Paediatric inflammatory multisystem syndrome in Canada: population-based surveillance and role of SARS-CoV-2 linkage.

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.

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.

Pediatricians' perceptions, practices, and barriers regarding COVID-19 vaccine for children: A cross-sectional survey in Ontario, Canada.

BACKGROUND: SARS-CoV-2 vaccination of all age-eligible populations is an important part of the COVID-19 pandemic response. In Ontario, vaccination coverage in 5-to-11-year-old children has remained lower than in other age groups. We sought to understand pediatricians' perception, practices, and barriers to SARS-CoV-2 vaccination in children, particularly children aged 5-to-11 years, to inform interventions and promote capacity of pediatricians as vaccinators and vaccination promoters. METHODS: This is a descriptive, cross-sectional study consisting of an online self-administered questionnaire distributed to 1,313 pediatricians in Ontario. Descriptive statistics, including Chi-square or Fisher's exact tests, were performed. RESULTS: In total, 152 Pediatricians responded (11.6% response rate), from February 17, 2022 to March 17, 2022. 78% of respondents were general pediatricians and 22% were pediatric subspecialists. Median years of practice was 17 (8-31), with 68% female, 32% male. Most pediatricians thought it was unlikely that children aged 5-to-11 years would become seriously ill from acute COVID-19 caused by Delta (66%) or Omicron (80%). 92% were very likely to recommend the COVID-19 vaccine for children aged 5-to-11 years. COVID-19 vaccine was perceived as safe, with higher safety perception in children aged 5-to-11 compared to 12-to-17 years (p < 0.0001). COVID-19 vaccines were thought to be effective in reducing hospitalization or severe illness, and reducing SARS-CoV-2 infection, with higher perceived effectiveness against Delta compared to Omicron (p < 0.0001). 97% felt confident counselling caregivers of children aged 5-to-11 years on the COVID-19 vaccine. Few pediatricians did not feel confident in accessing resources for health professionals (6%) or for patients/caregivers (12%). CONCLUSIONS: Most surveyed pediatricians were very likely to recommend COVID-19 vaccination for children aged 5-to-11-years, perceived COVID-19 vaccines as safe and effective, and felt confident in their COVID-19 vaccine counselling for children aged 5-to-11 years. However, there remains areas for further training and capacity development.

COVID-19 Vaccine Effectiveness Against Omicron Infection and Hospitalization

OBJECTIVES: This study aimed to provide real-world evidence on coronavirus disease 2019 vaccine effectiveness (VE) against symptomatic infection and severe outcomes caused by Omicron in children aged 5 to 11 years. METHODS: We used the test-negative study design and linked provincial databases to estimate BNT162b2 vaccine effectiveness against symptomatic infection and severe outcomes caused by Omicron in children aged 5 to 11 years between January 2 and August 27, 2022 in Ontario. We used multivariable logistic regression to estimate VE by time since the latest dose, compared with unvaccinated children, and we evaluated VE by dosing interval. RESULTS: We included 6284 test-positive cases and 8389 test-negative controls. VE against symptomatic infection declined from 24% (95% confidence interval [CI], 8% to 36%) 14 to 29 days after a first dose and 66% (95% CI, 60% to 71%) 7 to 29 days after 2 doses. VE was higher for children with dosing intervals of ≥56 days (57% [95% CI, 51% to 62%]) than 15 to 27 days (12% [95% CI, - 11% to 30%]) and 28 to 41 days (38% [95% CI, 28% to 47%]), but appeared to wane over time for all dosing interval groups. VE against severe outcomes was 94% (95% CI, 57% to 99%) 7 to 29 days after 2 doses and declined to 57% (95%CI, -20% to 85%) after ≥120 days. CONCLUSIONS: In children aged 5 to 11 years, 2 doses of BNT162b2 provide moderate protection against symptomatic Omicron infection within 4 months of vaccination and good protection against severe outcomes. Protection wanes more rapidly for infection than severe outcomes. Overall, longer dosing intervals confer higher protection against symptomatic infection, however protection decreases and becomes similar to shorter dosing interval starting 90 days after vaccination.

