristics of ESBL-producing Escherichia coli and Klebsiella pneumoniae in the pediatric population of Qatar. METHODS: Whole-genome sequencing was performed on ESBL-producing E. coli and K. pneumoniae isolates recovered from screening and clinical specimens from pediatric patients at Sidra Medicine in Doha from January to December 2018. RESULTS: A total of 327 ESBL producers were sequenced: 254 E. coli and 73 K. pneumoniae. Non-susceptibility rates to non-ß-lactam antibiotics for both species were 18.1 and 30.1% for gentamicin, 0.8 and 4.1% for amikacin, 41.3 and 41.1% for ciprofloxacin, and 65.8 and 76.1% for cotrimoxazole. The most common sequence types (STs) were ST131 (16.9%), ST38 and ST10 (8.2% each) in E. coli and ST307 (9.7%), and ST45 and ST268 (6.9% each) in K. pneumoniae. CTX-M type ESBLs were found in all but one isolate, with CTX-M-15 accounting for 87.8%. Among other ß-lactamases, TEM-1B and OXA-1 were coproduced in 41 and 19.6% of isolates. The most common plasmid-mediated quinolone resistance genes cocarried were qnr A/B/E/S (45.3%). Ninety percent of gentamicin non-susceptible isolates harbored genes encoding AAC(3) enzymes, mainly aac(3)-IIa. Only two of 57 isolates harboring aac(6')-Ib-cr were non-susceptible to amikacin. Chromosomal mutations in genes encoding DNA gyrase and topoisomerase IV enzymes were detected in 96.2% fluoroquinolone-non-susceptible E. coli and 26.7% fluoroquinolone-non-susceptible K. pneumoniae. CONCLUSION: Our data show that CTX-M enzymes are largely the most prevalent ESBLs in children in Qatar with a predominance of CTX-M-15. Carbapenem-sparing options to treat ESBL infections are limited, given the frequent coproduction of OXA-1 and TEM-1B enzymes and coresistance to antibiotic classes other than ß-lactams.

Mycobacterium fortuitum abdominal wall abscesses following liposuction.

We describe here a case of abdominal abscesses due to Mycobacterium fortuitum following liposuction. The abscesses developed three months after the procedure and diagnosis was delayed for five months. The clues for diagnosis were persistent pus discharge in spite of broad spectrum antibiotics and failure to grow any organisms on routine culture. This condition has been rarely reported; however, the increasing number of liposuction procedures done and awareness among physicians will probably result in the identification of more cases. Combination antibiotic therapy with surgical drainage in more extensive diseases is essential for cure.