Background and objectivesC-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.DesignSystematic review and meta-analysis.Data sourcesMEDLINE, EMBASE, CENTRAL and CINAHL from inception to 20 July 2017.Eligibility criteria for selecting studiesWe 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 synthesisTwo 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.ResultsOf 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.ConclusionThe 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 numberCRD42016038622

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Multisystem inflammatory syndrome in children (MIS-C) 1 manifests as immune dysregulation after SARS-CoV-2 infection. 2 The syndrome has no pathognomonic features. Thus, the diagnostic criteria of the Royal College of Paediatrics and Child Health (RCPCH), the Centers for Disease Control and Prevention (CDC) and the World Health Org anization (WHO) differ, but they all include fever, evidence of systemic inflammation and involvement of at least 1 organ or system. 3 Our primary objective was to assess initial clinical or laboratory features that predict severe illness in MIS-C. We also sought to explore changes in overall disease severity and cardiac involvement over time as it was the impression of many investigators that severity of MIS-C increased through pandemic waves.

ObjectiveTo identify risk factors for severe disease in children hospitalised for SARS-CoV-2 infection.DesignMulticentre retrospective cohort study.Setting18 hospitals in Canada, Iran and Costa Rica from 1 February 2020 to 31 May 2021.PatientsChildren<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 measureSeverity on the WHO COVID-19 Clinical Progression Scale was used for ordinal logistic regression analyses.ResultsWe 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.ConclusionWe 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.

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. Supplementary information The online version contains supplementary material available at 10.1007/s00431-022-04422-x.

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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.

BACKGROUND: SARS-CoV-2 infection can lead to multisystem inflammatory syndrome in children (MIS-C). We investigated risk factors for severe disease and explored changes in severity over time. METHODS: Children up to 17 years of age admitted March 1, 2020 through March 7th, 2021 to 15 hospitals in Canada, Iran and Costa Rica with confirmed or probable MIS-C were included. Descriptive analysis and comparison by diagnostic criteria, country, and admission date was performed. Adjusted absolute average risks (AR) and risk differences (RD) were estimated for characteristics associated with ICU admission or cardiac involvement. RESULTS: Of 232 cases (106 confirmed) with median age 5.8 years, 56% were male, and 22% had comorbidities. ICU admission occurred in 73 (31%) but none died. Median length of stay was 6 days (inter-quartile range 4-9). Children 6 to 12 years old had the highest AR for ICU admission (44%; 95% confidence interval [CI] 34-53). Initial ferritin greater than 500 mcg/L was associated with ICU admission. When comparing cases admitted up to October 31, 2020 to those admitted later, the AR for ICU admission increased from 25% (CI 17-33) to 37% (CI 29-46) and for cardiac involvement from 44% (CI 35-53) to 75% (CI 66-84). Risk estimates for ICU admission in the Canadian cohort demonstrated a higher risk in December 2020-March 2021 compared to March-May 2020 (RD 25%; 95%CI 7-44). INTERPRETATION: MIS-C occurred primarily in previously well children. Illness severity appeared to increase over time. Despite a high ICU admission incidence, most children were discharged within one week.