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.

Anaphylaxis: Revision of the Brighton collaboration case definition.

The Brighton Collaboration (BC) has formulated a number of case definitions which have primarily been applied to adverse events of special interest in the context of vaccine safety surveillance. This is a revision of the 2007 BC case definition for anaphylaxis. Recently, the BC definition has been widely used for evaluating reports of suspected anaphylaxis following COVID-19 vaccination. This has led to debate about the performance of the BC definition in comparison with those from the US National Institute of Allergy and Infectious Disease/Food Allergy Anaphylaxis Network (NIAID/FAAN) and the World Allergy Organization (WAO). BC convened an expert working group to revise the case definition based on their usual process of literature review and expert consensus. This manuscript presents the outcome of this process and proposes a revised case definition for anaphylaxis. Major and minor criteria have been re-evaluated with an emphasis on the reporting of observable clinical signs, rather than subjective symptoms, and a clearer approach to the ascertainment of levels of certainty is provided. The BC case definition has also been aligned with other contemporary and international case definitions for anaphylaxis.

Adverse Events Following Immunization with mRNA and Viral Vector Vaccines in Individuals with Previous SARS-CoV-2 Infection from the Canadian National Vaccine Safety Network.

BACKGROUND: Adults previously infected with SARS-CoV-2 develop short-term immunity and may have increased reactogenicity to COVID-19 vaccines. This prospective, multi-center active surveillance cohort study examined the short-term safety of COVID-19 vaccines in adults with a prior history of SARS-CoV-2. METHODS: Canadian adults vaccinated between December 22, 2020 and November 27, 2021 were sent an electronic questionnaire 7 days post dose 1, dose 2 and dose 3 vaccination. The main outcome was health events occurring in the first 7 days after each vaccination that prevented daily activities, resulted in work absenteeism or required a medical consultation, including hospitalization. RESULTS: Among 684,998 vaccinated individuals, 2.6% (18,127/684,998) reported a prior history of SARS-CoV-2 infection a median of 4 months (interquartile range 2-6 months) previously. After dose 1, individuals with moderate (bedridden) to severe (hospitalized) COVID-19 who received BNT162b2, mRNA1273 or ChAdox1-S vaccines had higher odds of a health event preventing daily activities, resulting in work absenteeism or requiring medical consultation; adjusted odds ratio (AOR) 3.96 (95% CI 3.67-4.28) for BNT162b2, 5.01 (4.57-5.50) for mRNA1273 and 1.84 (1.54-2.20) for ChAdox1-S compared to no infection. Following dose 2 and 3, the greater risk associated with previous infection was also present but attenuated compared to dose 1. For all doses, the association was lower or absent after mild or asymptomatic infection. CONCLUSION: Adults with moderate or severe previous SARS-CoV-2 infection were more likely to have a health event sufficient to impact routine activities or require medical assessment in the week following each vaccine doses.

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.

Advancing the Science of Vaccine Safety During the Coronavirus Disease 2019 (COVID-19) Pandemic and Beyond: Launching an International Network of Special Immunization Services.

Within 2 years after the start of the coronavirus disease 2019 (COVID-19) pandemic, novel severe acute respiratory syndrome coronavirus 2 vaccines were developed, rigorously evaluated in large phase 3 trials, and administered to more than 5 billion individuals globally. However, adverse events of special interest (AESIs) have been described post-implementation, including myocarditis after receipt of messenger RNA (mRNA) vaccines and thrombosis with thrombocytopenia syndrome after receipt of adenoviral vector vaccines. AESIs are rare (<1 to 10/100 000 vaccinees) and less frequent than COVID-19 complications, though they have associated morbidity and mortality. The diversity of COVID-19 vaccine platforms (eg, mRNA, viral vector, protein) and rates of AESIs both between and within platforms (eg, higher rate of myocarditis after mRNA-1273 vs BNT162b2 vaccines) present an important opportunity to advance vaccine safety science. The International Network of Special Immunization Services has been formed with experts in vaccine safety, systems biology, and other relevant disciplines to study cases of AESIs and matched controls to uncover the pathogenesis of rare AESIs and inform vaccine development.

