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Background: Interpretations of pediatric COVID-19 severity are complicated by novel lineages and COVID-19 vaccine introduction. We estimated the risk of severe COVID-19 by SARS-CoV-2 lineage and vaccination status among hospitalized Canadian children., Methods: Data were collected through the Canadian Paediatric Surveillance Program (April 2020-May 2021) and Canadian Immunization Monitoring Program, ACTive (June 2021-December 2022). Patients <17 years hospitalized for COVID-19 (excluding incidental SARS-CoV-2) at 13 pediatric hospitals were included. Lineages were defined via genetic sequencing or dominant lineage upon hospitalization. Severe disease included intensive care, ventilatory/hemodynamic requirements, systemic complications, and/or death., Results: We analyzed 3218 COVID-19 hospitalizations, including 81.4% admitted during Omicron predominance. Median age was highest among Delta cases (2.9 years, interquartile range [IQR] 0.2-10.9) and lowest among Omicron BQ.1 cases (0.6 years, IQR 0.2-1.8). Severe COVID-19 remained common in Omicron vs. ancestral cases (27.2% vs. 23.2%). The proportion of hospitalized cases aged 5-16 years declined following the introduction of age-specific COVID-19 vaccines. Vaccination reduced the risk of in-hospital severe disease for ages 12-16 years (two vs. zero doses; adjusted risk ratio 0.49, 95% confidence interval 0.32-0.77)., Conclusion: More children were hospitalized with Omicron lineages than all prior lineages. COVID-19 vaccination was associated with a lower burden of severe disease among ages 5-16 years., Impact Statement: This study estimates the effect of SARS-CoV-2 lineage, Omicron sub-lineage, and vaccination on COVID-19 disease severity, using data from two Canadian national surveillance programs. Few national studies describe the clinical presentation and severity of Omicron sub-lineages among hospitalized children. In Canada, Omicron lineages were associated with substantially more pediatric COVID-19 hospitalizations than all prior lineages combined, though risk of severe COVID-19 was highest during the Delta period. COVID-19 vaccines were associated with reductions in hospitalization (ages 5-16 years) and severe disease (ages 12-16 years) across Omicron sub-lineages., Competing Interests: Competing interests: O.D. and F.K. are supported by a Clinical Research Scholars Award from the Fonds de recherche du Québec—Santé. S.A.H. received funding from multiple vaccine manufacturers to undertake phase 1–3 clinical trials of candidate COVID-19 vaccines. J.P. reported grants from Merck, and personal fees from Enanta, outside the submitted work. M.S. is supported via salary awards from the BC Children’s Hospital Foundation and Michael Smith Health Research BC. M.S. has also been an investigator on projects funded by GlaxoSmithKline, Merck, Moderna, Pfizer, and Sanofi-Pasteur. All funds have been paid to his institute, and he has not received any personal payments. K.A.T. received grants from the Coalition for Epidemic Preparedness Innovations outside the submitted work. S.K.M. has received honoraria for lectures from GlaxoSmithKline and Sanofi Pasteur and has been a member of ad hoc advisory boards for Pfizer, Sanofi Pasteur, and Apotex, all unrelated to this study. All other authors have no conflicts of interest to disclose. Consent statement: The CPSP collects data elements for national child and youth health surveillance purposes on PHAC’s behalf, whose purpose is to support health protection and promotion under the Department of Health Act 4(2)c and the Public Health Agency of Canada Act 3(15). Healthcare providers are authorized under their provincial health privacy legislation (with the exception of Quebec) to disclose protected health information to public health agencies at the local, provincial, and federal levels for surveillance purposes. CPSP does not collect any individual data elements deemed to be unique identifiers. In Quebec, CPSP studies are conducted under center-specific research ethics board approvals and data transfer agreements. This is consistent with the Canadian Medical Association and Tri-Council Policy Statements, which allow for the collection of non-nominal and nonidentifiable information for conditions under surveillance. For the IMPACT COVID-19, investigators at each IMPACT center also obtained Research Ethics Board or hospital approvals from their institution, and received waivers of consent for secondary use of patient-level data., (© 2025. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Lassa virus (LASV) belongs to the Arenavirus family. LASV is endemic in several West Africa countries and causes viral hemorrhagic fevers. The Nigeria CDC has reported that an outbreak in 2024 in 28 states has resulted in 7767 suspected cases of Lassa fever, 971 confirmed cases and 166 confirmed deaths up to 11 August. Since infection with LASV can result in sensorineural hearing loss (SNHL) in up to 30% of patients, there are questions about whether triggering the immune response by immunization with LASV vaccines could potentially cause SNHL, although this has not been shown in clinical trials to date. To address this issue, the Coalition for Epidemic Preparedness Innovations (CEPI) and the Brighton Collaboration (BC) Safety Platform for Emergency vACcines (SPEAC) convened a three-hour webinar on 22 September 2023 to review what is known from both animal studies and human clinical trials and how hearing assessments in future clinical trials can help to assess the risk. This report summarizes the evidence presented and provides considerations for hearing assessment in expanded human trials of LASV vaccine candidates in children and adults., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Cornelia L. Dekker reports a relationship with The Task Force for Global Health that includes: consulting or advisory. Cornelia L. Dekker reports a relationship with Dynavax Technologies, Inc. that includes: equity or stocks. Nicholas S. Reed reports a relationship with Neosensory Inc. that includes: consulting or advisory. Carmen C. Brewer reports a relationship with Emergent Product Development that includes: consulting or advisory. Carmen C. Brewer reports a relationship with International Aids Vaccine Initiative that includes: consulting or advisory. Gideon Akintunde reports a relationship with Emergent BioSolutions Inc. that includes: equity or stocks. Lovelyn Charles reports a relationship with Emergent BioSolutions Inc. that includes: employment. Patricia Fast reports a relationship with International Aids Vaccine Initiative that includes: employment. Daniel D. Pinschewer reports a relationship with HOOKIPA Pharma Inc. that includes: consulting or advisory, equity or stocks, funding grants, and travel reimbursement. Daniel D. Pinschewer reports a relationship with Dodet Bioscience that includes: speaking and lecture fees. Karina A. Top reports a relationship with Coalition for Epidemic Preparedness Innovations that includes: funding grants. Steven B. Black reports a relationship with Coalition for Epidemic Preparedness Innovations that includes: funding grants. Daniel D. Pinschewer has patent with royalties paid to Licensee. Co-author editorial board for Ear and Hearing - CCB If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

This scoping review examines the role of digital solutions in active, participant-centered surveillance of adverse events following initial release of COVID-19 vaccines. The goals of this paper were to examine the existing literature surrounding digital solutions and technology used for active, participant centered, AEFI surveillance of novel COVID-19 vaccines approved by WHO. This paper also aimed to identify gaps in literature surrounding digital, active, participant centered AEFI surveillance systems and to identify and describe the core components of active, participant centered, digital surveillance systems being used for post-market AEFI surveillance of WHO approved COVID-19 vaccines, with a focus on the digital solutions and technology being used, the type of AEFI detected, and the populations under surveillance. The findings highlight the need for customized surveillance systems based on local contexts and the lessons learned to improve future vaccine monitoring and pandemic preparedness.