Pediatricians' Perceptions, Practices, and Barriers Regarding COVID-19 Vaccine for Children: A Cross-Sectional Survey in Ontario, Canada

Background SARS-CoV-2 vaccination of all age-eligible populations is an important part of the COVID-19 pandemic response. In Ontario, vaccination coverage in 5-to-11-year-old children has remained lower than in other age groups. We sought to understand pediatricians' perception, practices, and barriers to SARS-CoV-2 vaccination in children, particularly children aged 5-to-11 years, to inform interventions and promote capacity of pediatricians as vaccinators and vaccination promoters. Methods This is a descriptive, cross-sectional study consisting of an online self-administered questionnaire distributed to 1,313 pediatricians in Ontario. Descriptive statistics, including Chi-square or Fisher's exact tests, were performed. Results In total, 152 Pediatricians responded (11.6% response rate), from February 17, 2022 to March 17, 2022. 78% of respondents were general pediatricians and 22% were pediatric subspecialists. Median years of practice was 17 (8-31), with 68% female, 32% male. Most pediatricians thought it was unlikely that children aged 5-to-11 years would become seriously ill from acute COVID-19 caused by Delta (66%) or Omicron (80%). 92% were very likely to recommend the COVID-19 vaccine for children aged 5-to-11 years. COVID-19 vaccine was perceived as safe, with higher safety perception in children aged 5-to-11 compared to 12-to-17 years (p<0.0001). COVID-19 vaccines were thought to be effective in reducing hospitalization or severe illness, and reducing SARS-CoV-2 infection, with higher perceived effectiveness against Delta compared to Omicron (p<0.0001). 97% felt confident counselling caregivers of children aged 5-to-11 years on the COVID-19 vaccine. Few pediatricians did not feel confident in accessing resources for health professionals (6%) or for patients/caregivers (12%). Conclusions Most surveyed pediatricians were very likely to recommend COVID-19 vaccination for children aged 5-to-11-years, perceived COVID-19 vaccines as safe and effective, and felt confident in their COVID-19 vaccine counselling for children aged 5-to-11 years. However, there remains areas for further training and capacity development.

COVID-19 Vaccine Effectiveness Against Omicron Infection and Hospitalization.

OBJECTIVES: This study aimed to provide real-world evidence on coronavirus disease 2019 vaccine effectiveness (VE) against symptomatic infection and severe outcomes caused by Omicron in children aged 5 to 11 years. METHODS: We used the test-negative study design and linked provincial databases to estimate BNT162b2 vaccine effectiveness against symptomatic infection and severe outcomes caused by Omicron in children aged 5 to 11 years between January 2 and August 27, 2022 in Ontario. We used multivariable logistic regression to estimate VE by time since the latest dose, compared with unvaccinated children, and we evaluated VE by dosing interval. RESULTS: We included 6284 test-positive cases and 8389 test-negative controls. VE against symptomatic infection declined from 24% (95% confidence interval [CI], 8% to 36%) 14 to 29 days after a first dose and 66% (95% CI, 60% to 71%) 7 to 29 days after 2 doses. VE was higher for children with dosing intervals of ≥56 days (57% [95% CI, 51% to 62%]) than 15 to 27 days (12% [95% CI, -11% to 30%]) and 28 to 41 days (38% [95% CI, 28% to 47%]), but appeared to wane over time for all dosing interval groups. VE against severe outcomes was 94% (95% CI, 57% to 99%) 7 to 29 days after 2 doses and declined to 57% (95%CI, -20% to 85%) after ≥120 days. CONCLUSIONS: In children aged 5 to 11 years, 2 doses of BNT162b2 provide moderate protection against symptomatic Omicron infection within 4 months of vaccination and good protection against severe outcomes. Protection wanes more rapidly for infection than severe outcomes. Overall, longer dosing intervals confer higher protection against symptomatic infection, however protection decreases and becomes similar to shorter dosing interval starting 90 days after vaccination.

A narrative review of vaccine pharmacovigilance during mass vaccination campaigns: Focus on myocarditis and pericarditis after COVID-19 mRNA vaccination.

Vaccines have had a tremendous impact on reducing the burden of infectious diseases; however, they have the potential to cause adverse events following immunization (AEFIs). Prelicensure clinical trials are limited in their ability to detect rare AEFIs that may occur in less than one per thousand individuals. While postmarketing surveillance systems have shown COVID-19 mRNA vaccines to be safe, they led to the identification of rare cases of myocarditis and pericarditis after COVID-19 vaccination that were not initially detected in clinical trials. In this narrative review, we highlight concepts of vaccine pharmacovigilance during mass vaccination campaigns and compare the approaches used in the context of myocarditis and pericarditis following COVID-19 vaccination to historical examples. We describe mechanisms of passive and active surveillance, their strengths and limitations, and how they interacted to identify and characterize the safety signal of myocarditis and pericarditis after COVID-19 mRNA vaccination. Articles were synthesized from a PubMed search using relevant keywords for articles published on vaccine surveillance systems and myocarditis and pericarditis after COVID-19 vaccination, as well as the authors' collections of relevant publications and grey literature reports. The global experience around the identification and monitoring of myocarditis and pericarditis after COVID-19 mRNA vaccination has provided important lessons for vaccine safety surveillance and highlighted its importance in maintaining public trust in mass vaccination programmes in a pandemic context.

