Demographic and Outcome Characteristics of Children Hospitalized with Acute COVID-19 versus Multisystem Inflammatory Syndrome in Children in Canada (preprint)

Direct comparisons of pediatric hospitalizations for acute COVID-19 and multisystem inflammatory syndrome in children (MIS-C) can inform health system planning. While there were more hospitalizations and deaths from acute COVID-19 amongst Canadian children between March 2020-May 2021, MIS-C cases were more severe, requiring more intensive care and vasopressor support.

SARS-CoV-2 infection in technology dependent children: a multicenter case series (preprint)

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 COVID-19 in hospitalized children in Canada: A national prospective study from March 2020--May 2021 (preprint)

Background: Children living with chronic comorbid conditions are at increased risk for severe COVID-19, though there is limited evidence regarding the risks associated with specific conditions and which children may benefit from targeted COVID-19 therapies. The objective of this study was to identify factors associated with severe disease among hospitalized children with COVID-19 in Canada. Methods: We conducted a national prospective study on hospitalized children with microbiologically confirmed SARS-CoV-2 infection via the Canadian Paediatric Surveillance Program from April 2020--May 2021. Cases were reported voluntarily by a network of >2800 paediatricians. Hospitalizations were classified as COVID-19-related, incidental infection, or infection control/social admissions. Severe disease (among COVID-19-related hospitalizations only) was defined as disease requiring intensive care, ventilatory or hemodynamic support, select organ system complications, or death. Risk factors for severe disease were identified using multivariable Poisson regression, adjusting for age, sex, concomitant infections, and timing of hospitalization. Findings: We identified 544 children hospitalized with SARS-CoV-2 infection, including 60{middle dot}7% with COVID-19-related disease and 39{middle dot}3% with incidental infection or infection control/social admissions. Among COVID-19-related hospitalizations (n=330), the median age was 1{middle dot}9 years (IQR 0{middle dot}1--13{middle dot}3) and 43{middle dot}0% had chronic comorbid conditions. Severe disease occurred in 29{middle dot}7% of COVID-19-related hospitalizations (n=98/330), most frequently among children aged 2-4 years (48{middle dot}7%) and 12-17 years (41{middle dot}3%). Comorbid conditions associated with severe disease included technology dependence (adjusted risk ratio [aRR] 2{middle dot}01, 95% confidence interval [CI] 1{middle dot}37-2{middle dot}95), neurologic conditions (e.g. epilepsy and select chromosomal/genetic conditions) (aRR 1{middle dot}84, 95% CI 1{middle dot}32-2{middle dot}57), and pulmonary conditions (e.g. bronchopulmonary dysplasia and uncontrolled asthma) (aRR 1{middle dot}63, 95% CI 1{middle dot}12-2{middle dot}39). Interpretation: While severe outcomes were detected at all ages and among patients with and without comorbidities, neurologic and pulmonary conditions as well as technology dependence were associated with increased risk of severe COVID-19. These findings may help guide vaccination programs and prioritize targeted COVID-19 therapies for children. Funding: Financial support for the CPSP was received from the Public Health Agency of Canada.

Clinical manifestations and disease severity of SARS-CoV-2 infection among infants in Canada (preprint)

ImportanceThere are limited data on outcomes of SARS-CoV-2 infection among infants (<1 year of age). In the absence of approved vaccines for infants, understanding characteristics associated with hospitalization and severe disease from COVID-19 in this age group will help inform clinical management and public health interventions. ObjectiveThe objective of this study was to describe the clinical manifestations, disease severity, and characteristics associated with hospitalization among infants infected with the initial strains of SARS-CoV-2. DesignProspective study of infants with SARS-CoV-2 from April 8th 2020 to May 31st 2021. SettingNational study using the infrastructure of the Canadian Paediatric Surveillance Program, reporting inpatients and outpatients seen in clinics and emergency departments. ParticipantsInfants <1 year of age with microbiologically confirmed SARS-CoV-2 infection. ExposureInfant-level characteristics associated with hospitalization for COVID-19. Main outcomes and MeasuresCases were classified as either: 1) Non-hospitalized patient with SARS-CoV-2 infection; 2) COVID-19-related hospitalization; or 3) non-COVID-19-related hospitalization (e.g., incidentally detected SARS-CoV-2). Case severity was defined as asymptomatic, outpatient care, mild (inpatient care), moderate or severe disease. Multivariable logistic regression was performed to identify characteristics associated with hospitalization. ResultsA total of 531 cases were reported, including 332 (62.5%) non-hospitalized and 199 (37.5%) hospitalized infants. Among hospitalized infants, 141 of 199 infants (70.9%) were admitted because of COVID-19-related illness, and 58 (29.1%) were admitted for reasons other than acute COVID-19. Amongst all cases with SARS-CoV-2 infection, the most common presenting symptoms included fever (66.5%), coryza (47.1%), cough (37.3%) and decreased oral intake (25.0%). In our main analysis, infants with a comorbid condition had higher odds of hospitalization compared to infants with no comorbid conditions (aOR=4.53, 2.06-9.97), and infants <1 month had higher odds of hospitalization then infants aged 1-3 months (aOR=3.78, 1.97-7.26). In total, 20 infants (3.8%) met criteria for severe disease. Conclusions and RelevanceWe describe one of the largest cohorts of infants with SARS-CoV-2 infection. Overall, severe COVID-19 in this age group is uncommon with most infants having mild disease. Comorbid conditions and younger age were associated with COVID-19-related hospitalization amongst infants. Key PointsO_ST_ABSQuestionC_ST_ABSWhat are the spectrum of illness, disease severity, and characteristics associated with hospitalization in infants with SARS-CoV-2 infection? FindingsA total of 531 cases were reported to the Canadian Paediatric Surveillance Program, including 332 (62.5%) non-hospitalized and 199 (37.5%) hospitalized infants. In total, 20 infants met criteria for severe disease (3.8%). Infants characteristics associated with admission included age of less than one month and comorbid conditions. MeaningThis study provides data on the spectrum of disease, severity, and characteristics associated with admission due to COVID-19 in infants, which informs clinical management and public health interventions in this specific population.

