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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.

Background: Paediatric inflammatory multisystem syndrome (PIMS) is a rare condition temporally associated with SARS-CoV-2 infection. Using national surveillance data, we compare presenting features and outcomes among children hospitalized with PIMS by SARS-CoV-2 linkage, and identify risk factors for intensive care (ICU)., Methods: Cases were reported to the Canadian Paediatric Surveillance Program by a network of >2800 pediatricians between March 2020 and May 2021. Patients with positive versus negative SARS-CoV-2 linkages were compared, with positive linkage defined as any positive molecular or serologic test or close contact with confirmed COVID-19. ICU risk factors were identified with multivariable modified Poisson regression., Results: We identified 406 children hospitalized with PIMS, including 49.8% with positive SARS-CoV-2 linkages, 26.1% with negative linkages, and 24.1% with unknown linkages. The median age was 5.4 years (IQR 2.5-9.8), 60% were male, and 83% had no comorbidities. Compared to cases with negative linkages, children with positive linkages experienced 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). Children aged ≥6 years and those with positive linkages were more likely to require ICU., Conclusions: Although rare, 30% of PIMS hospitalizations required ICU or respiratory/hemodynamic support, particularly those with positive SARS-CoV-2 linkages., Impact: We describe 406 children hospitalized with paediatric inflammatory multisystem syndrome (PIMS) using nationwide surveillance data, the largest study of PIMS in Canada to date. Our surveillance case definition of PIMS did not require a history of SARS-CoV-2 exposure, and we therefore describe associations of SARS-CoV-2 linkages on clinical features and outcomes of children with PIMS. Children with positive SARS-CoV-2 linkages were older, had more gastrointestinal and cardiac involvement, and hyperinflammatory laboratory picture. Although PIMS is rare, one-third required admission to intensive care, with the greatest risk amongst those aged ≥6 years and those with a SARS-CoV-2 linkage., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

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., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

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., (© 2022 Wiley Periodicals LLC.)

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., Competing Interests: Competing interests: None., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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., Competing Interests: Competing interests: Joanna Merckx reports a role as medical director of bioMerieux Canada and as a volunteer member of the Belgian Pediatric Task Force for COVID-19 during the conduct of the study. She is also an independent researcher, with a contract with Public Health Belgium, Sciensano for a study on the seroprevalence of SARS-CoV-2 in schools. E. Ann Yeh reports grants from Biogen, Roche, Horizon Therapeutics and Alexion; honoraria from Prime and Novartis; and participation on advisory boards with Roche and Horizon Therapeutics. She is also involved with the editorial board or is an editor with Multiple Sclerosis and Related Disorders, Multiple Sclerosis Journal, PLOS ONE and Neurology. Jesse Papenburg reports grants from AbbVie, Sanofi Pasteur, Merck and MedImmune; consulting fees from Merck; and honoraria from AbbVie, AstraZeneca and Seegene. He is a member of the National Advisory Committee on Immunization. Marie-Astrid Lefebvre reports an honorarium from Takeda Canada. Tammie Dewan reports grants from the Sick Kids Hospital Foundation, the Canadian Institutes for Health Research (CIHR) and the Department of Pediatrics at the University of Calgary. She is a past president of the Complex Care Section of the Canadian Pediatric Society. Jared Bullard reports grants from CIHR, the Manitoba Medical Service Foundation and Research Manitoba, as well as participation on provincial and hospital leadership committees. He is also secretary of the Association of Medical Microbiology and Infectious Diseases. Manish Sadarangani reports grants from GlaxoSmithKline, Merck, Moderna, Pfizer, Sanofi Pasteur, Seqirus, Symvivo and VBI Vaccines, as well as participating on 2 data safety monitoring boards for COVID-19 vaccine trials. Rupeena Purewal reports honoraria and consulting fees from Verity Pharmaceuticals. Kirk Leifso reports a grant from the Hospital for Sick Children. Cheryl Foo reports an unpaid position with IMPACT. No other competing interests were declared., (© 2022 CMA Impact Inc. or its licensors.)