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.

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.

Clinical public health: harnessing the best of both worlds in sickness and in health. / Santé publique clinique : exploiter le meilleur des deux mondes pour la santé comme pour le traitement des maladies.

INTRODUCTION: Effective, sustained collaboration between clinical and public health professionals can lead to improved individual and population health. The concept of clinical public health promotes collaboration between clinical medicine and public health to address complex, real-world health challenges. In this commentary, we describe the concept of clinical public health, the types of complex problems that require collaboration between individual and population health, and the barriers towards and applications of clinical public health that have become evident during the COVID-19 pandemic. RATIONALE: The focus of clinical medicine on the health of individuals and the aims of public health to promote and protect the health of populations are complementary. Interdisciplinary collaborations at both levels of health interventions are needed to address complex health problems. However, there is a need to address the disciplinary, cultural and financial barriers to achieving greater and sustained collaboration. Recent successes, particularly during the COVID-19 pandemic, provide a model for such collaboration between clinicians and public health practitioners. CONCLUSION: A public health approach that fosters ongoing collaboration between clinical and public health professionals in the face of complex health threats will have greater impact than the sum of the parts.

INTRODUCTION: Une collaboration efficace et soutenue entre cliniciens et professionnels en santé publique peut améliorer la santé des individus et la santé de la population. Le concept de santé publique clinique favorise cette collaboration entre médecine clinique et santé publique et permet de relever des défis complexes en matière de santé. Dans ce commentaire, nous décrivons le concept de santé publique clinique, les types de problèmes complexes qui nécessitent une collaboration entre les professionnels responsables de la santé des individus et ceux responsables de la santé de la population, de même que les obstacles à la santé publique clinique et les applications de la santé publique clinique qui ont émergé pendant la pandémie de COVID-19. ARGUMENTAIRE: Il existe une complémentarité entre la médecine clinique, qui est axée sur la santé des individus, et la santé publique, qui est axée sur la promotion et la protection de la santé des populations. Une collaboration entre ces deux disciplines est nécessaire pour résoudre les problèmes de santé complexes. Pour ce faire, toutefois, il convient de s'attaquer aux obstacles relatifs aux disciplines, ainsi qu'aux obstacles culturels et financiers qui empêchent une collaboration accrue et durable en la matière. Les succès récents, particulièrement durant la pandémie de COVID-19, constituent un modèle de collaboration de ce type entre cliniciens et praticiens en santé publique. CONCLUSION: Une approche en matière de santé publique qui favorise une collaboration permanente entre cliniciens et professionnels en santé publique pour lutter contre des menaces sanitaires complexes aura plus d'impact que la somme de ses parties.

COVID-19 and multisystem inflammatory syndrome in children and adolescents.

As severe acute respiratory syndrome coronavirus 2 continues to spread worldwide, there have been increasing reports from Europe, North America, Asia, and Latin America describing children and adolescents with COVID-19-associated multisystem inflammatory conditions. However, the association between multisystem inflammatory syndrome in children and COVID-19 is still unknown. We review the epidemiology, causes, clinical features, and current treatment protocols for multisystem inflammatory syndrome in children and adolescents associated with COVID-19. We also discuss the possible underlying pathophysiological mechanisms for COVID-19-induced inflammatory processes, which can lead to organ damage in paediatric patients who are severely ill. These insights provide evidence for the need to develop a clear case definition and treatment protocol for this new condition and also shed light on future therapeutic interventions and the potential for vaccine development. TRANSLATIONS: For the French, Chinese, Arabic, Spanish and Russian translations of the abstract see Supplementary Materials section.

Clinical manifestations and disease severity of SARS-CoV-2 infection among infants in Canada.

BACKGROUND: There 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. The 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. METHODS: This is a national, prospective study of infants with SARS-CoV-2 from April 8th 2020 to May 31st 2021 using the infrastructure of the Canadian Paediatric Surveillance Program. Infants <1 year of age with microbiologically confirmed SARS-CoV-2 infection from both inpatients and outpatients seen in clinics and emergency departments were included. Cases 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. RESULTS: A 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: We describe one of the largest cohorts of infants with SARS-CoV-2 infection. Overall, severe COVID-19 in this age group was found to be uncommon. Comorbid conditions and younger age were associated with COVID-19-related hospitalization amongst infants.

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.

Risk factors for severe COVID-19 in hospitalized children in Canada: A national prospective study from March 2020-May 2021.

