Pediatric Infectious Disease Journal

There is increasing reporting by patients organization and researchers of long covid (or post-acute sequelae of SARS-CoV-2 - PASC), characterized by symptoms such as fatigue, dyspnea, chest pain, cognitive and sleeping disturbances, arthralgia and decline in quality of life. Immune system dysregulation with a hyperinflammatory state, direct viral toxicity, endothelial damage and microvascular injury have been proposed as pathologenic mechanisms. Recently, cohorts of children with PASC have been reported in Italy, Sweden and Russia. However, immunological studies of children with PASC have never been performed. In this study, we documented significant immunologic differences between children that completely recovered from acute infection and those with PASC, providing the first objective laboratory sign of the existence of PASC in children.

BackgroundMycoplasma pneumoniae pneumonia (MPP), often referred to as walking pneumonia, is a common cause of community-acquired pneumonia (CAP) in children and presents with a broad clinical spectrum. While many cases are mild and self-limiting, a subset progresses to severe disease marked by hyperinflammation and systemic complications. This clinical variability presents challenges in early diagnosis and risk stratification. This study aimed to identify prognostic markers associated with MPP severity and explore potential underlying inflammatory mechanisms. MethodsA total of 170 pediatric patients (1-14 years) were enrolled, including 120 MPP cases and 50 non-MPP controls. Serum levels of P2X7, NLRP3, IL-1{beta}, and IL-18 were measured by ELISA. Routine laboratory markers (CRP, LDH, D-dimer, and IgE) were evaluated for their association with severe MPP (sMPP). Pathway enrichment and STRING network analyses were performed to contextualize the clinical markers within inflammation-related molecular pathways. ROC curve analysis was used to assess the predictive value of individual biomarkers. ResultsMultivariate logistic regression identified CRP, LDH, D-dimer, and IgE as independent risk factors for sMPP (p<0.05). Pathway enrichment revealed these markers to be involved in acute-phase response, coagulation, cytokine signaling, and immune regulation. STRING network analysis further demonstrated their convergence on the NLRP3 inflammasome axis. Serum levels of P2X7, NLRP3, IL-1{beta}, and IL-18 were significantly elevated in sMPP cases compared to non-severe MPP and controls (p<0.001). ROC analysis showed all four had strong predictive performance (AUC > 0.7, p<0.001). ConclusionThis study confirms that elevated levels of CRP, LDH, D-dimer, and IgE are independently associated with severe Mycoplasma pneumoniae pneumonia (sMPP), reflecting systemic inflammation, tissue injury, and immune dysregulation. Importantly, the concurrent upregulation of P2X7, NLRP3, IL-1{beta}, and IL-18 in serum, supported by pathway enrichment and STRING network analyses, highlights a central role for inflammasome activation in sMPP pathogenesis. ROC curve analysis further demonstrated the strong predictive value of these inflammasome-related proteins. Collectively, these findings suggest that P2X7, NLRP3, IL-1{beta}, and IL-18, in combination with conventional markers such as CRP, LDH, D-dimer, and IgE, may serve as valuable biomarkers for the early identification and risk stratification of children at risk for severe MPP, thereby enhancing diagnostic precision and informing clinical decision-making.

BackgroundWith the rise of the COVID-19 pandemic, a new severe life-threatening inflammatory syndrome has been reported in some pediatric populations. Global attention was shifted towards the syndrome termed multisystem inflammatory syndrome in children (MIS-C), with new case reports flooding in. ObjectivesThe aim of this scoping review is to summarize the existing reports on MIS-C and focus on the demographics, diagnosis, clinical presentation, laboratory investigations, imaging studies, treatment, and patient outcomes. MethodsWe conducted a systemic search using LitCovid and MEDLINE electronic databases. We screened citations, titles and abstracts, then reviewed potentially relevant articles in full. After data extraction, we reported our final data under subheadings of demographics, diagnosis, clinical presentation, laboratory investigations, imaging studies, treatment, and patient outcomes. ResultsOur search strategy yielded 42 original studies reporting 674 pediatric patients fitting the case definition of MIS-C. The studies included 21 case reports, 16 case series and 5 cohort studies. The most common reported symptom of MIS-C was fever (98%). Gastrointestinal symptoms were common (N=557, 83%). Interleukin-6 (IL-6) levels were measured in 125 patients and was elevated in 94 % (N=117). Echocardiography detected coronary artery lesions in 100 patients. Prophylactic and/or therapeutic heparin was required in 34% (N=227) of patients. The most commonly administered treatment modality targeting MIS-C was intravenous immunoglobulin (IVIG) (N=490). Corticosteroids (N=347) and aspirin (N=112) were also integral parts of the treatment regimens. Biologic therapy was integrated into the treatment regimen for 116 patients. Intensive care unit (ICU) admission was alarming (N=478, 71%). 9 fatalities were recorded due to MIS-C ConclusionsWe believe MIS-C bears pathophysiological resemblance to the well-known Kawasaki disease but with some key differences highlighted. Understanding those differences will aid our management plan for such patients.

