Publications by authors named "Manish Sadarangani"

150 Publications

Re-vaccination and adverse event recurrence in patients with adverse events following immunization.

J Pediatr 2022 Aug 7. Epub 2022 Aug 7.

Department of Community Health and Epidemiology, Dalhousie University, Halifax, Nova Scotia, Canada; Canadian Center for Vaccinology, IWK Health, Nova Scotia Health, and Dalhousie University, Halifax, Nova Scotia, Canada; Department of Pediatrics, Dalhousie University. Electronic address:

Objectives: To estimate the risk of recurrence of adverse events following immunization (AEFIs) upon re-vaccination 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 (SIC) Network from 2013 to 2019 with AEFIs who required re-vaccination with the vaccine temporally associated with their AEFI. Participants underwent standardized assessment and data collection. SIC physicians used guidelines to inform their recommendations. Participants were followed up post-re-vaccination 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%), non-urticarial rash (51/627; 8%), seizures (26/627; 4%), and thrombocytopenia (11/627; 2%). Re-vaccination was recommended to 513/588 (87%) participants. Among participants recommended and due for re-vaccination during the study period, 63% (299/477) were re-vaccinated. 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 re-vaccinated, the negative predictive value of skin testing for AEFI recurrence was 96% (95% CI: 92.5-99.5%).

Conclusion: Most individuals with AEFIs were safely re-vaccinated. Among those with suspected vaccine allergy, skin testing may help determine the safety of re-vaccination.
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http://dx.doi.org/10.1016/j.jpeds.2022.07.019DOI Listing
August 2022

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

Lancet Reg Health Am 2022 Nov 1;15:100337. Epub 2022 Aug 1.

Centre for Global Child Health, The Hospital for Sick Children, Toronto, Canada.

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.
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http://dx.doi.org/10.1016/j.lana.2022.100337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9342862PMC
November 2022

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

Hum Vaccin Immunother 2022 Jul 26:2104019. Epub 2022 Jul 26.

Canadian Center for Vaccinology, IWK Health, Nova Scotia Health and Dalhousie University, Halifax, Canada.

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.
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http://dx.doi.org/10.1080/21645515.2022.2104019DOI Listing
July 2022

The epidemiology of aseptic meningitis in New Zealand children from 1991 to 2020.

J Paediatr Child Health 2022 Jul 21. Epub 2022 Jul 21.

Department of Paediatrics, University of Otago Christchurch, Christchurch, New Zealand.

Aim: Aseptic meningitis, including culture negative and viral meningitis, contributes a significant health-care burden, including unnecessary antibiotic use and hospitalisation to treat possible bacterial meningitis. This study analysed aseptic meningitis hospitalisations in New Zealand (NZ) children over 29 years.

Methods: In this population-based study, aseptic meningitis hospitalisations in NZ children <15 years old were analysed from 1991 to 2020. Incident rate ratios were calculated using Poisson regression models. Variations in hospitalisations by age, year, sex, ethnicity, geographical region and socio-economic deprivation were analysed.

Results: There were 5142 paediatric aseptic meningitis hospitalisations from 1991 to 2020. Most were unspecified viral meningitis (64%), followed by enterovirus (29%). Hospitalisation rates varied annually with a median of 18.4/100 000 children including a peak in 2001 of 56.4/100 000 (51.7-61.6). From 2002 to 2019, rates increased by 8.4%/year (7.2-9.5%) in infants <90 days old but decreased in all other age groups. In 2020, a reduction in hospitalisations to 9.6/100 000 (7.9-11.8) occurred, and in infants <90 days old were 0.37 times expected. Hospitalisations were 1.50 times (1.49-1.68) higher in males than females; higher in children of Māori (P < 0.001) and Pacific (P < 0.001) versus European ethnicity; and higher for children living in the most (2.44 times, (2.16-2.75)) versus least deprived households; and in northern versus southern NZ.

Conclusions: Aseptic meningitis hospitalisations increased in young infants during 29 years of surveillance, apart from 2020 when admissions reduced during the COVID-19 pandemic. In contrast, hospitalisations decreased in children aged >1 year. Further investigation into reasons for higher admissions by ethnic group, geographical location and increased deprivation are required.
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http://dx.doi.org/10.1111/jpc.16131DOI Listing
July 2022

Kawasaki disease following immunization reported to the Canadian Immunization Monitoring Program ACTive (IMPACT) from 2013 to 2018.

Hum Vaccin Immunother 2022 Jul 7:2088215. Epub 2022 Jul 7.

Department of Pediatrics, Dalhousie University, and Canadian Center for Vaccinology, IWK Health, Halifax, NS, Canada.

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.
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http://dx.doi.org/10.1080/21645515.2022.2088215DOI Listing
July 2022

Parents' perceptions on COVID-19 vaccination as the new routine for their children ≤ 11 years old.

Prev Med 2022 08 2;161:107125. Epub 2022 Jul 2.

Faculty of Nursing, University of Alberta, Edmonton, Alberta, Canada; School of Public Health, University of Alberta, Edmonton, Alberta, Canada. Electronic address:

Canadian children 5-11 years old became eligible for COVID-19 vaccination on November 19, 2021, with eligibility for younger children expected later. We aimed to descriptively assess parents' COVID-19 vaccine intentions and acceptability of future doses, including co-administration and annual vaccination for their children. We conducted a cross-sectional Canadian online survey of parents from October 14-November 12, 2021, just prior to authorization of the pediatric formulation of the BNT162b2 COVID-19 vaccine for children aged 5-11 years. We assessed parents' intention to vaccinate their children aged 5-11 years, 2-4 years, and 6-23 months; reasons for their intention; and preferences for delivery and access to vaccines. Of 1129 parents, 56% intended to vaccinate their child aged 5-11 years against COVID-19; intentions were lower for children aged 6-23 months (41.9%) and 2-4 years (45.4%). Most parents who intended to vaccinate supported co-administration with routine (61.1%) or influenza (55.4%) vaccines, administration at school (63.6%), receipt of booster doses of COVID-19 vaccine (57.8%), and annual vaccination (56.4%) for their child. Despite parents' high COVID-19 vaccination uptake for themselves (88.8%), intentions for children aged 5-11 years was low. Currently, 56.9% of Canadian children aged 5-11 years have received one dose of a COVID-19 vaccine, and only 37.1% are fully vaccinated. Given that intentions for children <5 years was lower than those 5-11 years, we can also expect low uptake in this group. Parents' preferences regarding delivery and access to COVID-19 vaccination should be considered by public health officials when planning vaccination strategies for children.
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http://dx.doi.org/10.1016/j.ypmed.2022.107125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9250244PMC
August 2022

": exploring health care providers' views and behaviours regarding COVID-19 vaccination.

