RESUMO
The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly worldwide, seriously endangering human health. Although SARS-CoV-2 had a lower impact on paediatric population, children with COVID-19 have been reported as suffering from gastrointestinal (GI) symptoms at a higher rate than adults. The aim of this work was to evaluate faeces as a source of potential biomarkers of severity in the paediatric population, with an emphasis on intestinal microbiota and faecal immune mediators, trying to identify possible dysbiosis and immune intestinal dysfunction associated with the risk of hospitalization. This study involved 19 patients with COVID-19 under 24 months of age hospitalized during the pandemic at 6 different hospitals in Spain, and it included a comparable age-matched healthy control group (n = 18). Patients and controls were stratified according to their age in two groups: newborns or young infants (from 0 to 3 months old) and toddlers (infants from 6 to 24 months old). To characterize microbial intestinal communities, sequencing with Illumina technology of total 16S rDNA amplicons and internal transcribed spacer (ITS) amplicons of bifidobacteria were used. Faecal calprotectin (FC) and a range of human cytokines, chemokines, and growth factors were measured in faecal samples using ELISA and a multiplex system. Significant reduction in the abundance of sequences belonging to the phylum Actinobacteria was found in those infants with COVID-19, as well as in the Bifidobacteriaceae family. A different pattern of bifidobacteria was observed in patients, mainly represented by lower percentages of Bifidobacterium breve, as compared with controls. In the group of hospitalized young infants, FC was almost absent compared to age-matched healthy controls. A lower prevalence in faecal excretion of immune factors in these infected patients was also observed. CONCLUSION: Hospitalized infants with COVID-19 were depleted in some gut bacteria, such as bifidobacteria, in particular Bifidobacterium breve, which is crucial for the proper establishment of a functional intestinal microbiota, and important for the development of a competent immune system. Our results point to a possible immature immune system at intestine level in young infants infected by SARS-CoV2 requiring hospitalization. WHAT IS KNOWN: ⢠Although SARS-CoV-2 had a lower impact on paediatric population, children with COVID-19 have been reported as suffering from gastrointestinal symptoms at a higher rate than adults. ⢠Changes in microbial composition have been described in COVID-19 adult patients, although studies in children are limited. WHAT IS NEW: ⢠The first evidence that hospitalized infants with COVID-19 during the pandemic had a depletion in bifidobacteria, particularly in Bifidobacterium breve, beneficial gut bacteria in infancy that are crucial for the proper establishment of a competent immune system. ⢠In young infants (under 3 months of age) hospitalized with SARS-CoV2 infection, the aberrant bifidobacterial profile appears to overlap with a poor intestinal immune development as seen by calprotectin and the trend of immunological factors excreted in faeces.
Assuntos
Bifidobacterium , COVID-19 , Adulto , Lactente , Recém-Nascido , Humanos , Pré-Escolar , Bifidobacterium/genética , Disbiose , RNA Viral , SARS-CoV-2 , Fezes/microbiologia , Complexo Antígeno L1 LeucocitárioRESUMO
OBJECTIVES: Escalation of the ustekinumab (UST) maintenance dosage was effective in adults with Crohn disease (CD), but no data are available for children. We evaluated the effectiveness and safety of dose escalation of UST in pediatric CD. METHODS: This was a retrospective multicenter study from 25 centers affiliated with the IBD Interest and Porto groups of ESPGHAN. We included children with CD who initiated UST at a standard dosing and underwent either dose escalation to intervals shorter than 8 weeks or re-induction of UST due to active disease. Demographic, clinical, laboratory, endoscopic, imaging, and safety data were collected up to 12 months of follow-up. RESULTS: Sixty-nine children were included (median age 15.8 years, interquartile range 13.8-16.9) with median disease duration of 4.3 years (2.9-6.3). Most children were biologic (98.6%)- and immunomodulator (86.8%)- experienced. Clinical response and remission were observed at 3 months after UST escalation in 46 (67%) and 29 (42%) children, respectively. The strongest predictor for clinical remission was lower weighted Pediatric Crohn Disease Activity Index (wPCDAI) at escalation ( P = 0.001). The median C-reactive protein level decreased from 14 (3-28.03) to 5 (1.1-20.5) mg/L ( P = 0.012), and the fecal calprotectin level from 1100 (500-2300) to 515 (250-1469) µg/g ( P = 0.012) 3 months post-escalation. Endoscopic and transmural healing were achieved in 3 of 19 (16%) and 2 of 15 (13%) patients, respectively. Thirteen patients (18.8%) discontinued therapy due to active disease. No serious adverse events were reported. CONCLUSIONS: Two-thirds of children with active CD responded to dose escalation of UST. Milder disease activity may predict a favorable outcome following UST dose escalation.