Reducing procedural discomfort for children requiring respiratory testing for SARS-CoV-2 is important in supporting testing strategies for case identification. Alternative sampling methods to nose and throat swabs, which can be self-collected, may reduce laboratory-based testing requirements and provide rapid results for clearance to attend school or hospital settings. The aim of this study was to compare preference and diagnostic sensitivity of a novel anterior nasal swab (ANS), and saliva, with a standard combined nose and throat (CTN) swab. The three samples were self-collected by children aged 5-18 years who had COVID-19 or were a household close contact. Samples were analysed by reverse transcription polymerase chain reaction (RT-PCR) on the Allplex SARS-CoV-2 Assay. Most children and parents preferred the ANS and saliva swab over the CTN swab for future testing. The ANS was highly sensitive (sensitivity 1.000 (95% Confidence Interval (CI) 0.920, 1.000)) for SARS-CoV-2 detection, compared to saliva (sensitivity 0.886, 95% CI 0.754, 0.962). We conclude the novel ANS is a highly sensitive and more comfortable method for SARS-CoV-2 detection when compared to CTN swab.

Data from adult studies how that COVID-19 is more severe in men than women. However, no data are available for the pediatric population. For this reason, we performed this study aiming to understand if sex influenced disease severity and outcomes in a large cohort of latin-american children with COVID-19 and Multisystem Inflammatory Syndrome (MIS-C). We found that a higher percentage of male children developed MIS-C (8.9% vs 5% in females) and died (1.2% and 0.4% in females), although on multivariate adjusted analyses the only statistically significant difference was found in need of hospitalization, with females less frequently admitted compared with boys (25.6% vs 35.4%). This data are preliminary and need further independent studies to better assess the role of sex.

Purposeto describe lung mechanics in Pediatric Acute Respiratory Disease Syndrome (PARDS) associated with COVID-19. We hypothesize two phenotypes according to respiratory system mechanics and clinical diagnosis. Methodsa concurrent multicenter observational study was performed, analyzing clinical variables and pulmonary mechanics of PARDS associated with COVID-19 in 4 Pediatric intensive care units (PICUs) of Peru. Subgroup analysis included PARDS associated with multisystem inflammatory syndrome in children (MIS-C), MIS-PARDS, and PARDS with COVID-19 primary respiratory infection, C-PARDS. In addition, receiver operator curve analysis (ROC) for mortality was performed. Results30 patients were included. Age was 7.5(4-11) years, 60% male, and mortality 23%. 47% corresponded to MIS-PARDS and 53% to C-PARDS phenotypes. C-PARDS had positive RT-PCR in 67% and MIS-PARDS none (p<0.001). C-PARDS group had more profound hypoxemia (P/Fratio<100, 86%vs38%,p<0.01) and higher driving-pressure (DP) [14(10-22)vs10(10-12)cmH2O], and lower compliance of the respiratory system (CRS)[0.5(0.3-0.6)vs 0.7(0.6-0.8)ml/kg/cmH2O] compared to MIS-PARDS (all p<0.05). ROC-analysis for mortality showed that DP had the best performance [AUC 0.91(95%CI0.81-1.00), with the best cut-point of 15 cmH2O (100% sensitivity and 87% of specificity). Mortality in C-PARDS was 38% and 7% in MIS-PARDS(p=0.09). MV free-days were 12(0-23) in C-PARDS and 23(21-25) in MIS-PARDS(p=0.02) Conclusioncritical pediatric COVID-19 is heterogeneous in children. COVID-19 PARDS had two phenotypes with distinctive pulmonary mechanics features. Characteristics of C-PARDS are like a classic primary PARDS, while a decoupling between compliance and hypoxemia was more frequent in MIS-PARDS. In addition, C-PARDS had fewer MV free-days. DP [&ge;] 15 cmH2O had the best performance of the quasi-static calculations to discriminate for mortality. Standardized pulmonary mechanics measurements in PARDS might reveal essential information to tailor the ventilatory strategy in pediatric critical COVID-19. Take-home messageO_LIPARDS associated with COVID-19 have two different phenotypes based on clinical diagnosis and pulmonary mechanics. C_LIO_LIC-PARDS group was characterized as a classic moderate to severe primary ARDS. A decoupling between compliance and hypoxemia was more frequent in MIS-PARDS. Regarding outcomes, C-PARDS had less VFD and a trend toward higher mortality. C_LIO_LIData from the quasi-static calculations were associated with mortality; DP[&ge;] 15 cmH2O was the best discriminator. C_LIO_LIStandardized pulmonary mechanics measurements in PARDS might reveal essential information to tailor the ventilatory strategy, characterizing different phenotypes and parameters associated with outcomes. C_LI TweetLung mechanics help to differentiate two different phenotypes in PARDS associated with COVID-19. C-PARDS associated with respiratory infection, and MIS-PARDS, associated with MIS-C. Also, lung mechanics variables were associated with mortality, being DP [&ge;] 15 cmH2O the best discriminator.

