Temporal trends in disparities in COVID-19 seropositivity among Canadian blood donors.

BACKGROUND: In Canada's largest COVID-19 serological study, SARS-CoV-2 antibodies in blood donors have been monitored since 2020. No study has analysed changes in the association between anti-N seropositivity (a marker of recent infection) and geographic and sociodemographic characteristics over the pandemic. METHODS: Using Bayesian multi-level models with spatial effects at the census division level, we analysed changes in correlates of SARS-CoV-2 anti-N seropositivity across three periods in which different variants predominated (pre-Delta, Delta and Omicron). We analysed disparities by geographic area, individual traits (age, sex, race) and neighbourhood factors (urbanicity, material deprivation and social deprivation). Data were from 420 319 blood donations across four regions (Ontario, British Columbia [BC], the Prairies and the Atlantic region) from December 2020 to November 2022. RESULTS: Seropositivity was higher for racialized minorities, males and individuals in more materially deprived neighbourhoods in the pre-Delta and Delta waves. These subgroup differences dissipated in the Omicron wave as large swaths of the population became infected. Across all waves, seropositivity was higher in younger individuals and those with lower neighbourhood social deprivation. Rural residents had high seropositivity in the Prairies, but not other regions. Compared to generalized linear models, multi-level models with spatial effects had better fit and lower error when predicting SARS-CoV-2 anti-N seropositivity by geographic region. CONCLUSIONS: Correlates of recent COVID-19 infection have evolved over the pandemic. Many disparities lessened during the Omicron wave, but public health intervention may be warranted to address persistently higher burden among young people and those with less social deprivation.

Innovations in public health surveillance: An overview of novel use of data and analytic methods.

Innovative data sources and methods for public health surveillance (PHS) have evolved rapidly over the past 10 years, suggesting the need for a closer look at the scientific maturity, feasibility, and utility of use in real-world situations. This article provides an overview of recent innovations in PHS, including data from social media, internet search engines, the Internet of Things (IoT), wastewater surveillance, participatory surveillance, artificial intelligence (AI), and nowcasting. Examples identified suggest that novel data sources and analytic methods have the potential to strengthen PHS by improving disease estimates, promoting early warning for disease outbreaks, and generating additional and/or more timely information for public health action. For example, wastewater surveillance has re-emerged as a practical tool for early detection of the coronavirus disease 2019 (COVID-19) and other pathogens, and AI is increasingly used to process large amounts of digital data. Challenges to implementing novel methods include lack of scientific maturity, limited examples of implementation in real-world public health settings, privacy and security risks, and health equity implications. Improving data governance, developing clear policies for the use of AI technologies, and public health workforce development are important next steps towards advancing the use of innovation in PHS.

Estimating the population effectiveness of interventions against COVID-19 in France: A modelling study.

BACKGROUND: Non-pharmaceutical interventions (NPIs) and vaccines have been widely used to manage the COVID-19 pandemic. However, uncertainty persists regarding the effectiveness of these interventions due to data quality issues, methodological challenges, and differing contextual factors. Accurate estimation of their effects is crucial for future epidemic preparedness. METHODS: To address this, we developed a population-based mechanistic model that includes the impact of NPIs and vaccines on SARS-CoV-2 transmission and hospitalization rates. Our statistical approach estimated all parameters in one step, accurately propagating uncertainty. We fitted the model to comprehensive epidemiological data in France from March 2020 to October 2021. With the same model, we simulated scenarios of vaccine rollout. RESULTS: The first lockdown was the most effective, reducing transmission by 84 % (95 % confidence interval (CI) 83-85). Subsequent lockdowns had diminished effectiveness (reduction of 74 % (69-77) and 11 % (9-18), respectively). A 6 pm curfew was more effective than one at 8 pm (68 % (66-69) vs. 48 % (45-49) reduction), while school closures reduced transmission by 15 % (12-18). In a scenario without vaccines before November 2021, we predicted 159,000 or 168 % (95 % prediction interval (PI) 70-315) more deaths and 1,488,000 or 300 % (133-492) more hospitalizations. If a vaccine had been available after 100 days, over 71,000 deaths (16,507-204,249) and 384,000 (88,579-1,020,386) hospitalizations could have been averted. CONCLUSION: Our results highlight the substantial impact of NPIs, including lockdowns and curfews, in controlling the COVID-19 pandemic. We also demonstrate the value of the 100 days objective of the Coalition for Epidemic Preparedness Innovations (CEPI) initiative for vaccine availability.