Introduction: The Canadian National Vaccine Safety Network (CANVAS) conducted active participant-based surveillance for adverse events following immunization during the COVID-19 vaccine campaign. This study evaluated the association between COVID-19 vaccination and neurological adverse events., Methods: Participants were invited to complete online surveys to report health events that prevented daily activities and/or required medical attention within 7 days after COVID-19 vaccination or 7 days prior to the survey (unvaccinated controls); follow-up surveys were sent 7 months later. Neurological events were health events where the most severe symptom reported was ≥1 of: numbness/tingling, loss of taste or smell, vision loss, facial weakness/paralysis, seizure, weakness/paralysis of arms or legs, confusion, change in personality or behavior, or difficulty with urination or defecation. Data were extracted from the CANVAS-COVID database for analysis., Results: Completed survey responses were received from 15,273 unvaccinated controls, 758,619 dose 1 recipients, 406,884 dose 2 recipients, and 126,586 dose 3 recipients. Rates of neurological events ranged from 15.9 (95 % CI 13.6-18.4) per 10,000 dose 1 ChAdOx1 recipients to 8.4 (6.5-10.8) and 7.9 (5.7-11.0) per 10,000 dose 3 mRNA-1273 and BNT162b2 recipients, respectively. Multivariable regression adjusted for age, sex, previous SARS-CoV-2 infection, and baseline health status showed an increased risk of neurological event among ChAdOx1 dose 1 recipients versus controls (adjusted OR 2.3, 95 % CI 1.2-4.3), but not among mRNA vaccine recipients after any dose. Risk of anaesthesia/paresthesia were increased following ChAdOx1 dose 1 (aOR 4.7, 1.7-13.1), and consistently but not statistically significantly higher following any dose of either mRNA vaccine. Risk of loss of smell/taste was decreased among recipients of any dose of either mRNA vaccine versus controls., Conclusions: The results support the safety of COVID-19 vaccines while confirming reported associations between ChAdOx1 dose 1 and neurological events. Participant-based AEFI surveillance is a useful component of post-market surveillance programs., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Julie A Bettinger reports financial support was provided by Canadian Institutes of Health Research. Julie A Bettinger reports financial support was provided by Public Health Agency of Canada. Manish Sadarangani reports financial support was provided by BC Children’s Hospital Foundation. Manish Sadarangani reports financial support was provided by Michael Smith Foundation for Health Research. M Sadarangani, OG Vanderkooi, JE Isenor reports a relationship with GlaxoSmithKline Inc that includes: funding grants. M Sadarangani, OG Vanderkooi, JD Kellner reports a relationship with Merck & Co Inc that includes: funding grants. M Sadarangani, JD Kellner reports a relationship with Moderna Inc that includes: funding grants. M Sadarangani, OG Vanderkooi, JD Kellner, L Valiquette reports a relationship with Pfizer Inc that includes: funding grants. M Sadarangani, JE Isenor reports a relationship with Sanofi Pasteur Inc that includes: funding grants. OG Vanderkooi reports a relationship with Seqirus Inc that includes: funding grants. A McGeer reports a relationship with GlaxoSmithKline Inc, Merck & Co Inc, Pfizer Inc, Sanofi Pasteur Inc, Seqirus Inc that includes: consulting or advisory and funding grants. A McGeer reports a relationship with Moderna Inc, AstraZeneca Canada Inc, Medicago Inc that includes: consulting or advisory and speaking and lecture fees. KA Top reports a relationship with Coalition for Epidemic Preparedness Innovations that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The Canadian National Vaccine Safety Network conducted active safety surveillance for COVID-19 vaccines. This study aimed to characterize the short-to-medium term safety of mRNA COVID-19 vaccines across the pediatric age spectrum., Methods: In this cohort study, vaccinated and unvaccinated children and adolescents aged 6 months to 19 years from eight Canadian provinces and territories were invited to participate. The outcome was a health event preventing daily activities, resulting in school absenteeism, or requiring medical consultation. Age-stratified multivariable regression models were used to examine health events associated with first and second doses of mRNA COVID-19 vaccines across different age groups: children under 5, children aged 5-11 years and adolescents aged 12-19 years., Findings: From January 2021 through February 2023, a total of 259,361 individuals from the dose one survey, 131,032 from the dose 2 survey, and 1179 from the control survey were included. In the week following dose two, vaccinated adolescents showed a higher proportion of health events [794 (4.6%) of 17,218 BNT162b2 recipients, 98 (8.5%) of 1153 mRNA-1273 recipients, 49 of (10.6%) of 464 heterologous schedule recipients] than unvaccinated adolescents [9 (3.7%) of 242 controls], but most events were self-limited and resolved within 7 days. No significant differences in proportion of health events following mRNA COVID-19 vaccines were observed between vaccinated and unvaccinated groups among adolescents after dose 1, or among children under 5 or those aged 5-11 years after any dose. Reported myocarditis/pericarditis cases within 0-28 days peaked among male adolescents following dose 2, in three of (0.037%) 8088 homologous BNT162b2 recipients, and two of (0.529%) 378 homologous mRNA-1273 recipients., Interpretation: Our findings suggest that reported health events, including myocarditis/pericarditis, vary by pediatric age group. Vaccinated adolescents reported health events more frequently following the second mRNA COVID-19 vaccine dose, while younger age groups did not report events more frequently than their unvaccinated counterparts., Funding: Canadian Immunization Research Network, Canadian Institutes of Health Research; Public Health Agency of Canada; COVID-19 Immunity Task Force., Competing Interests: GDS, HS, HW, LV, MN, KM and OGV have no competing interests. PS received personal payments for consulting from the Joint United Nations Programme on HIV/AIDS outside the submitted work. MS has been an investigator on projects funded by GlaxoSmithKline, Merck, Moderna, Pfizer and Sanofi-Pasteur outside the submitted work. All funds were paid to his institute, and he has not received any personal payments. MPM received payment testifying as an expert with respect to mandatory influenza and COVID-19 vaccination in healthcare settings. JDK has been an investigator on projects funded by Moderna Canada and Alberta Children’s Hospital Research Institute and Government of Alberta, all outside the submitted work. All funds have been paid to his institute, and he has not received any personal payments. KAT reports grants from Canadian Institute of Health Research and the Coalition of Epidemic Preparedness Innovations for COVID-19 vaccine studies. KAT received personal payments for consulting from World Health Organization. JEI has been an investigator on projects funded by GlaxoSmithKline and Sanofi-Pasteur outside the submitted work. All funds were paid to her institute, and she has not received any personal payment. AM reports grants to her institution from Pfizer, Merck, Sanofi, and Seqirus, as well as personal payments for consulting or honoraria from Sienna Senior Living, AstraZeneca, Merck, Biogen, Sanofi, GlaxoSmithKline, Moderna, Medicago, Janssen, Novavax, Pfizer, and Seqirus. JAB has served on the Research Leadership Committee at BC Children’s Hospital Research Institute and the National Advisory Committee on Immunization., (© 2024 The Author(s).)

Background: COVID-19 vaccination has been associated with anaphylaxis and hypersensitivity reactions. Infectious disease physicians and allergists in the Canadian Special Immunization Clinic (SIC) Network developed guidance for evaluating patients with adverse events following immunization (AEFI) including suspected hypersensitivity. This study evaluated management and adverse event recurrence following subsequent COVID-19 vaccinations., Methods: Individuals aged 12 years and older enrolled at participating SICs before February 28, 2023 who were referred for suspected or diagnosed hypersensitivity reaction following COVID-19 vaccination, or for prevaccination assessment of suspected allergy to a COVID-19 vaccine component were included. De-identified clinical assessments and revaccination data, captured in a centralized database, were analyzed. The Brighton Collaboration case definition (BCCD) for anaphylaxis (2023 version) was applied., Results: The analysis included 206 participants from 13 sites: 26 participants referred for pre-vaccination assessment and 180 participants referred for adverse events following COVID-19 vaccination (15/180 [8.3%] with BCCD confirmed anaphylaxis, 84 [46.7%] with immediate hypersensitivity symptoms not meeting BCCD, 33 [18.3%] with other diagnosed hypersensitivity reactions, and 48 [26.7%] participants with a final diagnosis of non-hypersensitivity AEFI). Among participants referred for AEFIs following COVID-19 vaccination, 166/180 (92.2%) were recommended for COVID-19 revaccination after risk assessment, of whom 158/166 (95.2%) were revaccinated (all with a COVID-19 mRNA vaccine). After revaccination, 1/15 (6.7%) participants with prior anaphylaxis, 1/77 (1.3%) with immediate hypersensitivity not meeting criteria for anaphylaxis and 1/24 (4.2%) with other physician diagnosed hypersensitivity developed recurrent AEFI symptoms that met the BCCD for anaphylaxis. All 26 participants referred pre-vaccination, including 9 (34.6%) with history of polyethylene glycol-asparaginase reactions, were vaccinated without occurrence of immediate hypersensitivity symptoms., Conclusions: Most individuals in this national cohort who experienced a hypersensitivity event following COVID-19 vaccination and were referred for specialist review were revaccinated without AEFI recurrence, suggesting that specialist evaluation can facilitate safe revaccination., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: MS has been an investigator on projects funded by GlaxoSmithKline, Merck, Moderna, Pfizer, and Sanofi-Pasteur; all funds have been paid to his institute, and he has not received any personal payments. VC received honoraria from Pfizer, Aralez pharmaceuticals and CSL Behring financial support for publication from CSL Behring. JEMU reports advisory board for Pfizer, clinical trials with Sanofi, and other from Novartis, all outside the current work. KZ reports honoraria from AstraZeneca and Regeneron. JMP is an investigator on projects funded by MedImmune and Merck; all funds have been paid to his institute, and he has not received any personal payments. ZA reports honoraria for speaker fees for Pfizer outside of the submitted work. AM received honoraria for presentations from Pfizer and Sanofi. ADR participated in multicentric studies with ALK for sublingual immunotherapy as investigator. AC received honoraria for presentations from Pfizer, AstraZeneca, GlaxoSmithKline and Moderna. JC received honoraria for presentations from Pfizer, AstraZeneca, and GlaxoSmithKline. KAT has received funding to her institution from the Coalition for Epidemic Preparedness Innovations for vaccine safety studies. All other authors report no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The Canadian National Vaccine Safety (CANVAS) network conducted a multi-center, prospective vaccine safety study to collect safety data after dose 1 and 2 of COVID-19 vaccines and follow up safety information 7 months after dose 1., Objective: This study aimed to describe and evaluate the recruitment methods used by CANVAS and the retention of participants by each modality., Methods: CANVAS deployed a multi-pronged recruitment approach to reach a larger sample, without in-person recruitment. Three primary recruitment strategies were used: passive recruitment, technology-assisted electronic invitation through the vaccine booking system (auto-invitation), or auto-registration through the vaccine registries (auto-enrollment)., Results: Between December 2020 and April 2022, approximately 1.3 million vaccinated adults either self-enrolled or were auto-enrolled in CANVAS, representing about 5% of the vaccinated adult Canadian population. Approximately 1 million participants were auto-enrolled, 300,000 were recruited by auto-invitation, and 5,000 via passive recruitment. Overall survey completion rates for dose 1, dose 2 and the 7-month follow-up surveys were 51.7% (681,198 of 1,318,838), 54.3% (369,552 of 681,198), and 66.4% (452,076 of 681,198), respectively. Completion rates were lower among auto-enrolled participants compared to passively recruited or auto-invited participants who self-enrolled. However, auto-enrolled samples were much larger, which offset the lower completion rates., Conclusion: Our data suggest that auto-enrollment provided an opportunity to reach and retain a larger number of individuals in the study compared to other recruitment modalities., Competing Interests: MS has been an investigator on projects funded by GlaxoSmithKline, Merck, Moderna, Pfizer, and Sanofi-Pasteur outside the submitted work. All funds have been paid to his institute, and he has not received any personal payments. LV reports grants from Pfizer outside the submitted work. KT reports grants from the Coalition of Epidemic Preparedness Innovations for COVID-19 vaccine studies. JI has been an investigator on projects funded by GlaxoSmithKline and Sanofi-Pasteur outside the submitted work. All funds have been paid to her institute, and she has not received any personal payment. AM reports grants to her institution from Pfizer and Sanofi-Pasteur, and personal payments for consulting from AstraZeneca, Merck, GlaxoSmithKline, Moderna, Novavax, Pfizer, and Seqirus. JK has been an investigator on projects funded by GlaxoSmithKline, Merck, Moderna, and Pfizer, all outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Soe, Sadarangani, Naus, Muller, Vanderkooi, Kellner, Top, Wong, Isenor, Marty, De Serres, Valiquette, McGeer and Bettinger.)