BackgroundDespite the growing literature on multisystem inflammatory syndrome in children (MIS-C), the data in European White population is limited. Our aim was to capture MIS-C emergence in Poland (central Europe) and to describe its characteristics with a focus on severity determinants. MethodsPatients who met the MIS-C definition (fever, multiorgan failure, inflammation, and proven SARS-CoV-2 infection or contact) were reported retrospectively and prospectively in an online survey. Study definitions fulfilment was automatically evaluated by a dedicated software. For the assessment of univariate relationships, either directed or divided by sex, age, or disease severity, we used the test for two categorical variables and the Kruskal-Wallis test for categorical-continuous variable pairs. FindingsThe analysis involved 274 children, 62.8% boys, median age 8.8 years. Besides one Asian, all were European White. Merely 23 (8.4%) required paediatric intensive care treatment (PICU). They were older (11.2 vs. 8.4 years), and at hospital admission had higher respiratory rate (30 v. 20/minute), lower systolic blood pressure (89 vs. 100 mmHg), prolonged capillary refill time (40% vs. 11%), and decreased consciousness (22% vs. 5%). Teenage boys had more common cardiac involvement (fraction 25.9% vs. 14.7%) and macrophage activation syndrome (31.0% vs. 15.2%) than others. Boys were also more often hospitalised in PICU with age (from median 11.2 years to 9.1). InterpretationThe severity of MIS-C is not as uniform as it seemed, ethnicity and sex may affect MIS-C phenotype. Management might not be universally applicable and should rather be adjusted to the specific population. FundingPSP: 501-D402-20-0006100

Abstract Background: Pediatric respiratory infections are a leading cause of morbidity and mortality globally, representing a major health challenge in children. Research Gap: Despite extensive studies on epidemiology, clinical management, and specific pathogens, no bibliometric analysis has systematically evaluated the most influential research in this field. Objectives: This study aimed to evaluate the characteristics of the top 50 most-cited articles on pediatric respiratory infections and to identify emerging research trends. Methods: The Web of Science database was searched without publication year restrictions. Independent reviewers screened studies based on predefined inclusion and exclusion criteria. Data were extracted using a standardized form, including study details. Results: The 50 most-cited articles ranged from 34 to 384 citations and showed a right-skewed distribution with a sharp drop after the top ten. Publication years ranged from 1978 to 2021, with over half published in the 2010s. Articles appeared in 31 journals, with Pediatrics contributing five. Leading countries were the United States (18%), China (12%), and Canada (10%), with research largely concentrated in high-income regions and limited multicenter collaboration. Cohort studies dominated (66%), while randomized trials (12%) and reviews/meta-analyses (16%) were less common. Research clustered around three themes: clinical outcomes (e.g., pneumonia, bronchiolitis); viral etiology/diagnostics (e.g., RSV, SARS-CoV-2); and antimicrobial stewardship. Conclusion: Over the past decades, pediatric respiratory infection research has developed but remains unbalanced, relying heavily on observational evidence from high-income countries, with limited randomized trials, systematic reviews, multicenter collaborations, and LMIC-led studies. These findings provide insights that may direct researchers to identify potential focal points and guide future research in the field.

