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Background Limited data is available on raltegravir (RAL) pharmacokinetics during pregnancy and the value of therapeutic drug monitoring (TDM) in pregnancy is unknown. This study aims to describe RAL trough plasma concentrations (Ctrough) during pregnancy and review the impact of RAL TDM on outcomes. Methods Women from the prospective mother-infant HIV cohort of Mother and Children’s Infectious Diseases Center who received RAL during their pregnancy between 2011-2020 were included. TDM reports were reviewed and Ctrough values estimated when possible, using historical RAL half-lives. Results We included 76 pregnant women of which 47 underwent TDM. We observed a significant association between virological response and Ctrough ( p-value .034) with an increase of 0.1 mg/L corresponding to a 2.96 reduction in the risk of having a detectable viral load. The results indicated that in pregnant women a RAL Ctrough threshold of 0.04 mg/L has a higher specificity (75%) as compared to our current Ctrough target value of 0.02 mg/L (25%) and an acceptable sensitivity (77%). No significant differences were observed between Ctrough at each trimester. When comparing pregnancies with and without TDM, no statistically significant differences were observed in the virologic response during pregnancy and at delivery, or with the need for triple antiretroviral prophylaxis in newborns. Conclusions An association between RAL Ctrough and viral load was observed and achieving a RAL Ctrough of 0.04 mg/L or greater is a predictor of virologic response in pregnant women. The impact of TDM in pregnancy, however, could not be demonstrated.

Résumé Objectifs Il est prioritaire de dépister et d’isoler rapidement les cas de SRAS-CoV-2 dans les milieux scolaires et les milieux de garde pour éviter de nouvelles éclosions. La présente étude visait à comparer les manifestations cliniques des infections par le SRAS-CoV-2 diagnostiquées chez des enfants d’âge préscolaire (moins de cinq ans) à celles des enfants d’âge scolaire (cinq ans ou plus), et notamment la probabilité qu’ils éprouvent un symptôme isolé comme une rhinorrhée ou un mal de gorge. Méthodologie Les chercheurs ont procédé à une étude rétrospective des enfants (de 18 ans ou moins) qui ont reçu un diagnostic de SRAS-CoV-2 à la clinique ambulatoire de COVID-19 ou à l’urgence du Centre hospitalier universitaire Sainte-Justine de Montréal, au Québec, entre février et mai 2020. Résultats Des 3 789 enfants soumis au dépistage, 105 (3 %) ont reçu un résultat positif au SRAS-CoV-2, et 104 ont été inclus dans l’analyse (49 de moins de cinq ans et 55 de cinq ans ou plus). La fièvre était le principal symptôme initial dans les deux groupes d’âge, mais en l’absence de fièvre, la majorité des cas (92 %) ressentait une combinaison d’au moins deux symptômes. La présence d’un seul symptôme isolé était peu courante (moins de 5 % des cas). Par-dessus tout, aucun enfant des deux groupes d’âge n’a souffert de rhinorrhée ou de mal de gorge isolé. Conclusion Les manifestations cliniques de la COVID-19 ne sont pas tout à fait les mêmes chez les enfants d’âge préscolaire et les enfants d’âge scolaire, mais dans les deux groupes d’âge, la rhinorrhée isolée n’était pas une manifestation de l’infection par le SRAS-CoV-2. Ces résultats pourraient contribuer à orienter les critères de dépistage et d’exclusion dans les milieux de garde et les milieux scolaires.

The emergence of novel SARS-CoV-2 variants of concern (VOCs) has altered the epidemiology and clinical characteristics of COVID-19. This study aims to describe the changes in COVID-19 manifestations in outpatients children and adolescents during the Parental, Delta, and Omicron eras.

Background In North American countries national guidelines have strongly recommended formula over breastmilk for people with HIV because of concern for HIV transmission. However, data from resource-limited settings suggest the risk is less than 1% among virally suppressed people. Information regarding breastfeeding experience in high resource settings is lacking. Methods A retrospective multi-site study was performed for individuals with HIV who breastfed from 2014-2022 in the United States (8 sites) and Canada (3 sites). Descriptive statistics were used for data analysis. Results Among the 72 cases reported, most had been diagnosed with HIV and were on antiretroviral therapy (ART) prior to the index pregnancy and had undetectable viral loads at delivery. Most commonly reported reasons for choosing to breastfeed were health benefits, community expectations, and parent-child bonding. Median duration of breastfeeding was 24 weeks (range 1 day to 72 weeks). Regimens for infant prophylaxis and protocols for testing of infants and birthing parents varied widely among institutions. No neonatal transmissions occurred among the 94% of infants for whom results were available >= 6 weeks after weaning. Conclusions This study describes the largest cohort to date of people with HIV who breastfed in North America. Findings demonstrate high variability among institutions in policies, infant prophylaxis, and infant and parental testing practices. The study describes challenges in weighing the potential risks of transmission with personal and community factors. Finally, this study highlights the relatively small numbers of patients living with HIV who chose to breastfeed at any one location, and the need for further multi-site studies to identify best care practices.