Background & Aims: Biologic therapies in the context of inflammatory bowel disease and pregnancy lead to improved maternal and fetal outcomes. Placental transfer results in detectable drug concentrations in infants. Rotavirus infection results in diarrheal related hospitalizations; however, the live oral vaccine is not currently recommended in biologic exposed infants. The aim of this study was to assess the effect of maternal biologic therapies on the infant immune system and safety of live rotavirus vaccination in biologic-exposed infants., Methods: Biologic-exposed infants underwent standardized clinical assessments, drug concentration, and immune function testing (complete blood count, differential, immunoglobulin levels, extended B-cell and T-cell subset enumeration, Recent Thymic Emigrants, regulatory T-cell numbers, mitogen stimulation assays, and review of T-cell Receptor Excision Circles in the newborn screen). Rotavirus vaccine-specific adverse effects following immunizations up to 42 days post the last dose of the vaccine series were recorded., Results: There were 57 infants born to 52 mothers with inflammatory bowel disease exposed to infliximab (n = 21), adalimumab (n = 19), vedolizumab (n = 10), and ustekinumab (n = 7) in the third trimester for a median of 39 weeks (interquartile range, 38-39 weeks) at delivery. Immunologic assessments validated for age were normal in all infants despite median infliximab concentrations of 6.1 ug/mL (range, 0.4-28.8 ug/mL), adalimumab concentrations of 1.7 ug/mL (range, 0.7-7.9 ug/mL), ustekinumab concentrations of 0.6 ug/mL (range, 0-1.1), and undetectable for vedolizumab at 10.7 weeks (interquartile range, 9.4-12.4) of age. The live oral rotavirus vaccine series was provided to 50 infants with the first dose given at a median of 13 weeks of age. No adverse effects following immunization were reported., Conclusion: Immune function testing was normal, and administration of live rotavirus vaccination appeared low-risk in biologic-exposed infants irrespective of circulating drug levels., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

This study examined short-to-medium term safety of COVID-19 vaccines among adults aged ≥65 years using the Canadian National Vaccine Safety Network active safety surveillance data. Both vaccinated and unvaccinated older adult participants recruited from seven provinces and territories were included in the analysis. Safety was assessed at 7 days after COVID-19 vaccination (dose 1, 2 and 3), and 7 months after dose 1. Multivariable logistic regression was used to examine the association between BNT162b2/mRNA-1273 COVID-19 vaccines and two short-term health events: 1) health event preventing daily activities and/or required medical consultation, 2) serious health events resulting in an emergency department visit and/or hospitalization within 7 days following each dose. We also assessed the rates of serious health events for the period between dose 1 and 2, and 7-months following dose 1. Between December 2020 and February 2022, a total of 173,038, 104,452, and 13,970 older adults completed dose 1, dose 2, and dose 3 surveys, respectively. The control survey was completed by 2,955 unvaccinated older adults. Health events occurred more frequently among recipients after dose 2 homologous mRNA-1273 (adjusted odds ratio [95 % confidence interval]: 2.91 [2.24-3.79]) and dose two heterologous (BNT162b2 followed by mRNA-1273): 1.50 [1.12-2.02] compared to unvaccinated counterparts. There was no difference in event rates after any dose of BNT162b2 and unvaccinated participants. The rates of serious health events following COVID-19 vaccination were very low (≤0.3 %) across all vaccine products and doses, and were not higher compared to unvaccinated controls, and were not associated with an emergency department visit or hospitalization within 7 days following vaccination. Reported symptoms were self-limited and rarely required medical assessment. Our findings further strengthen the current evidence that mRNA COVID-19 vaccines are safe and can be used to inform older adults about expected adverse events following COVID-19 vaccination., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Matthew P. Muller, Otto G. Vanderkooi, James D. Kellner, Karina A. Top, Manish Sadarangani, Jennifer E. Isenor, Gaston De Serres, Louis Valiquette, and Julie A. Bettinger reports financial support was provided by Canadian Institutes of Health Research. Matthew P. Muller, Otto G. Vanderkooi, James D. Kellner, Karina A. Top, Manish Sadarangani, Jennifer E. Isenor, Gaston De Serres, Louis Valiquette, and Julie A. Bettinger reports financial support was provided by Public Health Agency of Canada. Matthew P. Muller, Otto G. Vanderkooi, James D. Kellner, Karina A. Top, Manish Sadarangani, Jennifer E. Isenor, Gaston De Serres, Louis Valiquette, and Julie A. Bettinger reports financial support was provided by COVID-19 Immunity Task Force. PS, HW, MN, JAB, MPM, JDK, KM and OGV have no competing interests. MS has been an investigator on projects funded by GlaxoSmithKline, Merck, Pfizer, Sanofi-Pasteur, Seqirus, Symvivo and VBI Vaccines outside the submitted work. All funds have been paid to his institute, and he has not received any personal payments. GDS and LV report grants from Pfizer outside the submitted work. KAT reports grants from the Coalition of Epidemic Preparedness Innovations for COVID-19 vaccine studies. JEI has been an investigator on projects funded by GlaxoSmithKline and Sanofi-Pasteur outside the submitted work. All funds have been paid to her institute, and she has not received any personal payment. AM reports grants to her institution from Pfizer and Sanofi-Pasteur, and personal payments for consulting from AstraZeneca, Merck, GlaxoSmithKline, Moderna, Novavax, Pfizer, and Seqirus., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Bordetella pertussis, which causes a respiratory disease known as pertussis ("whooping cough") remains an important global challenge, with the incidence in pertussis cases increasing in recent years. Newborns and infants are at increased risk for severe morbidity and mortality from this bacterium. Vaccination in pregnancy has become an important strategy to both passively transfer immunity as well as prevent infection in pregnant persons, who are a major source of newborn infection, thus attempting to decrease the impact of this serious disease. It is considered safe for the pregnant person, the developing fetus, and the infant, and during the first 3 months of life it has been shown to be highly effective in preventing pertussis. There are a variety of strategies, recommendations, and adherence rates associated with pertussis vaccination in pregnancy around the world. We summarize the 2021 Global Pertussis Initiative Annual Meeting that reviewed the current global status of pertussis vaccination in pregnancy and remaining medical and scientific questions, with a focus on vaccination challenges and strategies for obstetric and gynecologic healthcare providers., (© 2024 International Federation of Gynecology and Obstetrics.)