BACKGROUNDEstimates of pediatric morbidity and mortality from COVID-19 are vital for planning optimal use of human and material resources throughout this pandemic. METHODSGovernment websites from countries with minimum 1000 cases in adults and children on April 13, 2020 were searched to find the number of cases confirmed in children, the age range, and the number leading to hospitalization, intensive care unit (ICU) admission or death. A systematic literature search was performed April 13, 2020 to find additional data from cases series. RESULTSData on pediatric cases were available from government websites for 23 of the 70 countries with minimum 1000 cases by April 13, 2020. Of 424 978 cases in these 23 countries, 8113 (1.9%) occurred in children. Nine publications provided data from 4251 cases in 4 additional countries. Combining data from the websites and the publications, 330 of 2361 cases required admission (14%). The ICU admission rate was 2.2 % of confirmed cases (44 of 2031) and 7.2% of admitted children (23 of 318). Death was reported for 15 cases. CONCLUSIONChildren accounted for 1.9% of confirmed cases. The true incidence of pediatric infection and disease will only be known once testing is expanded to individuals with less severe or no symptoms. Admission rates vary from 0.3 to 10% of confirmed cases (presumably varying with the threshold for testing) with about 7% of admitted children requiring ICU care. Death is rare in middle and high income countries.

BackgroundThe World Health Organization (WHO) has developed danger signs (DS) to help front-line health workers triage interventions in children with severe illnesses. Our objective was to evaluate the extent to which DS predict bacterial sepsis in young infants presenting with acute illness. Methodology/Principal FindingsThis prospective study evaluated nine DS in infants younger than 3 months with suspected sepsis in a large regional hospital in Lilongwe, Malawi, between June 2018 and April 2020. The main outcomes were positive blood or cerebrospinal fluid (CSF) cultures and mortality. Blood (n=85/401) and CSF (n=2/204) cultures were positive in 21.2% and 1% of infants, respectively (N=401; gestational age mean {+/-} SD: 37.1{+/-}3.3 weeks, birth weight 2865{+/-}785 grams). In-hospital deaths occurred in 9.7% (N=39/401) of infants (61.5% within 48h of admission). In univariate analyses, all DS were associated with mortality except for temperature instability and tachypnea, whereas "infant was unable to feed" was the only DS significantly associated with bacterial sepsis. After co-variable adjustments, number of DS predicted mortality (OR: 1.75; 95%CI: 1.43-2.16; p<0.001; AUC-ROC: 0.756) but not positive cultures (OR 1.08; 95%CI: 0.92-1.30; p=0.336). Whether potential bacterial contaminants were included or not did not change results meaningfully. Conclusion/SignificanceDS predicted fatal outcomes but not positive cultures in a large regional hospital setting. These data imply that the incidence of bacterial sepsis and attributable mortality are unlikely to be accurate based on clinical signs alone, in infants in LMIC settings.

ObjectiveThis scoping review aims to assess the evidence regarding miRNA associations with paediatric bacterial and viral infections. IntroductionFebrile children present a challenge in emergency care, often leading to unnecessary antibiotics due to difficulty distinguishing bacterial from viral infections. Current biomarkers lack specificity, contributing to diagnostic uncertainty and antimicrobial resistance. MicroRNAs (miRNAs), detectable in blood and responsive to disease, show promise as improved biomarkers, but their role in infection differentiation remains unclear. This scoping review aims to map known miRNA associations with paediatric infections and evaluates study methodologies to identify the best approaches for miRNA-based diagnostics. Inclusion criteriaStudies reporting on children under 18 years of age with acute bacterial or viral infections will be included. Articles must focus on host miRNA biomarkers in biofluids. Exclusions include chronic infections, parasitic infections, fungal infections, sexually transmitted infections, animal models, in vitro, tissue samples, and in silico studies. MethodsThe databases to be searched will include MEDLINE and Web of Science with an additional for grey literature search via Google, Google Scholar, and open Theses restricted to the English language. Titles and abstracts will be screened, and eligible articles will undergo full-text review. The results of the search and study inclusion/exclusion process will be reported. Reasons for exclusion during the full text review are presented in the PRISMA-ScR flow diagram. Data will be extracted into a chart, analysed as percentages to assess consensus, and summarized in descriptive text with tables.

