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Background and Objectives: Neurological involvement associated with SARS-CoV-2 infection is increasingly recognized. However, the specific characteristics and prevalence in pediatric patients remain unclear. The objective of this study was to describe the neurological involvement in a multinational cohort of hospitalized pediatric patients with SARS-CoV-2. Methods: This was a multicenter observational study of children Results: One-hundred forty-seven (21%) of 697 hospitalized children with SARS-CoV-2 infection had neurological signs/symptoms. Headache (n = 103), encephalopathy (n = 28), and seizures (n = 30) were the most reported. Neurological signs/symptoms were significantly associated with ICU admission (OR: 1.71, 95% CI: 1.15–2.55; p = 0.008), satisfaction of MIS-C criteria (OR: 3.71, 95% CI: 2.46–5.59; p < 0.001), fever during hospitalization (OR: 2.15, 95% CI: 1.46–3.15; p < 0.001), and gastrointestinal involvement (OR: 2.31, 95% CI: 1.58–3.40; p < 0.001). Non-headache neurological manifestations were significantly associated with ICU admission (OR: 1.92, 95% CI: 1.08–3.42; p = 0.026), underlying neurological disorders (OR: 2.98, 95% CI: 1.49–5.97, p = 0.002), and a history of fever prior to hospital admission (OR: 2.76, 95% CI: 1.58–4.82; p < 0.001). Discussion: In this study, approximately 21% of hospitalized children with SARS-CoV-2 infection had neurological signs/symptoms. Future studies should focus on pathogenesis and long-term outcomes in these children.

The objective of this study is to provide a direct short-term cost-avoidance analysis of expanded three-time prenatal syphilis screening in the context of Manitoba's ongoing outbreak.A conservative modelling approach increased all financial costs of prenatal screening and minimized the direct costs of congenital syphilis treatment. The cost of syphilis screening was calculated using instrument, reagent and consumable costs as well as laboratory overhead and labour costs as documented by Cadham Provincial Laboratory. The short-term direct costs of treating congenital syphilis were calculated using hospital costs and doctor's billing fees. All costs were calculated in 2021 Canadian dollars. These numbers were applied to Manitoba's 2021 congenital syphilis statistics to provide a pragmatic cost-avoidance analysis.The cost of applying three-time prenatal syphilis screening to all 16,800 yearly pregnancies in Manitoba equalled CAD $139,608.00 per year. The direct short-term cost of treating one uncomplicated case of congenital syphilis was $18,151.40. As 81 cases of congenital syphilis were treated in Manitoba in 2021, the short-term direct cost of treating congenital syphilis in Manitoba in 2021 was $1,470,263.40. Applying screening costs to the 125 adequately prevented cases of congenital syphilis in 2021, the screening program is associated with a cost-avoidance ratio of 16.25. If no prenatal syphilis program existed in Manitoba, an expanded screening program would be associated with a cost-avoidance ratio of 26.8.Expanding prenatal syphilis screening is highly cost-avoidant in Manitoba. The 81 cases of congenital syphilis treated in Manitoba in 2021 highlight the need for novel community-based approaches to increase accessibility and engagement with prenatal care.RéSUMé: OBJECTIF: Dans le contexte de l’éclosion de syphilis qui sévit actuellement au Manitoba, notre étude vise à présenter une analyse des coûts directs à court terme qui pourraient être évités en étendant le dépistage de la syphilis au cours des trois trimestres de la grossesse. MéTHODE: En adoptant une approche de modélisation prudente, nous avons accru tous les coûts financiers du dépistage anténatal et réduit les coûts de traitement directs de la syphilis congénitale. Les coûts de dépistage de la syphilis ont été calculés en utilisant les coûts des instruments, des réactifs et des consommables, ainsi que les frais généraux et les coûts de main-d’œuvre des laboratoires selon le Laboratoire provincial Cadham. Les coûts directs à court terme du traitement de la syphilis congénitale ont été calculés en utilisant les frais hospitaliers et les frais facturés par les médecins. Tous les coûts ont été calculés en dollars canadiens de 2021. Ces chiffres ont été appliqués aux statistiques de 2021 du Manitoba sur la syphilis congénitale pour produire une analyse pragmatique de prévention des coûts. RéSULTATS: Le coût d’étendre le dépistage de la syphilis au cours des trois trimestres de la grossesse aux 16 800 grossesses annuelles au Manitoba représentait 139 608 $ CAN par année. Le coût direct à court terme du traitement d’un cas de syphilis congénitale sans complications était de 18 151,40 $. Étant donné que 81 cas de syphilis congénitale ont été traités au Manitoba en 2021, le coût direct à court terme du traitement de syphilis congénitale dans la province en 2021 s’est élevé à 1 470 263,40 $. En appliquant les coûts de dépistage aux 125 cas de syphilis congénitale que l’on a réussi à prévenir en 2021, le programme de dépistage est associé à un rapport de prévention des coûts de 16,25. S’il n’existait aucun programme de dépistage anténatal de la syphilis au Manitoba, un programme de dépistage élargi serait associé à un rapport de prévention des coûts de 26,8. CONCLUSION: L’expansion du dépistage anténatal de la syphilis serait une mesure de prévention des coûts très efficace au Manitoba. Les 81 cas de syphilis congénitale traités dans la province en 2021 montrent qu’il faut adopter de nouvelles approches de proximité pour améliorer l’accès et la participation aux soins anténatals.

