Predictors of severe illness in children with multisystem inflammatory syndrome after SARS-CoV-2 infection: a multicentre cohort study.

BACKGROUND: SARS-CoV-2 infection can lead to multisystem inflammatory syndrome in children (MIS-C). We sought to investigate risk factors for admission to the intensive care unit (ICU) and explored changes in disease severity over time. METHODS: We obtained data from chart reviews of children younger than 18 years with confirmed or probable MIS-C who were admitted to 15 hospitals in Canada, Iran and Costa Rica between Mar. 1, 2020, and Mar. 7, 2021. Using multivariable analyses, we evaluated whether admission date and other characteristics were associated with ICU admission or cardiac involvement. RESULTS: Of 232 children with MIS-C (median age 5.8 yr), 130 (56.0%) were male and 50 (21.6%) had comorbidities. Seventy-three (31.5%) patients were admitted to the ICU but none died. We observed an increased risk of ICU admission among children aged 13-17 years (adjusted risk difference 27.7%, 95% confidence interval [CI] 8.3% to 47.2%), those aged 6-12 years (adjusted risk difference 25.2%, 95% CI 13.6% to 36.9%) or those with initial ferritin levels greater than 500 µg/L (adjusted risk difference 18.4%, 95% CI 5.6% to 31.3%). Children admitted to hospital after Oct. 31, 2020, had numerically higher rates of ICU admission (adjusted risk difference 12.3%, 95% CI -0.3% to 25.0%) and significantly higher rates of cardiac involvement (adjusted risk difference 30.9%, 95% CI 17.3% to 44.4%). At Canadian sites, the risk of ICU admission was significantly higher for children admitted to hospital between December 2020 and March 2021 than those admitted between March and May 2020 (adjusted risk difference 25.3%, 95% CI 6.5% to 44.0%). INTERPRETATION: We observed that age and higher ferritin levels were associated with more severe MIS-C. We observed greater severity of MIS-C later in the study period. Whether emerging SARS-CoV-2 variants pose different risks of severe MIS-C needs to be determined.

Infants hospitalized for acute COVID-19: disease severity in a multicenter cohort study.

Age is the most important determinant of COVID-19 severity. Infectious disease severity by age is typically J-shaped, with infants and the elderly carrying a high burden of disease. We report on the comparative disease severity between infants and older children in a multicenter retrospective cohort study of children 0 to 17 years old admitted for acute COVID-19 from February 2020 through May 2021 in 17 pediatric hospitals. We compare clinical and laboratory characteristics and estimate the association between age group and disease severity using ordinal logistic regression. We found that infants comprised one-third of cases, but were admitted for a shorter period (median 3 days IQR 2-5 versus 4 days IQR 2-7), had a lower likelihood to have an increased C-reactive protein, and had half the odds of older children of having severe or critical disease (OR 0.50 (95% confidence interval 0.32-0.78)).    Conclusion: When compared to older children, there appeared to be a lower threshold to admit infants but their length of stay was shorter and they had lower odds than older children of progressing to severe or critical disease. What is Known: • A small proportion of children infected with SARS-CoV-2 require hospitalization for acute COVID-19 with a subgroup needing specialized intensive care to treat more severe disease. • For most infectious diseases including viral respiratory tract infections, disease severity by age is J-shaped, with infants having more severe disease compared to older children. What is New: • One-third of admitted children for acute COVID-19 during the first 14 months of the pandemic were infants. • Infants had half the odds of older children of having severe or critical disease.

Enteroviral and herpes simplex virus central nervous system infections in infants < 90 days old: a Paediatric Investigators' Collaborative Network on Infections in Canada (PICNIC) study.