Impact of the COVID-19 pandemic on routine immunization coverage in children under 2 years old in Ontario, Canada: A retrospective cohort study (preprint)

Background: The COVID-19 pandemic has caused a disruption in childhood immunization coverage around the world. This study aimed to determine the change in immunization coverage for children under 2 years old in Ontario, Canada, comparing time periods pre-pandemic to during the pandemic. Methods: We conducted an observational retrospective open cohort study, using primary care electronic medical record data from the University of Toronto Practice-Based Research Network (UTOPIAN) database, from January 2019 to December 2020. Children under 2 years old who had at least 2 visits recorded in UTOPIAN were included. We measured up-to-date (UTD) immunization coverage rates, overall and by type of vaccine (DTaP-IPV-Hib, Pneu-C-13, Rot, Men-C-C, MMR, Var), and on-time immunization coverage rates by age milestone (2, 4, 6, 12, 15 and 18 months). We compared average coverage rates over 3 periods of time: January 2019-March 2020 (T1); March-July 2020 (T2); and August-December 2020 (T3). Results: 12,313 children were included. Overall UTD coverage for all children was 71.0% in T1, dropped by 5.7% (95% CI: -6.2, -5.1) in T2, slightly increased in T3 but remained lower than in T1. MMR vaccine UTD coverage slightly decreased in T2 and T3 by approximately 2%. The largest decreases were seen at ages 15-month and 18-month old, with drops in on-time coverage of 14.7% (95% CI: -18.7, -10.6) and 16.4% (95% CI: -20.0, -12.8) respectively during T2. When stratified by sociodemographic characteristics, no specific subgroup of children was found to have been differentially impacted by the pandemic. Conclusion: Childhood immunization coverage rates for children under 2 years in Ontario decreased significantly during the early period of the COVID-19 pandemic and only partially recovered during the rest of 2020. Public health and educational interventions for providers and parents are needed to ensure adequate catch-up of delayed/missed immunizations to prevent potential outbreaks of vaccine-preventable diseases.

Risk factors for severe PCR-positive SARS-CoV-2 infection in hospitalized children: a multicenter cohort study (preprint)

Importance: Children are less likely than adults to have severe outcomes from SARS-CoV-2 infection and the corresponding risk factors are not well established. Objective: To identify risk factors for severe disease in symptomatic children hospitalized for PCR-positive SARS-CoV-2 infection. Design: Cohort study, enrollment from February 1, 2020 until May 31, 2021 Setting 15 children's hospitals in Canada, Iran, and Costa Rica Participants: Patients <18 years of age hospitalized with symptomatic SARS-CoV-2 infection, including PCR-positive multisystem inflammatory syndrome in children (MIS-C) Exposures: Variables assessed for their association with disease severity included patient demographics, presence of comorbidities, clinical manifestations, laboratory parameters and chest imaging findings. Main Outcomes and Measures: The primary outcome was severe disease defined as a WHO COVID-19 clinical progression scale of [≥]6, i.e., requirement of non-invasive ventilation, high flow nasal cannula, mechanical ventilation, vasopressors, or death. Multivariable logistic regression was used to evaluate factors associated with severe disease. Results: We identified 403 hospitalizations. 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). Severe disease occurred in 33.8% (102/403). In multivariable analyses, presence of multiple comorbidities (adjusted odds ratio 2.24, 95% confidence interval 1.04-4.81), obesity (2.87, 1.19-6.93), neurological disorder (3.22, 1.37-7.56), anemia, and/or hemoglobinopathy (5.88, 1.30-26.46), shortness of breath (4.37, 2.08-9.16), bacterial and/or viral coinfections (2.26, 1.08-4.73), chest imaging compatible with COVID-19 (2.99, 1.51-5.92), neutrophilia (2.60, 1.35-5.02), and MIS-C diagnosis (3.86, 1.56-9.51) were independent risk factors for severity. Comorbidities, especially obesity (40.9% vs 3.9%, p<0.001), were more frequently present in adolescents [≥]12 years of age. Neurological disorder (3.16, 1.19-8.43) in children <12 years of age and obesity (3.21, 1.15-8.93) in adolescents were the specific comorbidities associated with disease severity in age-stratified adjusted analyses. Sensitivity analyses excluding the 81 cases with MIS-C did not substantially change the identified risk factors. Conclusions and Relevance: Pediatric risk factors for severe SARS-CoV-2 infection vary according to age and can potentially guide vaccination programs and treatment approaches in children.