Hum Vaccin Immunother 2022 Jun 29:2088970. Epub 2022 Jun 29.

Faculty of Nursing, University of Alberta, Edmonton, AB, Canada.

Background: Health care providers' knowledge and attitudes about vaccines are important determinants of their own vaccine uptake, their intention to recommend vaccines, and their patients' vaccine uptake. This qualitative study' objective was to better understand health care providers' vaccination decisions, their views on barriers to COVID-19 vaccine acceptance and proposed solutions, their opinions on vaccine policies, and their perceived role in discussing COVID-19 vaccination with patients.

Methods: Semi-structured interviews on perceptions of COVID-19 vaccines were conducted with Canadian health care providers (N = 14) in spring 2021. A qualitative thematic analysis using NVivo was conducted.

Results: Participants had positive attitudes toward vaccination and were vaccinated against COVID-19 or intended to do so once eligible (two delayed their first dose). Only two were actively promoting COVID-19 vaccination to their patients; others either avoided discussing the topic or only provided answers when asked questions. Participants' proposed solutions to enhance COVID-19 vaccine uptake in the public were in relation to access to vaccination services, information in multiple languages, and community outreach. Most participants were in favor of mandatory vaccination policies and had mixed views on the potential impact of the Canadian vaccine-injury support program.

Conclusions: While health care providers are recognized as a key source of information regarding vaccines, participants in our study did not consider it their role to provide advice on COVID-19 vaccination. This is a missed opportunity that could be avoided by ensuring health care providers have the tools and training to feel confident in engaging in vaccine discussions with their patients.
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http://dx.doi.org/10.1080/21645515.2022.2088970DOI Listing
June 2022

Estimating population-based incidence of community-acquired pneumonia and acute otitis media in children and adults in Ontario and British Columbia using health administrative data, 2005-2018: a Canadian Immunisation Research Network (CIRN) study.

BMJ Open Respir Res 2022 06;9(1)

Centre for Vaccine Preventable Diseases, University of Toronto, Toronto, Ontario, Canada

Background: There is a paucity of data on the burden of the full spectrum of community-acquired pneumonia (CAP) and acute otitis media (AOM) from outpatient and inpatient settings across the age spectrum.

Methods: We conducted a population-based retrospective study in Ontario and British Columbia (BC), Canada, to estimate the incidence rate of CAP and AOM in children and adults over a 14-year period using health administrative databases. CAP and AOM cases were identified from outpatient physician consultation and hospitalisation data in both provinces, and from emergency department visit data in Ontario.

Results: During 2005-2018, Ontario had 3 607 124 CAP, 172 290 bacterial CAP, 7814 pneumococcal pneumonia, and 8 026 971 AOM cases. The incidence rate of CAP declined from 3077/100 000 in 2005 to 2604/100 000 in 2010 before increasing to 2843/100 000 in 2018; bacterial CAP incidence rate also declined from 178/100 000 in 2005 to 112/100 000 in 2010 before increasing to 149/100 000 in 2018. The incidence rate of AOM decreased from 4192/100 000 in 2005 to 3178/100 000 in 2018. BC had 970 455 CAP, 317 913 bacterial CAP, 35 287 pneumococcal pneumonia and 2 022 871 AOM cases. The incidence rate of CAP in BC decreased from 2214/100 000 in 2005 to 1964/100 000 in 2010 before increasing to 2176/100 000 in 2018; bacterial CAP incidence rate increased from 442/100 000 in 2005 to 981/100 000 in 2018. The incidence rate of AOM decreased from 3684/100 000 in 2005 to 2398/100 000 in 2018. The incidence rate of bacterial CAP increased with age in older adults (≥65 years) with the highest burden in the oldest cohort aged ≥85 years both before and after 13-valent pneumococcal conjugate vaccine (PCV13) programme in both provinces. Hospitalised pneumococcal pneumonia decreased slightly but non-hospitalised pneumococcal pneumonia increased in BC during PCV13 period. No consistent direct benefit of PCV13 on CAP was observed in the paediatric population.

Conclusions: There is a substantial burden of CAP and AOM in Ontario and BC. Indirect benefits from childhood PCV vaccination and polysaccharide vaccination of older adults have not substantially decreased the burden of pneumococcal pneumonia in older adults.
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http://dx.doi.org/10.1136/bmjresp-2022-001218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9240885PMC
June 2022

Impact of vaccination during pregnancy on infants' immune responses to vaccinations- definitions and statistical approaches.

Vaccine 2022 Jul 22;40(32):4292-4295. Epub 2022 Jun 22.

Department of Pediatrics, Division of Infectious Diseases, University of British Columbia, Vancouver, British Columbia, Canada; Vaccine Evaluation Center, British Columbia Children's Hospital Research Institute, Vancouver, British Columbia, Canada. Electronic address:

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http://dx.doi.org/10.1016/j.vaccine.2022.06.045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9217140PMC
July 2022

Barriers to Accessing Contraception and Cervical and Breast Cancer Screening During the COVID-19 Pandemic.

J Obstet Gynaecol Can 2022 Jun 20. Epub 2022 Jun 20.

School of Population and Public Health, University of British Columbia, University of British Columbia, Vancouver, BC, Canada V6T 1Z4.

Objective: This study sought to examine how access to contraception and cervical and breast cancer screening British Columbia, Canada, has been affected by COVID-19 pandemic.