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.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.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%).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.

Background Understanding care patterns of persons living with HIV prior to diagnosis can inform prevention opportunities, earlier diagnosis, and engagement strategies. We examined healthcare utilization among HIV-positive individuals and compared them to HIV-negative controls. Methods Data were from a retrospective cohort from Manitoba, Canada. Participants included individuals living with HIV presenting to care between 2007 and 2011, and HIV-negative controls, matched (1:5) by age, sex, and region. Data from population-based administrative databases included physician visits, hospitalizations, drug dispensation, and chlamydia and gonorrhea testing. Diagnoses associated with physician visits were classified according to International Classification of Diseases chapters. Conditional logistic regression models were used to compare cases/controls, with adjusted odds ratios (AORs) and their 95% confidence intervals (95% CI) reported. Results A total of 193 cases and 965 controls were included. Physician visits and hospitalizations were higher for cases, compared to controls. In the 2 years prior to case date, cases were more likely to be diagnosed with “blood disorders” (AOR: 4.2, 95% CI: 2.0–9.0), be treated for mood disorders (AOR: 2.4, 95% CI: 1.6–3.4), and to have 1+ visits to a hospital (AOR: 2.2, 95% CI: 1.4–3.6). Conclusion Opportunities exist for prevention, screening, and earlier diagnosis. There is a need for better integration of healthcare services with public health.

Background: The literature suggests that the Jarisch–Herxheimer (J-H) reaction following antimicrobial treatment of syphilis is common and may precipitate uterine activity. Local practice is to transfer syphilitic parturients beyond gestational age of viability from rural locations to a tertiary care centre for treatment. Study objectives were to delineate local incidence and risk factors for the J-H reaction among pregnant women receiving treatment for syphilis. Methods: A retrospective chart review was conducted on pregnant women diagnosed with syphilis and treated during pregnancy at a tertiary care centre between 2012 and 2018. J-H reaction was defined as having ≥1 of the following symptoms within 24 hours of antibiotic treatment: fever (temperature ≥38°C), clinical description of a painful or itchy skin lesion, headache, hypotension (systolic blood pressure

BackgroundThe COVID-19 pandemic is affecting all Canadian families, with some impacted differently than others. Our study aims to: 1) determine the prevalence and transmission of SARS-CoV-2 infection among Canadian families, 2) identify predictors of infection susceptibility and severity of SARS-CoV-2 and 3) identify health and psychosocial impacts of the COVID-19 pandemic.MethodsThis study builds upon the CHILD Cohort Study, an ongoing multi-ethnic general population prospective cohort consisting of 3454 Canadian families with children born in Vancouver, Edmonton, Manitoba, and Toronto between 2009-12. During the pandemic, 1462 CHILD households (5378 individuals) consented to participate in the CHILD COVID-19 Add-On Study involving: (1) brief biweekly surveys about COVID-19 symptoms and testing; (2) quarterly questionnaires assessing COVID-19 exposure, testing and vaccination status, physical and mental health, and pandemic-driven life changes; (3) in-home biological sampling kits to collect blood and stool. Mean ages were 9 years (range 0-17) for children and 43 years (range 18-85) for adults. Prevalence of SARS-CoV-2 infection will be estimated from survey data and confirmed through serology testing. We will combine these new data with a wealth of pre-pandemic CHILD data and use multivariate modelling and machine learning methods to identify risk and resilience factors for susceptibility and severity to the direct and indirect effects of the pandemic.InterpretationOur short-term findings will inform key stakeholders and knowledge users to shape current and future pandemic responses. Additionally, this study provides a unique resource to study the long-term impacts of the pandemic as the CHILD Cohort Study continues.