IntroductionThe burden of morbidity and mortality from severe pneumonia remains high among children under five, particularly in resource-limited countries such as Burkina Faso. Targeted hospital-based interventions are essential to achieve Sustainable Development Goal 3.2, which aims to reduce under-five mortality to 25 deaths per 1,000 live births by 2030. MethodsA prospective cohort study was conducted in the pediatrics department of Regional Referral Hospital of Banfora, including 1,406 children aged 2-59 months hospitalized for severe pneumonia between August 2021 and January 2024. Predictors of mortality were identified using the Fine and Gray competing risk model. ResultsA total of 1,406 children were included in the analysis. The median age was 18 months (interquartile range: 9-32 months), and 53% were male. During hospitalization, 8.96% (126/1,406; 95% CI: 7.58-10.57) died, corresponding to a mortality rate of 1.93 per 100 person-days. Age < 12 months doubled the instantaneous risk of death. Additionally, hypoxemia (SaO2 < 90%) (adjusted subdistribution hazard ratio [aSHR]: 1.54; 95% CI: 1.02-2.32), hospitalization during the rainy season (aSHR: 1.73; 95% CI: 1.18-2.54), convulsions (aSHR: 2.93; 95% CI: 1.92-4.47), the presence of stridor (aSHR: 2.17; 95% CI: 1.46-3.22), and hypoglycemia (aSHR: 2.37; 95% CI: 1.45-3.88) increased the risk of death. However, the risk of death was significantly lower in children with moderate or severe anaemia (respectively aSHR = 0.45; 95% CI: 0.24 - 0.84 and aSHR = 0.26; 95% CI: 0.13 - 0.52) and having received antibiotic therapy (ceftriaxone alone [SHRa = 0.52; 95% CI: 0.30 - 0.90] or combined with gentamicin (SHRa = 0.45; 95% CI: 0.30-0.69); ampicillin [aSHR = 0,35; IC95%: 0,13-0,97] and ampicillin combined with gentamicin (SHRa = 0.43; CI: 0.20 - 0.95). ConclusionThe incidence and in-hospital mortality of severe pneumonia are a cause for concern at the Regional Referral Hospital of Banfora and in Burkina Faso. Targeted interventions in hospital settings are necessary and can help achieve Sustainable Development Goal 3.2 on reducing under-five mortality to 25 deaths per 1,000 live births by 2030.

IntroductionCOVID 19 is still a challenge in pediatrics due to variety of symptoms and different presentations AimTo describe clinical, laboratorial and treatment of confirmed COVID-19 pediatric admitted in hospitals. MethodsA retrospective study was conducted in children (0-18 years), admitted between March and November 15, 2020, with confirmed COVID-19 by reverse transcription polymerase chain reaction or serological tests. Clinical data about symptoms, laboratorial exams and treatments were analysed. Patients were evaluated according predominant (PRS) or non-predominant respiratory symptoms (non-PRS) ResultsSixty-four patients were evaluated, being the median age 5.6 years. Forty-seven (73.4%) children were admitted with PRS and 17 (26.4%) with non-PRS. The main symptoms in the PRS group were fever in 74.5% of children and cough in 66%; and fever in 76.5% and edema/cavitary effusion in 29.4% in the non-PRS group. The median of C-reactive protein (in mg/dl) was 2.5 in the PRS group and 6.1 in the non-PRS group. Antibiotics were used in 85.1% of the PRS group and 94.1% of non-group. Comorbidity was present in 30/47 (63.8%) of PRS group and 8/17 (47.1%) of non-PRS group (p=0.22). Length of stay until 7 days in patients with comorbidity was present in 27/64 (42.1%) and more than 7 days in 11/64 (17.1%) (p= 0.2) ConclusionNon-PRS represented more than one quarter of admitted patients. Fever was the main symptom detected, elevated CRP was frequent and antibiotics were commonly prescribed. Comorbidity was found in both groups and his presence was not associated with a longer length of stay.