Résumé Historique Même si les facteurs sociodémographiques sont liés à l’infection par le SRAS-CoV-2 et aux hospitalisations chez les adultes, peu de données portent sur l’association entre ces caractéristiques et les hospitalisations attribuables au SRAS-CoV-2 chez les enfants. La présente étude visait à déterminer l’association entre la défavorisation matérielle par quartier et l’incidence d’hospitalisations à cause du SRAS-CoV-2 chez les enfants. Méthodologie Les chercheurs ont réalisé une étude de cohorte rétrospective de tous les enfants (de 0 à 17 ans) atteints d’une infection par le SRAS-CoV-2 confirmée par un test d’amplification en chaîne par polymérase après transcription inverse (PCR) entre le 1er mars et le 31 mai 2021 dans un hôpital pédiatrique de soins tertiaires de Montréal, au Canada. Ils ont colligé les données par examen des dossiers et ont inclus l’âge, le sexe et les codes postaux, afin de pouvoir lier la défavorisation matérielle à l’échelle de l’aire de diffusion, mesurée au moyen des quintiles de l’indice de défavorisation matérielle de Pampalon. Ils ont examiné l’association entre les quintiles de cet indice et les hospitalisations à l’aide de la régression de Poisson. Résultats Pendant la période de l’étude, 964 enfants ont reçu un résultat positif au SRAS-CoV-2 confirmé par un test PCR, et 124 d’entre eux ont été hospitalisés. Au total, 40,7 % des enfants hospitalisés habitaient dans le quintile le plus défavorisé d’après l’indice de défavorisation matérielle de Pampalon. Le rapport du taux d’incidence des hospitalisations dans ce groupe était de 2,42 (intervalle de confiance à 95 % : 1,33; 4,41) par rapport au quintile le plus privilégié. Conclusion Plus du double des enfants qui habitaient dans les quartiers les plus défavorisés sur le plan matériel étaient hospitalisés à cause de la COVID-19 par rapport à ceux qui habitaient dans les quartiers les plus privilégiés. Il faudrait déployer des efforts particuliers pour protéger les enfants qui habitent dans des quartiers défavorisés, particulièrement dans l’attente de la vaccination des plus jeunes.

Background Although sociodemographic factors have been linked with SARS-CoV-2 infection and hospitalizations in adults, there are little data on the association between sociodemographic characteristics and SARS-CoV-2-related hospitalization in children. The objective of this study was to determine the association between area-level material deprivation and incidence of hospitalization with SARS-CoV-2 among children. Methods We conducted a retrospective cohort study of all children (0 to 17 years of age) with a PCR-confirmed SARS-CoV-2 infection March 1, 2020 through May 31, 2021 at a tertiary-care paediatric hospital, in Montreal, Canada. Data were collected through chart review and included age, sex, and postal code, allowing linkage to dissemination area-level material deprivation, measured with the Pampalon Material Deprivation Index (PMDI) quintiles. We examined the association between PMDI quintiles and hospitalization using Poisson regression. Results During the study period, 964 children had a positive PCR-confirmed SARS-CoV-2 test and 124 were hospitalized. Children living in the most deprived quintile of PMDI represented 40.7% of hospitalizations. Incidence rate ratio of hospitalization for this group compared to the most privileged quintile was 2.42 (95%CI: 1.33; 4.41). Conclusion Children living in the most materially deprived areas had more than twice the rate of hospitalizations for COVID-19 than children living in most privileged areas. Special efforts should be deployed to protect children who live in disadvantaged areas, especially pending vaccination of younger children.

The HIV care cascade is an indicators-framework used to assess achievement of HIV clinical targets including HIV diagnosis, HIV care initiation and retention, initiation of antiretroviral therapy, and attainment of viral suppression for people living with HIV.The HIV Care Cascade Research Development Team at the CIHR Canadian HIV Trials Network Clinical Care and Management Core hosted a two-day virtual workshop to present HIV care cascade data collected nationally from local and provincial clinical settings and national cohort studies. The article summarizes the workshop presentations including the indicators used and available findings and presents the discussed challenges and recommendations.Identified challenges included (1) inconsistent HIV care cascade indicator definitions, (2) variability between the use of nested UNAIDS's targets and HIV care cascade indicators, (3) variable analytic approaches based on differing data sources, (4) reporting difficulties in some regions due to a lack of integration across data platforms, (5) lack of robust data on the first stage of the care cascade at the sub-national level, and (6) inability to integrate key socio-demographic data to estimate population-specific care cascade shortfalls.There were four recommendations: standardization of HIV care cascade indicators and analyses, additional funding for HIV care cascade data collection, database maintenance and analyses at all levels, qualitative interviews and case studies characterizing the stories behind the care cascade findings, and employing targeted positive-action programs to increase engagement of key populations in each HIV care cascade stage.La cascade des soins du VIH est un cadre d’indicateurs utilisé pour évaluer l’atteinte des cibles cliniques du VIH, y compris le diagnostic, le début et le maintien des soins, le début du traitement antirétroviral et l’obtention de la suppression virale chez les personnes qui vivent avec le VIH.L’équipe de développement de la recherche sur la cascade des soins du VIH située au noyau de perfectionnement de la gestion clinique du Réseau canadien pour les essais VIH des IRSC a organisé un atelier virtuel de deux jours pour présenter les données sur la cascade des soins du VIH amassées dans les milieux cliniques locaux et provinciaux et les études de cohorte de tout le pays. L’article résume les présentations d’ateliers, y compris les indicateurs utilisés et les observations disponibles, et présente les défis et recommandations abordés.Les défis mis en évidence incluaient 1) les définitions hétérogènes des indicateurs de la cascade des soins sur le VIH, 2) la variabilité entre l’utilisation des cibles d’ONUSIDA imbriquées et les indicateurs de cascade des soins du VIH, 3) des approches analytiques variables d’après diverses sources de données, 4) la déclaration des difficultés dans certaines régions à cause de l’absence d’intégration entre les plateformes de données, 5) l’absence de données vigoureuses sur la première étape de la cascade des soins infranationaux et 6) l’incapacité d’intégrer les principales données sociodémographiques pour évaluer les écueils de la cascade des soins populationnels.Quatre recommandations ont été formulées : la standardisation des indicateurs et des analyses de la cascade des soins du VIH, le financement supplémentaire de la collecte de la cascade des soins du VIH, l’entretien des bases de données et les analyses à tous les échelons, les entrevues qualitatives et les études de cas qui caractérisent les histoires qui se cachent derrière les observations tirées de la cascade des soins et le recours à des programmes d’action positive ciblés pour accroître la participation de populations clés à chaque étape de la cascade des soins du VIH.