Competing Interests: Intérêts concurrents : Krista Baerg déclare avoir reçu du financement du Chronic Pain Network. Elle a été présidente sortante de la section de la pédiatrie communautaire de la Société canadienne de pédiatrie et membre du conseil d’administration de la Saskatchewan Pain Society; elle a reçu des droits d’auteur de Brush Education. Kevin Chan est président du Comité des soins aigus de la Société canadienne de pédiatrie. Elizabeth Donner est présidente du comité de recherche scientifique et administratrice d’Épilepsie Canada. Elle est aussi membre de Partners Against Mortality in Epilepsy et de comités consultatifs pour Cardiol, Pendopharm et Stoke Therapeutics. Catherine Farrell est présidente du comité directeur scientifique du Programme canadien de surveillance pédiatrique, ancienne présidente du Comité de spécialité en pédiatrie du Collège royal des médecins et chirurgiens du Canada, ancienne présidente de la Société canadienne de pédiatrie, présidente du Comité d’éthique et membre du conseil d’administration de la Société canadienne de soins intensifs. Elle a reçu un remboursement de frais de déplacement de la Société canadienne de pédiatrie et du Collège royal des médecins et chirurgiens du Canada. Elle a aussi reçu des honoraires pour une présentation lors d’un symposium de formation continue à l’Université de Sherbrooke. Sarah Forgie est présidente de l’Association pour la microbiologie médicale et l’infectiologie Canada. Fatima Kakkar a reçu des honoraires pour des présentations données à l’Association des pédiatres du Québec. Thuy Mai Luu est directrice du Réseau canadien de suivi néonatal. Charlotte Moore Hepburn est directrice de Santé mentale pour enfants Ontario et directrice des affaires médicales pour la Société canadienne de pédiatrie et le Programme canadien de surveillance pédiatrique. Shaun Morris a reçu des honoraires de GlaxoSmithKline pour des conférences. Il a été membre d’un comité consultatif ad hoc pour Pfizer Canada. Jesse Papenburg a reçu des honoraires de consultation d’AbbVie et des honoraires d’AbbVie et de Seegene, et il a bénéficié de fournitures pour des tests de dépistage de virus respiratoires remis par Seegene pour son établissement. Il a participé à des réunions de comités consultatifs ad hoc pour AbbVie et il est membre ayant droit de vote du Comité consultatif national de l’immunisation. Rupeena Purewal est consultante pour Verity Pharmaceuticals. Manish Sadarangani est membre du comité consultatif d’Astra Zeneca. Marina Salvadori est une employée de l’Agence de la santé publique du Canada. Aucun autre intérêt concurrent déclaré.