BACKGROUND: The relative contribution of viruses to central nervous system (CNS) infections in young infants is not clear. For viral CNS infections, there are limited data on features that suggest HSV etiology or on predictors of unfavorable outcome. METHODS: In this cross-sectional retrospective study, seven centers from the Pediatric Investigators Collaborative Network on Infections in Canada identified infants < 90 days of age with CNS infection proven to be due to enterovirus (EV) or herpes simplex virus (HSV) January 1, 2013 through December 31, 2014. RESULTS: Of 174 CNS infections with a proven etiology, EV accounted for 103 (59%) and HSV for 7 (4%). All HSV cases and 41 (40%) EV cases presented before 21 days of age. Four HSV cases (57%) and 5 EV cases (5%) had seizures. Three (43%) HSV and 23 (23%) EV cases lacked cerebrospinal fluid (CSF) pleocytosis. HSV cases were more likely to require ICU admission (p = 0.010), present with seizures (p = 0.031) and have extra-CNS disease (p < 0.001). Unfavorable outcome occurred in 12 cases (11% of all EV and HSV infections) but was more likely following HSV than EV infection (4 (57%) versus 8 (8%); p = 0.002). CONCLUSIONS: Viruses accounted for approximately two-thirds of proven CNS infections in the first 90 days of life. Empiric therapy for HSV should be considered in suspected CNS infections in the first 21 days even in the absence of CSF pleocytosis unless CSF parameters are suggestive of bacterial meningitis. Neurodevelopmental follow-up should be considered in infants whose course of illness is complicated by seizures.

Risk factors for severe PCR-positive SARS-CoV-2 infection in hospitalised children.

OBJECTIVE: To identify risk factors for severe disease in children hospitalised for SARS-CoV-2 infection. DESIGN: Multicentre retrospective cohort study. SETTING: 18 hospitals in Canada, Iran and Costa Rica from 1 February 2020 to 31 May 2021. PATIENTS: Children<18 years of age hospitalised for symptomatic PCR-positive SARS-CoV-2 infection, including PCR-positive multisystem inflammatory syndrome in children (MIS-C). MAIN OUTCOME MEASURE: Severity on the WHO COVID-19 Clinical Progression Scale was used for ordinal logistic regression analyses. RESULTS: We identified 403 hospitalisations. Median age was 3.78 years (IQR 0.53-10.77). At least one comorbidity was present in 46.4% (187/403) and multiple comorbidities in 18.6% (75/403). Eighty-one children (20.1%) met WHO criteria for PCR-positive MIS-C. Progression to WHO clinical scale score ≥6 occurred in 25.3% (102/403). In multivariable ordinal logistic regression analyses adjusted for age, chest imaging findings, laboratory-confirmed bacterial and/or viral coinfection, and MIS-C diagnosis, presence of a single (adjusted OR (aOR) 1.90, 95% CI 1.13 to 3.20) or multiple chronic comorbidities (aOR 2.12, 95% CI 1.19 to 3.79), obesity (aOR 3.42, 95% CI 1.76 to 6.66) and chromosomal disorders (aOR 4.47, 95% CI 1.25 to 16.01) were independent risk factors for severity. Age was not an independent risk factor, but different age-specific comorbidities were associated with more severe disease in age-stratified adjusted analyses: cardiac (aOR 2.90, 95% CI 1.11 to 7.56) and non-asthma pulmonary disorders (aOR 3.07, 95% CI 1.26 to 7.49) in children<12 years old and obesity (aOR 3.69, 1.45-9.40) in adolescents≥12 years old. Among infants<1 year old, neurological (aOR 10.72, 95% CI 1.01 to 113.35) and cardiac disorders (aOR 10.13, 95% CI 1.69 to 60.54) were independent predictors of severe disease. CONCLUSION: We identified risk factors for disease severity among children hospitalised for PCR-positive SARS-CoV-2 infection. Comorbidities predisposing children to more severe disease may vary by age. These findings can potentially guide vaccination programmes and treatment approaches in children.

