Age-specific predictors of disease severity in children with respiratory syncytial virus infection beyond infancy and through the first 5 years of age.

BACKGROUND: Respiratory syncytial virus (RSV) infection is associated with significant morbidity in infants. Risk factors for severe disease beyond the first 2 years of life have not been fully defined. METHODS: Children <5 years hospitalized with virologically confirmed RSV infection were identified over six respiratory seasons (10/2012-4/2018) and their medical records manually reviewed. Multivariable analyses were performed to define the age-specific (<6, 6-24, and >24-59 months) risk factors associated with oxygen administration, PICU admission, mechanical ventilation, and duration of hospitalization. RESULTS: We identified 5143 children hospitalized with RSV infection: 53.5% (n = 2749) <6 months; 31.7% (n = 1631) 6-24 months; and 14.8% (n = 763) >24-59 months. Rates of ICU admission were high (35%-36%) and comparable across age groups, while children >24-59 and 6-24 versus those <6 months required supplemental oxygen more frequently (73%; 71%; 68%, respectively; p = .003). The presence of comorbidities increased with age (25%, <6 months; 46%, 6-24 months; 70%, >24-59 months; p < .001). Specifically, neuromuscular disorders, chronic lung disease, and reactive airway disease/asthma were predictive of worse clinical outcomes in children aged 6-24 and >24-59 months, while RSV-viral codetections increased the risk of severe outcomes in children aged <6 and 6-24 months of age. CONCLUSIONS: Almost half of children hospitalized with RSV infection were >6 months. Underlying comorbidities increased with age and remained associated with severe disease in older children, while RSV-viral codetections were predictive of worse clinical outcomes in the youngest age groups. These data suggest the importance of defining the clinical phenotype associated with severe RSV according to age, and the persistent burden associated with RSV beyond infancy.

Use of Antibiotics following Snakebite in the Era of Antimicrobial Stewardship.

Even though there are guidelines for the management of snakebite envenoming (SBE), the use of antibiotics in this pathology remains controversial. The aim of this study is to provide a narrative review of the literature and recommendations based on the best available evidence regarding antibiotic use in SBE. We performed a narrative review of relevant literature regarding SBE and antibiotic use as prophylaxis or treatment. A total of 26 articles were included. There is wide use of antibiotics in SBE; nevertheless, infection was not necessarily documented. The antibiotics used varied according to the study, from beta lactams to lincosamide and nitroimidazoles, and from monotherapy to combined antimicrobials. The most common recommendations were to manage skin and soft tissue infections and avoid infectious complications, but these suggestions are not necessarily based on bacteriological findings. Prophylactic use of antibiotics in SBE is discouraged in most studies. Antibiotic prescription in SBE should be based on the susceptibility of microorganisms isolated from the affected tissue or identified in snakes' oral cavities. Antibiotics should be reserved only for patients with a demonstrated infection, or those at a high risk of developing an infection, i.e., presenting severe local envenoming, local signs of infection, or those with incorrect manipulation of wounds. Prospective studies are needed to correlate microbiological findings at the wound site and the response to antibiotic use.

Neurological involvement in hospitalized children with SARS-CoV-2 infection: a multinational study.

