Risk of transmission of HIV to infants during breast/chest feeding when mothers/birthing parents living with HIV are on antiretroviral therapy: a protocol for a rapid review.

INTRODUCTION: HIV is a major public health issue affecting millions globally. Women and girls account for 46% of new HIV infections in 2022 and approximately 1.3 million females become pregnant every year. Vertical transmission of HIV from persons living with HIV (PLHIV) to infants may occur through different modalities, such as through breast/chest feeding. Notably, 82% of PLHIV who chose to breast/chest feed are on antiretroviral therapy (ART) when feeding their infants. Precise estimates of the risk of postpartum transmission to infants during breast/chest feeding at varying viral load levels remain a significant gap in the literature. METHODS AND ANALYSIS: A rapid systematic search of electronic databases will be conducted from January 2005 to the present, including Medline, Embase and Global Health. The objective of this rapid review is to explore and assess the available evidence on the effect of varying viral load levels on the risk of HIV transmission to infants during breast/chest feeding when the birthing or gestational parent living with HIV is on ART. Study characteristics will be summarised and reported to support the narrative summary of the findings. The focus will be on the absolute risk of HIV transmission from birthing parent to infant during chest/breast feeding. The findings will also be stratified by month, including the risk of HIV transmission for 6 months and greater than 6 months postpartum. We will ascertain the risk of bias using A Measurement Tool to Assess Systematic Reviews 2, Quality of Prognosis Studies and Downs and Black checklist for the appropriate study type. A summary score will not be calculated, rather the strengths and limitations of the studies will be narratively described. ETHICS AND DISSEMINATION: No human subjects will be involved in the research. The findings of this rapid review will inform a future systematic review and will be disseminated through peer-reviewed publications, presentations and conferences. PROSPERO REGISTRATION NUMBER: CRD42024499393.

Neurological involvement in hospitalized children with SARS-CoV-2 infection: a multinational study.

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 <18 years of age with confirmed SARS-CoV-2 infection or multisystemic inflammatory syndrome (MIS-C) and laboratory evidence of SARS-CoV-2 infection in children, admitted to 15 tertiary hospitals/healthcare centers in Canada, Costa Rica, and Iran February 2020-May 2021. Descriptive statistical analyses were performed and logistic regression was used to identify factors associated with neurological involvement. 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.

Test negative design for vaccine effectiveness estimation in the context of the COVID-19 pandemic: A systematic methodology review.

BACKGROUND: During the height of the global COVID-19 pandemic, the test-negative design (TND) was extensively used in many countries to evaluate COVID-19 vaccine effectiveness (VE). Typically, the TND involves the recruitment of care-seeking individuals who meet a common clinical case definition. All participants are then tested for an infection of interest. OBJECTIVES: To review and describe the variation in TND methodology, and disclosure of potential biases, as applied to the evaluation of COVID-19 VE during the early vaccination phase of the pandemic. METHODS: We conducted a systematic review by searching four biomedical databases using defined keywords to identify peer-reviewed articles published between January 1, 2020, and January 25, 2022. We included only original articles that employed a TND to estimate VE of COVID-19 vaccines in which cases and controls were evaluated based on SARS-CoV-2 laboratory test results. RESULTS: We identified 96 studies, 35 of which met the defined criteria. Most studies were from North America (16 studies) and targeted the general population (28 studies). Outcome case definitions were based primarily on COVID-19-like symptoms; however, several papers did not consider or specify symptoms. Cases and controls had the same inclusion criteria in only half of the studies. Most studies relied upon administrative or hospital databases assembled for a different (non-evaluation) clinical purpose. Potential unmeasured confounding (20 studies), misclassification of current SARS-CoV-2 infection (16 studies) and selection bias (10 studies) were disclosed as limitations by some studies. CONCLUSION: We observed potentially meaningful deviations from the validated design in the application of the TND during the COVID-19 pandemic.

Diagnostic accuracy of qPCR and microscopy for cutaneous leishmaniasis in rural Ecuador: A Bayesian latent class analysis.