INTRODUCTIONInfants, especially neonates, present with jaundice with an unclear association with urinary tract infection. Evidence for such association is unclear, especially in a specific group of otherwise well-appearing infants born > 35 weeks. EVIDENCE ACQUISITIONO_ST_ABSData sourcesC_ST_ABSWe used the following databases: Medline, Embase, CINAHL Plus, Scopus, and Cochrane library. Study selectionWe included observational studies that included infants born > 35 weeks gestation, younger than 12 months, asymptomatic other than jaundice, and urinary tract infection. Data extraction: After reviewing the eligibility, two reviewers extracted data and assessed the quality of each study using the Newcastle-Ottawa scale. EVIDENCE SYNTHESISWe analyzed sixteen studies for a total of 2933 infants. The pooled incidence of UTI was 9.6% (95% confidence interval of 6% to 15%). The subgroup analysis failed to show any difference in incidence within the publication year, sample size, study design, study region, urine collection method, and age group. There was no explanation of heterogeneity noted by the meta-regression for UTI incidence with publication year, total bilirubin, sample size, and study quality. The funnel plot and Eggers test revealed publication bias. CONCLUSIONSNearly 1 in 10 otherwise asymptomatic infants with jaundice have a UTI. We recommend a rigorous large prospective study to confirm this finding.

BackgroundBabies born to mothers with active tuberculosis disease (ATB) are at risk of poor clinical outcomes such as low birth weight and perinatal mortality. However, little is known about the influence of maternal ATB exposure on their vaccine responses during infancy. The study aimed to explore how maternal ATB affects infants vaccine responses, hypothesising reduced responses to BCG and other infant vaccines. MethodsThis was a case-control study with a longitudinal component of babies born to mothers with bacteriologically confirmed ATB (cases) and babies born to mothers without ATB (controls) carried out between September 2021 and June 2022. Quantitative BCG, diphtheria, tetanus, and measles-specific IgG ELISA assays were performed on infant plasma harvested from lithium-heparin blood collected on first encounter after birth (0), at 3, 6, and 9 months. We used prism v10.1.2, Mixed-effects modelling, and Tukeys multiple comparison testing to determine mean differences (MD) between the cases and controls at all time points. ResultsInfants cases had reduced IgG titres to BCG at baseline compared to the controls (p=0.04), with a mean of 125.8/141.1 IU/mL, respectively. This difference was, however, not sustained at the other time points. Similarly, we demonstrated strong trends of reduced responses to tetanus, diphtheria, and measles vaccines among infant cases at baseline and three-month time points and weakly at months six and nine. The mean titres for tetanus at baseline and 3 months for cases versus controls are 1.744/2.917 IU/mL and 1.716/2.344 IU/mL (p<0.0001/0.018), respectively. The mean titres for diphtheria at 3 months were 0.022/0.075 IU/mL (p=0.006), respectively. ConclusionWe have demonstrated that maternal TB disease influences vaccine responses to BCG and other infant vaccines. This has implications for increased risk of childhood TB and other preventable diseases.

BackgroundNunavut is a northern Canadian territory in Inuit Nunangat (Inuit homeland in Canada). Approximately 85% of the population identifies as Inuit. A high proportion of infants in Nunavut are admitted to hospital with acute respiratory tract infection (ARI) but previous studies have been limited in regional and/or short duration of coverage. This study aimed to estimate the incidence rate, microbiology and outcomes of ARI hospitalizations in Nunavut infants. MethodsWe conducted chart reviews with a retrospective cohort of infants aged <1 year from Nunavut at six Canadian hospitals, including two regional and four tertiary pediatric hospitals January 1, 2010, to June 30, 2020. Descriptive statistics and multivariable logistic regression were performed. ResultsWe identified 1189 ARI admissions of infants during the study period, with an incidence rate of 133.9 per 1000 infants per year (95% confidence interval (CI): 126.8, 141.3). Of these admissions, 56.0% (n=666) were to regional hospitals alone, 72.3% (n=860) involved hospitalization outside of Nunavut, 15.6% (n=185) were admitted into intensive care, and 9.2% (n=109) underwent mechanical ventilation. Of the 730 admissions with a pathogen identified, 45.8% had respiratory syncytial virus (RSV; n=334), for a yearly incidence rate of 37.8 hospitalizations per 1000 infants (95% CI: 33.9, 42.1). Among RSV hospitalizations, 41.1% (n=138) were infants 0-2 months of age and 32.1% (n=108) were > 6months. InterpretationUnderstanding the high burden of ARI among Nunavut infants can inform health policy and serve as a baseline for assessing the impact of any new interventions targeting infant ARIs.