BACKGROUND AND OBJECTIVES: Neurological involvement associated with SARS-CoV-2 infection is increasingly recognized. However, the specific characteristics and prevalence in pediatric patients remain unclear. The objective of this study was to describe the neurological involvement in a multinational cohort of hospitalized pediatric patients with SARS-CoV-2. METHODS: This was a multicenter observational study of children <18 years of age with confirmed SARS-CoV-2 infection or multisystemic inflammatory syndrome (MIS-C) and laboratory evidence of SARS-CoV-2 infection in children, admitted to 15 tertiary hospitals/healthcare centers in Canada, Costa Rica, and Iran February 2020-May 2021. Descriptive statistical analyses were performed and logistic regression was used to identify factors associated with neurological involvement. RESULTS: One-hundred forty-seven (21%) of 697 hospitalized children with SARS-CoV-2 infection had neurological signs/symptoms. Headache (n = 103), encephalopathy (n = 28), and seizures (n = 30) were the most reported. Neurological signs/symptoms were significantly associated with ICU admission (OR: 1.71, 95% CI: 1.15-2.55; p = 0.008), satisfaction of MIS-C criteria (OR: 3.71, 95% CI: 2.46-5.59; p < 0.001), fever during hospitalization (OR: 2.15, 95% CI: 1.46-3.15; p < 0.001), and gastrointestinal involvement (OR: 2.31, 95% CI: 1.58-3.40; p < 0.001). Non-headache neurological manifestations were significantly associated with ICU admission (OR: 1.92, 95% CI: 1.08-3.42; p = 0.026), underlying neurological disorders (OR: 2.98, 95% CI: 1.49-5.97, p = 0.002), and a history of fever prior to hospital admission (OR: 2.76, 95% CI: 1.58-4.82; p < 0.001). DISCUSSION: In this study, approximately 21% of hospitalized children with SARS-CoV-2 infection had neurological signs/symptoms. Future studies should focus on pathogenesis and long-term outcomes in these children.

Trends in Age and Disease Severity in Children Hospitalized With RSV Infection Before and During the COVID-19 Pandemic.

This cohort study evaluates respiratory syncytial virus (RSV)­related hospitalizations and disease severity from 2012 to 2023 in children younger than 5 years.

SARS-CoV-2 infection in technology-dependent children: a multicenter case series.

PURPOSE: The objective of this study was to describe the clinical course and outcomes in children with technology dependence (TD) hospitalized with SARS-CoV-2 infection. METHODS: Seventeen pediatric hospitals (15 Canadian and one each in Iran and Costa Rica) included children up to 17 years of age admitted February 1, 2020, through May 31, 2021, with detection of SARS-CoV-2. For those with TD, data were collected on demographics, clinical course and outcome. RESULTS: Of 691 children entered in the database, 42 (6%) had TD of which 22 had feeding tube dependence only, 9 were on supplemental oxygen only, 3 had feeding tube dependence and were on supplemental oxygen, 2 had a tracheostomy but were not ventilated, 4 were on non-invasive ventilation, and 2 were on mechanical ventilation prior to admission. Three of 42 had incidental SARS-CoV-2 infection. Two with end-stage underlying conditions were transitioned to comfort care and died. Sixteen (43%) of the remaining 37 cases required increased respiratory support from baseline due to COVID-19 while 21 (57%) did not. All survivors were discharged home. CONCLUSION: Children with TD appear to have an increased risk of COVID-19 hospitalization. However, in the absence of end-stage chronic conditions, all survived to discharge.

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.

Thrombosis and hemorrhage experienced by hospitalized children with SARS-CoV-2 infection or MIS-C: Results of the PICNIC registry.

INTRODUCTION: Coagulopathy and thrombosis associated with SARS-CoV-2 infection are well defined in hospitalized adults and leads to adverse outcomes. Pediatric studies are limited. METHODS: An international multicentered (n = 15) retrospective registry collected information on the clinical manifestations of SARS-CoV-2 and multisystem inflammatory syndrome (MIS-C) in hospitalized children from February 1, 2020 through May 31, 2021. This sub-study focused on coagulopathy. Study variables included patient demographics, comorbidities, clinical presentation, hospital course, laboratory parameters, management, and outcomes. RESULTS: Nine hundred eighty-five children were enrolled, of which 915 (93%) had clinical information available; 385 (42%) had symptomatic SARS-CoV-2 infection, 288 had MIS-C (31.4%), and 242 (26.4%) had SARS-CoV-2 identified incidentally. Ten children (1%) experienced thrombosis, 16 (1.7%) experienced hemorrhage, and two (0.2%) experienced both thrombosis and hemorrhage. Significantly prevalent prothrombotic comorbidities included congenital heart disease (p-value .007), respiratory support (p-value .006), central venous catheter (CVC) (p = .04) in children with primary SARS-CoV-2 and in those with MIS-C included respiratory support (p-value .03), obesity (p-value .002), and cytokine storm (p = .012). Comorbidities prevalent in children with hemorrhage included age >10 years (p = .04), CVC (p = .03) in children with primary SARS-CoV-2 infection and in those with MIS-C encompassed thrombocytopenia (p = .001) and cytokine storm (p = .02). Eleven patients died (1.2%), with no deaths attributed to thrombosis or hemorrhage. CONCLUSION: Thrombosis and hemorrhage are uncommon events in children with SARS-CoV-2; largely experienced by those with pre-existing comorbidities. Understanding the complete spectrum of coagulopathy in children with SARS-CoV-2 infection requires ongoing research.