CONTEXTE: Le rôle des enfants dans la propagation et la transmission communautaire du coronavirus du syndrome respiratoire aigu sévère 2 (SRAS-CoV-2) est encore mal compris. Nous visons à quantifier l’infectivité du SRAS-CoV-2 d’échantillons nasopharyngés provenant d’enfants comparativement à ceux provenant d’adultes. MÉTHODES: Nous avons obtenu des écouvillons nasopharyngés de cas adultes et pédiatriques de la maladie à coronavirus 2019 (COVID-19) ainsi que de leurs contacts qui ont obtenu un résultat positif à la présence du SRAS-CoV-2 lors d’un test de dépistage au Manitoba entre les mois de mars et décembre 2020. Nous avons comparé la croissance virale en culture cellulaire, les valeurs de cycle seuil de test d’amplification en chaîne par polymérase couplé à une transcription inverse (RT-PCR) de l’enveloppe (E) du gène du SRAS-CoV-2 et de la dose infectieuse pour 50 % de la culture tissulaire (DICT50/mL) entre les adultes et les enfants. RÉSULTATS: Parmi les 305 échantillons positifs à la présence du SRAS-CoV-2 validés par RT-PCR, 97 échantillons provenaient d’enfants de 10 ans et moins, 78 échantillons d’enfants de 11–17 ans et 130 échantillons d’adultes (≥ 18 ans). On a observé une croissance virale en culture dans 31 % des échantillons, dont 18 (19 %) échantillons d’enfants de 10 ans et moins, 18 (23 %) d’enfants de 11–17 ans et 57 (44 %) d’adultes (enfants c. adultes, rapport de cotes 0,45; intervalle de confiance [IC] à 95 % 0,28–0,72). Le cycle seuil était de 25,1 (IC à 95 % 17,7–31,3) chez les enfants de 10 ans et moins, 22,2 (IC à 95 % 18,3–29,0) chez les enfants de 11–17 ans et 18,7 (IC à 95 % 17,9–30,4) chez les adultes (p < 0,001). La DICT50/mL médiane était considérablement plus faible chez les enfants de 11–17 ans (316, écart interquartile [EI] 178–2125) que chez les adultes (5620, EI 1171–17 800, p < 0,001). Le cycle seuil était un indicateur exact d’une culture positive chez les enfants et les adultes (aire sous la courbe de la fonction d’efficacité du récepteur, 0,87, IC à 95 % 0,81–0,93 c. 0,89, IC à 95 % 0,83–0,96, p = 0,6). INTERPRÉTATION: Comparés aux adultes, les enfants qui ont obtenu un résultat positif à un test de dépistage du SRAS-CoV-2 à l’aide d’un écouvillon nasopharyngé étaient moins susceptibles de présenter une croissance du virus en culture et obtenaient un cycle seuil plus élevé et une concentration virale moins élevée, indiquant que les enfants ne sont pas les principaux vecteurs de la transmission du SRAS-CoV-2.

This report presents 2 pediatric cases of multisystem inflammatory syndrome in children and adults (MIS-C/A) post severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination (MIS-V). Both children presented with MIS-V within 6 weeks of receiving their first and only dose of Pfizer-BioNTech’s SARS-CoV-2 vaccine. The first patient had symptoms of MIS-C/A with peri-myocarditis and shock, and the second 1 had classic Kawasaki disease features. Both responded well to intravenous immunoglobulins and/or systemic corticosteroids. Both children were positive only for SARS-2-CoV antispike (S) (and not for antinucleocapsid [NC]) antibodies consistent with a postvaccine, and not a postinfection, event. Surveillance for rare adverse events following immunization should continue, especially now that SARS-CoV-2 vaccination is approved in the 5 to 11 year age group that has had the highest risk of developing MIS-C post SARS-CoV-2 infection. Our patients did not receive any further SARS-CoV-2 vaccines. Our report highlights the importance of measuring differentiating antibodies (anti-S and anti-NC) that can be used within a specific timeframe to help determine if a patient has MIS-V post vaccine (only anti-S present), or MIS-C/A post SARS-CoV-2 infection (both anti-S and anti-NC present).