Coagulopathy and thrombosis associated with SARS-CoV-2 infection are well defined in hospitalized adults and leads to adverse outcomes. Pediatric studies are limited.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.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 age10 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.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.

Objective To assess the choice and attitude of pregnant women regarding CMV serological screening and CMV prevention behaviors in pregnancy. Study design In this cross-sectional study, pregnant women were recruited in a single center during routine prenatal screening tests at 11–16 weeks. Participants filled out a questionnaire assessing knowledge about congenital CMV (cCMV) infection, risk perception and willingness to have CMV serological screening as well as their attitude toward CMV prevention behaviors. Results Among 234 pregnant women, 74.4 % (95 % confidence interval: 68.8–80.0 %) wanted CMV serological screening in pregnancy. The factors significantly associated with the desire for screening were perceived risk and perceived severity of cCMV. An informed choice regarding CMV screening (value-consistent, based on good knowledge and deliberated) was performed by 54 % of women who chose the screening and 30 % of women who declined the screening (p = 0.039). The median scores regarding attitudes toward CMV prevention behaviors were 3.7/5 for avoiding sharing behaviors and 4.0/5 for not kissing a child on the lips. Conclusion The majority of pregnant women want to have CMV serological screening once informed about congenital CMV infection. New tools need to be developed to allow for informed choice regarding CMV serological screening in pregnancy.

Resume Contexte: Les facteurs de risque de complications graves de l’infection par le SRAS-CoV-2 n’ont pas ete bien etablis chez les enfants. Nous avons voulu decrire les hospitalisations pediatriques associees au SRAS-CoV-2 au Canada et identifier les facteurs de risque de maladie grave. Methodes: Nous avons procede a une etude prospective nationale en utilisant l’infrastructure du Programme canadien de surveillance pediatrique (PCSP). Les hospitalisations d’enfants ayant contracte une infection par le SRAS-CoV-2 confirmee en laboratoire de microbiologie ont ete rapportees du 8 avril au 31 decembre 2020 au moyen de questionnaires hebdomadaires en ligne distribues au reseau du PCSP, qui compte plus de 2800 pediatres. Nous avons categorise les hospitalisations comme suit : liees a la COVID-19, infections decouvertes fortuitement, ou hospitalisations pour des raisons sociales ou de controle des infections, et degage les facteurs de risque associes a la gravite de la maladie chez les patients hospitalises. Resultats: Sur les 264 hospitalisations d’enfants ayant contracte le SRAS-CoV-2 au cours de la periode de l’etude de 9 mois, 150 (56,8 %) ont ete associees a la COVID-19 et 100 (37,9 %) etaient des cas decouverts fortuitement (admission pour d’autres raisons et decouverte fortuite du SRAS-CoV-2 par depistage positif). Les nourrissons (37,3 %) et les adolescents (29,6 %) representaient la majorite des cas. Parmi les hospitalisations liees a la COVID-19, 52 patients (34,7 %) etaient atteints d’une forme grave de la maladie, dont 42 (28,0 % des cas lies a la COVID-19) ont eu besoin d’une forme d’assistance respiratoire ou hemodynamique, et 59 (39,3 %) presentaient au moins 1 comorbidite sous-jacente. Les enfants atteints d’obesite, de maladies neurologiques chroniques ou de maladies pulmonaires chroniques, a l’exclusion de l’asthme, etaient plus susceptibles de presenter une forme grave ou critique de la COVID-19. Interpretation: Parmi les enfants hospitalises au Canada chez lesquels on a diagnostique une infection par le SRAS-CoV-2 au debut de la pandemie de COVID-19, la decouverte fortuite du SRAS-CoV-2 a ete frequente. Chez les enfants hospitalises pour une COVID-19 aigue, l’obesite et les comorbidites neurologiques et respiratoires ont ete associees a une gravite accrue.