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.

Safety of COVID-19 vaccines in pregnancy: a Canadian National Vaccine Safety (CANVAS) network cohort study.

BACKGROUND: Pregnant individuals have been receiving COVID-19 vaccines following pre-authorisation clinical trials in non-pregnant people. This study aimed to determine the frequency and nature of significant health events among pregnant females after COVID-19 vaccination, compared with unvaccinated pregnant controls and vaccinated non-pregnant individuals. METHODS: We did an observational cohort study, set in seven Canadian provinces and territories including Ontario, Quebec, British Columbia, Alberta, Nova Scotia, Yukon, and Prince Edward Island. Eligibility criteria for vaccinated individuals were a first dose of a COVID-19 vaccine within the previous 7 days; an active email address and telephone number; ability to communicate in English or French; and residence in the aforementioned provinces or territories. Study participants were pregnant and non-pregnant females aged 15-49 years. Individuals were able to participate as controls if they were unvaccinated and fulfilled the other criteria. Data were collected primarily by self-reported survey after both vaccine doses, with telephone follow-up for those reporting any medically attended event. Participants reported significant health events (new or worsening of a health event sufficient to cause work or school absenteeism, medical consultation, or prevent daily activities) occurring within 7 days of vaccination or within the past 7 days for unvaccinated individuals. We employed multivariable logistic regression to examine significant health events associated with mRNA vaccines, adjusting for age group, previous SARS-CoV-2 infection, and trimester, as appropriate. FINDINGS: As of Nov 4, 2021, 191 360 women aged 15-49 years with known pregnancy status had completed the first vaccine dose survey and 94 937 had completed the second dose survey. 180 388 received one dose and 94 262 received a second dose of an mRNA vaccine, with 5597 pregnant participants receiving dose one and 3108 receiving dose two, and 174 765 non-pregnant participants receiving dose one and 91 131 receiving dose two. Of 6179 included unvaccinated control participants, 339 were pregnant and 5840 were not pregnant. Overall, 226 (4·0%) of 5597 vaccinated pregnant females reported a significant health event after dose one of an mRNA vaccine, and 227 (7·3%) of 3108 after dose two, compared with 11 (3·2%) of 339 pregnant unvaccinated females. Pregnant vaccinated females had an increased odds of a significant health event within 7 days of the vaccine after dose two of mRNA-1273 (adjusted odds ratio [aOR] 4·4 [95% CI 2·4-8·3]) compared with pregnant unvaccinated controls within the past 7 days, but not after dose one of mRNA-1273 or any dose of BNT162b2. Pregnant vaccinated females had decreased odds of a significant health event compared with non-pregnant vaccinated females after both dose one (aOR 0·63 [95% CI 0·55-0·72]) and dose two (aOR 0·62 [0·54-0·71]) of any mRNA vaccination. There were no significant differences in any analyses when restricted to events which led to medical attention. INTERPRETATION: COVID-19 mRNA vaccines have a good safety profile in pregnancy. These data can be used to appropriately inform pregnant people regarding reactogenicity of COVID-19 vaccines during pregnancy, and should be considered alongside effectiveness and immunogenicity data to make appropriate recommendations about best use of COVID-19 vaccines in pregnancy. FUNDING: Canadian Institutes of Health Research, 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.

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.

Vaccine regulation should require and enforce the inclusion of pregnant and breastfeeding women in prelicensure clinical trials.

Exclusion of pregnant and breastfeeding women from the pivotal randomized controlled trials for COVID-19 vaccines that led to emergency regulatory approval created gaps in data needed for vaccine policy, healthcare provider recommendations, and women's decisions about vaccination. We argue that such knowledge gaps increase potential for vaccine hesitancy and misinformation relating to the health of women and infants, and that these gaps in evidence are avoidable. Over several decades, ethical and scientific guidance, scholarship, and advocacy in favor of pregnant and breastfeeding women's participation in clinical development of vaccines has accumulated. Guidance on how to include pregnant and breastfeeding women in vaccine trials ethically and safely predates the COVID-19 pandemic but has yet to be routinely incorporated in vaccine development. We highlight the important role regulatory authorities could play in requiring that pregnant and breastfeeding women be eligible as volunteer participants in prelicensure vaccine trials for products that are expected to be used in this population. Inclusion of pregnant and breastfeeding populations in clinical trials leading to market approval or emergency use authorization should be undertaken early or concurrently at the time of trials in the general population.