Background: Immune checkpoint inhibitor (ICI) therapy for patients undergoing cancer treatment carries a risk of severe immune-related adverse events (IRAEs). Questions remain about whether seasonal influenza vaccination might increase the risk of developing IRAEs among these patients given that vaccines are immunomodulatory. Previous vaccine safety studies on patients with cancer prescribed ICI therapy have demonstrated conflicting results., Methods: Using health administrative data from Ontario, Canada among adults diagnosed with cancer who had been prescribed ICI therapy and who had received an influenza vaccine from 2012 to 2019, we conducted a self-controlled case series study. The pre-vaccination control period started 42-days post-ICI initiation until 14-days prior to vaccination, the risk period was 1-42 days post-vaccination, and the post-vaccination control period was after the risk period until ICI discontinuation or a maximum period of two years. Emergency department (ED) visit(s) and/or hospitalization for any cause after ICI initiation was used to identify severe IRAEs. We fitted a fixed-effects Poisson regression model accounting for seasonality and calendar time to estimate relative incidence of IRAEs between risk and control periods., Results: We identified 1133 records of cancer patients who received influenza vaccination while prescribed ICI therapy. Most were aged ≥ 66 years (73 %), were male (63 %), had lung cancer (54 %), and had received ICI therapy with a programmed cell death protein 1(PD-1) inhibitor (91 %). A quarter (26 %) experienced an ED visit and/or hospitalization during the observation period. Rates of ED visits and/or hospitalizations in the risk vs. control periods were similar, with an incidence rate ratio of 1.04 (95 % CI: 0.75-1.45). Subgroup and sensitivity analyses yielded similar results., Conclusion: Seasonal influenza vaccination was not associated with an increased incidence of ED visit or hospitalization among adults with cancer treated with ICI therapy and our results support further evidence of vaccine safety., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ‘PSB has received honoraria from Canada’s Drug and Health Technology Agency (CADTH). JR has received honoraria from Roche and consulted for Lilly, Merck, AstraZeneca and Novartis. MES has received funding from GSK for a study unrelated to influenza vaccine. AC received honoraria from Pfizer, GSK and Moderna; AC consulted for Merck, Pfizer, GSK, Moderna, Innomed and Palladin Labs; AC has received funding from GSK and Pfizer for studies unrelated to influenza vaccine. All other authors report no conflicts.’., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Live attenuated varicella vaccine (LAVV) has historically been contraindicated in children who are immunocompromised due to solid organ transplant (SOT) because of safety concerns. Recently, clinical guidelines were developed that support post-transplant varicella vaccination in selected SOT recipients based on emerging evidence of LAVV safety. This qualitative study sought to explore barriers and facilitators to implementing the new guidelines, as well as acceptability of LAVV among healthcare providers (HCPs) and parents., Methods: HCPs and parents of transplant recipients were recruited from four sites using purposive sampling. Data from semi-structured interviews were analyzed using an Interpretive Description approach that incorporated data from the interviews, academic knowledge and clinical experience, and drew from Grounded Theory and Thematic Analysis. The theoretical framework used was Adaptive Leadership., Results: Thirty-four participants (16 HCPs and 18 parents) were included in the analysis. Parents developed skills in adaptive leadership that included strategies to protect their child against infectious diseases. Foundational information that live vaccines were absolutely contraindicated post-transplant "stuck" with parents and led them to develop strategies other than vaccination to keep their child safe. Some parents struggled to understand that information previously presented as a certainty (contraindication of LAVV) could change. Their approach to adaptive leadership informed their appraisal of the new vaccination guidelines and willingness to accept vaccination., Conclusions: HCPs should adopt a family-centered approach to communicating changing guidelines that considers parents' approach to adaptive leadership and discusses the changing nature of medical evidence. Trust between HCPs and parents can facilitate these conversations., (© 2023 The Authors. Pediatric Transplantation published by Wiley Periodicals LLC.)

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.)

This study aimed to synthesize the available evidence on the immunogenicity, safety, and effectiveness of live-attenuated varicella vaccine in solid organ transplant recipients. Medline and EMBASE were searched using predefined search terms to identify relevant studies. The included articles reported varicella vaccine administration in the posttransplant period in children and adults. A pooled proportion of transplant recipients who seroconverted and who developed vaccine-strain varicella and varicella disease was generated. Eighteen articles (14 observational studies and 4 case reports) were included, reporting on 711 transplant recipients who received the varicella vaccine. The pooled proportion was 88.2% (95% confidence interval 78.0%-96.0%, 13 studies) for vaccinees who seroconverted, 0% (0%-1.2%, 13 studies) for vaccine-strain varicella, and 0.8% (0%-4.9%, 9 studies) for varicella disease. Most studies followed clinical guidelines for administering live-attenuated vaccines, with criteria that could include being at least 1 year posttransplant, 2 months postrejection episode, and on low-dose immunosuppressive medications. Varicella vaccination in transplant recipients was overall safe in the included studies, with few cases of vaccine-strain-induced varicella or vaccine failure, and although it was immunogenic, the proportion of recipients who seroconverted was lower than that seen in the general population. Our data support varicella vaccination in select pediatric solid organ transplant recipients., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: This study was supported by funding from The Hospital for Sick Children Transplant and Regenerative Medicine Centre (TRMC). PPPR has been co-investigator on an investigator-led project funded by Pfizer that is unrelated to this study. JU reports being a past investigator for Sanofi/Regeneron, fees from Pfizer and AstraZeneca, all unrelated to vaccines. SKM has received honoraria for lectures from GlaxoSmithKline, was a member of ad hoc advisory boards for Pfizer, Sanofi Pasteur, and Merck and is a co-investigator on an investigator-led grant from Pfizer, all unrelated to this study. All authors have no conflict of interest relevant to this publication to declare. The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation., (Copyright © 2023 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: Individuals and healthcare providers may be uncertain about the safety of revaccination after an adverse event following immunization (AEFI). We identified factors associated with physician recommendation for revaccination and participant intention to be revaccinated among patients with adverse events following immunization (AEFIs) assessed in the Canadian Special Immunization Clinic (SIC) Network from 2013 to 2019., Methods: This prospective observational study included patients assessed in the Canadian Special Immunization Clinic Network from 2013 to 2019 for an AEFI who required additional doses of the vaccine temporally associated with their AEFI. Participants underwent standardized assessment and data collection. Physician recommendations regarding revaccination and participant intent for revaccination were recorded. AEFI impact on daily activities and need for medical attention was captured as low, moderate, high impact and serious (e.g., requiring hospitalization). Multivariable logistic regression analysis identified factors associated with physician recommendation and participant intention for revaccination, controlling for province of assessment., Results: Physician recommendation was significantly associated with the type of AEFI and AEFI impact. Compared to large local reaction, physician recommendation for revaccination was reduced for immediate hypersensitivity (aOR: 0.24 [95% CI: 0.08-0.76]) and new onset autoimmune disease (aOR: 0.16; 95% CI: 0.04-0.69). Compared to low impact AEFIs, physician recommendation was reduced for moderate (aOR: 0.22 [95% CI: 0.07-0.65]), high impact (aOR: 0.08 [95% CI: 0.02-0.30]), and serious AEFIs (aOR: 0.11 [95% CI: 0.03-0.37]). Participant intention for revaccination was significantly associated with AEFI impact, with reduced odds for high versus low impact AEFIs (aOR: 0.12 [95% CI: 0.04-0.42])., Conclusion: Physicians appear to use AEFI type and impact to guide recommendations while patients use primarily AEFI impact to form intentions for revaccination. The findings may help inform counselling for patients with AEFIs., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Karina A Top reports financial support was provided by Canadian Institutes of Health Research. Manish Sadarangani reports financial support was provided by Michael Smith Foundation for Health Research. Caroline E Munoz reports financial support was provided by Dalhousie Medical Research Foundation. Karina A Top reports a relationship with the Coalition for Epidemic Preparedness Innovations that includes: funding grants. Honoraria for speaker fees for GlaxoSmithKline, Merck all outside of the submitted work and grants as co-investigator from GSK and Merck - CC Grants outside the submitted work from Pfizer - GDS Served on ad hoc advisory committees and received contracts for undertaking clinical trials from multiple vaccine manufacturers outside the submitted work - SAH Served on an advisory board for Pfizer and Viiv outside of the submitted work - AM co-PI on an investigator led grant from Pfizer, has served on ad hoc advisory boards for Pfizer and Sanofi Pasteur, and has received speaker’s fees from GSK, all outside of the submitted work - SKM Reports grants from MedImmune outside the submitted work - JMP Has been an investigator on projects funded by GlaxoSmithKline, Merck, Moderna, Pfizer, Sanofi-Pasteur, Seqirus, Symvivo and VBI Vaccines; all funds have been paid to his institute, and he has not received any personal payments - MS Research grants from GSK, Merck and Pfizer all outside of the submitted work - BT Served on an advisory board for Sanofi outside the submitted work - WV]., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: People with inflammatory or autoimmune diseases are recommended to continue immunomodulatory biologic agents throughout pregnancy. However, concerns regarding potential immunosuppression in infants exposed to biologic agents have led to recommendations to avoid live vaccines in the first 6-12 months of life. We aimed to examine whether live rotavirus vaccine could be administered safely to infants exposed to biologic agents, assessed in the Canadian Special Immunization Clinic (SIC) Network., Methods: In this prospective cohort study, infants exposed to biologic agents in utero were referred to one of six SIC sites in Canada for rotavirus vaccination recommendations. Children with other contraindications to rotavirus vaccination or older than 15 weeks were excluded. Clinical and laboratory evaluations were conducted according to a standard clinical pathway. Data were collected for relevant medical history, pregnancy outcomes, biologic agent exposure history, physical examination, laboratory results of the child, SIC recommendations for rotavirus vaccination, rotavirus vaccine series completion, and adverse events after immunisation. After parental consent, deidentified data were transferred to a central database for analysis. Children recommended for rotavirus vaccination were followed up for 8 months after series initiation to ascertain severe and serious adverse events, including severe diarrhoea, vomiting, and intussusception., Findings: Between May 1, 2017, and Dec 31, 2021, 202 infants were assessed and 191 eligible infants were enrolled (97 [51%] were female and 94 [49%] were male). When including those exposed to multiple agents, the most common biologic agents to which infants were exposed were infliximab (67 [35%] of 191), adalimumab (49 [26%]), ustekinumab (18 [9%]), and vedolizumab (17 [9%]). Biologic agent exposure continued into the third trimester for 178 (93%) infants. No clinically significant abnormalities in lymphocyte subsets, quantitative immunoglobulins, or mitogen responses were detected. After SIC assessment, rotavirus vaccination was recommended for 187 (98%) of 191 infants, all of whom were followed up. By end of follow-up on Aug 19, 2022, 168 (90%) infants had initiated rotavirus vaccination; 150 (80%) completed the series. No serious adverse events after immunisation were reported, but three (2%) infants required medical attention, one for vomiting and change in stools who was subsequently diagnosed with gastroesophageal reflux disease, one for rash on labia unrelated to vaccination, and one for vomiting and diarrhoea associated with a milk allergy., Interpretation: Findings from this study suggest that lymphocyte subsets and the safety of live rotavirus vaccination are generally not affected by in-utero exposure to biologic agents. Rotavirus vaccination can be offered to infants exposed to anti-TNF agents in utero., Funding: Public Health Agency of Canada and Canadian Institutes of Health Research through the Canadian Immunization Research Network., Competing Interests: Declaration of interests KAT receives grants from the Public Health Agency of Canada, Canadian Institutes of Health Research, and Coalition for Epidemic Preparedness Innovations; honorarium and travel support from Healio; and support for conference attendance from the Canadian Public Health Association. CC has been a co-investigator on projects funded by GlaxoSmithKline, Merck, and Pfizer. MS has been an investigator on projects funded by GlaxoSmithKline, Merck, Moderna, Pfizer, Sanofi-Pasteur, Seqirus, Symvivo, and VBI Vaccines, for which payment has been received by his institute. SKM receives speaker fees from GlaxoSmithKline Canada and Johnson & Jonson China; has been on advisory boards for Pfizer, Sanofi-Pasteur, and Merck; and is co-investigator on an investigator-led grant funded by Pfizer. CHS receives honoraria for participation in advisory boards and speaking fees from Janssen, AbbVie, Takeda, Pfizer, Fresenius Kabi, and Bristol Myers Squibb. LM-F receives honoraria for participation in a data and safety monitoring committee from Encoded Therapeutics. P-PP-R has been a co-investigator on an investigator-led grant funded by Pfizer. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

