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.

Epidemiology and role of SARS-CoV-2 Linkage in Paediatric Inflammatory Multisystem Syndrome (PIMS): A Canadian Paediatric Surveillance Program National Prospective Study (preprint)

Background: Paediatric inflammatory multisystem syndrome (PIMS) is a rare but serious condition temporally associated with SARS CoV2 infection. Using the Canadian Paediatric Surveillance Program (CPSP), a national surveillance system, we aimed to 1) study the impact of SARS CoV2 linkage on clinical and laboratory characteristics, and outcomes in hospitalized children with PIMS across Canada 2) identify risk factors for ICU admission, and 3) establish the minimum national incidence of hospitalizations due to PIMS and compare it to acute COVID 19. Methods: Weekly online case reporting was distributed to the CPSP network of more than 2800 pediatricians, from March 2020 to May 2021. Comparisons were made between cases with respect to SARS CoV2 linkage. Multivariable modified Poisson regression was used to identify risk factors for ICU admission and Minimum incidence proportions were calculated. Findings: In total, 406 PIMS cases were analyzed, of whom 202 (49.8%) had a positive SARS CoV2 linkage, 106 (26.1%) had a negative linkage, and 98 (24.1%) had an unknown linkage. The median age was 5.4 years (IQR 2.5 to 9.8), 60% were male, and 83% had no identified comorbidities. Compared to cases with a negative SARS CoV2 linkage, children with a positive SARS CoV2 linkage were older (8.1 years [IQR 4.2 to 11.9] vs 4.1 years [IQR 1.7 to 7.7]; p<0.001), had more cardiac involvement (58.8% vs 37.4%; p<0.001), gastrointestinal symptoms (88.6% vs 63.2%; p<0.001), and shock (60.9% vs 16.0%; p<0.001). At risk groups for ICU admission include children >=6 years and those with a positive SARS CoV2 linkage. No deaths were reported. The minimum incidence of PIMS hospitalizations during the study period was 5.6 hospitalizations per 100,000 population <18 years. Interpretation: While PIMS is rare, almost 1 in 3 hospitalized children required ICU admission and respiratory/hemodynamic support, particularly those >=6 years and with a positive SARS CoV2 linkage. Funding: Financial support for the CPSP was received from the Public Health Agency of Canada.

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.

Hematologic manifestations of SARS-CoV-2 infection and MIS-C in hospitalized children. Results of the PICNIC registry. (preprint)

Introduction: Hematologic complications of SARS-CoV-2 infection are well described in hospitalized adults with correlation to adverse outcomes. Information published in children has been limited. Methods: An international multi-centered retrospective registry was established to collect data on the clinical manifestations of SARS-CoV-2 or multisystem inflammatory syndrome (MIS-C) in hospitalized children between February 1, 2020 – May 31, 2021. This sub-study focused on hematologic manifestations. Study variables included patient demographics, comorbidities, clinical presentation, course, laboratory parameters, management, and outcomes. Results: Nine hundred and eighty-five children were enrolled and 915 (93%) had clinical information available; 385 (42%) had symptomatic SARS-CoV-2 infection upon admission, 288 had MIS-C (31.4%) and 242 (26.4%) had alternate diagnosis with SARS-CoV-2 identified incidentally. During hospitalization, 10 children (1%) experienced a thrombotic event, 16 (1.7%) had hemorrhage and 2 (0.2%) had both thrombotic and hemorrhagic episodes. Significant prothrombotic comorbidities included congenital heart disease (p-value = 0.007), central venous catheter (p = 0.04) in children with primary SARS-CoV-2 infection; and obesity (p-value= 0.002), cytokine storm (p= 0.012) in those with MIS-C. Significant pro- hemorrhagic conditions included age > 10 years (p = 0.04), CVC (p= 0.03) in children with primary SARS-CoV-2infection; and thrombocytopenia (0.001), cytokine storm (0.02) in those with MIS-C. Eleven patients died (1.2 %) with no deaths attributed to thrombosis or hemorrhage Conclusion: Thrombotic and hemorrhagic complications are uncommon in children with SARS-CoV-2 infection and observed with underlying co-morbid conditions. Understanding the complete spectrum of hematologic complications in children with SARS-CoV-2 infection or MIS-C requires ongoing multi-center studies.

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.