Assuntos
Doença de Crohn , Ustekinumab , Humanos , Adulto , Criança , Adolescente , Ustekinumab/efeitos adversos , Doença de Crohn/tratamento farmacológico , Estudos Retrospectivos , Cicatrização , Resultado do Tratamento , Indução de RemissãoRESUMO
BACKGROUND AND OBJECTIVES: Current data on ustekinumab therapy in children with ulcerative colitis (UC) or unclassified inflammatory bowel disease (IBDU) are limited. We aimed to evaluate the effectiveness and safety of ustekinumab in pediatric UC and IBDU. METHODS: This multicenter retrospective study included 16 centers affiliated with the IBD Interest and Porto groups of ESPGHAN. Children with UC or IBDU treated with ustekinumab were enrolled. Demographic, clinical, laboratory, endoscopic, and imaging data as well as adverse events were recorded. Analyses were all based on the intention-to-treat principle. RESULTS: Fifty-eight children (39 UC and 19 IBDU, median age 14.5 [IQR 11.5-16.5] years) were included. All had failed biologic therapies, and 38 (66%) had failed two or more biologics. Corticosteroid-free clinical remission (CFR) was observed in 27 (47%), 33 (57%), and 37 (64%) children at 16, 26, and 52 weeks, respectively. Normalization of C-reactive protein and calprotectin < 150 µg/g were achieved in 60% and 52%, respectively, by 52 weeks. Endoscopic and radiologic remissions were reached in 8% and 23%, respectively. The main predictors of CFR were diagnosis of UC compared with IBDU (hazard ratio [HR] 2.2, 95% CI 1.03-4.85; p = 0.041) and no prior vedolizumab therapy (HR 2.1, 95% CI 1.11-4.27; p = 0.023). Ustekinumab serum levels were not associated with disease activity. Adverse events were recorded in six (10%) children, leading to discontinuation of the drug in three. CONCLUSION: Based on these findings, ustekinumab appears as an effective therapy for pediatric refractory UC and IBDU. The potential efficacy should be weighed against the risks of serious adverse events.
Assuntos
Colite Ulcerativa , Ustekinumab , Humanos , Ustekinumab/uso terapêutico , Ustekinumab/efeitos adversos , Colite Ulcerativa/tratamento farmacológico , Estudos Retrospectivos , Masculino , Feminino , Adolescente , Criança , Resultado do Tratamento , Indução de RemissãoRESUMO
BACKGROUND: Respiratory tract infections are one of the most frequent problems in pediatric clinics and generate an elevated prescription of antibiotics. The aim of this study was to find out the standard of care practice about antibiotic use in these infections in a pediatric emergency department and to evaluate compliance with clinical guidelines. METHODS: A pediatric emergency department database was reviewed from July 2005 to October 2007 under the category "respiratory infection", including variables such as age, antibiotic prescription and compliance with current clinical recommendations. RESULTS: Out of the 23,114 reviewed reports, 32.7% (7,567) were upper respiratory tract infections (URTI) (cold, acute otitis media [AOM], sinusitis and tonsillopharyngitis) or lower respiratory tract infections (LRTI) (laryngitis, bronchitis, bronchiolitis and pneumonia). Children under the age of 2 were the most represented age group. Amongst URTI, rhinopharyngitis was the most frequent infection, while bronchitis was the most frequent among LRTI. Antibiotic therapy (mainly amoxicillin) was prescribed in 30.8% of URTI (5.7% rhinopharyngitis, 96.5% AOM, and 36.7% tonsillopharyngitis) and in 12.4% of LRTI. CONCLUSIONS: The percentage of respiratory tract infections was similar to previous studies and the antibiotic prescriptions followed current guidelines, except for cases diagnosed with AOM. Prescription compliance and clinical course of the cases should be monitored.