CODA: an open-source platform for federated analysis and machine learning on distributed healthcare data.

OBJECTIVES: Distributed computations facilitate multi-institutional data analysis while avoiding the costs and complexity of data pooling. Existing approaches lack crucial features, such as built-in medical standards and terminologies, no-code data visualizations, explicit disclosure control mechanisms, and support for basic statistical computations, in addition to gradient-based optimization capabilities. MATERIALS AND METHODS: We describe the development of the Collaborative Data Analysis (CODA) platform, and the design choices undertaken to address the key needs identified during our survey of stakeholders. We use a public dataset (MIMIC-IV) to demonstrate end-to-end multi-modal FL using CODA. We assessed the technical feasibility of deploying the CODA platform at 9 hospitals in Canada, describe implementation challenges, and evaluate its scalability on large patient populations. RESULTS: The CODA platform was designed, developed, and deployed between January 2020 and January 2023. Software code, documentation, and technical documents were released under an open-source license. Multi-modal federated averaging is illustrated using the MIMIC-IV and MIMIC-CXR datasets. To date, 8 out of the 9 participating sites have successfully deployed the platform, with a total enrolment of >1M patients. Mapping data from legacy systems to FHIR was the biggest barrier to implementation. DISCUSSION AND CONCLUSION: The CODA platform was developed and successfully deployed in a public healthcare setting in Canada, with heterogeneous information technology systems and capabilities. Ongoing efforts will use the platform to develop and prospectively validate models for risk assessment, proactive monitoring, and resource usage. Further work will also make tools available to facilitate migration from legacy formats to FHIR and DICOM.

Impact of a vaccine passport on first-dose SARS-CoV-2 vaccine coverage by age and area-level social determinants of health in the Canadian provinces of Quebec and Ontario: an interrupted time series analysis.

BACKGROUND: In Canada, all provinces implemented vaccine passports in 2021 to reduce SARS-CoV-2 transmission in non-essential indoor spaces and increase vaccine uptake (policies active September 2021-March 2022 in Quebec and Ontario). We sought to evaluate the impact of vaccine passport policies on first-dose SARS-CoV-2 vaccination coverage by age, and area-level income and proportion of racialized residents. METHODS: We performed interrupted time series analyses using data from Quebec's and Ontario's vaccine registries linked to census information (population of 20.5 million people aged ≥ 12 yr; unit of analysis: dissemination area). We fit negative binomial regressions to first-dose vaccinations, using natural splines adjusting for baseline vaccination coverage (start: July 2021; end: October 2021 for Quebec, November 2021 for Ontario). We obtained counterfactual vaccination rates and coverage, and estimated the absolute and relative impacts of vaccine passports. RESULTS: In both provinces, first-dose vaccination coverage before the announcement of vaccine passports was 82% (age ≥ 12 yr). The announcement resulted in estimated increases in coverage of 0.9 percentage points (95% confidence interval [CI] 0.4-1.2) in Quebec and 0.7 percentage points (95% CI 0.5-0.8) in Ontario. This corresponds to 23% (95% CI 10%-36%) and 19% (95% CI 15%-22%) more vaccinations over 11 weeks. The impact was larger among people aged 12-39 years. Despite lower coverage in lower-income and more-racialized areas, there was little variability in the absolute impact by area-level income or proportion racialized in either province. INTERPRETATION: In the context of high vaccine coverage across 2 provinces, the announcement of vaccine passports had a small impact on first-dose coverage, with little impact on reducing economic and racial inequities in vaccine coverage. Findings suggest that other policies are needed to improve vaccination coverage among lower-income and racialized neighbourhoods and communities.

The evolution of SARS-CoV-2 seroprevalence in Canada: a time-series study, 2020-2023.