ObjectivesTo understand the international epidemiology of critical pediatric COVID-19 and compare presentation, treatments, and outcomes of younger (<2 years) and older (>2 years) children. DesignProspective, observational study from April 1 to December 31, 2020 SettingInternational multicenter study from 55 sites from North America, Latin America, and Europe. ParticipantsPatients <19 years old hospitalized with critical COVID-19 Interventionsnone Main outcomes measuredClinical course, treatments, and outcomes were compared between younger and older children. Multivariable logistic regression was used to calculate adjusted odds ratios (aOR) for hospital mortality. Results557 subjects (median age, 8 years; 24% <2 years) were enrolled from 55 sites (63% Latin American). Half had comorbidities. Younger children had more respiratory findings (56% vs 44%), viral pneumonia (45% vs 29%), and treatment with invasive ventilation (50% vs 37). Gastrointestinal (28% vs 69%) or mucocutaneous (16% vs 44%) findings, vasopressor requirement (44% vs 60%), and MIS-C (15% vs 40%) were less common in younger children. Hospital mortality was 10% overall but 15% in younger children (odds ratio 1.89 [95%CI 1.05-3.39]). When adjusted for age, sex, region, and illness severity, mortality-associated factors included cardiac (aOR 2.6; 95%CI 1.07-6.31) or pulmonary comorbidities (aOR 4.4; 95%CI 1.68-11.5), admission hypoxemia (aOR 2.33; 95%CI 1.24-4.37), and lower respiratory symptoms (aOR 2.83; 95%CI 1.49-5.39). Gastrointestinal (aOR 0.49; 95%CI 0.26-0.92) or mucocutaneous symptoms (aOR 0.31; 95%CI 0.15-0.64), treatment with intravenous immune globulin (aOR 0.33; 95%CI 0.17-0.65), and MIS-C (aOR 0.26; 95%CI 0.11-0.64) were associated with lower mortality. ConclusionsWe identified age-related differences in presentation and mortality for critical pediatric COVID-19 that should prompt more attention to improving management in younger children, especially in developing countries. Table of Contents SummaryThis is a multinational study describing critical pediatric COVID-19 clinical spectrum and related mortality in high and low-middle income countries during 2020. Whats known on this subjectPediatric critical illness due to COVID-19 is uncommon and have lower mortality compared to adults when hospitalized. While larger cohorts are from high-income countries (HICs), studies including data from low-middle-income countries (LMICs) remain scarce. What this study addsIn our multinational cohort of critical pediatric COVID-19, we identified higher mortality than previously reported and age-related disease patterns. Children <2 years old had more respiratory disease and higher mortality, and older children had more non-pulmonary disease and better outcomes.

BackgroundThe COVID-19 pandemic affected Respiratory Syncytial Virus (RSV) circulation and surveillance, causing logistical complexity for health systems. Our objective was to describe changes in epidemiology and clinical severity of RSV cases in British Columbia, Canada. MethodsComparative analysis of RSV detections in children <36 months at BC Childrens Hospital (BCCH) between September 1 and August 31 of 2017-18, 2018-19, 2019-20, 2020-21 and 2021-22. ResultsAbout one-fifth of children tested RSV positive on average across all periods. The median age of RSV cases was 11.8 [IQR: 3.8-22.3] months in 2021-22 versus 6.3 [IQR: 1.9-16.7] months in 2017-20 (p<0.001). Increased testing in 2021-22 (n=3,120) compared to 2017-20 (average n=1,222/period) detected milder infections with lower proportion hospitalized in all age subgroups <6 (26.0%), 6-11 (12.3%), 12-23 (12.2%) and 24-35 (16.0%) months versus 2017-20 (49.3%, 53.5%, 62.6%, 57.5%, respectively) (all p<0.001). Children <6 months consistently comprised most hospitalizations and those born prematurely <29 weeks or with chronic respiratory co-morbidities remained at highest hospitalization risk in 2021-22. Among hospitalized cases, intensive care, respiratory support or supplemental oxygen use did not differ between the 2017-20 and 2021-22 periods. ConclusionsRSV circulation halted during the pandemic, but with the lifting of mitigation measures a subsequent resurgence in children <36 months of age was accompanied by shift toward older (24-35 month) cases in 2021-22, without increased severity. For the 2022-23 period, increased circulation and residual vulnerability in additional birth cohorts spared from RSV infection during the pandemic could have marked cumulative healthcare impact, even without increase in proportion hospitalized.