The objective of this study was to describe the clinical course and outcomes in children with technology dependence (TD) hospitalized with SARS-CoV-2 infection.Seventeen pediatric hospitals (15 Canadian and one each in Iran and Costa Rica) included children up to 17 years of age admitted February 1, 2020, through May 31, 2021, with detection of SARS-CoV-2. For those with TD, data were collected on demographics, clinical course and outcome.Of 691 children entered in the database, 42 (6%) had TD of which 22 had feeding tube dependence only, 9 were on supplemental oxygen only, 3 had feeding tube dependence and were on supplemental oxygen, 2 had a tracheostomy but were not ventilated, 4 were on non-invasive ventilation, and 2 were on mechanical ventilation prior to admission. Three of 42 had incidental SARS-CoV-2 infection. Two with end-stage underlying conditions were transitioned to comfort care and died. Sixteen (43%) of the remaining 37 cases required increased respiratory support from baseline due to COVID-19 while 21 (57%) did not. All survivors were discharged home.Children with TD appear to have an increased risk of COVID-19 hospitalization. However, in the absence of end-stage chronic conditions, all survived to discharge.

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.

Background: Like endemic coronaviruses, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is believed to have emerged in humans from a zoonotic source and may ultimately develop a seasonal pattern. A seasonal pattern, particularly if combined with other seasonal outbreaks of respiratory virus infections, may have significant impacts on the healthcare system. We evaluated the seasonal pattern of existing endemic coronaviruses and several other common respiratory viruses to determine the potential impacts of added burden of respiratory disease should SARS-CoV-2 establish seasonality. Methods: National surveillance data for laboratory confirmations of endemic coronaviruses, influenza A and B viruses, rhinovirus/enterovirus, human metapneumovirus, respiratory syncytial virus and parainfluenza virus for the past 10 years were obtained from the Government of Canada Open Data and FluWatch. Epidemic curves were generated from total case numbers and percent of samples testing positive for each respiratory virus by epidemiological week. Results: In Canada, endemic coronaviruses and other common respiratory viruses cause annual seasonal outbreaks in the winter months. Should SARS-CoV-2 develop a seasonal pattern similar to endemic coronaviruses and respiratory viruses, co-circulation would be expected to peak between January and March. Peak endemic coronavirus activity occurs during the nadir of rhinovirus/enterovirus and parainfluenza activity. Conclusion: Healthcare settings, assisted-living and long-term care homes, schools and essential services employers should anticipate and have contingencies for seasonal outbreaks of SARS-CoV-2 and co-circulating respiratory viruses during peak seasons. Given the likelihood of co-circulation, diagnostic multiplex testing targeting co-circulating pathogens may be more efficient than single target assays for symptomatic individuals if a seasonal pattern to coronavirus disease 2019 (COVID-19) is established.

This retrospective study included allDuring the study period, 1014

Background Reverse-transcription polymerase chain reaction (RT-PCR) has become the primary method to diagnose viral diseases, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). RT-PCR detects RNA, not infectious virus; thus, its ability to determine duration of infectivity of patients is limited. Infectivity is a critical determinant in informing public health guidelines/interventions. Our goal was to determine the relationship between E gene SARS-CoV-2 RT-PCR cycle threshold (Ct) values from respiratory samples, symptom onset to test (STT), and infectivity in cell culture. Methods In this retrospective cross-sectional study, we took SARS-CoV-2 RT-PCR–confirmed positive samples and determined their ability to infect Vero cell lines. Results Ninety RT-PCR SARS-CoV-2–positive samples were incubated on Vero cells. Twenty-six samples (28.9%) demonstrated viral growth. Median tissue culture infectious dose/mL was 1780 (interquartile range, 282–8511). There was no growth in samples with a Ct > 24 or STT > 8 days. Multivariate logistic regression using positive viral culture as a binary predictor variable, STT, and Ct demonstrated an odds ratio (OR) for positive viral culture of 0.64 (95% confidence interval [CI], .49–.84; P 24. Conclusions SARS-CoV-2 Vero cell infectivity was only observed for RT-PCR Ct 24 and duration of symptoms > 8 days may be low. This information can inform public health policy and guide clinical, infection control, and occupational health decisions. Further studies of larger size are needed.

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.

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.

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 and objectives We describe the third documented case of autochthonous human babesiosis in Canada and the second in a Canadian blood donor. Materials and methods Multiple laboratory investigations were carried out on the donor and the immunocompromised recipient of an associated, potentially infectious red blood cell product. Results The donor had not travelled except for outdoor exposure in south-eastern Manitoba, followed by illness and hospital admission. The donor had a notable parasitaemia, positive for Babesia microti using whole blood nucleic acid testing (NAT). The recipient was negative for B. microti by both serology and NAT. Conclusion There was no evidence of transfusion-transmitted babesiosis.