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.

Use of Meropenem in a Tertiary Pediatric Hospital in Costa Rica and Its Role in the Era of Antimicrobial Stewardship.

Background Understanding antibiotic profiles and their resistance patterns can improve hospital quality care and optimize clinical outcomes. This paper characterizes the use of meropenem in the National Children's Hospital of Caja Costarricense del Seguro Social (CCSS) in Costa Rica, and its role in antibiotic stewardship. Methods This is a retrospective observational study from hospitalized patients under 13 years of age that received meropenem as part of their treatment. Patients were identified through medical and pharmacy records. Data was summarized using frequencies and percentages for categorical variables, means and standard deviations for normally distributed continuous variables, and medians with interquartile ranges (IQR) for non-normally distributed continuous variables. Results A total of 181 of the 309 selected patients met inclusion criteria. Median age was 21 months (IQR: 4.0-79.0). Mean length of stay was 31 days (16.0-58.0). The most frequent diagnosis was septic shock (29%). 87% of patients received at least one antibiotic prior to receiving meropenem; 71% of patients received a second antibiotic simultaneously with meropenem. In 113 (62%) cases, meropenem was prescribed as empirical therapy. The most frequent isolate was extended-spectrum ß-lactamase Escherichia coli (24%). 74% of patients who received meropenem as targeted therapy had a favorable outcome. Conclusions Meropenem can be used as monotherapy for complicated, multi-drug resistant, gram negative, bacterial infections, due to its susceptibility profile, convenient dosing schedule, and minimum adverse effects. However, it should be restricted to cases where no other drug is available in order to safeguard its value.

Age-dependent Interactions Among Clinical Characteristics, Viral Loads and Disease Severity in Young Children With Respiratory Syncytial Virus Infection.

BACKGROUND: Age-dependent differences in clinical presentation and viral loads in infants and young children with respiratory syncytial virus (RSV) infection, and their correlation with disease severity are poorly defined. METHODS: Previously healthy children <2 years old with mild (outpatients) and severe (inpatients) RSV infection were enrolled and viral loads measured by polymerase chain reaction in nasopharyngeal swabs. Patients were stratified by age in 0-<3, 3-6 and >6-24 months, and multivariable analyses were performed to identify clinical and viral factors associated with severe disease. RESULTS: From 2014 to 2018, we enrolled 534 children with RSV infection, 130 outpatients with mild RSV infection and 404 inpatients with severe RSV disease. Median duration of illness was 4 days for both groups, yet viral loads were higher in outpatients than in inpatients (P < 0.001). In bivariate analyses, wheezing was more frequent in outpatients of older age (>3 months) than in inpatients (P < 0.01), while fever was more common in inpatients than outpatients (P < 0.01) and its frequency increased with age. Adjusted analyses confirmed that increased work of breathing and fever were consistently associated with hospitalization irrespective of age, while wheezing in infants >3 months, and higher RSV loads in children >6-24 months were independently associated with reduced disease severity. CONCLUSIONS: Age had a significant impact defining the interactions among viral loads, specific clinical manifestations and disease severity in children with RSV infection. These observations highlight the importance of patient stratification when evaluating interventions against RSV.

