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.

The impact of the COVID-19 pandemic on children with medical complexity (preprint)

Background Descriptions of the COVID-19 pandemics indirect consequences on children are emerging. We aimed to describe the impacts of the pandemic on children with medical complexity (CMC) and their families. Methods A one-time survey of Canadian paediatricians using the Canadian Paediatric Surveillance Program (CPSP) was conducted in Spring 2021. Results A total of 784 paediatricians responded to the survey, with 70% (n=540) providing care to CMC. Sixty-seven (12.4%) reported an adverse health outcome due to a COVID-19 pandemic-related disruption in healthcare delivery. Disruption of the supply of medication and equipment was reported by 11.9% of respondents (n=64). Respondents reported an interruption in family caregiving (47.5%, n=252) and homecare delivery (40.8%, n=218). Almost 47% of respondents (n=253) observed a benefit to CMC due to COVID-19 related changes in healthcare delivery, including increased availability of virtual care and reduction in respiratory illness. Some (14.4%) reported that CMC were excluded from in-person learning when their peers without medical complexity were not. Conclusion Canadian paediatricians reported that CMC experienced adverse health outcomes during the COVID-19 pandemic, including disruptions to family caregiving and community supports. These results highlight the need for healthcare, community and education policymakers to collaborate with families to optimize their health.

Disruptions in Care: Consequences of the COVID-19 Pandemic in a Children's Hospital (preprint)

Background Public health restrictions are an essential strategy to prevent the spread of COVID-19; however, unintended consequences of these interventions may have led to significant delays, deferrals and disruptions in medical care. This study explores clinical cases where the care of children was perceived to have been negatively impacted as a result of public health measures and changes in healthcare delivery and access due to the COVID-19 pandemic. Methods This study used a qualitative multiple case study design with descriptive thematic analysis of clinician-reported consequences of the COVID-19 pandemic on care provided at a childrens hospital. A quantitative analysis of overall hospital activity data during the study period was performed. Results The COVID-19 pandemic has resulted in significant change to hospital activity at our tertiary care hospital, including an initial reduction in Emergency Department attendance by 38% and an increase in ambulatory virtual care from 4% before COVID-19, to 67% in August, 2020. Two hundred and twelve clinicians reported a total of 116 unique cases. Themes including (1) timeliness of care, (2) disruption of patient-centered care, (3) new pressures in the provision of safe and efficient care and (4) inequity in the experience of the COVID-19 pandemic emerged, each impacting patients, their families and healthcare providers. Conclusion Being aware of the breadth of the impact of the COVID-19 pandemic across all of the identified themes is important to enable the delivery of timely, safe, high-quality, family-centred pediatric care moving forward.

Safety of Administration of BNT162b2 mRNA (Pfizer-BioNTech) COVID-19 Vaccine in Youths and Young Adults with a History of Acute Lymphoblastic Leukaemia and Allergy to PEG-Asparaginase (preprint)

Vaccination is a critical tool in the prevention of COVID-19 infection for individuals and for communities. The mRNA vaccines contain polyethylene glycol (PEG) as a stabilizer. Currently in North America only the BNT162b2 (Pfizer-BioNTech) mRNA vaccine is approved individuals 12 to 17 years of age. Most patients treated with contemporary regimens for acute lymphoblastic leukemia receive Peg-asparaginase and 10-30% will develop allergic reactions. Optimizing access and safety for vaccine administration for these patients critical. This report describes a process developed to support COVID vaccination in a cohort of adolescents and young adults with a history of PEG-asparaginase allergy.