Methods: From August 2020 to March 2021, 3691 female residents of British Columbia (age 25-69 y) participated in this study. We used generalized estimating equations to analyze the proportion of females accessing contraception and the proportion having difficulty accessing contraception across the phases of pandemic control measures, and logistic regression to analyze cervical and breast cancer screening. We added sociodemographic and biological variables individually into the models. Self-reported barriers to accessing contraception and attending screening were summarized.

Results: During phases with the highest pandemic controls, self-reported access to contraception was lower (OR 0.94; 95% CI 0.90-0.98; P = 0.005) and difficulty with access was higher (OR 2.74; 95% CI 1.54-4.88; P = 0.001). A higher proportion of adults aged 25-34 years reported difficulty accessing contraception than those aged 35-39 years (P < 0.0001), and participants identifying as Indigenous had higher odds of access difficulties (OR 5.56; 95% CI 2.44-12.50; P < 0.001). Of those who required screening during the COVID-19 pandemic, 62% and 54.5% did not attend at least one of their cervical or breast screening appointments, respectively. Those with a history of breast cancer had significantly higher odds of self-reporting having attended their mammogram appointment compared with those without a history of breast cancer (OR 5.62; 95% CI 2.69-13.72; P < 0.001). The most common barriers to screening were difficulty getting an appointment and appointments being considered non-urgent.

Conclusions: The COVID-19 pandemic has uniquely affected access to contraception and cancer screening participation for various demographics. Self-reported data present potential avenues for mitigating barriers.
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http://dx.doi.org/10.1016/j.jogc.2022.05.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9212845PMC
June 2022

Naturally acquired antibody against Haemophilus influenzae type a in pediatric saliva.

J Immunol Methods 2022 Aug 12;507:113306. Epub 2022 Jun 12.

Vaccine Evaluation Center, BC Children's Hospital Research Institute, Vancouver, British Columbia, Canada; Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada.

We developed a salivary assay for the detection of naturally acquired IgA antibody against Haemophilus influenzae type a (Hia) capsular polysaccharide in healthy Indigenous children from Northwestern Ontario, Canada. Hia-specific IgA antibody was detected in the saliva of 93% of Indigenous children aged 2-7 years.
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http://dx.doi.org/10.1016/j.jim.2022.113306DOI Listing
August 2022

Thrombosis and hemorrhage experienced by hospitalized children with SARS-CoV-2 infection or MIS-C: Results of the PICNIC registry.

Pediatr Blood Cancer 2022 09 11;69(9):e29793. Epub 2022 Jun 11.

Department of Pediatrics, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.

Introduction: Coagulopathy and thrombosis associated with SARS-CoV-2 infection are well defined in hospitalized adults and leads to adverse outcomes. Pediatric studies are limited.

Methods: An international multicentered (n = 15) retrospective registry collected information on the clinical manifestations of SARS-CoV-2 and multisystem inflammatory syndrome (MIS-C) in hospitalized children from February 1, 2020 through May 31, 2021. This sub-study focused on coagulopathy. Study variables included patient demographics, comorbidities, clinical presentation, hospital course, laboratory parameters, management, and outcomes.

Results: Nine hundred eighty-five children were enrolled, of which 915 (93%) had clinical information available; 385 (42%) had symptomatic SARS-CoV-2 infection, 288 had MIS-C (31.4%), and 242 (26.4%) had SARS-CoV-2 identified incidentally. Ten children (1%) experienced thrombosis, 16 (1.7%) experienced hemorrhage, and two (0.2%) experienced both thrombosis and hemorrhage. Significantly prevalent prothrombotic comorbidities included congenital heart disease (p-value .007), respiratory support (p-value .006), central venous catheter (CVC) (p = .04) in children with primary SARS-CoV-2 and in those with MIS-C included respiratory support (p-value .03), obesity (p-value .002), and cytokine storm (p = .012). Comorbidities prevalent in children with hemorrhage included age >10 years (p = .04), CVC (p = .03) in children with primary SARS-CoV-2 infection and in those with MIS-C encompassed thrombocytopenia (p = .001) and cytokine storm (p = .02). Eleven patients died (1.2%), with no deaths attributed to thrombosis or hemorrhage.

Conclusion: Thrombosis and hemorrhage are uncommon events in children with SARS-CoV-2; largely experienced by those with pre-existing comorbidities. Understanding the complete spectrum of coagulopathy in children with SARS-CoV-2 infection requires ongoing research.
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http://dx.doi.org/10.1002/pbc.29793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9350140PMC
September 2022

Factors associated with intention to receive vaccines for bacterial sexually transmitted infections among young HPV-vaccinated Canadian women.

Can J Public Health 2022 May 26. Epub 2022 May 26.

BC Women's Hospital and Health Service, Women's Health Research Institute, Box 42, Room H203G - 4500 Oak Street, Vancouver, BC, V6H 3N1, Canada.

Objective: The aim of this study was to explore the acceptability of bacterial STI vaccines among young HPV-vaccinated Canadian women to inform future vaccine program implementation.

Methods: A 20-item cross-sectional questionnaire was administered from June 2019 to June 2020 to HPV-vaccinated participants of the pan-Canadian QUEST cohort. Multivariable logistic regression models assessed interest in chlamydia, syphilis, and gonorrhea vaccines using a priori variables and factors significant in bivariate analysis.

Results: Of the 1092 respondents analyzed, 82% indicated interest in receiving one or more future STI vaccines. Respondents had a median age of 19.6 years (range 16.9-23.4), and 75% of respondents identified as white/European descent. In adjusted analyses, intent to engage in positive health behaviours was associated with vaccine interest for syphilis (OR = 5.76, 95% CI 4.03-8.27), chlamydia (OR = 5.27, 95% CI 3.66-7.63), and gonorrhea (OR = 5.96, 95% CI 4.15-8.60). Willingness to pay for an STI vaccine was also associated with vaccine interest for syphilis (OR = 2.02, 95% CI 1.29-3.19), chlamydia (OR = 2.41, 95% CI 1.50-3.90), and gonorrhea (OR = 2.29, 95% CI 1.44-3.63). Ever having sexual intercourse and identifying as LGBTQ were significantly associated with vaccine interest for all infections, while age and ever being immunosuppressed were not significant in any adjusted models.