Long-term sequelae secondary to snakebite envenoming: a single centre retrospective study in a Costa Rican paediatric hospital.

OBJECTIVES: Although devastating acute effects associated with snake envenoming are well described, the long-term sequelae resulting from these envenomings have not been adequately addressed, especially in the paediatric population. The aim of our study is to describe the clinical characteristics among paediatric patients in Costa Rica who developed long-term sequelae secondary to snakebite envenoming. DESIGN: Retrospective descriptive study of paediatric patients under 13 years who were admitted with a history of a recent snakebite at the National Children's Hospital in Costa Rica from January 2001 to December 2014. RESULTS: We enrolled 74 patients admitted to our centre due to envenoming, and separated those who did not develop sequelae (50 patients) from those who did (24 patients). Of those who presented acute complications during hospitalisation, local wound infection and clinically diagnosed compartmental syndrome were significantly higher in the group that developed sequelae thereafter. Hypertrophic scars (66.7%), functional limitation of affected limb (37.5%) and the need of skin graft (37.5%) were the most common sequelae. The median follow-up of patients with long-term sequelae after discharge was 25.4 months (5.6-59.4). No deaths were reported during this time period. CONCLUSIONS: Given the high economic, personal and healthcare burden that entails follow-up of these patients, efforts should be carried out to prevent the factors associated with sequelae among the affected population.

Snakebite envenoming in children: A neglected tropical disease in a Costa Rican pediatric tertiary care center.

BACKGROUND: Introduced in June 2017 by the World Health Organization (WHO) as a Neglected Tropical Diseases, snakebite envenoming is a global health problem. In Costa Rica, an incidence of 15 per 100,000 inhabitants and a mortality rate of 0.15 per 100,000 inhabitants per year were reported from 2005-2012. Children are also affected and prone to complications. METHODS: Retrospective descriptive 14-year study of children with envenomings by Viperidae snakebites managed at the tertiary pediatric hospital in Costa Rica. FINDINGS: 80 patients (pts) were included and classified as having mild (17 pts, 29.3%), moderate (58 pts, 72.5%) or severe (5 pts, 6.2%) envenoming. 52/80 (65%) patients received treatment within the first four hours, three (3.75%) between 5-8 h, three between 9-12 h, four (4%) between 13-16 h, two (2.5%) between 17-20 h, and seven (8.75%) after 20 h. Edema was documented in 76/80 (95%), pain in 58 (72.5%), local bleeding in 23 (28.8%), emesis in 10 (12.5%), bullae formation in 8 (10%), and tissue necrosis in three (3.8%) pts. Complications presented according with degree of envenoming, being more common in severe cases: wound infection occurred in 14/58 (24.1%) with moderate envenoming and 5/5 pts with severe envenoming (p < 0.0001), bleeding presented in 3/58 (5.2%) with moderate cases, and 2/5 (40%) in pts with severe envenoming (p = 0.004); and compartmental syndrome occurred in 3/17 (17.6%) pts with mild envenoming, in 33/58 (56.9%), and 5/5 of moderate and severe envenomed pts, respectively (p = 0.0014). Sequelae were documented 25/80 (31%).

Bacterial Infections Associated with Viperidae Snakebites in Children: A 14-Year Experience at the Hospital Nacional de Niños de Costa Rica†.

Secondary bacterial infections following Viperidae snakebite envenomation in children are common. Among 75 patients admitted because of snakebites at the only pediatric hospital in Costa Rica, 16 (21.3%) had a culture-confirmed secondary bacterial infection. Morganella morganii (37.5%), Aeromonas hydrophila (31.2%), and Providencia rettgeri (18.7%) were the most common pathogens. Empiric prophylaxis is still recommended and should be based on local etiological agents and antimicrobial susceptibilities.