Deferring Risk: Limitations to the Evidence in Product Labels for Vaccine Use in Pregnancy.

Background: The gaps in clinical trial evidence about vaccination in pregnancy have serious implications for health care worker and public misunderstandings. Contradictions between National Immunization Technical Advisory Group (NITAG) recommendations and regulatory product labeling information contribute to misinformation about vaccine safety and effectiveness. Methods: A mixed methods approach that included a stakeholder consensus decision-making workshop and a national survey of Canadian health care providers (HCPs). Results: We identified knowledge gaps and serious limitations concerning the information in vaccine product labels. Stakeholders were troubled that some HCPs rely on regulatory product labels to inform their decisions without knowing their limitations in content. Our survey showed that HCPs were uncertain about the purpose of product labels and the evidence contained in them. Over a third of respondents incorrectly thought that product labels and NITAG recommendations are based on the same evidence and that the information they contain is regularly updated. Conclusions: Applying social risk theories, we show how such gaps in information defer responsibility for decisions about disease risk and vaccine safety from regulatory agencies and vaccine manufacturers onto HCPs and their clients. This may be especially relevant for COVID-19 and other emerging vaccines that are initially authorized for conditional or emergency use, and especially in understudied populations such as pregnant people. More frequent updating and alignment of robust, unbiased, and independently reviewed clinical trial and postmarket safety and effectiveness evidence with NITAG recommendations would allay HCP and public misunderstandings.

A scoping review of active, participant-centred, digital adverse events following immunization (AEFI) surveillance: A Canadian immunization research network study.

BACKGROUND: Post-licensure adverse events following immunization (AEFI) surveillance is conducted to monitor vaccine safety, such as identifying batch/brand issues and rare reactions, which consequently improves community confidence. The integration of technology has been proposed to improve AEFI surveillance, however, there is an absence of description regarding which digital solutions are successfully being used and their unique characteristics. OBJECTIVES: The objectives of this scoping review were to 1) map the research landscape on digital systems used for active, participant-centred, AEFI surveillance and 2) describe their core components. METHODS: We conducted a scoping review informed by the PRISMA Extension for Scoping Reviews (PRSIMA-ScR) guideline. OVID-Medline, Embase Classic + Embase, and Medrxiv were searched by a medical librarian from January 1, 2000 to January 28th, 2021. Two independent reviewers determined which studies met inclusion based on pre-specified eligibility criteria. Data extraction was conducted using pre-made tables with specific variables by one investigator and verified by a second. RESULTS: Twenty-seven publications met inclusion, the majority of which came from Australia (n = 15) and Canada (n = 6). The most studied active, participant-centred, digital AEFI surveillance systems were SmartVax (n = 8) (Australia), Vaxtracker (n = 7) (Australia), and Canadian National Vaccine Safety (CANVAS) Network (Canada) (n = 6). The two most common methods of communicating with vaccinees reported were short-message-service (SMS) (n = 15) and e-mail (n = 14), with online questionnaires being the primary method of data collection (n = 20). CONCLUSION: Active, participant-centred, digital AEFI surveillance is an area actively being researched as depicted by the literature landscape mapped by this scoping reviewWe hypothesize that the AEFI surveillance approach herein described could become a primary method of collecting self-reported subjective symptoms and reactogenicity from vaccinees, complementing existing systems. Future evaluation of identified digital solutions is necessary to bring about improvements to current vaccine surveillance systems to meet contemporary and future public health needs.

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.

Caractéristiques des hospitalisations au Canada d'enfants ayant contracté une infection aiguë par le SRAS-CoV-2 en 2020.