BACKGROUND: Clinical and laboratory diagnosis of cutaneous leishmaniasis (CL) is hampered by under-ascertainment of direct microscopy. METHODS: This study compared the diagnostic accuracy of qPCR on DNA extracted from filter paper to the accuracy of direct smear slide microscopy in participants presenting with a cutaneous lesion suspected of leishmaniasis to 16 rural healthcare centers in the Ecuadorian Amazon and Pacific regions, from January 2019 to June 2021. We used Bayesian latent class analysis to estimate test sensitivity, specificity, likelihood ratios (LR), and predictive values (PV) with their 95% credible intervals (95%CrI). The impact of sociodemographic and clinical characteristics on predictive values was assessed as a secondary objective. RESULTS: Of 320 initially included participants, paired valid test results were available and included in the diagnostic accuracy analysis for 129 from the Amazon and 185 from the Pacific region. We estimated sensitivity of 68% (95%CrI 49% to 82%) and 73% (95%CrI 73% to 83%) for qPCR, and 51% (95%CrI 36% to 66%) and 76% (95%CrI 65% to 86%) for microscopy in the Amazon and Pacific region, respectively. In the Amazon, with an estimated disease prevalence among participants of 73%, negative PV for qPCR was 54% (95%CrI 5% to 77%) and 44% (95%CrI 4% to 65%) for microscopy. In the Pacific, (prevalence 88%) the negative PV was 34% (95%CrI 3% to 58%) and 37% (95%CrI 3% to 63%). The addition of qPCR parallel to microscopy in the Amazon increases the observed prevalence from 38% to 64% (+26 (95%CrI 19 to 34) percentage points). CONCLUSION: The accuracy of either qPCR on DNA extracted from filter paper or microscopy for CL diagnosis as a stand-alone test seems to be unsatisfactory and region-dependent. We recommend further studies to confirm the clinically relevant increment found in the diagnostic yield due to the addition of qPCR.

SARS-CoV-2 infection prevention and control measures in Belgian schools between December 2020 and June 2021 and their association with seroprevalence: a cross-sectional analysis of a prospective cohort study.

BACKGROUND: To protect school-aged children from the potential consequences of a new viral infection, public health authorities recommended to implement infection prevention and control (IPC) measures in school settings. Few studies evaluated the implementation of these measures and their effect on SARS-CoV-2 infection rates among pupils and staff. The aim of this study was to describe the implementation of infection prevention and control (IPC) measures in Belgian schools and assess its relation to the prevalence of anti-SARS-CoV-2 antibodies among pupils and staff. METHODS: We conducted a prospective cohort study in a representative sample of primary and secondary schools in Belgium between December 2020 and June 2021. The implementation of IPC measures in schools was assessed using a questionnaire. Schools were classified according to their compliance with the implementation of IPC measures as 'poor', 'moderate' or 'thorough'. Saliva samples were collected from pupils and staff to determine the SARS-CoV-2 seroprevalence. To assess the association between the strength of implementation of IPC measures and SARS-CoV-2 seroprevalence among pupils and staff, we conducted a cross-sectional analysis using the data collected in December 2020/January 2021. RESULTS: A variety of IPC measures (ventilation, hygiene and physical distancing) was implemented by more than 60% of schools, with most attention placed on hygiene measures. In January 2021, poor implementation of IPC measures was associated with an increase in anti-SARS-CoV-2 antibody prevalence among pupils from 8.6% (95%CI: 4.5 - 16.6) to 16.7% (95%CI: 10.2 - 27.4) and staff from 11.5% (95%CI: 8.1 - 16.4) to 17.6% (95%CI: 11.5 - 27.0). This association was only statistically significant for the assessment of all IPC measures together in the population comprised of pupils and staff. CONCLUSIONS: Belgian schools were relatively compliant with recommended IPC measures at the school level. Higher SARS-CoV-2 seroprevalence among pupils and staff was found in schools with poor implementation of IPC measures, compared to schools with thorough implementation. TRIAL REGISTRATION: This trial is registered under the NCT04613817 ClinicalTrials.gov Identifier on November 3, 2020.

SARS-CoV-2 seroprevalence and determinants for salivary seropositivity among pupils and school staff: a prospective cohort study.