Background Infectious syphilis has been increasing in incidence in Manitoba since 2012, especially in heterosexual women of childbearing age resulting in an increasing number of infants with in utero exposure and who are at risk for congenital syphilis (CS). We aimed to evaluate the impact of syphilis in pregnancy on infants and to describe our experience with CS. Methodology This retrospective 2012 to 2018 cohort study reviewed women with syphilis in pregnancy and short-term infant outcomes. We grouped mother–infant pairs into high risk and low risk for CS and compared their management and outcomes. We also describe our cases of confirmed and possible CS. Results Seventy-nine mothers and 80 infants met inclusion criteria. Thirty mother–infant pairs were classified as high risk for CS. Nine of their infants were diagnosed with confirmed CS and four with possible CS. All confirmed CS cases were asymptomatic at birth but two were not recognized to have CS until they later presented with symptoms. One of these infants had negative serologies (treponemal and non-treponemal) at birth, but at 3 months old had reactive serologies. Two months of age was the earliest clearance of maternal treponemal antibodies amongst low-risk infants compared to 6 months in high-risk infants. Most infants who did not have confirmed CS had non-reactive non-treponemal tests by 6 months old. Interpretation Our study shows that symptoms and paired maternal-infant non-treponemal titres at birth are not sensitive for diagnosing CS. Serologies can be falsely negative with recent infection. Regardless of investigations or clinical findings, 10 days of intravenous penicillin G should be considered for all high-risk infants.

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.

BACKGROUNDSARS-CoV-2 infection can lead to multisystem inflammatory syndrome in children (MIS-C). We investigated risk factors for severe disease and explored changes in severity over time.METHODSChildren up to 17 years of age admitted March 1, 2020 through March 7th, 2021 to 15 hospitals in Canada, Iran and Costa Rica with confirmed or probable MIS-C were included. Descriptive analysis and comparison by diagnostic criteria, country, and admission date was performed. Adjusted absolute average risks (AR) and risk differences (RD) were estimated for characteristics associated with ICU admission or cardiac involvement.RESULTSOf 232 cases (106 confirmed) with median age 5.8 years, 56% were male, and 22% had comorbidities. ICU admission occurred in 73 (31%) but none died. Median length of stay was 6 days (inter-quartile range 4-9). Children 6 to 12 years old had the highest AR for ICU admission (44%; 95% confidence interval [CI] 34-53). Initial ferritin greater than 500 mcg/L was associated with ICU admission. When comparing cases admitted up to October 31, 2020 to those admitted later, the AR for ICU admission increased from 25% (CI 17-33) to 37% (CI 29-46) and for cardiac involvement from 44% (CI 35-53) to 75% (CI 66-84). Risk estimates for ICU admission in the Canadian cohort demonstrated a higher risk in December 2020-March 2021 compared to March-May 2020 (RD 25%; 95%CI 7-44).INTERPRETATIONMIS-C occurred primarily in previously well children. Illness severity appeared to increase over time. Despite a high ICU admission incidence, most children were discharged within one week.

Vaccines against SARS-CoV-2 have shown high efficacy in clinical trials, yet a full immunologic characterization of these vaccines, particularly within the upper respiratory tract, remains lacking. We enumerated and phenotyped T cells in nasal mucosa and blood before and after vaccination with the Pfizer-BioNTech COVID-19 vaccine (n =21). Tissue-resident memory (Trm) CD8+ T cells expressing CD69+CD103+ expanded ∼12 days following the first and second doses, by 0.31 and 0.43 log10cells per swab respectively (p=0.058 and p=0.009 in adjusted linear mixed models). CD69+CD103+CD8+ T cells in the blood decreased post-vaccination. Similar increases in nasal CD8+CD69+CD103-T cells were observed, particularly following the second dose. CD4+ Th17 cells were also increased in abundance following both doses. Following stimulation with SARS-CoV-2 spike peptides, CD8+ T cells increased expression of CD107a and CD154. These data suggest that nasal T cells may be induced and contribute to the protective immunity afforded by this vaccine.