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.)

Early in COVID-19 vaccine rollout, expert recommendations about vaccination while pregnant and breastfeeding changed rapidly. This paper addresses the (re)production of gendered power relations in these expert discourses and recommendations in Canada. We collected texts about COVID-19 vaccine use in pregnancy (N ​= ​52) that Canadian health organizations (e.g., professional societies, advisory groups, health authorities) and vaccine manufacturers made publicly available online. A discourse analysis was undertaken to investigate intertextuality (relations between texts), social construction (incorporation of assumptions about gender), and contradictions between and within texts. National expert recommendations varied in stating COVID-19 vaccines are recommended , should be offered , or may be offered , while manufacturer texts consistently stated there was no evidence. Provincial and territorial texts reproduced discrepancies between the Society of Obstetricians and Gynaecologists of Canada and National Advisory Committee on Immunization recommendations, including that COVID-19 vaccines should be versus may be offered in pregnancy. Our findings suggest gaps in data and discrepant COVID-19 vaccine recommendations, eligibility, and messaging limit guidance regarding vaccination in pregnancy. We argue that these discrepancies magnified the already common practice of deferring responsibility for the uncertainties of vaccination in pregnancy onto parents and healthcare providers. The deferral of responsibility could be reduced by harmonizing recommendations, regularly updating texts that describe evidence and recommendations, and prioritizing research into disease burden, vaccine safety, and efficacy before vaccine rollout., Competing Interests: TM, KT, and JG have no conflicts to declare., (© 2023 The Authors.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Adults previously infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop short-term immunity and may have increased reactogenicity to coronavirus disease 2019 (COVID-19) vaccines. This prospective, multicenter, 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 22 December 2020 and 27 November 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 (interquartile range: 2-6) months previously. After dose 1, individuals with moderate (bedridden) to severe (hospitalized) COVID-19 who received BNT162b2, mRNA-1273, 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 [95% confidence interval]: 3.96 [3.67-4.28] for BNT162b2, 5.01 [4.57-5.50] for mRNA-1273, and 1.84 [1.54-2.20] for ChAdox1-S compared with no infection). Following dose 2 and 3, the greater risk associated with previous infection was also present but was attenuated compared with dose 1. For all doses, the association was lower or absent after mild or asymptomatic infection., Conclusions: 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 dose., Competing Interests: Potential conflicts of interest. M. S. has been an investigator on projects funded by GlaxoSmithKline, Merck, Moderna, Pfizer, Sanofi-Pasteur, Seqirus, Symvivo, and VBI Vaccines, outside the submitted work. All funds have been paid to his institution, and he has not received any personal payments; he is also the Chair/Deputy Chair of 2 Data Safety and Monitoring Boards (DSMBs) for coronavirus disease 2019 (COVID-19) vaccine trials, involving different vaccines. O. G. V. has been an investigator, coinvestigator, and/or expert panelist on projects funded by GlaxoSmithKline, Merck, Pfizer, and Seqirus, outside the submitted work, and reports grants or contracts from Pfizer Canada and a Pneumococcal Grant in AID (paid to their institution) and consulting fees from Merck, Pfizer, Seqirus, AstraZeneca, and Sanofi-Pasteur. J. D. K. has been an investigator on projects funded by GlaxoSmithKline, Merck, Moderna, and Pfizer, outside the submitted work, and reports grants or contracts as Site Investigator for a phase 2/3, 2-part, open-label, dose-escalation, age de-escalation and randomized, observer-blind, placebo-controlled expansion study to evaluate the safety, tolerability, reactogenicity, and effectiveness of mRNA-1273 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in healthy children 6 months to less than 12 years of age (mRNA-1273-P204 Study; ClinicalTrials.gov Identifier: NCT04796896); a DSMB, VIDO (University of Saskatchewan Vaccine and Infectious Disease Organization)–sponsored COVID-19 vaccine clinical trial, “A Randomized, Observer-Blind, Dose-Escalation, Phase 1/2 Clinical Trial of COVAC Vaccines in Healthy Adults” (unpaid volunteer position); a leadership or fiduciary role in other board, society, committee, or advocacy group; the Canadian COVID-19 Immunity Task Force: Member, Leadership Group; Co-chair, Field Studies Working Party; and Lead, Pediatric Network (unpaid volunteer position). All funds have been paid to his institution, and he has not received any personal payments. K. A. T. has been an investigator on projects funded by GlaxoSmithKline, outside the submitted work, and reports grants or contracts from Canadian Institutes of Health Research, Public Health Agency of Canada (payment to their institution for vaccine safety evaluation studies), and Coalition for Epidemic Preparedness Innovations (payment to their institution for a vaccine safety study); payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing, or educational events for the Canadian Society of Allergy and Clinical Immunology (speaker’s fees on COVID-19 vaccines) and Family Practice Renewal Program (Newfoundland) (speaker’s fees for COVID-19 vaccines); consulting fees for the World Health Organization (payments to author for leading vaccines safety training in middle-income countries); support for attending meetings and/or travel from Canadian Public Health Association (support to attend in person and virtual Canadian Immunization Conference). All funds have been paid to her institution, and she has not received any personal payments. J. E. I. has been an investigator on projects funded by the Canadian Institutes of Health Research, Drug Evaluation Alliance of Nova Scotia, Dalhousie Pharmacy Endowment Fund, Shoppers Drug Mart, GlaxoSmithKline, Sanofi-Pasteur, Canadian Frailty Network, and Nova Scotia Health Research fund. All funds have been paid to her institution, and she has not received any personal payments. A. M. has been an investigator on projects funded by GlaxoSmithKline, Merck, Pfizer, Sanofi-Pasteur, and Seqirus, with funds paid to her institution, and has received honoraria for participation in advisory boards from AstraZeneca, GlaxoSmithKline, Medicago, Merck, Moderna, Pfizer, Sanofi-Pasteur, and Seqirus, and for presentations from AstraZeneca, and Moderna, including participation on a DSMB or advisory board for Pfizer, GlaxoSmithKline, Moderna, Medicago, Janssen, and AstraZeneca. G. D. S. and L. V. have been investigators on a project funded by Pfizer, outside the submitted work. All funds have been paid to their institution, and they have not received any personal payments. L. V. also reports being a co-founder and stockholder for Lumed, a company developing and commercializing expert systems in the fields of antimicrobial stewardship, infection control, and oncology. J. A. B. reports participation on an Advisory Committee for the National Advisory Committee on Immunization as a member (volunteer, unpaid participation). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