Background Although sociodemographic factors have been linked with SARS-CoV-2 infection and hospitalizations in adults, there are little data on the association between sociodemographic characteristics and SARS-CoV-2-related hospitalization in children. Objectives The objective of this study was to determine the association between area-level material deprivation and incidence of hospitalization with SARS-CoV-2 among children. Design/Methods We conducted a retrospective cohort study of all children (0-17 years of age) with a PCR-confirmed SARS-CoV-2 infection between March 1, 2020, and May 31, 2021, at a tertiary care pediatric hospital. Data were collected through chart review and included age, sex, and postal code. Postal codes were then assigned a dissemination area-level material deprivation score, measured via the Pampalon Material Deprivation Index (PMDI) quintiles. The Pampalon Material Deprivation Index (PMDI) uses postal codes to describe factors related to material deprivation obtained from the Canadian census, which are proxies for individual data in a geographic area. Specifically, the PMDI integrates data regarding (i) the proportion of persons without a high school diploma; (ii) the employment-to-population ratio; (iii) average personal income which is aggregated at the dissemination area level. We examined the association between PMDI quintiles and hospitalization using Poisson regression. Results During the study period, 964 children had a positive PCR-confirmed SARS-CoV-2 test and 124 were hospitalized due to SARS-CoV-2 infection. Children from the most deprived PMDI quintile represented 31.6% of positive cases and 40.7% of hospitalizations (Figure 1 and 2). Both in bivariate and multivariable regression analyses, there was evidence of greater proportion of positive test results in the most deprived PMDI quintile (Quintile 5) compared to the least deprived quintile (Quintile 1) (rate ratio 1.77, 95%CI: 1.36; 2.62) (Table 1). The incidence of hospitalization due to SARS-CoV-2 infection was 2.42 times greater in the most deprived quintile compared to the least deprived quintile (95%CI: 1.33; 4.41) (table 1). In a post-hoc analysis, the risk for severe disease appeared higher for children living in Q5 areas relative to other areas but the difference did not reach statistical significance. Conclusion In conclusion, in this study we found evidence that Canadian children living in neighbourhoods with high material deprivation had a higher incidence of infection and hospitalizations related to SARS-Cov-2 compared to children living in neighbourhoods with less material deprivation. Public health authorities should take these disparities into account when devising public health policy and interventions especially at this crucial point in the pandemic. Special efforts should be deployed to protect children from these more disadvantaged areas, especially as vaccination is not yet available to a majority of children.

BackgroundPaediatric inflammatory multisystem syndrome (PIMS) is a rare but serious condition temporally associated with SARS-CoV-2 infection. Using the Canadian Paediatric Surveillance Program (CPSP), a national surveillance system, we aimed to 1) study the impact of SARS-CoV-2 linkage on clinical and laboratory characteristics, and outcomes in hospitalized children with PIMS across Canada 2) identify risk factors for ICU admission, and 3) establish the minimum national incidence of hospitalizations due to PIMS and compare it to acute COVID-19.MethodsWeekly online case reporting was distributed to the CPSP network of more than 2800 pediatricians, from March 2020 to May 2021. Comparisons were made between cases with respect to SARS-CoV-2 linkage. Multivariable modified Poisson regression was used to identify risk factors for ICU admission and Minimum incidence proportions were calculated.FindingsIn total, 406 PIMS cases were analyzed, of whom 202 (49· 8%) had a positive SARS-CoV-2 linkage, 106 (26· 1%) had a negative linkage, and 98 (24· 1%) had an unknown linkage. The median age was 5· 4 years (IQR 2· 5–9· 8), 60% were male, and 83% had no identified comorbidities. Compared to cases with a negative SARS-CoV-2 linkage, children with a positive SARS-CoV-2 linkage were older (8· 1 years [IQR 4· 2–11· 9] vs. 4· 1 years [IQR 1· 7–7· 7]; pInterpretationWhile PIMS is rare, almost 1 in 3 hospitalized children required ICU admission and respiratory/hemodynamic support, particularly those ≥ 6 years and with a positive SARS-CoV-2 linkage.FundingFinancial support for the CPSP was received from the Public Health Agency of Canada.

BACKGROUND Premature development of cardiovascular disease in children living with HIV-1 (CLWH) may be associated with compromised gut barrier function, microbial translocation, immune activation, systemic inflammation and endothelial activation. Biomarkers of these pathways may provide insights into pathogenesis of atherosclerotic disease in CLWH. METHODS This was a cross-sectional study of CLWH enrolled in the multicentre Early Pediatric Initiation-Canadian Child Cure Cohort (EPIC4 ) who were on antiretroviral therapy (ART) with undetectable viral load. Plasma biomarkers of intestinal epithelial injury [intestinal fatty acid binding protein-1 (IFABP)], systemic inflammation [tumour necrosis factor (TNF) and interleukin-6 (IL-6)] and endothelial activation [angiopoietin-2 (Ang2), soluble vascular endothelial growth factor-1 (sVEGFR1) and soluble endoglin (sEng)] were quantified by enzyme-linked immunosorbent assay. Correlation and factor analysis of biomarkers were used to examine associations between innate immune pathways. RESULTS Among 90 CLWH, 16% of Ang2, 15% of sVEGFR1 and 23% of sEng levels were elevated relative to healthy historic controls. Pairwise rank correlations between the three markers of endothelial activation were statistically significant (ρ = 0.69, ρ = 0.61 and ρ = 0.65, P