Background: Risk factors for severe outcomes of SARS-CoV-2 infection are not well established in children. We sought to describe pediatric hospital admissions associated with SARS-CoV-2 infection in Canada and identify risk factors for more severe disease., Methods: We conducted a national prospective study using the infrastructure of the Canadian Paediatric Surveillance Program (CPSP). Cases involving children who were admitted to hospital with microbiologically confirmed SARS-CoV-2 infection were reported from Apr. 8 to Dec. 31 2020, through weekly online questionnaires distributed to the CPSP network of more than 2800 pediatricians. We categorized hospital admissions as related to COVID-19, incidental, or for social or infection control reasons and determined risk factors for disease severity in hospital., Results: Among 264 hospital admissions involving children with SARS-CoV-2 infection during the 9-month study period, 150 (56.8%) admissions were related to COVID-19 and 100 (37.9%) were incidental infections (admissions for other reasons and found to be positive for SARS-CoV-2 on screening). Infants (37.3%) and adolescents (29.6%) represented most cases. Among hospital admissions related to COVID-19, 52 (34.7%) had critical disease, 42 (28.0%) of whom required any form of respiratory or hemodynamic support, and 59 (39.3%) had at least 1 underlying comorbidity. Children with obesity, chronic neurologic conditions or chronic lung disease other than asthma were more likely to have severe or critical COVID-19., Interpretation: Among children who were admitted to hospital with SARS-CoV-2 infection in Canada during the early COVID-19 pandemic period, incidental SARS-CoV-2 infection was common. In children admitted with acute COVID-19, obesity and neurologic and respiratory comorbidities were associated with more severe disease., Competing Interests: Competing interests: Krista Baerg reports funding from the Chronic Pain Network. She also served as Past President of the Community Paediatrics Section of the Canadian Paediatric Society and on the Board of Directors for Saskatchewan Pain Society, and has received royalties from Brush Education. Kevin Chan is Chair of the Acute Care Committee of the Canadian Paediatric Society. Elizabeth Donner is Chair of the Scientific Research Committee and a director of Epilepsy Canada. She is also a member of Partners Against Mortality in Epilepsy and the advisory boards of Cardiol, Pendopharm and Stoke Therapeutics. Catherine Farrell is Chair of the Scientific Steering Committee for the Canadian Paediatric Surveillance Program, former Chair of the Specialty Committee in Pediatrics of the Royal College of Physicians and Surgeons of Canada, former President of the Canadian Paediatric Society, and Chair of the Ethics Committee and a member of the Board of Directors of the Canadian Critical Care Society. She has received reimbursement for travel expenses from Canadian Paediatric Society and the Royal College of Physicians and Surgeons of Canada. She has also received an honorarium for a presentation at a continuing education conference from the Université de Sherbrooke. Sarah Forgie is the President of the Association of Medical Microbiology and Infectious Disease Canada. Fatima Kakkar has received honoraria for presentations given to the Association des Pédiatres du Québec. Thuy Mai Luu is the Director of the Canadian Neonatal Follow-Up Network. Charlotte Moore Hepburn is the Director of Children’s Mental Health of Ontario, and the Director of medical affairs for the Canadian Paediatric Society and the Canadian Paediatric Surveillance Program. Shaun Morris has received honouraria for lectures from GlaxoSmithKline. He was a member of an ad hoc advisory board for Pfizer Canada. Jesse Papenburg has received consultant fees from AbbVie, honouraria from AbbVie and Seegene, and he received respiratory virus testing materials from Seegene for his institution. He has participated in ad hoc advisory board meetings for AbbVie and is a voting member of the National Advisory Committee on Immunization. Rupeena Purewal is a consultant for Verity Pharmaceuticals. Manish Sadarangani is a member of the advisory board of Astra Zeneca. Marina Salvadori is an employee of the Public Health Agency of Canada. No other competing interests were declared., (© 2021 CMA Joule Inc. or its licensors.)

Background: Risk factors for severe outcomes of SARS-CoV-2 infection are not well established in children. We sought to describe pediatric hospital admissions associated with SARS-CoV-2 infection in Canada and identify risk factors for more severe disease.Methods: We conducted a national prospective study using the infrastructure of the Canadian Paediatric Surveillance Program (CPSP). Cases involving children who were admitted to hospital with microbiologically confirmed SARS-CoV-2 infection were reported from Apr. 8 to Dec. 31 2020, through weekly online questionnaires distributed to the CPSP network of more than 2800 pediatricians. We categorized hospital admissions as related to COVID-19, incidental, or for social or infection control reasons and determined risk factors for disease severity in hospital.Results: Among 264 hospital admissions involving children with SARS-CoV-2 infection during the 9-month study period, 150 (56.8%) admissions were related to COVID-19 and 100 (37.9%) were incidental infections (admissions for other reasons and found to be positive for SARS-CoV-2 on screening). Infants (37.3%) and adolescents (29.6%) represented most cases. Among hospital admissions related to COVID-19, 52 (34.7%) had critical disease, 42 (28.0%) of whom required any form of respiratory or hemodynamic support, and 59 (39.3%) had at least 1 underlying comorbidity. Children with obesity, chronic neurologic conditions or chronic lung disease other than asthma were more likely to have severe or critical COVID-19.Interpretation: Among children who were admitted to hospital with SARS-CoV-2 infection in Canada during the early COVID-19 pandemic period, incidental SARS-CoV-2 infection was common. In children admitted with acute COVID-19, obesity and neurologic and respiratory comorbidities were associated with more severe disease. [ABSTRACT FROM AUTHOR]