Representative school data on SARS-CoV-2 past-infection are scarce, and differences between pupils and staff remain ambiguous. We performed a nation-wide prospective seroprevalence study among pupils and staff over time and in relation to determinants of infection using Poisson regression and generalised estimating equations. A cluster random sample was selected with allocation by region and sociodemographic (SES) background. Surveys and saliva samples were collected in December 2020, March, and June 2021, and also in October and December 2021 for primary pupils. We recruited 885 primary and 569 secondary pupils and 799 staff in 84 schools. Cumulative seroprevalence (95% CI) among primary pupils increased from 11.0% (7.6; 15.9) at baseline to 60.4% (53.4; 68.3) in December 2021. Group estimates were similar at baseline; however, in June they were significantly higher among primary staff (38.9% (32.5; 46.4)) compared to pupils and secondary staff (24.2% (20.3; 28.8)). Infections were asymptomatic in 48-56% of pupils and 28% of staff. Seropositivity was associated with individual SES in pupils, and with school level, school SES and language network in staff in June. Associations with behavioural characteristics were inconsistent. Seroconversion rates increased two- to four-fold after self-reported high-risk contacts, especially with adults. Seroprevalence studies using non-invasive sampling can inform public health management.

Proactive Contact Tracing.

The COVID-19 pandemic has spurred an unprecedented demand for interventions that can reduce disease spread without excessively restricting daily activity, given negative impacts on mental health and economic outcomes. Digital contact tracing (DCT) apps have emerged as a component of the epidemic management toolkit. Existing DCT apps typically recommend quarantine to all digitally-recorded contacts of test-confirmed cases. Over-reliance on testing may, however, impede the effectiveness of such apps, since by the time cases are confirmed through testing, onward transmissions are likely to have occurred. Furthermore, most cases are infectious over a short period; only a subset of their contacts are likely to become infected. These apps do not fully utilize data sources to base their predictions of transmission risk during an encounter, leading to recommendations of quarantine to many uninfected people and associated slowdowns in economic activity. This phenomenon, commonly termed as "pingdemic," may additionally contribute to reduced compliance to public health measures. In this work, we propose a novel DCT framework, Proactive Contact Tracing (PCT), which uses multiple sources of information (e.g. self-reported symptoms, received messages from contacts) to estimate app users' infectiousness histories and provide behavioral recommendations. PCT methods are by design proactive, predicting spread before it occurs. We present an interpretable instance of this framework, the Rule-based PCT algorithm, designed via a multi-disciplinary collaboration among epidemiologists, computer scientists, and behavior experts. Finally, we develop an agent-based model that allows us to compare different DCT methods and evaluate their performance in negotiating the trade-off between epidemic control and restricting population mobility. Performing extensive sensitivity analysis across user behavior, public health policy, and virological parameters, we compare Rule-based PCT to i) binary contact tracing (BCT), which exclusively relies on test results and recommends a fixed-duration quarantine, and ii) household quarantine (HQ). Our results suggest that both BCT and Rule-based PCT improve upon HQ, however, Rule-based PCT is more efficient at controlling spread of disease than BCT across a range of scenarios. In terms of cost-effectiveness, we show that Rule-based PCT pareto-dominates BCT, as demonstrated by a decrease in Disability Adjusted Life Years, as well as Temporary Productivity Loss. Overall, we find that Rule-based PCT outperforms existing approaches across a varying range of parameters. By leveraging anonymized infectiousness estimates received from digitally-recorded contacts, PCT is able to notify potentially infected users earlier than BCT methods and prevent onward transmissions. Our results suggest that PCT-based applications could be a useful tool in managing future epidemics.

SARS-CoV-2 infection in technology-dependent children: a multicenter case series.

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

COVID-19 surveillance in the Flemish school system: development of systematic data collection within the public health school system and descriptive analysis of cases reported between October 2020 and June 2021.