Conclusion: Findings indicate over 80% of participants in a cohort of young HPV-vaccinated Canadian women are interested in receiving future bacterial STI vaccines. Further exploration of STI vaccine acceptability among diverse populations is required to inform future bacterial STI vaccine program implementation.
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http://dx.doi.org/10.17269/s41997-022-00648-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9134722PMC
May 2022

COVID-19 vaccine uptake and intention during pregnancy in Canada.

Can J Public Health 2022 08 27;113(4):547-558. Epub 2022 Apr 27.

Faculty of Nursing, University of Alberta, Edmonton, AB, Canada.

Objective: To investigate COVID-19 vaccine uptake and intent among pregnant people in Canada, and determine associated factors.

Methods: We conducted a national cross-sectional survey among pregnant people from May 28 through June 7, 2021 (n = 193). Respondents completed a questionnaire to determine COVID-19 vaccine acceptance (defined as either received or intend to receive a COVID-19 vaccine during pregnancy), factors associated with vaccine acceptance, and rationale for accepting/not accepting the vaccine.

Results: Of 193 respondents, 57.5% (n = 111) reported COVID-19 vaccine acceptance. Among those who did not accept the vaccine, concern over vaccine safety was the most commonly cited reason (90.1%, n = 73), and 81.7% (n = 67) disagreed with receiving a vaccine that had not been tested in pregnant people. Confidence in COVID-19 vaccine safety (aOR 16.72, 95% CI: 7.22, 42.39), Indigenous self-identification (aOR 11.59, 95% CI: 1.77, 117.18), and employment in an occupation at high risk for COVID-19 exposure excluding healthcare (aOR 4.76, 95% CI: 1.32, 18.60) were associated with vaccine acceptance. Perceived personal risk of COVID-19 disease was not associated with vaccine acceptance in the multivariate model.

Conclusion: Vaccine safety is a primary concern for this population. Safety information should be communicated to this population as it emerges, along with clear messaging on the benefits of vaccination, as disease risk is either poorly understood or poorly valued in this population.
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http://dx.doi.org/10.17269/s41997-022-00641-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9045023PMC
August 2022

Two-dose SARS-CoV-2 vaccine effectiveness with mixed schedules and extended dosing intervals: test-negative design studies from British Columbia and Quebec, Canada.

Clin Infect Dis 2022 Apr 19. Epub 2022 Apr 19.

BC Centre for Disease Control, Public Health Laboratory, Vancouver, British Columbia, Canada.

Background: The Canadian COVID-19 immunization strategy deferred second doses and allowed mixed schedules. We compared two-dose vaccine effectiveness (VE) by vaccine type (mRNA and/or ChAdOx1), interval between doses, and time since second dose in two of Canada's larger provinces.

Methods: Two-dose VE against SARS-CoV-2 infection or hospitalization among adults ≥18-years-old, including due to Alpha, Gamma and Delta variants of concern (VOC), was assessed at ≥14 days post-vaccination by test-negative design studies separately conducted in British Columbia and Quebec, Canada between May 30 and November 27 (epi-weeks 22-47), 2021.

Results: In both provinces, all homologous or heterologous mRNA and/or ChAdOx1 two-dose schedules were associated with ≥90% reduction in SARS-CoV-2 hospitalization risk for at least 7 months. With slight decline from a peak of >90%, VE against infection was ≥80% for at least 6 months following homologous mRNA vaccination, lower by ∼10% when both doses were ChAdOx1 but comparably-high following heterologous ChAdOx1 + mRNA receipt. Findings were similar by age group, sex and VOC. VE was significantly higher with longer 7-8-week vs. manufacturer-specified 3-4-week interval between mRNA doses.

Conclusions: Two doses of any mRNA and/or ChAdOx1 combination gave substantial and sustained protection against SARS-CoV-2 hospitalization, spanning Delta-dominant circulation. ChAdOx1 VE against infection was improved by heterologous mRNA series completion. A 7-8-week interval between first and second doses improved mRNA VE and may be the optimal schedule outside periods of intense epidemic surge. Findings support interchangeability and extended intervals between SARS-CoV-2 vaccine doses, with potential global implications for low-coverage areas and, going forward, for children.
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http://dx.doi.org/10.1093/cid/ciac290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9047203PMC
April 2022

Predictors of severe illness in children with multisystem inflammatory syndrome after SARS-CoV-2 infection: a multicentre cohort study.

CMAJ 2022 04;194(14):E513-E523

Department of Epidemiology (Merckx), Biostatistics and Occupational Health, McGill University, Montréal, Que.; Department of Pediatrics (Cooke, Dewan, Restivo), University of Calgary, Calgary, Alta.; Department of Pediatrics (El Tal, Bitnun, Morris, Yeh, Yea, Gill), University of Toronto, Toronto, Ont.; Department of Pediatrics (Papenburg, Lefebvre, Scuccimarri), McGill University, Montréal, Que.; Department of Pediatrics (Ulloa-Gutierrez, Brenes-Chacon, Yock-Corrales, Ivankovich-Escoto, Soriano-Fallas, Hernandez-de Mezerville), Hospital Nacional de Niños Dr. Carlos Sáenz Herrera, Caja Costarricense de Seguro Social, San José, Costa Rica; Department of Pediatrics (Nateghian, Haghighi Aski, Manafi), Iran University of Medical Sciences, Tehran, Iran; Department of Pediatrics (Dwilow, Bullard), University of Manitoba, Winnipeg, Man.; Department of Pediatrics (Lopez, Sadarangani, Roberts), University of British Columbia; Vaccine Evaluation Center (Sadarangani), BC Children's Hospital Research Institute, Vancouver, BC; Department of Pediatrics (Barton, Petel), Western University, London, Ont.; Department of Pediatrics (Le Saux, Bowes), University of Ottawa, Ottawa, Ont.; Department of Pediatrics (Purewal, Lautermilch, Tehseen), University of Saskatchewan, Saskatoon, Sask.; Department of Pediatrics (Bayliss), Trillium Health Partners, Mississauga, Ont.; Department of Pediatrics (Wong), McMaster University, Hamilton, Ont.; Department of Pediatrics (Leifso), Queen's University, Kingston, Ont.; Department of Pediatrics (Foo), Memorial University, St John's, NL; Department of Pediatrics (Robinson), University of Alberta, Edmonton, Alta.