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., (© 2022 British Pharmacological Society.)

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.

Kawasaki disease (KD) is an acute systemic vasculitis primarily affecting children younger than 5 y of age that has been reported as an adverse event following immunization (AEFI). The Canadian Immunization Monitoring Program ACTive (IMPACT) conducts active surveillance for KD following immunization across Canada. We characterized KD cases reported to IMPACT between 2013 and 2018. Cases admitted to an IMPACT hospital with a physician diagnosis of complete or incomplete KD with onset 0-42 d following vaccination were reviewed. Cases meeting the Brighton Collaboration case definition (BCCD) levels of diagnostic certainty levels 1 a/b, 2a/b or 3a-e were defined as KD cases. Demographic and vaccination characteristics were compared between KD cases and non-cases. Of 84 cases reviewed, 58 met the BCCD: 47 (81%) cases met level 1a (Complete KD), 8 (14%) met level 1b (Incomplete KD), 2 (3%) met level 2a, and 1 (2%) met level 2c (Probable KD). Median age at admission was 13 months (interquartile range 7-26 months). A median of 9.5 cases were reported per year (range 4-14). Thirty-one (53%) KD cases were temporally associated with diphtheria-tetanus acellular pertussis containing vaccinations, followed by 21 (36%) cases with pneumococcal conjugate vaccines. Symptom onset was 0-14 d after vaccination in 32 (55%) cases. Echocardiogram results were available for 43 (74%) cases with 22 reported as abnormal. Age, sex, interval to symptom onset, and vaccines received were similar between KD cases and non-cases. No safety signals were detected in these data.

Competing Interests: The authors have nothing to disclose.

Objectives: To estimate the risk of recurrence of adverse events following immunization (AEFIs) upon revaccination and to determine among patients with suspected vaccine allergy whether allergy skin test positivity was associated with AEFI recurrence., Study Design: This prospective observational study included patients assessed in the Canadian Special Immunization Clinic Network from 2013 to 2019 with AEFIs who required revaccination with the vaccine temporally associated with their AEFI. Participants underwent standardized assessment and data collection. Special Immunization Clinic physicians used guidelines to inform their recommendations. Participants were followed up after revaccination to capture AEFI recurrences. Data were transferred to a central database for descriptive analysis., Results: Overall, 588 participants were assessed for 627 AEFIs; 570 (91%) AEFIs occurred in children <18 years of age. AEFIs included immediate hypersensitivity (130/627; 21%), large local reactions (110/627; 18%), nonurticarial rash (51/627; 8%), seizures (26/627; 4%), and thrombocytopenia (11/627; 2%). Revaccination was recommended to 513 of 588 (87%) participants. Among participants recommended and due for revaccination during the study period, 63% (299/477) were revaccinated. AEFI recurrence was 10% (31/299) overall, 31% (15/49) for large local reactions, and 7% (5/66) for immediate hypersensitivity. No recurrence was serious. Among 92 participants with suspected vaccine allergy who underwent skin testing and were revaccinated, the negative predictive value of skin testing for AEFI recurrence was 96% (95% CI 92.5%-99.5%)., Conclusions: Most individuals with AEFIs were safely revaccinated. Among those with suspected vaccine allergy, skin testing may help determine the safety of revaccination., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: Declaration of interests MS has been an investigator on projects funded by GlaxoSmithKline, Merck, Moderna, Pfizer, Sanofi-Pasteur, Seqirus, Symvivo, and VBI Vaccines. All funds have been paid to his institute, and he has not received any personal payments. OGV has been an investigator, coinvestigator, or expert panelist on projects funded by GlaxoSmithKline, Merck, Pfizer, and Seqirus, outside of the submitted work. JDK has been an investigator on projects funded by GlaxoSmithKline, Merck, Moderna, and Pfizer. All funds have been paid to his institute, and he has not received any personal payments. KAT has been an investigator on projects funded by GlaxoSmithKline. All funds have been paid to her institute, and she has not received any personal payments. JEI has been an investigator on projects funded by GlaxoSmithKline, and Sanofi-Pasteur. All funds have been paid to her institute, and she has not received any personal payments. AJM has been an investigator on projects funded by GlaxoSmithKline, Merck, Pfizer, Sanofi-Pasteur, and Seqirus, with funds paid to her institution, and has received honoraria for participation in advisory boards from Astra-Zeneca, GlaxoSmithKline, Medicago, Merck, Moderna, Pfizer, Sanofi-Pasteur, Seqirus, and for presentations from Astra-Zeneca, and Moderna. GDS has been an investigator on a project funded by Pfizer. All funds have been paid to his institute, and he has not received any personal payments. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

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., Competing Interests: Kevin Chan is Chair of the Acute Care Committee of the Canadian Paediatric Society, and served on the billing/finance committee of the Pediatric Section of the Ontario Medical Association. Catherine Farrell is Chair of the Scientific Steering Committee for the Canadian Paediatric Surveillance Program and a member of the Board of Directors of the Canadian Critical Care Society. She has received funding from Health Canada and the Canadian Institutes of Health Research, as well as 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, and received an honorarium for participation in the Senior Medical Advisory Committee at Ryerson Medical School. Fatima Kakkar has received salary support for a protected time from the FRQS Chercheur Boursieurs Program, and received honoraria for presentations given to the Association des Pédiatres du Québec. She has also served on the Quebec COVID-19 maternal-child health advisory committee and received grants from FRQS Reseau SIDA Maladies Infectieuses and Foundation of Stars. 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 honoraria for lectures from GlaxoSmithKline. He was a member of ad hoc advisory boards for Pfizer Canada and Sanofi Pasteur. Jesse Papenburg has received consultant fees from Merck, honoraria from Astra-Zeneca and Seegene, and is a voting member of the National Advisory Committee on Immunization. He is also site principal investigator for industry trials by MedImmune, Merck, Astra-Zeneca, and Sanofi, and is Medical Lead of the Study Steering Committee for AbbVie. Rupeena Purewal is a consultant for Verity Pharmaceuticals. Christina Ricci and Marina Salvadori are employees of the Public Health Agency of Canada. Manish Sadarangani has been an investigator on projects, unrelated to the current work, funded by GlaxoSmithKline, Merck, Moderna, Pfizer, Sanofi-Pasteur, Seqirus, Symvivo and VBI Vaccines. He is also Chair/Deputy Chair of Data Safety Monitoring Boards for two COVID-19 vaccine trials. Karina Top received a grant from GlaxoSmithKline to her institution outside the submitted work. No other competing interests were declared., (© 2022 The Authors.)