While treatment guidelines for HIV in adults have evolved rapidly with the advent of new antiretroviral (ARV) treatment, those for the prevention of vertical HIV transmission in pregnancy have evolved more slowly due to safety and efficacy concerns. Here we describe Canadian prescribing patterns for ARV treatments during pregnancy and compare them to perinatal HIV prescribing guidelines of the United States Department of Health and Human Services (HHS), that are commonly used in Canada and include recommendations for newly commercialized therapies.The Canadian Perinatal HIV Surveillance Program (CPHSP) captures annual medical data on mothers living with HIV and their infants from 23 sites across Canada. Women from this cohort who received an ARV treatment during pregnancy and who gave birth between 2004 and 2020 were included in the study. ARV treatments were designated as 'preferred/alternative' as per HHS HIV perinatal guidelines, or 'other than preferred/alternative'.We identified 3673 pregnancies from 2720 women. The proportion of women that conceived while on ARV treatment increased from 29% in 2003 to 90% in 2020. Other than preferred/alternative ARV treatments were received in 1112 (30%) of pregnancies and this was significantly associated with having initiated ARV treatment before conception.In Canada during the study period, a high number of women were prescribed an other than preferred/alternative ARV treatment during pregnancy. Further optimization of ARV treatment in women of childbearing age living with HIV is warranted.

Introduction: Hematologic complications of SARS-CoV-2 infection are well described in hospitalized adults with correlation to adverse outcomes. Information published in children has been limited. Methods: An international multi-centered retrospective registry was established to collect data on the clinical manifestations of SARS-CoV-2 or multisystem inflammatory syndrome (MIS-C) in hospitalized children between February 1, 2020 – May 31, 2021. This sub-study focused on hematologic manifestations. Study variables included patient demographics, comorbidities, clinical presentation, course, laboratory parameters, management, and outcomes. Results: Nine hundred and eighty-five children were enrolled and 915 (93%) had clinical information available; 385 (42%) had symptomatic SARS-CoV-2 infection upon admission, 288 had MIS-C (31.4%) and 242 (26.4%) had alternate diagnosis with SARS-CoV-2 identified incidentally. During hospitalization, 10 children (1%) experienced a thrombotic event, 16 (1.7%) had hemorrhage and 2 (0.2%) had both thrombotic and hemorrhagic episodes. Significant prothrombotic comorbidities included congenital heart disease (p-value = 0.007), central venous catheter (p = 0.04) in children with primary SARS-CoV-2 infection; and obesity (p-value= 0.002), cytokine storm (p= 0.012) in those with MIS-C. Significant pro- hemorrhagic conditions included age > 10 years (p = 0.04), CVC (p= 0.03) in children with primary SARS-CoV-2infection; and thrombocytopenia (0.001), cytokine storm (0.02) in those with MIS-C. Eleven patients died (1.2 %) with no deaths attributed to thrombosis or hemorrhage Conclusion: Thrombotic and hemorrhagic complications are uncommon in children with SARS-CoV-2 infection and observed with underlying co-morbid conditions. Understanding the complete spectrum of hematologic complications in children with SARS-CoV-2 infection or MIS-C requires ongoing multi-center studies.

ImportanceChildren are less likely than adults to have severe outcomes from SARS-CoV-2 infection and the corresponding risk factors are not well established.ObjectiveTo identify risk factors for severe disease in symptomatic children hospitalized for PCR-positive SARS-CoV-2 infection.DesignCohort study, enrollment from February 1, 2020 until May 31, 2021Setting15 children’s hospitals in Canada, Iran, and Costa RicaParticipantsPatients ExposuresVariables assessed for their association with disease severity included patient demographics, presence of comorbidities, clinical manifestations, laboratory parameters and chest imaging findings.Main Outcomes and MeasuresThe primary outcome was severe disease defined as a WHO COVID-19 clinical progression scale of ≥6, i.e., requirement of non-invasive ventilation, high flow nasal cannula, mechanical ventilation, vasopressors, or death. Multivariable logistic regression was used to evaluate factors associated with severe disease.ResultsWe identified 403 hospitalizations. 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). Severe disease occurred in 33.8% (102/403). In multivariable analyses, presence of multiple comorbidities (adjusted odds ratio 2.24, 95% confidence interval 1.04-4.81), obesity (2.87, 1.19-6.93), neurological disorder (3.22, 1.37-7.56), anemia, and/or hemoglobinopathy (5.88, 1.30-26.46), shortness of breath (4.37, 2.08-9.16), bacterial and/or viral coinfections (2.26, 1.08-4.73), chest imaging compatible with COVID-19 (2.99, 1.51-5.92), neutrophilia (2.60, 1.35-5.02), and MIS-C diagnosis (3.86, 1.56-9.51) were independent risk factors for severity. Comorbidities, especially obesity (40.9% vs 3.9%, pConclusions and RelevancePediatric risk factors for severe SARS-CoV-2 infection vary according to age and can potentially guide vaccination programs and treatment approaches in children.Key pointsQuestionWhat are the risk factors for severe disease in children hospitalized for PCR-positive SARS-CoV-2 infection?FindingsIn this multinational cohort study of 403 children, multiple comorbidities, obesity, neurological disorder, anemia, and/or hemoglobinopathy, shortness of breath, bacterial and/or viral coinfections, chest imaging compatible with COVID-19, neutrophilia, and MIS-C diagnosis were independent risk factors for severity. The risk profile and presence of comorbidities differed between pediatric age groups, but age itself was not associated with severe outcomes.MeaningThese results can inform targeted treatment approaches and vaccine programs that focus on patient groups with the highest risk of severe outcomes.