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 (CPSP) 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 60·7% with COVID-19-related disease and 39·3% with incidental infection or infection control/social admissions. Among COVID-19-related hospitalizations (n=330), the median age was 1·9 years (IQR 0·1-13·3) and 43·0% had chronic comorbid conditions. Severe disease occurred in 29·7% of COVID-19-related hospitalizations (n=98/330 including 60 admitted to intensive care), most frequently among children aged 2-4 years (48·7%) and 12-17 years (41·3%). Comorbid conditions associated with severe disease included pre-existing technology dependence requirements (adjusted risk ratio [aRR] 2·01, 95% confidence interval [CI] 1·37-2·95), body mass index Z-scores ≥3 (aRR 1·90, 95% CI 1·10-3·28), neurologic conditions (e.g. epilepsy and select chromosomal/genetic conditions) (aRR 1·84, 95% CI 1·32-2·57), and pulmonary conditions (e.g. bronchopulmonary dysplasia and uncontrolled asthma) (aRR 1·63, 95% CI 1·12-2·39). 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.

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.

Probable congenital SARS-CoV-2 infection in a neonate born to a woman with active SARS-CoV-2 infection: CMAJ

Kirtsman et al discuss the probable congenital SARS-CoV-2 infection in a neonate born to a woman with active SARS-CoV-2 infection. They present a case study of a 40-year-old woman who was admitted to a tertiary hospital in Toronto, Ontario. She had familial neutropenia, gestational diabetes and a history of frequent bacterial infections during pregnancy, which resolved with antibiotic treatment. Details of the maternal course and outcome have been published separately because of her hematologic condition. A nasopharyngeal swab was positive for suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) gene targets via reverse transcription polymerase chain reaction (RT-PCR) testing. There were no fetal concerns during the pregnancy or following admission. A semiurgent cesarean delivery was done under regional anesthesia, with airborne, droplet and contact precautions, owing to worsening coagulopathy and reducing platelet count at 35 weeks. Artificial rupture of membranes was performed at operation. The male neonate was vigorous and did not require resuscitation. His Apgar scores were 9 at 1 minute and 9 at 5 minutes, but all 3 of the neonate's nasopharyngeal swabs were positive for SARS-CoV-2 gene targets via RT-PCR testing.

Underestimation of travel-associated risks by adult and paediatric travellers compared to expert assessment: A cross-sectional study at a hospital-based family pre-travel clinic.

BACKGROUND: Travellers' perception of their risk for acquiring travel-related conditions is an important contributor to decisions and behaviors during travel. In this study, we aimed to assess the differences between traveller-perceived and expert-assessed risk of travel-related conditions in children and adults travelling internationally and describe factors that influence travellers' perception of risk. METHODS: Children and adults were recruited at the Hospital for Sick Children's Family Travel Clinic between October 2014 and July 2015. A questionnaire was administered to participants to assess their perceived risk of acquiring 32 travel-related conditions using a 7-point Likert scale. Conditions were categorized as vector-borne diseases, vaccine-preventable diseases, food and water borne diseases, sexually transmitted infections and other conditions. Two certified travel medicine experts reviewed each patient's chart and assigned a risk score based on the same 7-point Likert scale. Traveller and expert risk scores were compared using paired t-tests. RESULTS: In total, 207 participants were enrolled to participate in this study, 97 children (self-reported, n = 8; parent-reported, n = 89), and 110 adults. Travel-related risk for adults and parents answering for their children were significantly underestimated when compared to expert-assessed risk for 26 of the 32 assessed conditions. The underestimated conditions were the same for both adults and parents answering for children. Travel-related risk was not over-estimated for any condition. CONCLUSIONS: Adults underestimated their children's and their own risk for most travel-related conditions. Strategies to improve the accuracy of risk perception of travel-related conditions by travellers are needed to optimize healthy travel for children and their families.

The effect of the COVID-19 pandemic on influenza-related hospitalization, intensive care admission and mortality in children in Canada: A population-based study