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., Competing Interests: Potential conflicts of interest. K. A. T. reports funding from the Canadian Institutes of Health Research and Public Health Agency of Canada for safety evaluation of coronavirus disease 2019 (COVID-19) vaccines and grants from GlaxoSmithKline outside the submitted work. O. L. is a named inventor on patents relating to adjuvants and human in vitro systems that predict vaccine safety assessments and reports grants for the Precision Vaccines Program from the Boston Children’s Hospital Department of Pediatrics and the Chief Scientific Office and consulting fees from Moody’s analytics. C. B. C. reports grants and contracts from the NIH and CDC for vaccine clinical trials including NIH Vaccine and Treatment Evaluation Unit (including the Moderna COVE study, Janssen ENSEMBLE study, Moderna KidCOVE study) and CDC Clinical Immunization Safety Assessment Network; grants from Merck; royalties for contributions to the UpToDate program; multiple small honoraria for lectures on COVID-19 vaccines and other vaccines; consultation fees from Altimmune (COVID-19 vaccine development), Janssen (respiratory syncytial virus vaccine development), Astellas (clinical trial data and safety monitoring board), Horizon Pharma (consultation related to care of children with chronic granulomatous disease), and Vir (influenza monoclonal antibody development); payment for expert testimony from multiple legal firms for general medical malpractice; US patent 10,981,979 B2; and serving as the president of the Pediatric Infectious Diseases Society. K. G. reports grants from the Task Force for Global Health and the CDC via the Global Vaccine Data Network for sentinel surveillance and personal fees from the CDC via the Global Vaccine Data Network for vaccine safety training materials. C. L. C. reports a grant from GAVI, the Vaccine Alliance, for vaccine safety surveillance and serving as a member of the Brighton Collaboration Scientific committee and the Institutional Biosafety committee. G. A. P. reports funding from ICW Ventures and the NIH (AI 48793, AI 33144, and AI 132348); consulting fees from Contec, Inc, 3D Communications, AstraZeneca UK Ltd, Bank of America Corporation, Eli Lily and Company, Emergent BioSolutions, Exelixis Inc, ExpertConnect, Genevant Sciences, Inc, GlaxoSmithKline, Janssen Global Services, LLC, Janssen Research & Development, LLC, Medicago USA, Medscape, LLC, Merck, Regeneron Pharmaceuticals Inc, Sanofi Pasteur SA, Syneos Health, and Vyriad; and participation on a data safety monitoring or advisory board for 3D Communications, AstraZeneca UK Ltd, Bavarian Nordic A/S, Dynavax Technologies, Genentech, Inc, GlaxoSmithKline, Janssen Global Services, LLC, and Janssen Pharmaceuticals, Inc. N. C. reports a Medical Research Future Fund grant and serving on a government advisory committee for the Australian Technical Advisory Group on Immunisation-ATAGI. B. C. reports a CDC grant and serving as a board member for the Rare Disease Foundation. R. T. C. reports grants from the Coalition for Epidemic Preparedness and Innovation and the CDC; travel support from Elsevier; honoraria payments from the Brighton Collaboration; serving as the scientific director at the Brighton Collaboration; and serving as a co-lead on the COVAX Vaccine Safety Working Group. All remaining authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.)

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.)

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.

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., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kumanan Wilson, Julie Bettinger reports financial support was provided by Canadian Immunization Research Network. Kumanan Wilson reports a relationship with CANImmunize Inc. that includes: board membership and equity or stocks. Karina Top reports a relationship with GlaxoSmithKline USA that includes: funding grants. KW is cofounder and CEO of CANImmunize; KW served as a member of the independent data safety advisory board for the COVID-19 Medicago vaccine trial., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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 and Objectives: Safety and effectiveness concerns may preclude physicians from recommending vaccination in mild/moderate inborn errors of immunity (IEI). This study describes attitudes and practices regarding vaccination among physicians who care for patients with mild/moderate B cell or mild/moderate combined immunodeficiencies (CID) and vaccination completeness among patients diagnosed with IEIs., Methods: Canadian physicians caring for children with IEI were surveyed about attitudes and practices regarding vaccination in mild/moderate IEI. Following informed consent, immunization records of pediatric patients with IEI evaluated before 7 years of age were reviewed. Vaccine completeness was defined at age 2 years as 4 doses of diphtheria-tetanus-pertussis (DTaP), 3 doses pneumococcal conjugate (PCV), and 1 dose measles-mumps-rubella (MMR) vaccines. At 7 years 5 doses of DTP and 2 doses MMR were required., Results: Forty-five physicians from 8 provinces completed the survey. Most recommended inactivated vaccines for B cell deficiency: (84% (38/45) and CID (73% (33/45). Fewer recommended live attenuated vaccines (B cell: 53% (24/45), CID 31% (14/45)). Of 96 patients with IEI recruited across 7 centers, vaccination completeness at age 2 was 25/43 (58%) for predominantly antibody, 3/13 (23%) for CID, 7/35 (20%) for CID with syndromic features, and 4/4 (100%) for innate/phagocyte defects. Completeness at age 7 was 15%, 17%, 5%, and 33%, respectively., Conclusion: Most physicians surveyed recommended inactivated vaccines in children with mild to moderate IEI. Vaccine completeness for all IEI was low, particularly at age 7. Further studies should address the reasons for low vaccine uptake among children with IEI and whether those with mild-moderate IEI, where vaccination is recommended, eventually receive all indicated vaccines., (© 2022. The Author(s).)

Background: Invasive pneumococcal disease due to Streptococcus pneumoniae can cause mortality and severe morbidity due to sepsis, meningitis and pneumonia, particularly in young children and the elderly. Recurrent invasive pneumococcal disease is rare yet serious sequelae of invasive pneumococcal disease that is associated with the immunocompromised and leads to a high mortality rate., Method: This retrospective study reviewed recurrent invasive pneumococcal disease cases from the Canadian Immunization Monitoring Program, ACTive (IMPACT) between 1991 and 2019, an active network for surveillance of vaccine-preventable diseases and adverse events following immunization for children ages 0-16 years. Data were collected from 12 pediatric tertiary care hospitals across all 3 eras of public pneumococcal conjugate vaccine implementation in Canada., Results: The survival rate within our cohort of 180 recurrent invasive pneumococcal disease cases was 98.3%. A decrease of 26.4% in recurrent invasive pneumococcal disease due to vaccine serotypes was observed with pneumococcal vaccine introduction. There was also a 69.0% increase in the rate of vaccination in children with preexisting medical conditions compared with their healthy peers., Conclusion: The decrease in recurrent invasive pneumococcal disease due to vaccine-covered serotypes has been offset by an increase of non-vaccine serotypes in this sample of Canadian children., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Competing Interests: KAT has received grants from GlaxoSmithKline to her institution for work related to vaccines that could be given to pregnant women. FMM is a member of the Data and Safety Monitoring Boards for vaccines manufactured by Pfizer (respiratory syncytial virus [RSV]), Moderna (RSV, human metapneumovirus, parainfluenza, SARS-CoV-2, influenza), Virometix (RSV), and Meissa (RSV vaccines). FMM is an investigator in research supported by Pfizer (SARS-CoV-2 vaccines), Gilead (remdesivir), the US National Institutes of Health (safety of vaccines in pregnancy, Zika virus), and the US Centers for Disease Control and Prevention (respiratory virus epidemiology) for work directly or indirectly related to vaccines that could be given to pregnant women. TM has received funding from an IWK Health Centre postdoctoral fellowship grant and is funded by the Public Health Agency of Canada and Canadian Institutes of Health Research through a Canadian Immunization Research Network postdoctoral grant. FB declares no competing interests.

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., Competing Interests: Competing interests: JAB, MPM, JDK, AMcG, JEI and KM have no competing interests. MS has been an investigator on projects funded by GlaxoSmithKline, Merck, Pfizer, Sanofi-Pasteur, Seqirus, Symvivo and VBI Vaccines outside the submitted work. All funds have been paid to his institute, and he has not received any personal payments. GDS and LV report grants from Pfizer outside the submitted work. KAT reports consultancy fees from Pfizer and a grant from GSK outside the submitted work. OGV has been an investigator, coinvestigator and/or expert panellist on projects funded by GlaxoSmithKline, Merck, Pfizer and Seqirus, outside the submitted work., (© 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.)

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.

Competing Interests: Intérêts concurrents: Anne Pham-Huy déclare avoir reçu des honoraires de la Société canadienne d’allergie et d’immunologie clinique et de l’Université de Calgary pour des présentations. Elle est présidente d’Immunisation Canada. Karina Top est co-investigatrice pour des projets subventionnés par GSK, indépendamment des travaux soumis. Elle déclare également avoir reçu des honoraires de la Société canadienne d’allergie et d’immunologie clinique, une rémunération du ministère de la Procureure générale de l’Ontario pour avoir témoigné en tant qu’experte et des honoraires à titre de conférencière de l’Association canadienne de la santé publique, indépendamment des travaux soumis. Elle est directrice du Conseil de l’AMMI Canada et membre de l’Association canadienne pour la recherche, l’évaluation et l’éducation en immunisation. Cora Constantinescu déclare avoir reçu des honoraires à titre de conférencière de GSK et Pfizer. Cynthia Seow fait partie de comités consultatifs et déclare avoir reçu des honoraires à titre de conférencière de Janssen, Abbvie, Takeda, Ferring, Shire, Pfizer, Sandoz, Pharmascience. Aucun autre intérêt concurrent n’a été déclaré.