Background: SARS-CoV-2 infection can lead to multisystem inflammatory syndrome in children (MIS-C). We sought to investigate risk factors for admission to the intensive care unit (ICU) and explored changes in disease severity over time.

Methods: We obtained data from chart reviews of children younger than 18 years with confirmed or probable MIS-C who were admitted to 15 hospitals in Canada, Iran and Costa Rica between Mar. 1, 2020, and Mar. 7, 2021. Using multivariable analyses, we evaluated whether admission date and other characteristics were associated with ICU admission or cardiac involvement.

Results: Of 232 children with MIS-C (median age 5.8 yr), 130 (56.0%) were male and 50 (21.6%) had comorbidities. Seventy-three (31.5%) patients were admitted to the ICU but none died. We observed an increased risk of ICU admission among children aged 13-17 years (adjusted risk difference 27.7%, 95% confidence interval [CI] 8.3% to 47.2%), those aged 6-12 years (adjusted risk difference 25.2%, 95% CI 13.6% to 36.9%) or those with initial ferritin levels greater than 500 μg/L (adjusted risk difference 18.4%, 95% CI 5.6% to 31.3%). Children admitted to hospital after Oct. 31, 2020, had numerically higher rates of ICU admission (adjusted risk difference 12.3%, 95% CI -0.3% to 25.0%) and significantly higher rates of cardiac involvement (adjusted risk difference 30.9%, 95% CI 17.3% to 44.4%). At Canadian sites, the risk of ICU admission was significantly higher for children admitted to hospital between December 2020 and March 2021 than those admitted between March and May 2020 (adjusted risk difference 25.3%, 95% CI 6.5% to 44.0%).

Interpretation: We observed that age and higher ferritin levels were associated with more severe MIS-C. We observed greater severity of MIS-C later in the study period. Whether emerging SARS-CoV-2 variants pose different risks of severe MIS-C needs to be determined.
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http://dx.doi.org/10.1503/cmaj.210873DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9001008PMC
April 2022

Physician vaccination practices in mild to moderate inborn errors of immunity and retrospective review of vaccine completeness in IEI: results from the Canadian Immunization Research Network.

Allergy Asthma Clin Immunol 2022 Apr 9;18(1):32. Epub 2022 Apr 9.

Departments of Pediatrics and Community Health and Epidemiology, Canadian Center for Vaccinology, IWK Health Centre, Dalhousie University, Halifax, Canada.

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.
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http://dx.doi.org/10.1186/s13223-022-00667-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8994318PMC
April 2022

Does a humoral correlate of protection exist for SARS-CoV-2? A systematic review.

PLoS One 2022 8;17(4):e0266852. Epub 2022 Apr 8.

Public Health Ontario, Toronto, Ontario, Canada.

Background: A correlate of protection (CoP) is an immunological marker associated with protection against infection. Despite an urgent need, a CoP for SARS-CoV-2 is currently undefined.

Objectives: Our objective was to review the evidence for a humoral correlate of protection for SARS-CoV-2, including variants of concern.

Methods: We searched OVID MEDLINE, EMBASE, Global Health, Biosis Previews and Scopus to January 4, 2022 and pre-prints (using NIH iSearch COVID-19 portfolio) to December 31, 2021, for studies describing SARS-CoV-2 re-infection or breakthrough infection with associated antibody measures. Two reviewers independently extracted study data and performed quality assessment.

Results: Twenty-five studies were included in our systematic review. Two studies examined the correlation of antibody levels to VE, and reported values from 48.5% to 94.2%. Similarly, several studies found an inverse relationship between antibody levels and infection incidence, risk, or viral load, suggesting that both humoral immunity and other immune components contribute to protection. However, individual level data suggest infection can still occur in the presence of high levels of antibodies. Two studies estimated a quantitative CoP: for Ancestral SARS-CoV-2, these included 154 (95% confidence interval (CI) 42, 559) anti-S binding antibody units/mL (BAU/mL), and 28.6% (95% CI 19.2, 29.2%) of the mean convalescent antibody level following infection. One study reported a CoP for the Alpha (B.1.1.7) variant of concern of 171 (95% CI 57, 519) BAU/mL. No studies have yet reported an Omicron-specific CoP.

Conclusions: Our review suggests that a SARS-CoV-2 CoP is likely relative, where higher antibody levels decrease the risk of infection, but do not eliminate it completely. More work is urgently needed in this area to establish a SARS-CoV-2 CoP and guide policy as the pandemic continues.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0266852PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8993021PMC
April 2022

SARS-CoV-2 seroprevalence among Vancouver public school staff in British Columbia, Canada: a cross-sectional study.

BMJ Open 2022 04 5;12(4):e057846. Epub 2022 Apr 5.

British Columbia Children's Hospital Research Institute, Vancouver, British Columbia, Canada

Objectives: Few studies reported COVID-19 cases in schools during the 2020/21 academic year in a setting of uninterrupted in-person schooling. The main objective was to determine the SARS-CoV-2 seroprevalence among school staff in Vancouver public schools.

Design: Cumulative incident COVID-19 cases among all students and school staff based on public health data, with an embedded cross-sectional serosurvey among a school staff sample that was compared to period, age, sex and geographical location-weighted data from blood donors.

Setting: Vancouver School District (British Columbia, Canada) from kindergarten to grade 12.

Participants: Active school staff enrolled from 3 February to 23 April 2021 with serology testing from 10 February to 15 May 2021.

Main Outcome Measures: SARS-CoV-2 seroprevalence among school staff, based on spike (S)-based (unvaccinated staff) or N-based serology testing (vaccinated staff).