BACKGROUND: During the first year of the COVID-19 pandemic, the proportion of reported cases of COVID-19 among Canadians was under 6%. Although high vaccine coverage was achieved in Canada by fall 2021, the Omicron variant caused unprecedented numbers of infections, overwhelming testing capacity and making it difficult to quantify the trajectory of population immunity. METHODS: Using a time-series approach and data from more than 900 000 samples collected by 7 research studies collaborating with the COVID-19 Immunity Task Force (CITF), we estimated trends in SARS-CoV-2 seroprevalence owing to infection and vaccination for the Canadian population over 3 intervals: prevaccination (March to November 2020), vaccine roll-out (December 2020 to November 2021), and the arrival of the Omicron variant (December 2021 to March 2023). We also estimated seroprevalence by geographical region and age. RESULTS: By November 2021, 9.0% (95% credible interval [CrI] 7.3%-11%) of people in Canada had humoral immunity to SARS-CoV-2 from an infection. Seroprevalence increased rapidly after the arrival of the Omicron variant - by Mar. 15, 2023, 76% (95% CrI 74%-79%) of the population had detectable antibodies from infections. The rapid rise in infection-induced antibodies occurred across Canada and was most pronounced in younger age groups and in the Western provinces: Manitoba, Saskatchewan, Alberta and British Columbia. INTERPRETATION: Data up to March 2023 indicate that most people in Canada had acquired antibodies against SARS-CoV-2 through natural infection and vaccination. However, given variations in population seropositivity by age and geography, the potential for waning antibody levels, and new variants that may escape immunity, public health policy and clinical decisions should be tailored to local patterns of population immunity.

Survival Modelling For Data From Combined Cohorts: Opening the Door to Meta Survival Analyses and Survival Analysis using Electronic Health Records.

Non-parametric estimation of the survival function using observed failure time data depends on the underlying data generating mechanism, including the ways in which the data may be censored and/or truncated. For data arising from a single source or collected from a single cohort, a wide range of estimators have been proposed and compared in the literature. Often, however, it may be possible, and indeed advantageous, to combine and then analyze survival data that have been collected under different study designs. We review non-parametric survival analysis for data obtained by combining the most common types of cohort. We have two main goals: (i) To clarify the differences in the model assumptions, and (ii) to provide a single lens through which some of the proposed estimators may be viewed. Our discussion is relevant to the meta analysis of survival data obtained from different types of study, and to the modern era of electronic health records.

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.

Clinical and clinicopathological features and outcomes of cats with suspected dietary induced pancytopenia.

BACKGROUND: After a strong epidemiological link to diet was established in an outbreak of pancytopenia in cats in spring 2021 in the United Kingdom, 3 dry diets were recalled. Concentrations of the hemato- and myelotoxic mycotoxins T-2, HT-2 and diacetoxyscirpenol (DAS) greater than the European Commission guidance for dry cat foods were detected in the recalled diets. OBJECTIVES: To describe clinical and clinicopathological findings in cats diagnosed with suspected diet induced pancytopenia. ANIMALS: Fifty cats presenting with pancytopenia after exposure to a recalled diet. METHODS: Multicenter retrospective case series study. Cats with known exposure to 1 of the recalled diets were included if presented with bi- or pancytopenia and underwent bone marrow examination. RESULTS: Case fatality rate was 78%. Bone marrow aspirates and biopsy examination results were available in 23 cats; 19 cats had a bone marrow aspirate, and 8 cats had a biopsy core, available for examination. Bone marrow hypo to aplasia-often affecting all cell lines-was the main feature in all 31 available core specimens. A disproportionately pronounced effect on myeloid and megakaryocytic cells was observed in 19 cats. Myelofibrosis or bone marrow necrosis was not a feature. CONCLUSION AND CLINICAL IMPORTANCE: Mycotoxin induced pancytopenia should be considered as differential diagnosis in otherwise healthy cats presenting with bi- or pancytopenia and bone marrow hypo- to aplasia.

Protective effectiveness of previous SARS-CoV-2 infection and hybrid immunity against the omicron variant and severe disease: a systematic review and meta-regression.