Despite ample evidence of the safety and efficacy of the influenza vaccine and the tetanus, diphtheria, and acellular pertussis (Tdap) vaccine during pregnancy, two-thirds of pregnant women do not receive these vaccines. Providers have a significant role in increasing prenatal vaccine uptake. It is important to understand how different sources of vaccine prescribing information, such as Food and Drug Administration package inserts, influence provider recommendations. We aimed to examine the role of vaccine package inserts in provider recommendations and perceptions of safety and effectiveness of vaccines during pregnancy. A cross-sectional survey was mailed to a random, weighted sample of American College of Obstetricians and Gynecologists Fellows living in the United States in March 2019. Providers were asked about their attitudes toward package inserts, and to evaluate sample package insert statements following two different labeling rules. Their evaluations of each rule were then compared. Of the 321 respondents, the majority (90%, 288/321) recommended and/or administered maternal vaccinations. Few respondents (7.8%, 25/321) read package inserts for information regarding vaccination. Respondents were less likely to recommend sample vaccines with Pregnancy and Lactation Labeling Rule-complying inserts (46.1%, 148/321) than vaccines with Pregnancy Category inserts (87.5%, 282/321). Although most providers did not actively utilize vaccine package inserts to inform recommendations, the previous Pregnancy Categories rule was preferred compared to the Pregnancy and Lactation Labeling Rule. Collaborative efforts to update inserts with current clinical practices for pregnancy would be valuable in reducing apprehensiveness around package inserts to generate safer and more cogent recommendations for pregnant women.

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.)

Group A Streptococcus (GAS) pharyngitis is a common clinical syndrome in primary care, yet controversy remains regarding the best approach to diagnosis and treatment, including the benefits of antibiotics. Children who are likely to have GAS pharyngitis based on history or physical examination should have a throat swab and, when positive, be treated with amoxicillin or penicillin. The disproportionate burden of acute rheumatic fever in Indigenous populations in Canada and special considerations for testing and treatment are discussed., (© Canadian Paediatric Society 2021. Published by Oxford University Press on behalf of the Canadian Paediatric Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Competing Interests: Competing interests: Anne Pham-Huy reports presentation honoraria from the Canadian Society of Allergy and Clinical Immunology and the University of Calgary. She is the chair of Immunize Canada. Karina Top is a co-investigator on grants from GSK, outside the submitted work. She also reports an honorarium from the Canadian Society of Allergy and Clinical Immunology, payment for expert testimony from the Ontario Ministry of the Attorney General and conference support from the Canadian Public Health Association, outside the submitted work. She is the director of the AMMI Canada Council and a member of the Canadian Association for Immunization Research Evaluation and Education. Cora Constantinescu reports speaker fees from GSK and Pfizer. Cynthia Seow sits on the advisory boards for and reports speaker fees from Janssen, Abbvie, Takeda, Ferring, Shire, Pfizer, Sandoz, Pharmascience. No other competing interests were declared.

Importance: Seasonal influenza vaccination in pregnancy can reduce influenza illness among pregnant women and newborns. Evidence is limited on whether seasonal influenza vaccination in pregnancy is associated with adverse childhood health outcomes., Objective: To assess the association between maternal influenza vaccination during pregnancy and early childhood health outcomes., Design, Setting, and Participants: Retrospective cohort study, using a birth registry linked with health administrative data. All live births in Nova Scotia, Canada, between October 1, 2010, and March 31, 2014, were included, with follow-up until March 31, 2016. Adjusted hazard ratios (HRs) and incidence rate ratios (IRRs) with 95% confidence intervals were estimated while controlling for maternal medical history and other potential confounders using inverse probability of treatment weighting., Exposures: Seasonal influenza vaccination during pregnancy., Main Outcomes and Measures: Childhood outcomes studied were immune-related (eg, asthma, infections), non-immune-related (eg, neoplasms, sensory impairment), and nonspecific (eg, urgent or inpatient health care utilization), measured from emergency department and hospitalization databases., Results: Among 28 255 children (49% female, 92% born at ≥37 weeks' gestation), 10 227 (36.2%) were born to women who received seasonal influenza vaccination during pregnancy. During a mean follow-up of 3.6 years, there was no significant association between maternal influenza vaccination and childhood asthma (incidence rate, 3.0 vs 2.5 per 1000 person-years; difference, 0.53 per 1000 person-years [95% CI, -0.15 to 1.21]; adjusted HR, 1.22 [95% CI, 0.94 to 1.59]), neoplasms (0.32 vs 0.26 per 1000 person-years; difference, 0.06 per 1000 person-years [95% CI, -0.16 to 0.28]; adjusted HR, 1.26 [95% CI, 0.57 to 2.78]), or sensory impairment (0.80 vs 0.97 per 1000 person-years; difference, -0.17 per 1000 person-years [95% CI, -0.54 to 0.21]; adjusted HR, 0.82 [95% CI, 0.49 to 1.37]). Maternal influenza vaccination in pregnancy was not significantly associated with infections in early childhood (incidence rate, 184.6 vs 179.1 per 1000 person-years; difference, 5.44 per 1000 person-years [95% CI, 0.01 to 10.9]; adjusted IRR, 1.07 [95% CI, 0.99 to 1.15]) or with urgent and inpatient health services utilization (511.7 vs 477.8 per 1000 person-years; difference, 33.9 per 1000 person-years [95% CI, 24.9 to 42.9]; adjusted IRR, 1.05 [95% CI, 0.99 to 1.16])., Conclusions and Relevance: In this population-based cohort study with mean follow-up duration of 3.6 years, maternal influenza vaccination during pregnancy was not significantly associated with an increased risk of adverse early childhood health outcomes.

This is a Brighton Collaboration Case Definition of the term "Multisystem Inflammatory Syndrome in Children and Adults (MIS-C/A)" to be utilized in the evaluation of adverse events following immunization. The case definition was developed by topic experts convened by the Coalition for Epidemic Preparedness Innovations (CEPI) in the context of active development of vaccines for SARS-CoV-2. The format of the Brighton Collaboration was followed, including an exhaustive review of the literature, to develop a consensus definition and defined levels of certainty. The document underwent peer review by the Brighton Collaboration Network and by selected expert external reviewers prior to submission. The comments of the reviewers were taken into consideration and edits incorporated into this final manuscript., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: NP Klein has received research support from Pfizer for COVID-19 vaccine clinical trials and from Pfizer, Merck, GSK, Sanofi Pasteur and Protein Science (now Sanofi Pasteur) for unrelated studies. FM Munoz is a consultant for the Coalition for Epidemic Preparedness Innovations (CEPI) for the development of Brighton Collaboration Case Definitions for the Safety Platform for Emergency vACcines (SPEAC) Project. The following authors have no conflict of interests to disclose: TP Vogel, KA Top, C Karatzios, DC Hilmers, LI Tapia, P Moceri, L Giovannini-Chami, N Wood, R Chandler, EP Schlaudecker, MC Poli, E Muscal. The findings, opinions and assertions contained in the consensus document are those of the individual scientific professional members of the working group. They do not necessarily represent the official positions of each participant’s organization (e.g., government, university or corporation). Specifically, the findings and conclusions in the paper are those of the authors and do not necessarily represent the views of their respective institutions., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The World Health Organization recommends immunization with inactivated influenza vaccine (IIV) and tetanus-diphtheria-acellular pertussis (Tdap) vaccine during pregnancy. Yet, product labelling information for IIV and Tdap sends a different message. In a previous study, we developed evidence-based statements about vaccination in pregnancy that could be included in product information. This study compares healthcare providers' perceptions of the revised statements to those currently used in vaccine product labelling information., Methods: A 30-item online survey with qualitative and quantitative components was distributed to Canadian maternal healthcare providers via professional organizations and public health. Participants read excerpts from revised and existing IIV and Tdap product labelling information and answered questions about how they perceived the safety and effectiveness of the vaccines, whether they would recommend each vaccine during pregnancy, and which statements they preferred., Results: From June to August 2018, 449 healthcare providers completed the survey, including physicians (45%), nurses (24%), midwives (27%) and others (5%). Most participants perceived the vaccines to be safe and effective based on the revised statements. Over twice as many participants said they would recommend the IIV and Tdap vaccines in pregnancy based on the revised rather than the existing statements (64% versus 21% for IIV and 63% versus 27% for Tdap). Most participants selected that the revised statements better explained the risks and benefits of vaccination in pregnancy (65% versus 21% for IIV; 51% versus 27% for Tdap). Qualitative comments highlighted the strengths of the revised statements and areas for improvement., Conclusions: The majority of participants demonstrated preferences for the revised IIV and Tdap product label statements over the existing statements. Comments suggested the revised statements include improvements to the evidence-base and readability. Involving stakeholders improved the development of product labelling information, but further improvement is needed to support the evidence-based use of vaccines in pregnancy., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Karina A Top has received grants from GSK and consultancy fees from Pfizer outside the submitted work. All other authors report no conflicts of interest., (Copyright © 2021 Elsevier Ltd. All rights reserved.)