Background There are limited data on outcomes of SARS-CoV-2 infection among infants ( Objectives The objective of this study was to describe the clinical manifestations, disease severity, and characteristics associated with hospitalization among infants infected with the initial strains of SARS-CoV-2. Design/Methods This is a nationwide prospective observational study using the infrastructure of the Canadian Paediatric Surveillance Program. All cases of infants aged Results A total of 531 cases were reported, including 332 (62.5%) non-hospitalized and 199 (37.5%) hospitalized infants. Among hospitalized infants, 141 of 199 infants (70.9%) were admitted because of COVID-19-related illness, and 58 (29.1%) were admitted for reasons other than acute COVID-19. Amongst all cases with SARS-CoV-2 infection, the most common presenting symptoms included fever (66.5%), coryza (47.1%), cough (37.3%) and decreased oral intake (25.0%). In our main analysis, infants with a comorbid condition had higher odds of hospitalization compared to infants with no comorbid conditions, and infants Conclusion We describe one of the largest cohorts of infants with SARS-CoV-2 infection. Overall, severe COVID-19 in this age group is uncommon with most infants having mild disease. Comorbid conditions and younger age were associated with COVID-19-related hospitalization amongst infants.

Objectives Rapid identification and isolation of SARS-CoV-2 cases are priorities in school and child care settings to prevent further outbreaks. The objective of this study was to compare the clinical presentation of SARS-CoV-2 infections among preschool ( Methods Retrospective study of children (≤18 years of age) diagnosed with SARS-CoV-2 in the outpatient COVID-19 clinic or the Emergency Department at the Centre Hospitalier Universitaire Sainte-Justine (Montreal, Quebec, Canada) February through May 2020. Results Of 3,789 children tested, 105 (3%) were positive for SARS-CoV-2, and 104 included in the analysis (n=49 age Conclusions While there are differences in the clinical manifestations of COVID-19 in preschool- versus school-aged children, in both age groups, isolated rhinorrhea was not a manifestation of SARS-CoV-2 infection. These results could help further guide testing criteria and exclusion criteria in child care and school settings.

Background Studies from multiple countries have suggested impaired immunity in perinatally human immunodeficiency virus (HIV)–exposed uninfected children (HEU), with elevated rates of all-cause hospitalization and infections. We estimated and compared the incidence of all-cause hospitalization and infection-related hospitalization in the first 2 years of life among HEU and HIV-unexposed uninfected children (HUU) in the United States. Among HEU, we evaluated associations of maternal HIV disease–related factors during pregnancy with risk of child hospitalization. Methods HEU data from subjects enrolled in the Surveillance Monitoring for Antiretroviral Therapy Toxicities Study (SMARTT) cohort who were born during 2006–2017 were analyzed. HUU comparison data were obtained from the Medicaid Analytic Extract database, restricted to states participating in SMARTT. We compared rates of first hospitalization, total hospitalizations, first infection-related hospitalization, total infection-related hospitalizations, and mortality between HEU and HUU using Poisson regression. Among HEU, multivariable Poisson regression models were fitted to evaluate associations of maternal HIV factors with risk of hospitalization. Results A total of 2404 HEU and 3 605 864 HUU were included in the analysis. HEU children had approximately 2 times greater rates of first hospitalization, total hospitalizations, first infection-related hospitalization, and total infection-related hospitalizations compared with HUUs. There was no significant difference in mortality. Maternal HIV disease factors were not associated with the risk of child infection or hospitalization. Conclusions Compared with HUU, HEU children in the United States have higher rates of hospitalization and infection-related hospitalization in the first 2 years of life, consistent with studies in other countries. Closer monitoring of HEU infants for infection and further elucidation of immune mechanisms is needed.

Objective Dolutegravir is recommended worldwide as a first-line antiretroviral therapy (ART) for individuals living with HIV. A recent study reported increased rates of neural tube defects in infants of dolutegravir-treated women. This study examined rates of congenital anomalies in infants born to women living with HIV (WLWH) in Canada. Design The Canadian Perinatal HIV Surveillance Programme captures surveillance data on pregnant WLWH and their babies and was analysed to examine the incidence of congenital anomalies. Setting Paediatric HIV clinics. Population Live-born infants born in Canada to WLWH between 2007 and 2017. Methods Data on mother-infant pairs, including maternal ART use at conception and during pregnancy, are collected by participating sites. Main outcome measures Congenital anomalies. Results Of the 2423 WLWH, 85 (3.5%, 95% CI 2.85-4.36%) had non-chromosomal congenital anomalies. There was no evidence of a significant difference in rates of congenital anomalies between women who were on ART in their first trimester (3.9%, CI 1.7-7.6%) or later in the pregnancy (3.9%, 95% CI 2.6-5.6%). Four of the 80 (5.0%, 95% CI 1.4-12.3%) neonates born to WLWH on dolutegravir during the first trimester had congenital anomalies, none were neural tube defects (95% CI 0.00-3.10%). Conclusion Despite recent evidence raising a safety concern, this analysis found no signal for increased congenital anomalies. Tweetable abstract Five percent of the infants of Canadian women living with HIV on dolutegravir at conception had congenital anomalies; none had neural tube defects.