BACKGROUND: The global surge in the omicron (B.1.1.529) variant has resulted in many individuals with hybrid immunity (immunity developed through a combination of SARS-CoV-2 infection and vaccination). We aimed to systematically review the magnitude and duration of the protective effectiveness of previous SARS-CoV-2 infection and hybrid immunity against infection and severe disease caused by the omicron variant. METHODS: For this systematic review and meta-regression, we searched for cohort, cross-sectional, and case-control studies in MEDLINE, Embase, Web of Science, ClinicalTrials.gov, the Cochrane Central Register of Controlled Trials, the WHO COVID-19 database, and Europe PubMed Central from Jan 1, 2020, to June 1, 2022, using keywords related to SARS-CoV-2, reinfection, protective effectiveness, previous infection, presence of antibodies, and hybrid immunity. The main outcomes were the protective effectiveness against reinfection and against hospital admission or severe disease of hybrid immunity, hybrid immunity relative to previous infection alone, hybrid immunity relative to previous vaccination alone, and hybrid immunity relative to hybrid immunity with fewer vaccine doses. Risk of bias was assessed with the Risk of Bias In Non-Randomized Studies of Interventions Tool. We used log-odds random-effects meta-regression to estimate the magnitude of protection at 1-month intervals. This study was registered with PROSPERO (CRD42022318605). FINDINGS: 11 studies reporting the protective effectiveness of previous SARS-CoV-2 infection and 15 studies reporting the protective effectiveness of hybrid immunity were included. For previous infection, there were 97 estimates (27 with a moderate risk of bias and 70 with a serious risk of bias). The effectiveness of previous infection against hospital admission or severe disease was 74·6% (95% CI 63·1-83·5) at 12 months. The effectiveness of previous infection against reinfection waned to 24·7% (95% CI 16·4-35·5) at 12 months. For hybrid immunity, there were 153 estimates (78 with a moderate risk of bias and 75 with a serious risk of bias). The effectiveness of hybrid immunity against hospital admission or severe disease was 97·4% (95% CI 91·4-99·2) at 12 months with primary series vaccination and 95·3% (81·9-98·9) at 6 months with the first booster vaccination after the most recent infection or vaccination. Against reinfection, the effectiveness of hybrid immunity following primary series vaccination waned to 41·8% (95% CI 31·5-52·8) at 12 months, while the effectiveness of hybrid immunity following first booster vaccination waned to 46·5% (36·0-57·3) at 6 months. INTERPRETATION: All estimates of protection waned within months against reinfection but remained high and sustained for hospital admission or severe disease. Individuals with hybrid immunity had the highest magnitude and durability of protection, and as a result might be able to extend the period before booster vaccinations are needed compared to individuals who have never been infected. FUNDING: WHO COVID-19 Solidarity Response Fund and the Coalition for Epidemic Preparedness Innovations.

Global SARS-CoV-2 seroprevalence from January 2020 to April 2022: A systematic review and meta-analysis of standardized population-based studies.

BACKGROUND: Our understanding of the global scale of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection remains incomplete: Routine surveillance data underestimate infection and cannot infer on population immunity; there is a predominance of asymptomatic infections, and uneven access to diagnostics. We meta-analyzed SARS-CoV-2 seroprevalence studies, standardized to those described in the World Health Organization's Unity protocol (WHO Unity) for general population seroepidemiological studies, to estimate the extent of population infection and seropositivity to the virus 2 years into the pandemic. METHODS AND FINDINGS: We conducted a systematic review and meta-analysis, searching MEDLINE, Embase, Web of Science, preprints, and grey literature for SARS-CoV-2 seroprevalence published between January 1, 2020 and May 20, 2022. The review protocol is registered with PROSPERO (CRD42020183634). We included general population cross-sectional and cohort studies meeting an assay quality threshold (90% sensitivity, 97% specificity; exceptions for humanitarian settings). We excluded studies with an unclear or closed population sample frame. Eligible studies-those aligned with the WHO Unity protocol-were extracted and critically appraised in duplicate, with risk of bias evaluated using a modified Joanna Briggs Institute checklist. We meta-analyzed seroprevalence by country and month, pooling to estimate regional and global seroprevalence over time; compared seroprevalence from infection to confirmed cases to estimate underascertainment; meta-analyzed differences in seroprevalence between demographic subgroups such as age and sex; and identified national factors associated with seroprevalence using meta-regression. We identified 513 full texts reporting 965 distinct seroprevalence studies (41% low- and middle-income countries [LMICs]) sampling 5,346,069 participants between January 2020 and April 2022, including 459 low/moderate risk of bias studies with national/subnational scope in further analysis. By September 2021, global SARS-CoV-2 seroprevalence from infection or vaccination was 59.2%, 95% CI [56.1% to 62.2%]. Overall seroprevalence rose steeply in 2021 due to infection in some regions (e.g., 26.6% [24.6 to 28.8] to 86.7% [84.6% to 88.5%] in Africa in December 2021) and vaccination and infection in others (e.g., 9.6% [8.3% to 11.0%] in June 2020 to 95.9% [92.6% to 97.8%] in December 2021, in European high-income countries [HICs]). After the emergence of Omicron in March 2022, infection-induced seroprevalence rose to 47.9% [41.0% to 54.9%] in Europe HIC and 33.7% [31.6% to 36.0%] in Americas HIC. In 2021 Quarter Three (July to September), median seroprevalence to cumulative incidence ratios ranged from around 2:1 in the Americas and Europe HICs to over 100:1 in Africa (LMICs). Children 0 to 9 years and adults 60+ were at lower risk of seropositivity than adults 20 to 29 (p < 0.001 and p = 0.005, respectively). In a multivariable model using prevaccination data, stringent public health and social measures were associated with lower seroprevalence (p = 0.02). The main limitations of our methodology include that some estimates were driven by certain countries or populations being overrepresented. CONCLUSIONS: In this study, we observed that global seroprevalence has risen considerably over time and with regional variation; however, over one-third of the global population are seronegative to the SARS-CoV-2 virus. Our estimates of infections based on seroprevalence far exceed reported Coronavirus Disease 2019 (COVID-19) cases. Quality and standardized seroprevalence studies are essential to inform COVID-19 response, particularly in resource-limited regions.