CONTEXTE: Les facteurs de risque de complications graves de l'infection par le SRAS-CoV-2 n'ont pas été bien établis chez les enfants. Nous avons voulu décrire les hospitalisations pédiatriques associées au SRAS-CoV-2 au Canada et identifier les facteurs de risque de maladie grave. MÉTHODES: Nous avons procédé à une étude prospective nationale en utilisant l'infrastructure du Programme canadien de surveillance pédiatrique (PCSP). Les hospitalisations d'enfants ayant contracté une infection par le SRAS-CoV-2 confirmée en laboratoire de microbiologie ont été rapportées du 8 avril au 31 décembre 2020 au moyen de questionnaires hebdomadaires en ligne distribués au réseau du PCSP, qui compte plus de 2800 pédiatres. Nous avons catégorisé les hospitalisations comme suit : liées à la COVID-19, infections découvertes fortuitement, ou hospitalisations pour des raisons sociales ou de contrôle des infections, et dégagé les facteurs de risque associés à la gravité de la maladie chez les patients hospitalisés. RÉSULTATS: Sur les 264 hospitalisations d'enfants ayant contracté le SRAS-CoV-2 au cours de la période de l'étude de 9 mois, 150 (56,8 %) ont été associées à la COVID-19 et 100 (37,9 %) étaient des cas découverts fortuitement (admission pour d'autres raisons et découverte fortuite du SRAS-CoV-2 par dépistage positif). Les nourrissons (37,3 %) et les adolescents (29,6 %) représentaient la majorité des cas. Parmi les hospitalisations liées à la COVID-19, 52 patients (34,7 %) étaient atteints d'une forme grave de la maladie, dont 42 (28,0 % des cas liés à la COVID-19) ont eu besoin d'une forme d'assistance respiratoire ou hémodynamique, et 59 (39,3 %) présentaient au moins 1 comorbidité sous-jacente. Les enfants atteints d'obésité, de maladies neurologiques chroniques ou de maladies pulmonaires chroniques, à l'exclusion de l'asthme, étaient plus susceptibles de présenter une forme grave ou critique de la COVID-19. INTERPRÉTATION: Parmi les enfants hospitalisés au Canada chez lesquels on a diagnostiqué une infection par le SRAS-CoV-2 au début de la pandémie de COVID-19, la découverte fortuite du SRAS-CoV-2 a été fréquente. Chez les enfants hospitalisés pour une COVID-19 aiguë, l'obésité et les comorbidités neurologiques et respiratoires ont été associées à une gravité accrue.

The Canadian National Vaccine Safety Network: surveillance of adverse events following immunisation among individuals immunised with the COVID-19 vaccine, a cohort study in Canada.

INTRODUCTION: COVID-19 vaccines require enhanced safety monitoring after emergency approval. The Canadian National Vaccine Safety Network monitors the safety of COVID-19 vaccines and provides enhanced monitoring for healthy, auto-immune, immunocompromised, pregnant and breastfeeding populations and allows for the detection of safety signals. METHODS AND ANALYSIS: Online participant reporting of health events in vaccinated and unvaccinated individuals 12 years of age and older is captured in three surveys: 1 week after dose 1, 1 week after dose 2 and 7 months after dose 1. Medically attended events are followed up by telephone. The number, percentage, rate per 10 000 and incident rate ratios with 95% CIs are calculated by health event, vaccine type, sex and in 10-year age groups. ETHICS AND DISSEMINATION: Each study site has Research Ethics Board approvals for the project (UBC Children's & Women's, CIUSSS de l'Estrie-CHUS, Health PEI, Conjoint Health Research Ethics Board, University of Calgary and Alberta Health Services, IWK Health, Unity Health Toronto and CHU de Québec-Université Laval Research Ethics Boards). Individuals are invited to participate in this active surveillance and electronic consent is given before proceeding to each survey. Weekly reports are shared with public health and posted on the study website. At least one peer-reviewed manuscript is produced.

Characteristics of children admitted to hospital with acute SARS-CoV-2 infection in Canada in 2020.

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.