BACKGROUND: The age-specific distribution of SARS-CoV-2 cases in schools is not well described. Reported statistics reflect the intensity of community transmission while being shaped by biases from age-dependent testing regimes, as well as effective age-specific interventions. A case surveillance system was introduced within the Flemish school and health-prevention network during the 2020-2021 school year. We present epidemiological data of in-school reported cases in pre-, primary and secondary schools identified by the case surveillance system, in conjunction with test data and community cases from October 2020 to June 2021. METHODS: We describe the development of the surveillance system and provide the number of reported cases and standardized rates per grade over time. We calculated absolute and relative differences in case incidence according to school grade (primary: grades 1-6, and secondary: grades 7-12) using grades 7-8 as a comparator, relating them to non-pharmaceutical infection prevention interventions. Cumulative population incidences (IP) stratified by age, province and socioeconomic status (SES) of the school population are presented with their 95% confidence intervals (CI). RESULTS: A total of 59,996 COVID-19 cases were reported in the school surveillance system, with the highest population adjusted IP in grade 11-12 of 7.39% (95%CI 7.24-7.53) and ranging from 2.23% to 6.25% from pre-school through grade 10. Age-specific reductions in mask introduction and in-person teaching were temporally associated with decreased case incidence, while lower pupil SES was associated with an increase in cumulative cases (excess 2,739/100,000 pupils compared to highest SES tertile). Community testing volumes varied more for children compared to adults, with overall higher child test-positivity. Holidays influence capturing of cases by the system, however efficiency increased to above 75% after further automation and integration in existing structures. CONCLUSION: We demonstrate that effective integration of case surveillance within an electronic school health system is feasible, provides valuable data regarding the evolution of an epidemic among schoolchildren, and is an integral component of public health surveillance and pandemic preparedness. The relationship towards community transmission needs careful evaluation because of age-different testing regimens. In the Flemish region, case incidence within schools exhibited an age gradient that was mitigated through grade-specific interventions, though differences by SES remain.

SARS-CoV-2 Transmission in Belgian French-Speaking Primary Schools: An Epidemiological Pilot Study.

Schools have been a point of attention during the pandemic, and their closure one of the mitigating measures taken. A better understanding of the dynamics of the transmission of SARS-CoV-2 in elementary education is essential to advise decisionmakers. We conducted an uncontrolled non-interventional prospective study in Belgian French-speaking schools to describe the role of attending asymptomatic children and school staff in the spread of COVID-19 and to estimate the transmission to others. Each participant from selected schools was tested for SARS-CoV-2 using a polymerase chain reaction (PCR) analysis on saliva sample, on a weekly basis, during six consecutive visits. In accordance with recommendations in force at the time, symptomatic individuals were excluded from school, but per the study protocol, being that participants were blinded to PCR results, asymptomatic participants were maintained at school. Among 11 selected schools, 932 pupils and 242 school staff were included between January and May 2021. Overall, 6449 saliva samples were collected, of which 44 came back positive. Most positive samples came from isolated cases. We observed that asymptomatic positive children remaining at school did not lead to increasing numbers of cases or clusters. However, we conducted our study during a period of low prevalence in Belgium. It would be interesting to conduct the same analysis during a high prevalence period.

Risk factors for severe PCR-positive SARS-CoV-2 infection in hospitalised children.

OBJECTIVE: To identify risk factors for severe disease in children hospitalised for SARS-CoV-2 infection. DESIGN: Multicentre retrospective cohort study. SETTING: 18 hospitals in Canada, Iran and Costa Rica from 1 February 2020 to 31 May 2021. PATIENTS: Children<18 years of age hospitalised for symptomatic PCR-positive SARS-CoV-2 infection, including PCR-positive multisystem inflammatory syndrome in children (MIS-C). MAIN OUTCOME MEASURE: Severity on the WHO COVID-19 Clinical Progression Scale was used for ordinal logistic regression analyses. RESULTS: We identified 403 hospitalisations. Median age was 3.78 years (IQR 0.53-10.77). At least one comorbidity was present in 46.4% (187/403) and multiple comorbidities in 18.6% (75/403). Eighty-one children (20.1%) met WHO criteria for PCR-positive MIS-C. Progression to WHO clinical scale score ≥6 occurred in 25.3% (102/403). In multivariable ordinal logistic regression analyses adjusted for age, chest imaging findings, laboratory-confirmed bacterial and/or viral coinfection, and MIS-C diagnosis, presence of a single (adjusted OR (aOR) 1.90, 95% CI 1.13 to 3.20) or multiple chronic comorbidities (aOR 2.12, 95% CI 1.19 to 3.79), obesity (aOR 3.42, 95% CI 1.76 to 6.66) and chromosomal disorders (aOR 4.47, 95% CI 1.25 to 16.01) were independent risk factors for severity. Age was not an independent risk factor, but different age-specific comorbidities were associated with more severe disease in age-stratified adjusted analyses: cardiac (aOR 2.90, 95% CI 1.11 to 7.56) and non-asthma pulmonary disorders (aOR 3.07, 95% CI 1.26 to 7.49) in children<12 years old and obesity (aOR 3.69, 1.45-9.40) in adolescents≥12 years old. Among infants<1 year old, neurological (aOR 10.72, 95% CI 1.01 to 113.35) and cardiac disorders (aOR 10.13, 95% CI 1.69 to 60.54) were independent predictors of severe disease. CONCLUSION: We identified risk factors for disease severity among children hospitalised for PCR-positive SARS-CoV-2 infection. Comorbidities predisposing children to more severe disease may vary by age. These findings can potentially guide vaccination programmes and treatment approaches in children.