Synthetic data as an enabler for machine learning applications in medicine.

Synthetic data generation is the process of using machine learning methods to train a model that captures the patterns in a real dataset. Then new or synthetic data can be generated from that trained model. The synthetic data does not have a one-to-one mapping to the original data or to real patients, and therefore has the potential of privacy preserving properties. There is a growing interest in the application of synthetic data across health and life sciences, but to fully realize the benefits, further education, research, and policy innovation is required. This article summarizes the opportunities and challenges of SDG for health data, and provides directions for how this technology can be leveraged to accelerate data access for secondary purposes.

Assessing the potential for virtualizable care in the pediatric emergency department.

INTRODUCTION: There is increasing interest for patient-to-provider telemedicine in pediatric acute care. The suitability of telemedicine (virtualizability) for visits in this setting has not been formally assessed. We estimated the proportion of in-person pediatric emergency department (PED) visits that were potentially virtualizable, and identified factors associated with virtualizable care. METHODS: This was a retrospective analysis of in-person visits at the PED of a Canadian tertiary pediatric hospital (02/2018-12/2019). Three definitions of virtualizable care were developed: (1) a definition based on "resource use" classifying visits as virtualizable if they resulted in a home discharge, no diagnostic testing, and no return visit within 72 h; (2) a "diagnostic definition" based on primary ED diagnosis; and (3) a stringent "combined definition" by which visits were classified as virtualizable if they met both the resource use and diagnostic definitions. Multivariable logistic regression was used to identify factors associated with telemedicine suitability. RESULTS: There were 130,535 eligible visits from 80,727 individual patients during the study period. Using the most stringent combined definition of telemedicine suitability, 37.9% (95% confidence interval (CI) 37.6%-38.2%) of in-person visits were virtualizable. Overnight visits (adjusted odds ratio (aOR) 1.16-1.37), non-Canadian citizenship (aOR 1.10-1.18), ethnocultural vulnerability (aOR 1.14-1.22), and a consultation for head trauma (aOR 3.50-4.60) were associated with higher telemedicine suitability across definitions. DISCUSSION: There is a high potential for patient-to-provider telemedicine in the PED setting. Local patient and visit-level characteristics must be considered in the design of safe and inclusive telemedicine models for pediatric acute care.

Applied artificial intelligence in healthcare: Listening to the winds of change in a post-COVID-19 world.

This editorial article aims to highlight advances in artificial intelligence (AI) technologies in five areas: Collaborative AI, Multimodal AI, Human-Centered AI, Equitable AI, and Ethical and Value-based AI in order to cope with future complex socioeconomic and public health issues.

Modeling electronic health record data using an end-to-end knowledge-graph-informed topic model.