BackgroundA cohort study was conducted to describe and compare the characteristics of SARS-CoV-2 infection in hospitalized children in three countries.MethodsThis was a retrospective cohort of consecutive children admitted to 15 hospitals (13 in Canada and one each in Iran and Costa Rica) up to November 16, 2020. Cases were included if they had SARS-CoV-2 infection or multi-system inflammatory syndrome in children (MIS-C) with molecular detection of SARS-CoV-2 or positive SARS-CoV-2 serology.ResultsOf 211 included cases (Canada N=95; Costa Rica N=84; Iran N=32), 103 (49%) had a presumptive diagnosis of COVID-19 or MIS-C at admission while 108 (51%) were admitted with other diagnoses. Twenty-one (10%) of 211 met criteria for MIS-C. Eighty-seven (41%) had comorbidities. Children admitted in Canada were older than those admitted to non-Canadian sites (median 4.1 versus 2.2 years; pConclusionsApproximately half of hospitalized children with confirmed SARS-CoV-2 infection or MIS-C were admitted with other suspected diagnoses. Disease severity was higher at non-Canadian sites. Neonates, children with comorbidities and those with chest radiographs compatible with COVID-19 were at increased risk for severe or critical COVID-19.Main pointsApproximately half of hospitalized children with laboratory confirmed MIS-C or SARS-CoV-2 infection were admitted with another primary diagnoses. The severity of disease was higher in the middle income countries (Costa Rica and Iran) than in Canada.

Background: Knowledge about neurological manifestations of SARS-CoV-2 in children is limited. We describe neurological manifestations in an international cohort of hospitalized pediatric patients. Methods: This is a multi-national observational study involving tertiary healthcare institutions in Canada, Costa Rica and Iran. We included patients 1 day-18 years admitted for any medical reason February 1, 2020-January 31, 2021 with laboratory evidence of SARS-CoV-2 infection by RT-PCR or serological testing. Descriptive analyses and logistic regression were performed where appropriate using JASP version 0⋅13. Findings: 298 hospitalized children with confirmed SARS-CoV-2 infection (median age 3⋅9 years [IQR 0⋅6-10⋅1]) from Canada (n=152), Costa Rica (n=115) and Iran (n=31) were included. Fifty-one (17%) had neurological manifestations, of which headache (73%), seizures (23%) and altered mental status (6%) were most frequently seen. Children with neurological symptoms had equivalent rates of comorbidities overall but were more likely to have underlying chronic neurological conditions. Additionally, those with neurological symptoms were more likely to be admitted to the ICU (15/51 [29%] vs. 32/247 [13%]; p =0⋅0033) and had longer length of hospital stay (6 days [IQR 3-8] vs. 4 days [IQR 2-7]; p =0⋅0060). Abnormalities were found in all children with neurological manifestations who received neuroimaging (n=6). Neurological manifestations were seen in 19% of the Iranian cohort, 23% of the Costa Rican cohort, and 12% of the Canadian cohort. Country of residence Costa Rica (adjusted OR: 2⋅520, 95% CI: 1⋅325-4⋅791, p =0⋅005), ICU admission (adjusted OR: 2⋅678, 95% CI: 1⋅307-5⋅486, p =0⋅007) and number of acute SARS-CoV-2 infection symptoms (adjusted OR: 1⋅355, 95% CI: 1⋅232-1⋅491, p

The coronavirus disease (COVID-19) pandemic is causing wide-spread interruptions in medical education. With little warning, clinical rotations were cancelled and medical students were sent home. While pre-clinical students transitioned to online curricula, clinical students were left without discreet educational goals. Simultaneously, medical doctors were scrambling to maintain competence in the face of rapidly evolving COVID-19 information. Here, we describe an education program that integrates medical students into interdisciplinary teams to review emerging COVID-19 research that directly answers questions sent in by medical doctors.

The goal of this document was to provide Canadian laboratories with a framework for consistent reporting and monitoring of multidrug resistant organisms (MDRO) and extensively drug resistant organisms (XDRO) for common gram-negative pathogens. This is the final edition of the interim recommendations, which were modified after one year of broad consultative review. This edition represents a consensus of peer-reviewed information and was co-authored by the Canadian Public Health Laboratory Network and the Canadian Association of Clinical Microbiology and Infectious Diseases. There are two main recommendations. The first recommendation provides standardized definitions for MDRO and XDRO for gram-negative organisms in clinical specimens. These definitions were limited to antibiotics that are commonly tested clinically and, to reduce ambiguity, resistance (rather than non-susceptibility) was used to calculate drug resistance status. The second recommendation identifies the use of standardized laboratory reporting of organisms identified as MDRO or XDRO. Through the broad consultation, which included public health and infection prevention and control colleagues, these definitions are ready to be applied for policy development. Both authoring organizations intend to review these recommendations regularly as antibiotic resistance testing evolves in Canada.