BackgroundThe soluble form of the urokinase plasminogen activator receptor (SuPAR) is a potential biomarker in various inflammatory, infectious, and autoimmune conditions. ObjectivesIn this stusy, we aimed to evaluate its diagnostic utility in febrile children to distinguish between Kawasaki disease (KD) and infections, and to investigate any association with the development of coronary artery aneurysms (CAA) KD. MethodsIn this retrospective observational cohort study we enrolled 17 children with fever lasting more than 5 days and without suggestive diagnostic signs on admission to hospital. Serum SuPAR concentrations were measured on admission and compared between children with confirmed KD and those with infections, as well as between children with KD who did or did not develop CAA. ResultsKD was later confirmed in seven children (median age 25 months), and febrile infections in 10. There was no significant difference in suPAR concentrations between both groups: 5.35 {+/-} 2.76 ng/mL in KD, and 5.57 {+/-} 1.69 ng/mL in febrile infections (p=0.84). The best cut-off value for suPAR, [&ge;] 7.74 ng/mL, was the best to correctly classify 64.7% of the cases, with a sensitivity of 28.6% and specificity of 90%. However, it had a low diagnostic performance (Youden index 18.6%, area under the curve curve 60%), and therefore failed to differentiate between KD and infections. In the seven children with KD, only one child developed CAA (SuPAR 4.69 ng/mL) while six other did not (SuPAR 5.47 {+/-} 1.04 ng/mL) but the statistical significance could not be computed. ConclusionIn febrile children, serum suPAR concentrations failed to distinguish between KD and infections, and were not associated with the development of CAA in KD. Therefore, SuPAR is not a useful biomarker in the diagnosis or prognosis of KD.

BackgroundImmunizing infants with various vaccines, including Bacillus Calmette-Guerin (BCG), Diphtheria-Pertusis-Tetanus (DPT), and measles, aims to enhance immunity. In instances where vaccine responses have been reported to be compromised, individuals are prone to infection. The BCG vaccine, for example, induces strong type 1 immune responses, particularly interferon-gamma (IFN-{gamma}) expression, that are essential for protection against Mycobacterium tuberculosis (Mtb). However, there is scanty evidence on whether this effect is established or sustained when infants are exposed to Mtb either in utero or after birth. We compared TB-specific cytokine responses for IFN-{gamma}, interleukin (IL)-2 (IL-2), tumour necrosis factor-alpha (TNF-), IL-17A, and Granulocyte-macrophage colony-stimulating factor (GM-CSF) using supernatants harvested from QFT-Plus Blood Collection Tubes. MethodsThis cross-sectional study compared 22 infants born to mothers with bacteriologically confirmed active tuberculosis (TB), defined as TB exposed or cases, to 20 infants born to mothers without active TB, defined as TB non-exposed or controls. Plasma harvested from the QFT-plus tubes (TB1 and TB2) was used to perform a 5-plex Luminex assay using the LX 100/200 Luminex machine and measured in pg/mL. Data was analysed using R (v.4.4.1). The Mann-Whitney U test was used to determine statistical significance at a p-value less than 0.05 and a 95% confidence interval. Data was expressed as median and interquartile ranges (IQR). ResultsTB-exposed infants showed IFN{gamma} responses were slightly higher among TB-exposed infants compared to non-exposed (Medians (IQR): 15.49 (14.58-16.49) versus 14.96 (14.60-16.60), p=0.68, respectively. There was a strong expression of total IL-17A among TB-exposed compared to non-exposed 11.91 (10.89-13.50) versus 10.69 (10.17-11.64), p=0.035. We observed no differences in IL-2, TNF, and GM-CSF responses. ConclusionTB exposure among infants slightly alters their Mtb-specific cytokine responses, especially IL-17A cytokine responses. This suggests possible ongoing Mtb infection among TB-exposed infants. Follow-up studies of such infants are necessary to assess their risk of future TB infection and disease and the potential need for TB chemoprophylaxis.