Impact of the COVID-19 pandemic on the provision of routine childhood immunizations in Ontario, Canada (preprint)

BackgroundThe COVID-19 pandemic has a worldwide impact on all health services, including childhood immunizations. In Canada, there is limited data to quantify and characterize this issue. MethodsWe conducted a descriptive, cross-sectional study by distributing online surveys to physicians across Ontario. The survey included three sections: provider characteristics, impact of COVID-19 on professional practice, and impact of COVID-19 on routine childhood immunization services. Multivariable logistic regression identified factors associated with modification of immunization services. ResultsA total of 475 respondents answered the survey from May 27th to July 3rd 2020, including 189 family physicians and 286 pediatricians. The median proportion of in-person visits reported by physicians before the pandemic was 99% and dropped to 18% during the first wave of the pandemic in Ontario. In total, 175 (44.6%) of the 392 respondents who usually provide vaccination to children acknowledged a negative impact caused by the pandemic on their immunization services, ranging from temporary closure of their practice (n=18; 4.6%) to postponement of vaccines in certain age groups (n=103; 26.3%). Pediatricians were more likely to experience a negative impact on their immunization services compared to family physicians (adjusted odds ratio [aOR]=2.64, 95% CI: 1.48-4.68), as well as early career physicians compared to their more senior colleagues (aOR=2.69, 95% CI: 1.30-5.56), whereas physicians from suburban settings were less impacted than physicians from urban settings (aOR=0.62, 95% CI: 0.39-0.99). The most frequently identified barriers to immunizations during the pandemic were parental concerns around COVID-19 (n=305; 77.8%), lack of personal protective equipment (PPE; n=123; 31.3%) and healthcare workers concerns of contracting COVID-19 (n=105; 26.8%). ConclusionsCOVID-19 has caused substantial modifications to pediatric immunization services across Ontario. Strategies to mitigate barriers to immunizations during the pandemic need to be implemented in order to avoid immunity gaps that could lead to an increase in vaccine preventable diseases. HIGHLIGHTSO_LIWe have conducted a descriptive, cross-sectional study by distributing online surveys to pediatricians and family physicians across Ontario to assess the impact of the COVID-19 pandemic on their immunization practices. C_LIO_LIThe COVID-19 pandemic has caused a substantial decrease in in-person visits and a related disruption to routine childhood immunization services during the first wave of the pandemic. C_LIO_LIThe main barriers to immunizations during the pandemic included parents and healthcare providers concerns of contracting COVID-19, and lack of appropriate personal protective equipment (PPE). C_LIO_LISolutions to maintain childhood immunizations during the pandemic included assistance in providing PPE to clinical practices, dedicated centers for vaccination, and parental education. C_LI

Multicenter cohort study of children hospitalized with SARS-CoV-2 infection (preprint)

Background: A cohort study was conducted to describe and compare the burden and characteristics of SARS-CoV-2 infection in hospitalized children in three countries. Methods: This was a retrospective cohort of consecutive children admitted to 15 hospitals (13 in Canada and one each in Iran and Costa Rica) up to November 16, 2020. Cases were included if they had SARS-CoV-2 infection or multi-system inflammatory syndrome in children (MIS-C) with molecular detection of SARS-CoV-2 or positive SARS-CoV-2 serology. Results: Of 211 included cases (Canada N=95; Costa Rica N=84; Iran N=32), 103 (49%) had a presumptive diagnosis of COVID-19 or MIS-C at admission while 108 (51%) were admitted with other diagnoses. Twenty-one (10%) of 211 met criteria for MIS-C. Eighty-seven (41%) had comorbidities. Children admitted in Canada were older than those admitted to non-Canadian sites (median 4.1 versus 2.2 years; p<0.001) and less likely to require mechanical ventilation (3/95 [3%] versus 15/116 [13%]; p<0.05). Requirement for oxygen or ICU occurred in 64 (30%) and death in four, three of whom. had malignancies. Age < 30 days, admission outside of Canada, presence of at least one comorbidity and chest imaging compatible with COVID-19 predicted severe disease. Conclusions: Approximately half of hospitalized children with confirmed SARS-CoV-2 infection or MIS-C were admitted with other suspected diagnoses. Disease was more severe at non-Canadian sites. Neonates, children with comorbidities and those with chest radiographs compatible with COVID-19 were at increased risk for severe disease.