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

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.

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

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.

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

Age is the most important determinant of COVID-19 severity. Infectious disease severity by age is typically J-shaped, with infants and the elderly carrying a high burden of disease. We report on the comparative disease severity between infants and older children in a multicenter retrospective cohort study of children 0 to 17 years old admitted for acute COVID-19 from February 2020 through May 2021 in 17 pediatric hospitals. We compare clinical and laboratory characteristics and estimate the association between age group and disease severity using ordinal logistic regression. We found that infants comprised one-third of cases, but were admitted for a shorter period (median 3 days IQR 2-5 versus 4 days IQR 2-7), had a lower likelihood to have an increased C-reactive protein, and had half the odds of older children of having severe or critical disease (OR 0.50 (95% confidence interval 0.32-0.78)).    Conclusion: When compared to older children, there appeared to be a lower threshold to admit infants but their length of stay was shorter and they had lower odds than older children of progressing to severe or critical disease. What is Known: • A small proportion of children infected with SARS-CoV-2 require hospitalization for acute COVID-19 with a subgroup needing specialized intensive care to treat more severe disease. • For most infectious diseases including viral respiratory tract infections, disease severity by age is J-shaped, with infants having more severe disease compared to older children. What is New: • One-third of admitted children for acute COVID-19 during the first 14 months of the pandemic were infants. • Infants had half the odds of older children of having severe or critical disease.

Age-dependent seroprevalence of SARS-CoV-2 antibodies in school-aged children from areas with low and high community transmission.

It is not yet clear to what extent SARS-CoV-2 infection rates in children reflect community transmission, nor whether infection rates differ between primary schoolchildren and young teenagers. A cross-sectional serosurvey compared the SARS-CoV2 attack-rate in a sample of 362 children recruited from September 21 to October 6, 2020, in primary (ages 6-12) or lower secondary school (ages 12-15) in a municipality with low community transmission (Pelt) to a municipality with high community transmission (Alken) in Belgium. Children were equally distributed over grades and regions. Blood samples were tested for the presence of antibodies to SARS-CoV-2 with an enzyme-linked immunosorbent assay. We found anti-SARS-CoV-2 antibodies in 4.4% of children in the low transmission region and in 14.4% of children in the high transmission region. None of the primary schoolchildren were seropositive in the low transmission region, whereas the seroprevalence among primary and secondary schoolchildren did not differ significantly in the high transmission region. None of the seropositive children suffered from severe disease. Children who were in contact with a confirmed case (RR 2.9; 95%CI 1.6-4.5), who participated in extracurricular activities (RR 5.6; 95%CI 1.2-25.3), or whose caregiver is a healthcare worker who had contact with COVID-19 patients (RR 2.2; 95%CI 1.0-4.6) were at higher risk of seropositivity. If SARS-CoV2 circulation in the community is high, this will be reflected in the pediatric population with similar infection rates in children aged 6-12 years and 12-15 years. What is Known: •Children are generally less affected by COVID-19 than adults but SARS-CoV2 infection rates among children are not well known. •There were large regional differences in infection rates during the first wave of the SARS-CoV2 pandemic. What is New: •None of the primary schoolchildren (6-12 years) were seropositive for SARS-CoV2 in an area with a low community transmission, but infection rates were higher in adolescents (12-15 years). •In an area with high community transmission, seroprevalence rates in younger children were more comparable to those in adolescents.

Use of Racial and Ethnic Categories in Medical Testing and Diagnosis: Primum Non Nocere.