Results: Public health data showed the cumulative incidence of COVID-19 among students attending in-person was 9.8 per 1000 students (n=47 280), and 13 per 1000 among school staff (n=7071). In a representative sample of 1689 school staff, 78.2% had classroom responsibilities, and spent a median of 17.6 hours in class per week (IQR: 5.0-25 hours). Although 21.5% (363/1686) of surveyed staff self-reported close contact with a COVID-19 case outside of their household (16.5% contacts were school-based), 5 cases likely acquired the infection at school based on viral testing. Sensitivity/Specificity-adjusted seroprevalence in 1556/1689 staff (92.1%) was 2.3% (95% CI: 1.6% to 3.2%), comparable to a sex, age, date and residency area-weighted seroprevalence of 2.6% (95% CI: 2.2% to 3.1%) among 5417 blood donors.

Conclusion: Seroprevalence among staff was comparable to a reference group of blood donors from the same community. These data show that in-person schooling could be safely maintained during the 2020/21 school year with mitigation measures, in a large school district in Vancouver, Canada.
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http://dx.doi.org/10.1136/bmjopen-2021-057846DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8983418PMC
April 2022

Child transmission of SARS-CoV-2: a systematic review and meta-analysis.

BMC Pediatr 2022 04 2;22(1):172. Epub 2022 Apr 2.

Department of Pediatrics, BC Children's Hospital, 4500 Oak Street, V6H 3N1, Vancouver, BC, Canada.

Background: Understanding of the role of children in COVID-19 transmission has significant implications for school and childcare policies, as well as appropriate targeting of vaccine campaigns. The objective of this systematic review was to identify the role of children in SARS-CoV-2 transmission to other children and adults.

Methods: MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, and Web of Science were electronically searched for articles published before March 31, 2021. Studies of child-to-child and child-to-adult transmission and quantified the incidence of index and resulting secondary attack rates of children and adults in schools, households, and other congregate pediatric settings were identified. All articles describing confirmed transmission of SARS-CoV-2 from a child were included. PRISMA guidelines for data abstraction were followed, with each step conducted by two reviewers.

Results: 40 of 6110 articles identified met inclusion criteria. Overall, there were 0.8 secondary cases per primary index case, with a secondary attack rate of 8.4% among known contacts. The secondary attack rate was 26.4% among adult contacts versus 5.7% amongst child contacts. The pooled estimate of a contact of a pediatric index case being infected as secondary case was 0.10 (95% CI 0.03-0.25).

Conclusions: Children transmit COVID-19 at a lower rate to children than to adults. Household adults are at highest risk of transmission from an infected child, more so than adults or children in other settings.
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http://dx.doi.org/10.1186/s12887-022-03175-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8975734PMC
April 2022

Vaccine effectiveness of the 7-valent and 13-valent pneumococcal conjugate vaccines in Canada: An IMPACT study.

Vaccine 2022 04 26;40(19):2733-2740. Epub 2022 Mar 26.

Department of Pediatrics, University of Calgary, Calgary, AB, Canada; Alberta Children's Hospital, Calgary Zone, Alberta Health Services, Calgary, AB, Canada. Electronic address:

We used an indirect cohort analysis in children under 5 years-old from 2002 to 2018 to examine vaccine effectiveness (VE) of the 7-valent pneumococcal conjugate vaccine (PCV) (3 + 1 doses in most regions) and the 13-valent PCV (2 + 1 doses in all regions) against invasive pneumococcal disease (IPD) caused by vaccine serotypes in children in Canada. Cases were identified from the Canadian Immunization Monitoring Program ACTive (IMPACT), a national active surveillance network of 12 tertiary care pediatric hospitals that represent about 90% of tertiary care hospital beds in Canada. There were 1477 children evaluated for PCV7 VE and 489 for PCV13 VE. PCV7 VE in children with vaccination up to date for their age was 96% (95% CI: 67-99%) after a single dose and 95% (95% CI: 92-97%) after ≥2 doses. The VE was 91% (95% CI: 85-94%) in children who had received doses but were not up to date for their age. PCV13 VE in children with vaccinations up to date for their age was 55% (95% CI: 28-72%) after ≥2 doses. The PCV13-vaccine serotypes causing breakthrough IPD in children up to date for their age with 2+ doses of PCV13 were 3 (13/27, 48.2%),19A (11/27, 40.7%), and 19F (3/27, 11.1%). When serotype 3 and 19A were excluded, the VE of PCV13 against the remaining vaccine serotypes was 89% (95% CI: 64-97%) in children with ≥2 doses. The lower VE of PCV13 may be due to lower effectiveness against serotypes 3 and 19A, which could be influenced by the change in dosing schedule from 4 to 3 total doses with the introduction of PCV13, combined with vaccine uptake of 80%. However, PCV13 still provides the benefit of protection against more serotypes than PCV7, and good VE against all serotypes except 3 and 19A.
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http://dx.doi.org/10.1016/j.vaccine.2022.03.048DOI Listing
April 2022

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

Lancet Reg Health Am 2022 Mar 5;7:100132. Epub 2021 Dec 5.

Division of Infectious Diseases, The Hospital for Sick Children, Department of Pediatrics, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.

Background: The COVID-19 pandemic resulted in unprecedented implementation of wide-ranging public health measures globally. During the pandemic, dramatic decreases in seasonal influenza virus detection have been reported worldwide. Information on the impact on paediatric influenza-related hospitalisations is limited. We describe influenza-related hospitalisation in children in Canada following the onset of the COVID-19 pandemic.

Methods: Data on influenza-related hospitalisations, intensive care unit (ICU) admissions and in-hospital deaths in children across Canada were obtained from the Canadian Immunisation Monitoring Program, ACTive (IMPACT). This national active surveillance initiative comprises 90% of all tertiary care paediatric beds in Canada. The study period included eleven influenza seasons, from the 2010/2011 season until the 2020/2021 season inclusive. Time series modelling was used to compare the observed to predicted influenza-related hospitalisations following the COVID-19 pandemic.