The rapid growth of electronic health record (EHR) datasets opens up promising opportunities to understand human diseases in a systematic way. However, effective extraction of clinical knowledge from EHR data has been hindered by the sparse and noisy information. We present Graph ATtention-Embedded Topic Model (GAT-ETM), an end-to-end taxonomy-knowledge-graph-based multimodal embedded topic model. GAT-ETM distills latent disease topics from EHR data by learning the embedding from a constructed medical knowledge graph. We applied GAT-ETM to a large-scale EHR dataset consisting of over 1 million patients. We evaluated its performance based on topic quality, drug imputation, and disease diagnosis prediction. GAT-ETM demonstrated superior performance over the alternative methods on all tasks. Moreover, GAT-ETM learned clinically meaningful graph-informed embedding of the EHR codes and discovered interpretable and accurate patient representations for patient stratification and drug recommendations. GAT-ETM code is available at https://github.com/li-lab-mcgill/GAT-ETM .

Global Variations in Event-Based Surveillance for Disease Outbreak Detection: Time Series Analysis.

BACKGROUND: Robust and flexible infectious disease surveillance is crucial for public health. Event-based surveillance (EBS) was developed to allow timely detection of infectious disease outbreaks by using mostly web-based data. Despite its widespread use, EBS has not been evaluated systematically on a global scale in terms of outbreak detection performance. OBJECTIVE: The aim of this study was to assess the variation in the timing and frequency of EBS reports compared to true outbreaks and to identify the determinants of variability by using the example of seasonal influenza epidemic in 24 countries. METHODS: We obtained influenza-related reports between January 2013 and December 2019 from 2 EBS systems, that is, HealthMap and the World Health Organization Epidemic Intelligence from Open Sources (EIOS), and weekly virological influenza counts for the same period from FluNet as the gold standard. Influenza epidemic periods were detected based on report frequency by using Bayesian change point analysis. Timely sensitivity, that is, outbreak detection within the first 2 weeks before or after an outbreak onset was calculated along with sensitivity, specificity, positive predictive value, and timeliness of detection. Linear regressions were performed to assess the influence of country-specific factors on EBS performance. RESULTS: Overall, while monitoring the frequency of EBS reports over 7 years in 24 countries, we detected 175 out of 238 outbreaks (73.5%) but only 22 out of 238 (9.2%) within 2 weeks before or after an outbreak onset; in the best case, while monitoring the frequency of health-related reports, we identified 2 out of 6 outbreaks (33%) within 2 weeks of onset. The positive predictive value varied between 9% and 100% for HealthMap and from 0 to 100% for EIOS, and timeliness of detection ranged from 13% to 94% for HealthMap and from 0% to 92% for EIOS, whereas system specificity was generally high (59%-100%). The number of EBS reports available within a country, the human development index, and the country's geographical location partially explained the high variability in system performance across countries. CONCLUSIONS: We documented the global variation of EBS performance and demonstrated that monitoring the report frequency alone in EBS may be insufficient for the timely detection of outbreaks. In particular, in low- and middle-income countries, low data quality and report frequency impair the sensitivity and timeliness of disease surveillance through EBS. Therefore, advances in the development and evaluation and EBS are needed, particularly in low-resource settings.

Timeliness of reporting of SARS-CoV-2 seroprevalence results and their utility for infectious disease surveillance.

Seroprevalence studies have been used throughout the COVID-19 pandemic to monitor infection and immunity. These studies are often reported in peer-reviewed journals, but the academic writing and publishing process can delay reporting and thereby public health action. Seroprevalence estimates have been reported faster in preprints and media, but with concerns about data quality. We aimed to (i) describe the timeliness of SARS-CoV-2 serosurveillance reporting by publication venue and study characteristics and (ii) identify relationships between timeliness, data validity, and representativeness to guide recommendations for serosurveillance efforts. We included seroprevalence studies published between January 1, 2020 and December 31, 2021 from the ongoing SeroTracker living systematic review. For each study, we calculated timeliness as the time elapsed between the end of sampling and the first public report. We evaluated data validity based on serological test performance and correction for sampling error, and representativeness based on the use of a representative sample frame and adequate sample coverage. We examined how timeliness varied with study characteristics, representativeness, and data validity using univariate and multivariate Cox regression. We analyzed 1844 studies. Median time to publication was 154 days (IQR 64-255), varying by publication venue (journal articles: 212 days, preprints: 101 days, institutional reports: 18 days, and media: 12 days). Multivariate analysis confirmed the relationship between timeliness and publication venue and showed that general population studies were published faster than special population or health care worker studies; there was no relationship between timeliness and study geographic scope, geographic region, representativeness, or serological test performance. Seroprevalence studies in peer-reviewed articles and preprints are published slowly, highlighting the limitations of using the academic literature to report seroprevalence during a health crisis. More timely reporting of seroprevalence estimates can improve their usefulness for surveillance, enabling more effective responses during health emergencies.