Background The COVID-19 pandemic resulted in unprecedented implementation of wide-ranging public health measures globally. During the pandemic, dramatic decreases in seasonal influenza virus detection have been reported worldwide. Information on the impact on paediatric influenza-related hospitalisations is limited. We describe influenza-related hospitalisation in children in Canada following the onset of the COVID-19 pandemic. Methods Data on influenza-related hospitalisations, intensive care unit (ICU) admissions and in-hospital deaths in children across Canada were obtained from the Canadian Immunisation Monitoring Program, ACTive (IMPACT). This national active surveillance initiative comprises 90% of all tertiary care paediatric beds in Canada. The study period included eleven influenza seasons, from the 2010/2011 season until the 2020/2021 season inclusive. Time series modelling was used to compare the observed to predicted influenza-related hospitalisations following the COVID-19 pandemic. Results Following the COVID-19 pandemic there was a significant decrease in paediatric influenza-related hospitalisations compared to predicted influenza-related hospitalisations for this time period (p < 0•0001). No paediatric influenza-related hospitalisations, ICU admission or deaths were reported for the 2020/2021 influenza season. Conclusions We show complete absence of paediatric influenza infection-related hospitalisation in a Canadian National Surveillance Network during the 2020/2021 influenza season. This significant decrease is likely related in large part to non-pharmacological public health interventions implemented during the COVID-19 pandemic, although the potential role of viral interference is unknown. Funding The Canadian Immunisation Monitoring Program, Active (IMPACT) influenza surveillance is a national surveillance initiative managed by the Canadian Paediatric Society and conducted by the IMPACT network of paediatric investigators on behalf of the Public Health Agency of Canada's Centre for Immunisation and Respiratory Infectious Diseases.

Delay in childhood vaccinations during the COVID-19 pandemic.

OBJECTIVES: In many jurisdictions, routine medical care was reduced in response to the COVID-19 pandemic. The objective of this study was to determine whether the frequency of on-time routine childhood vaccinations among children age 0-2 years was lower following the COVID-19 declaration of emergency in Ontario, Canada, on March 17, 2020, compared to prior to the pandemic. METHODS: We conducted a longitudinal cohort study of healthy children aged 0-2 years participating in the TARGet Kids! primary care research network in Toronto, Canada. A logistic mixed effects regression model was used to determine odds ratios (ORs) for delayed vaccination (> 30 days vs. ≤ 30 days from the recommended date) before and after the COVID-19 declaration of emergency, adjusted for confounding variables. A Cox proportional hazards model was used to explore the relationship between the declaration of emergency and time to vaccination. RESULTS: Among 1277 children, the proportion of on-time vaccinations was 81.8% prior to the COVID-19 declaration of emergency and 62.1% after (p < 0.001). The odds of delayed vaccination increased (odds ratio = 3.77, 95% CI: 2.86-4.96), and the hazard of administration of recommended vaccinations decreased after the declaration of emergency (hazard ratio = 0.75, 95% CI: 0.60-0.92). The median vaccination delay time was 5 days (95% CI: 4-5 days) prior to the declaration of emergency and 17 days (95% CI: 12-22 days) after. CONCLUSION: The frequency of on-time routine childhood vaccinations was lower during the first wave of the COVID-19 pandemic. Sustained delays in routine vaccinations may lead to an increase in rates of vaccine-preventable diseases.

RéSUMé: OBJECTIFS: Dans plusieurs juridictions, les soins médicaux systématiques étaient réduits à cause de la pandémie de COVID-19. L'objectif de cette étude était de déterminer si la fréquence de donner les vaccinations systématiques aux enfants de l'âge de 0 à 2 ans était réduite en conséquence de la déclaration d'urgence de COVID-19 en Ontario, Canada dès le 17 mars 2020, comparer avec la fréquence avant la pandémie. MéTHODES: Nous avons mené une étude de cohorte longitudinale des enfants en bonne santé âgés de 0 à 2 ans qui participent dans le réseau de recherche en soins primaires TARGet Kids! à Toronto, Canada. Un modèle de régression logistique à effets mixtes était utilisé pour déterminer le rapport de cotes (RC) pour les vaccinations retardées (> 30 jours c. ≤ 30 jours de la date recommandée) et était équilibré pour les variables confondantes. Le modèle à risques proportionnels de Cox était utilisé pour examiner le lien entre la déclaration d'urgence et le temps jusqu'à la vaccination. RéSULTATS: Parmi 1 277 enfants, la proportion de vaccination à l'heure était 81,8 % avant la déclaration d'urgence de COVID-19 et 62,1 % après (p < 0,001). La possibilité de vaccination retardée était augmentée (RC = 3,77; IC95% : 2,86­4,96), et le taux d'administration recommandé pour les vaccinations était réduit après la déclaration d'urgence (ratio de hasard = 0,75; IC95% : 0,60­0,92). Le médian temps de retard pour les vaccinations était 5 jours (IC95% : 4­5 jours) avant la déclaration d'urgence et 17 jours (IC95% : 12­22 jours) après. CONCLUSION: La fréquence de vaccinations systématiques aux enfants à l'heure était inférieure pendant la première vague de la pandémie COVID-19. Des retards soutenus pour recevoir les vaccinations systématiques peuvent entrainer une augmentation des taux de maladies évitables par la vaccination.

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.