Results: Following the COVID-19 pandemic there was a significant decrease in paediatric influenza-related hospitalisations compared to predicted influenza-related hospitalisations for this time period ( < 0•0001). No paediatric influenza-related hospitalisations, ICU admission or deaths were reported for the 2020/2021 influenza season.

Conclusions: We show complete absence of paediatric influenza infection-related hospitalisation in a Canadian National Surveillance Network during the 2020/2021 influenza season. This significant decrease is likely related in large part to non-pharmacological public health interventions implemented during the COVID-19 pandemic, although the potential role of viral interference is unknown.

Funding: The Canadian Immunisation Monitoring Program, Active (IMPACT) influenza surveillance is a national surveillance initiative managed by the Canadian Paediatric Society and conducted by the IMPACT network of paediatric investigators on behalf of the Public Health Agency of Canada's Centre for Immunisation and Respiratory Infectious Diseases.
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http://dx.doi.org/10.1016/j.lana.2021.100132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8913102PMC
March 2022

Performance of Immunoglobulin G Serology on Finger Prick Capillary Dried Blood Spot Samples to Detect a SARS-CoV-2 Antibody Response.

Microbiol Spectr 2022 04 10;10(2):e0140521. Epub 2022 Mar 10.

British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.

We investigate the diagnostic accuracy and predictive value of finger prick capillary dried blood spot (DBS) samples tested by a quantitative multiplex anti-immunoglobulin G (IgG) assay to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies after infection or vaccination. This cross-sectional study involved participants ( = 6,841) from several serological surveys conducted in nonhospitalized children and adults throughout 2020 and 2021 in British Columbia (BC), Canada. Analysis used paired DBS and serum samples from a subset of participants ( = 642) prior to vaccination to establish signal thresholds and calculate diagnostic accuracy by logistic regression. Discrimination of the logistic regression model was assessed by receiver operator curve (ROC) analysis in an  = 2,000 bootstrap of the paired sample ( = 642). The model was cross-validated in a subset of vaccinated persons ( = 90). Unpaired DBS samples ( = 6,723) were used to evaluate anti-IgG signal distributions. In comparison to paired serum, DBS samples from an unvaccinated population possessed a sensitivity of 79% (95% confidence interval [95% CI]: 58 to 91%) and specificity of 97% (95% CI: 95 to 98%). ROC analysis found that DBS samples accurately classify SARS-CoV-2 seroconversion at an 88% percent rate (area under the curve [AUC] = 88% [95% CI: 80 to 95%]). In coronavirus disease 2019 (COVID-19) vaccine dose one or two recipients, the sensitivity of DBS testing increased to 97% (95% CI: 83 to 99%) and 100% (95% CI: 88 to 100%). Modeling found that DBS testing possesses a high positive predictive value (98% [95% CI: 97 to 98%]) in a population with 75% seroprevalence. We demonstrate that DBS testing should be considered to reliably detect SARS-CoV-2 seropositivity from natural infection or vaccination. Dried blood spot samples have comparable diagnostic accuracy to serum collected by venipuncture when tested by an electrochemiluminescent assay for antibodies and should be considered to reliably detect seropositivity following SARS-CoV-2 infection and/or vaccination.
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http://dx.doi.org/10.1128/spectrum.01405-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9045222PMC
April 2022

Infants hospitalized for acute COVID-19: disease severity in a multicenter cohort study.

Eur J Pediatr 2022 Jun 25;181(6):2535-2539. Epub 2022 Feb 25.

Department of Pediatrics, University of Ottawa, Ottawa, ON, Canada.

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.
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http://dx.doi.org/10.1007/s00431-022-04422-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8880297PMC
June 2022

Cutaneous CpG adjuvant conditioning to enhance vaccine responses.

Vaccine 2022 03 8;40(10):1385-1389. Epub 2022 Feb 8.

Department of Dermatology & Skin Science, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address:

Adjuvant activity of the Toll receptor 9 agonist CpG 1826 was compared when given subcutaneously (s.c.) together with ovalbumin (s.c.[CpG + Ova]), or when given by either s.c. or intradermally (i.d.) routes two days prior to s.c. ovalbumin. Frequencies of CD8 + effector (T) and central memory (T) T cells along with total IgG, IgG2c, and IgG1 titres were measured to ascertain how timing and location of CpG conditioning influenced vaccination outcome. Prior treatment with CpG enhanced T, T, as well as total IgG responses. T and T responses were greatest when CpG was given intradermally and prior to s.c. ovalbumin, conditions that eliminated the fraction of T 'non-responders' observed after s.c.[CpG + Ova] vaccination. IgG responses were polarized toward IgG2c after early s.c. CpG but toward IgG1 after early i.d. CpG. Separating CpG adjuvant and antigen application in time and space can improve vaccination outcome.
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http://dx.doi.org/10.1016/j.vaccine.2021.12.060DOI Listing
March 2022

Clinical Presentations and Outcomes of Children in Canada With Recurrent Invasive Pneumococcal Disease From the IMPACT Surveillance Network.

Pediatr Infect Dis J 2022 04;41(4):e166-e171

BC Children's Hospital, Vancouver, BC.

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.
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http://dx.doi.org/10.1097/INF.0000000000003454DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8920017PMC
April 2022

Comparative single-dose mRNA and ChAdOx1 vaccine effectiveness against SARS-CoV-2, including variants of concern: test-negative design, British Columbia, Canada.

J Infect Dis 2022 Jan 27. Epub 2022 Jan 27.

BC Centre for Disease Control, Public Health Laboratory, Vancouver, British Columbia, Canada.

Introduction: In British Columbia, Canada, most adults 50-69 years old became SARS-CoV-2 vaccine-eligible in April 2021, with ChAdOx1 restricted to ≥55-year-olds and second doses deferred ≥6 weeks to optimize single-dose coverage.

Methods: Among adults 50-69-years-old, single-dose mRNA and ChAdOx1 VE against SARS-CoV-2 infection and hospitalization, including variant-specific, was assessed by test-negative design between April 4-October 2, 2021.