Use of C-reactive protein to tailor antibiotic use: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: C-reactive protein (CRP) has been proposed to guide the use of antibiotics. However, study results are controversial regarding the benefits of such a strategy. We synthesised the evidence of CRP-based algorithms on antibiotic treatment initiation and on antibiotic treatment duration in adults, children and neonates, as well as their safety profile. DESIGN: Systematic review and meta-analysis. DATA SOURCES: MEDLINE, EMBASE, CENTRAL and CINAHL from inception to 20 July 2017. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We included randomised controlled trials (RCTs), non-RCTs and cohort studies (prospective or retrospective) investigating CRP-guided antibiotic use in adults, children and neonates with bacterial infection. DATA EXTRACTION AND SYNTHESIS: Two researchers independently screened all identified studies and retrieved the data. Outcomes were duration of antibiotic use, antibiotic initiation, mortality, infection relapse and hospitalisation. We assessed the quality of the included studies using the Cochrane Collaboration's tool (RCTs), and A Cochrane Risk Of Bias Assessment Tool: for Non-Randomized Studies of Interventions and the Newcastle-Ottawa scale (non-RCTs). We analysed our results using descriptive statistics and random effects models. RESULTS: Of 11 165 studies screened, 15 were included. In five RCTs in adult outpatients, the risk difference for antibiotic treatment initiation in the CRP group was -7% (95% CI: -10% to -4%), with no difference in hospitalisation rate. In neonates, CRP-based algorithms shortened antibiotic treatment duration by -1.45 days (95% CI -2.61 to -0.28) in two RCTs, and by -1.15 days (95% CI -2.06 to -0.24) in two cohort studies, with no differences in mortality or infection relapse. CONCLUSION: The use of CRP-based algorithms seems to reduce antibiotic treatment duration in neonates, as well as to decrease antibiotic treatment initiation in adult outpatients. However, further high-quality studies are still needed to assess safety, particularly in children outside the neonatal period. PROSPERO REGISTRATION NUMBER: CRD42016038622.

Inter-rater agreement in the evaluation of abdominal radiographs for necrotizing enterocolitis.

PURPOSE: Abdominal radiographs are frequently employed in the surveillance of patients with necrotizing enterocolitis (NEC), with typical findings well described. Clinicians interpret and act upon these films at different intervals, however, and inter-rater agreement has not been evaluated to date. METHODS: Thirty abdominal radiographs of premature infants were distributed to attending radiologists (4), pediatric surgeons (4), and trainees (4), who evaluated for findings of NEC from a list of eight potential choices (1=normal, 8=perforation). Fleiss's Kappa (FK) was used to evaluate concordance between multiple raters with 0-0.2=slight association and 0.8-1=almost perfect agreement. RESULTS: Practicing surgeons had an FK of 0.77 overall (95% CI: 0.67-0.87), but demonstrated poor agreement when evaluating decubitus films (FK: 0.39, 95% CI:0.12-0.65). Radiologists had excellent inter-rater agreement (FK: 0.81, 95% CI: 0.74-0.88), but had only modest agreement with surgeons (FK: 0.59, 95% CI: 0.56-0.63) and poor agreement for decubitus films (FK: 0.15, 95% CI: 0.47-0.26). Surgical and radiology trainees had fair agreement with their respective attendings (0.60, 95% CI: 0.55-0.65 and 0.64, 95% CI: 0.60-0.69, respectively). CONCLUSIONS: While inter-rater agreement was good-excellent among attending staff, it was only moderate between radiologists and surgeons and between trainees and their attendings. This highlights the importance of inter-disciplinary and hierarchical communication to optimize clinical decision-making. Decubitus films may be of limited value in evaluating patients with NEC.

Percutaneous pigtail catheter versus tube thoracostomy for pediatric empyema: A comparison of outcomes.

PURPOSE: Randomized trials have shown no benefit to thoracoscopic decortication over pleural drainage with fibrinolytic installation for pediatric empyema. However, the optimal method of pleural drainage has not been defined. The present study compares outcomes of 8.5-Fr soft pigtail catheters (PC) placed via Seldinger technique with larger caliber, stiff chest tubes (12- to 24-Fr) placed via tube thoracostomy (TT). METHODS: A retrospective review of all pediatric patients treated for empyema during a 5-year period (2006-2011) was conducted. Clinical, therapeutic, and outcomes data from patients treated by PC were compared with those treated by TT. Treatment failure, the primary outcome, was defined as need for an additional invasive thoracic procedure (second tube or catheter or thoracoscopic decortication). RESULTS: We treated 43 patients, 21 by PC and 22 by TT. Fibrinolytics were used in 71% of the PC and 64% of the TT groups. Baseline clinical parameters were not different between the 2 groups. Treatment failure was significantly higher in the PC group (43% vs 14%; P = .045). When the analysis was limited to patients who received fibrinolytics, the failure rate was greater in the PC group (40% vs 14%; P = .129), and duration of illness was shorter (18.3 ± 1.0 vs 25.6 ± 3.5 days; P = .048). CONCLUSION: Soft PCs are associated with higher failure rates but shorter total duration of illness in the treatment of pediatric empyema. The ideal method for draining pediatric empyema may be a small-caliber, stiff chest tube placed percutaneously.