MixEHR-Guided: A guided multi-modal topic modeling approach for large-scale automatic phenotyping using the electronic health record.

Electronic Health Records (EHRs) contain rich clinical data collected at the point of the care, and their increasing adoption offers exciting opportunities for clinical informatics, disease risk prediction, and personalized treatment recommendation. However, effective use of EHR data for research and clinical decision support is often hampered by a lack of reliable disease labels. To compile gold-standard labels, researchers often rely on clinical experts to develop rule-based phenotyping algorithms from billing codes and other surrogate features. This process is tedious and error-prone due to recall and observer biases in how codes and measures are selected, and some phenotypes are incompletely captured by a handful of surrogate features. To address this challenge, we present a novel automatic phenotyping model called MixEHR-Guided (MixEHR-G), a multimodal hierarchical Bayesian topic model that efficiently models the EHR generative process by identifying latent phenotype structure in the data. Unlike existing topic modeling algorithms wherein the inferred topics are not identifiable, MixEHR-G uses prior information from informative surrogate features to align topics with known phenotypes. We applied MixEHR-G to an openly-available EHR dataset of 38,597 intensive care patients (MIMIC-III) in Boston, USA and to administrative claims data for a population-based cohort (PopHR) of 1.3 million people in Quebec, Canada. Qualitatively, we demonstrate that MixEHR-G learns interpretable phenotypes and yields meaningful insights about phenotype similarities, comorbidities, and epidemiological associations. Quantitatively, MixEHR-G outperforms existing unsupervised phenotyping methods on a phenotype label annotation task, and it can accurately estimate relative phenotype prevalence functions without gold-standard phenotype information. Altogether, MixEHR-G is an important step towards building an interpretable and automated phenotyping system using EHR data.

SARS-CoV-2 infection in Africa: a systematic review and meta-analysis of standardised seroprevalence studies, from January 2020 to December 2021.

INTRODUCTION: Estimating COVID-19 cumulative incidence in Africa remains problematic due to challenges in contact tracing, routine surveillance systems and laboratory testing capacities and strategies. We undertook a meta-analysis of population-based seroprevalence studies to estimate SARS-CoV-2 seroprevalence in Africa to inform evidence-based decision making on public health and social measures (PHSM) and vaccine strategy. METHODS: We searched for seroprevalence studies conducted in Africa published 1 January 2020-30 December 2021 in Medline, Embase, Web of Science and Europe PMC (preprints), grey literature, media releases and early results from WHO Unity studies. All studies were screened, extracted, assessed for risk of bias and evaluated for alignment with the WHO Unity seroprevalence protocol. We conducted descriptive analyses of seroprevalence and meta-analysed seroprevalence differences by demographic groups, place and time. We estimated the extent of undetected infections by comparing seroprevalence and cumulative incidence of confirmed cases reported to WHO. PROSPERO: CRD42020183634. RESULTS: We identified 56 full texts or early results, reporting 153 distinct seroprevalence studies in Africa. Of these, 97 (63%) were low/moderate risk of bias studies. SARS-CoV-2 seroprevalence rose from 3.0% (95% CI 1.0% to 9.2%) in April-June 2020 to 65.1% (95% CI 56.3% to 73.0%) in July-September 2021. The ratios of seroprevalence from infection to cumulative incidence of confirmed cases was large (overall: 100:1, ranging from 18:1 to 954:1) and steady over time. Seroprevalence was highly heterogeneous both within countries-urban versus rural (lower seroprevalence for rural geographic areas), children versus adults (children aged 0-9 years had the lowest seroprevalence)-and between countries and African subregions. CONCLUSION: We report high seroprevalence in Africa suggesting greater population exposure to SARS-CoV-2 and potential protection against COVID-19 severe disease than indicated by surveillance data. As seroprevalence was heterogeneous, targeted PHSM and vaccination strategies need to be tailored to local epidemiological situations.