Results: Single-dose VE included 11,861 cases and 99,544 controls. Median (interquartile range) of post-vaccination follow-up was 32 (15-52) days. Alpha, Gamma and Delta variants comprised 23%, 18% and 56% of genetically-characterized viruses. At 21-55 days post-vaccination, single-dose mRNA and ChAdOx1 VE was 74% (95%CI: 71-76) and 59% (95%CI:53-65) against any infection and 86% (95%CI:80-90) and 94% (95%CI:85-97) against hospitalization, respectively. VE was similar against Alpha and Gamma infections for mRNA (80%;95%CI:76-84 and 80%;95%CI:75-84) and ChAdOx1 (69%;95%CI:60-76 and 66%;95%CI:56-73). mRNA VE was lower at 63% (95%CI:56-69) against Delta but 85% (95%CI:71-92) against Delta-associated hospitalization [non-estimable, ChAdOx1].

Conclusions: A single mRNA or ChAdOx1 vaccine dose gave important protection against SARS-CoV-2, including early variants-of-concern. ChAdOx1 VE was lower against infection but one dose of either vaccine reduced the hospitalization risk by >85% to at least 8 weeks post-vaccination. Findings inform program options, including longer dosing intervals.
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http://dx.doi.org/10.1093/infdis/jiac023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8807316PMC
January 2022

Human B Cell Responses to Dominant and Subdominant Antigens Induced by a Meningococcal Outer Membrane Vesicle Vaccine in a Phase I Trial.

mSphere 2022 02 26;7(1):e0067421. Epub 2022 Jan 26.

Oxford Vaccine Group, Department of Paediatrics, University of Oxfordgrid.4991.5 and the NIHR Oxford Biomedical Research Centre, Oxford, United Kingdom.

Neisseria meningitidis outer membrane vesicle (OMV) vaccines are safe and provide strain-specific protection against invasive meningococcal disease (IMD) primarily by inducing serum bactericidal antibodies against the outer membrane proteins (OMP). To design broader coverage vaccines, knowledge of the immunogenicity of all the antigens contained in OMVs is needed. In a Phase I clinical trial, an investigational meningococcal OMV vaccine, MenPF1, made from a meningococcus genetically modified to constitutively express the iron-regulated FetA induced bactericidal responses to both the PorA and the FetA antigen present in the OMP. Using peripheral blood mononuclear cells collected from this trial, we analyzed the kinetics of and relationships between IgG, IgA, and IgM B cell responses against recombinant PorA and FetA, including (i) antibody-secreting cells, (ii) memory B cells, and (iii) functional antibody responses (opsonophagocytic and bactericidal activities). Following MenPF1vaccination, PorA-specific IgG secreting cell responses were detected in up to 77% of participants and FetA-specific responses in up to 36%. Memory B cell responses to the vaccine were low or absent and mainly detected in participants who had evidence of preexisting immunity ( = 0.0069). Similarly, FetA-specific antibody titers and bactericidal activity increased in participants with preexisting immunity and is consistent with the idea that immune responses are elicited to minor antigens during asymptomatic carriage, which can be boosted by OMV vaccines. Neisseria meningitidis outer membrane vesicles (OMV) are a component of the capsular group B meningococcal vaccine 4CMenB (Bexsero) and have been shown to induce 30% efficacy against gonococcal infection. They are composed of multiple antigens and are considered an interesting delivery platform for vaccines against several bacterial diseases. However, the protective antibody response after two or three doses of OMV-based meningococcal vaccines appears short-lived. We explored the B cell response induced to a dominant and a subdominant antigen in a meningococcal OMV vaccine in a clinical trial and showed that immune responses are elicited to minor antigens. However, memory B cell responses to the OMV were low or absent and mainly detected in participants who had evidence of preexisting immunity against the antigens. Failure to induce a strong B cell response may be linked with the low persistence of protective responses.
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http://dx.doi.org/10.1128/msphere.00674-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8791392PMC
February 2022

Impact of the COVID-19 pandemic on vaccine coverage for early childhood vaccines in Alberta, Canada: a population-based retrospective cohort study.

BMJ Open 2022 01 25;12(1):e055968. Epub 2022 Jan 25.

Alberta Health, Government of Alberta, Edmonton, Alberta, Canada.

Objective: To assess the impact of the COVID-19 pandemic on early childhood vaccination coverage in Alberta, Canada.

Setting: Alberta, a western Canadian province, which has a population of 4.4 million and approximately 50 000 births annually.

Design: In this retrospective cohort study, population-based administrative health data were analysed to determine the vaccination coverage for measles-containing, pertussis-containing and rotavirus vaccines.

Primary Outcome Measure: We measured monthly and cumulative vaccine coverage. We assessed the absolute difference in monthly and cumulative coverage for each vaccine dose by comparing children due for vaccination in each month of 2019 and 2020, with follow-up to determine if missed doses were caught up later.

Participants: We included 114 178 children in the 2019 analysis cohort and 106 530 children in the 2020 analysis cohort.

Results: Monthly vaccination coverage in 2020 was higher than 2019 until March, when coverage significantly declined. Comparing April 2020 to 2019, coverage was 9.9% (95% CI 7.9% to 12.0%) lower for measles vaccine; 4.9% (95% CI 3.3% to 6.5%), 7.1% (95% CI 5.2% to 9.1%), 5.2% (95% CI 3.1% to 7.4%) and 8.8% (95% CI 6.6% to 10.9%) lower for first, second, third and fourth doses of pertussis-containing vaccine, respectively; and 4.0% (95% CI 2.3% to 5.7%), 7.1% (95% CI 5.1% to 9.2%) and 4.6% (95% CI 2.4% to 6.7%) lower for first, second and third doses of rotavirus vaccine, respectively. Monthly coverage improved during May to July 2020; however, some doses experienced a second decline during September to October 2020. The cumulative coverage analysis showed that the measles-containing vaccine had the largest difference in coverage at the end of follow-up.

Conclusions: Children who were due for vaccination early in the pandemic and in Fall 2020, especially those due for measles vaccination, may require additional catch-up.
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http://dx.doi.org/10.1136/bmjopen-2021-055968DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8795926PMC
January 2022
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