BACKGROUND Systemic inflammation, platelet dysfunction, and endothelial activation persist in people living with HIV despite sustained virologic suppression (SVS) with combined antiretroviral therapy (cART) and may lead to complications such as atherosclerosis and cardiovascular disease. Angiopoietin-1 (Ang-1) is a key regulator of angiogenesis and endothelial activation and has been studied as an objective biomarker in disease states such as atherosclerosis, sepsis, and severe malaria. SETTING Eight pediatric HIV care centers across Canada. METHODS Cross-sectional study of 61 children living with vertically acquired HIV on cART with undetectable RNA viral load. Plasma levels of Ang-1 were measured by ELISA and analyzed in relation to clinical characteristics abstracted from medical records. RESULTS Ang-1 levels were directly correlated with clinical indices of virologic control: cumulative proportion of life on effective cART (ρ = +0.35, P = 0.0078) and cumulative proportion of life with SVS (ρ = +0.36, P = 0.0049). Furthermore, higher Ang-1 levels were associated with younger age at SVS (ρ = -0.56, P < 0.0001). These associations remained statistically significant in multivariable linear regression models adjusting for potential confounders (P < 0.05 for all associations). CONCLUSIONS Early effective cART and SVS were associated with higher Ang-1 levels in children living with vertically acquired HIV-1.

ObjectiveTo identify risk factors for severe disease in children hospitalised for SARS-CoV-2 infection.DesignMulticentre retrospective cohort study.Setting18 hospitals in Canada, Iran and Costa Rica from 1 February 2020 to 31 May 2021.PatientsChildrenMain outcome measureSeverity on the WHO COVID-19 Clinical Progression Scale was used for ordinal logistic regression analyses.ResultsWe 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 childrenConclusionWe 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.

PurposeChildhood tuberculosis disease is difficult to diagnose and manage and is an under-recognised cause of morbidity and mortality. Reported data from Canada do not focus on childhood tuberculosis or capture key epidemiologic, clinical and microbiologic details. The purpose of this study was to assess demographics, presentation and clinical features of childhood tuberculosis in Canada.MethodsWe conducted prospective surveillance from 2013 to 2016 of over 2700 paediatricians plus vertical tuberculosis programmes for incident tuberculosis disease in children younger than 15 years in Canada using the Canadian Paediatric Surveillance Program (CPSP).ResultsIn total, 200 cases are included in this study. Tuberculosis was intrathoracic in 183 patients of whom 86% had exclusively intrathoracic involvement. Central nervous system tuberculosis occurred in 16 cases (8%). Fifty-one per cent of cases were hospitalised and 11 (5.5%) admitted to an intensive care unit. Adverse drug reactions were reported in 9% of cases. The source case, most often a first-degree relative, was known in 73% of cases. Fifty-eight per cent of reported cases were Canadian-born Indigenous children. Estimated study rates of reported cases (per 100 000 children per year) were 1.2 overall, 8.6 for all Indigenous children and 54.3 for Inuit children.ConclusionChildhood tuberculosis may cause significant morbidity and resource utilisation. Key geographies and groups have very high incidence rates. Elimination of childhood tuberculosis in Canada will require well-resourced community-based efforts that focus on these highest risk groups.

We wished to evaluate the efficacy, safety, and acceptability of cabergoline for lactation inhibition in women who live with HIV. In this multicenter prospective observational study, cabergoline was offered as a single oral dose of 1 mg within the first 48 h postpartum. Women were recruited if they delivered a live infant after 35 weeks of gestational age. Participants filled out a questionnaire regarding symptoms of lactation and cabergoline adverse effects on day 2 and day 14 postpartum. On day 14, they also completed a questionnaire about their satisfaction with cabergoline treatment. Prolactin serum level was measured on both visits. Among 68 participants, all but one received cabergoline. The overall effectiveness defined by partial or complete success at day 14 was 98.3% (confidence intervals: 89.5–99.9). At day 14, 67.4% of women who received cabergoline had prolactin serum levels

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.

Congenital infections are infections transmitted from mother to child during pregnancy (transplacentally) or delivery (peripartum). They have the potential to adversely affect fetal development and long-term neurodevelopmental outcome through inflammatory, destructive, developmental, or teratogenic lesions of the brain. Because the fetal/neonatal brain has a limited capacity to respond to injury, early inflammatory changes may be difficult to visualize and only manifest as neurocognitive disability later in life. Teratogenic effects, which may include aberrations of neuronal proliferation and migration, are more easily visible on imaging, but may be equally difficult to use to predict long-term neurocognitive outcomes. This chapter reviews the general pathophysiology of congenital infection and describes the epidemiology, the antenatal and postnatal diagnosis, and the treatment of congenital infections as well as the long-term neurodevelopmental outcomes.