BACKGROUND: Use of race and ethnicity is common in medical tests and procedures, even though these categories are defined by sociological, historical, and political processes, and vary considerably in their definitions over time and place. Because all societies organize themselves around these constructs in some way, they are undeniable facets of the human experience, with myriad health consequences. In the biomedical literature, they are also commonly interpreted as representing biological heterogeneity that is relevant for health and disease. CONTENT: We review the use of race and ethnicity in medical practice, especially in the USA, and provide 2 specific examples to represent a large number of similar instances. We then critique these uses along a number of different dimensions, including limitations in measurement, within- versus between-group variance, and implications for informativeness of risk markers for individuals, generalization from arbitrary or nonrepresentative samples, perpetuation of myths and stereotypes, instability in time and place, crowding out of more relevant risk markers, stigmatization, and the tainting of medicine with the history of oppression. We conclude with recommendations to improve practice that are technical, ethical, and pragmatic. SUMMARY: Medicine has evolved from a mystical healing art to a mature science of human health through a rigorous process of quantification, experimentation, and evaluation. Folkloric traditions, such as race- and ethnic-specific medicine will fade from use as we become increasingly critical of outdated and irrational clinical practices and replace these with personalized, evidenced-based tests, algorithms, and procedures that privilege patients' individual humanity over obsolete and misleading labels.

Characteristics and outcomes of pregnant women with SARS-CoV-2 infection and other severe acute respiratory infections (SARI) in Brazil from January to November 2020.

BACKGROUND: Knowledge about COVID-19 in pregnancy is limited, and evidence on the impact of the infection during pregnancy and postpartum is still emerging. AIM: To analyze maternal morbidity and mortality due to severe acute respiratory infections (SARI), including COVID-19, in Brazil. METHODS: National surveillance data from the SIVEP-Gripe (Sistema de Informação de Vigilância Epidemiológica da Gripe) was used to describe currently and recently pregnant women aged 10-49 years hospitalized for SARI from January through November, 2020. SARI cases were grouped into: COVID-19; influenza or other detected agent SARI; and SARI of unknown etiology. Characteristics, symptoms and outcomes were presented by SARI type and region. Binomial proportion and 95% confidence intervals (95% CI) for outcomes were obtained using the Clopper-Pearson method. RESULTS: Of 945,460 SARI cases in the SIVEP-Gripe, we selected 11,074 women aged 10-49 who were pregnant (7964) or recently pregnant (3110). COVID-19 was confirmed in 49.4% cases; 1.7% had influenza or another etiological agent; and 48.9% had SARI of unknown etiology. The pardo race/ethnic group accounted for 50% of SARI cases. Hypertension/Other cardiovascular diseases, chronic respiratory diseases, diabetes, and obesity were the most common comorbidities. A total of 362 women with COVID-19 (6.6%; 95%CI 6.0-7.3) died. Mortality was 4.7% (2.2-8.8) among influenza patients, and 3.3% (2.9-3.8) among those with SARI of unknown etiology. The South-East, Northeast and North regions recorded the highest frequencies of mortality among COVID-19 patients. CONCLUSION: Mortality among pregnant and recently pregnant women with SARIs was elevated among those with COVID-19, particularly in regions where maternal mortality is already high.

Identifiability and Estimation Under the Test-negative Design With Population Controls With the Goal of Identifying Risk and Preventive Factors for SARS-CoV-2 Infection.

Owing to the rapidly evolving coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, quick public health investigations of the relationships between behaviors and infection risk are essential. Recently the test-negative design (TND) was proposed to recruit and survey participants who are symptomatic and being tested for SARS-CoV-2 infection with the goal of evaluating associations between the survey responses (including behaviors and environment) and testing positive on the test. It was also proposed to recruit additional controls who are part of the general population as a baseline comparison group to evaluate risk factors specific to SARS-CoV-2 infection. In this study, we consider an alternative design where we recruit among all individuals, symptomatic and asymptomatic, being tested for the virus in addition to population controls. We define a regression parameter related to a prospective risk factor analysis and investigate its identifiability under the two study designs. We review the difference between the prospective risk factor parameter and the parameter targeted in the typical TND where only symptomatic and tested people are recruited. Using missing data directed acyclic graphs, we provide conditions and required data collection under which identifiability of the prospective risk factor parameter is possible and compare the benefits and limitations of the alternative study designs and target parameters. We propose a novel inverse probability weighting estimator and demonstrate the performance of this estimator through simulation study.