BackgroundCombination antiretroviral therapy (cART) during pregnancy prevents vertical transmission, but many antiretrovirals cross the placenta and several can affect mitochondria. Exposure to maternal human immunodeficiency virus (HIV) and/or cART could have long-term effects on children who are HIV exposed and uninfected (CHEU). Our objective was to compare blood mitochondrial DNA (mtDNA) content in CHEU and children who are HIV unexposed and uninfected (CHUU), at birth and in early life.MethodsWhole-blood mtDNA content at birth and in early life (age 0–3 years) was compared cross-sectionally between CHEU and CHUU. Longitudinal changes in mtDNA content among CHEU was also evaluated.ResultsAt birth, CHEU status and younger gestational age were associated with higher mtDNA content. These remained independently associated with mtDNA content in multivariable analyses, whether considering all infants, or only those born at term. Longitudinally, CHEU mtDNA levels remained unchanged during the first 6 months of life, and gradually declined thereafter. A separate age- and sex-matched cross-sectional analysis (in 214 CHEU and 214 CHUU) illustrates that the difference in mtDNA between the groups remains detectable throughout the first 3 years of life.ConclusionThe persistently elevated blood mtDNA content observed among CHEU represents a long-term effect, possibly resulting from in utero stresses related to maternal HIV and/or cART. The clinical impact of altered mtDNA levels is unclear.

Transitioning from pediatric to adult care is a complicated process for youth with chronic illnesses. This study elucidates the unique factors affecting transition preparedness and perception of adult HIV care among a cohort of young women with HIV. Between 2013 and 2015, 48 women with HIV, who had experience with pediatric HIV care, were enrolled in a large Canadian cohort study. Variables were self-reported during peer-administered surveys. Only 60% reported feeling prepared for transition. Having never had contact with child protection services ( P = .049), never been in foster care ( P = .011), never been in a group home ( P = .036), reporting a higher current CD4 count ( P = .033), and reporting a younger ideal age for transition ( P = .041) were associated with transition preparedness. Eighty-four percent reported equivalent or better HIV care following transition. Correlates of equivalent/better care following transition included lower personal income ( P = .023), higher CD4 count ( P = .021), care by an adult infectious diseases specialist ( P = .002), and transition preparedness ( P = .005). Our findings highlight the importance of adequate transition preparation and its effect on perception of care following transition.

Leukocyte telomere length (LTL) and whole blood mitochondrial DNA (WB mtDNA) content are aging markers impacted by chronic diseases such as human immunodeficiency virus (HIV) infection. We characterized the relationship between these two markers in 312 women ≥12 years of age living with HIV and 300 HIV-negative controls. We found no relationship between the two markers cross-sectionally. In multivariable models, age, ethnicity, HIV, and tobacco smoking were independently associated with shorter LTL, and the former three with lower WB mtDNA. Longitudinally, among a subgroup of 228 HIV participants and 68 HIV-negative controls with ≥2 biospecimens ≥1 year apart, an inverted pattern was observed between the rates of change in LTL and WB mtDNA content per year, whereby faster decline of one was associated with the preservation of the other. Furthermore, if HIV viral control was not maintained between visits, increased rates of both LTL attrition and WB mtDNA loss were observed. We describe a novel relationship between two established aging markers, whereby rates of change in LTL and WB mtDNA are inversely related. Our findings highlight the importance of maintaining HIV viral control, the complementary longitudinal relationship between the two markers, and the need to consider both in aging studies.

Objective There is no consensus on the use of cytomegalovirus (CMV)–specific hyperimmunoglobulins (CSHIGs) for suspected congenital CMV infections during pregnancy, but this therapy is currently used in some countries. The objectives of this study were to describe tolerability and pregnancy outcome following treatment with monthly intravenous CSHIG and compare rates of positive PCR and postnatal symptoms according to whether CSHIGs were given or not. Methods This retrospective cohort study included all pregnant women who were diagnosed with primary CMV infection or congenital CMV infection at the Centre Hospitalier Universitaire Sainte-Justine (Montreal, QC) between 2005 and 2016. CSHIG was discussed with pregnant women who received positive CMV PCR results from amniotic fluid or if ultrasound anomalies suggested congenital infection and there was serologic evidence of maternal primary infection (therapeutic group). CSHIG was also offered as prophylaxis in pregnant women without fetal ultrasound anomalies but with evidence of maternal primary infection, when amniocentesis either had negative results or was not performed (prophylactic group). A matched analysis was performed to control for timing of maternal infection, amniocentesis, and type and timing of ultrasound anomaly. Results Sixteen women received CSHIG, and 55 had no CMV-specific treatment. CSHIG treatment was well-tolerated. In bivariate analyses, the risk of congenital CMV infection and postnatal symptoms did not significantly decrease with CSHIG treatment, in both the therapeutic and the prophylactic groups. After matching, there was still no difference in outcomes between CSHIG-treated and untreated women. Conclusion The effectiveness of CSHIG in preventing congenital CMV infection and its clinical manifestations could not be demonstrated.