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Background: Over the past four years, the COVID-19 pandemic has exerted a profound impact on public health, including on mortality trends. This study investigates mortality patterns in Belgium by examining all-cause mortality, excess mortality, and cause-specific mortality., Methods: We retrieved all-cause mortality data from January 1, 2009, to December 31, 2022, stratified by age group and sex. A linear mixed model, informed by all-cause mortality from 2009 to 2019, was used to predict non-pandemic all-cause mortality rates in 2020-2022 and estimate excess mortality. Further, we also analyzed trends in cause-specific and premature mortality., Results: Different all-cause mortality patterns could be observed between the younger (<45 years) and older age groups. The impact of the COVID-19 pandemic was particularly evident among older age groups. The highest excess mortality occurred in 2020, while a reversal in this trend was evident in 2022. We observed a notable effect of COVID-19 on cause-specific and premature mortality patterns over the three-year period., Conclusions: Despite a consistent decline in COVID-19 reported mortality over this three-year period, it remains imperative to meticulously monitor mortality trends in the years ahead., (© 2024. The Author(s).)

The COVID-19 pandemic led to unprecedented changes in behaviour. To estimate if these persisted, a final round of the CoMix social contact survey was conducted in four countries at a time when all societal restrictions had been lifted for several months. We conducted a survey on a nationally representative sample in the UK, Netherlands (NL), Belgium (BE), and Switzerland (CH). Participants were asked about their contacts and behaviours on the previous day. We calculated contact matrices and compared the contact levels to a pre-pandemic baseline to estimate R 0 . Data collection occurred from 17 November to 7 December 2022. 7477 participants were recruited. Some were asked to undertake the survey on behalf of their children. Only 14.4 % of all participants reported wearing a facemask on the previous day. Self-reported vaccination rates in adults were similar for each country at around 86 %. Trimmed mean recorded contacts were highest in NL with 9.9 (95 % confidence interval [CI] 9.0-10.8) contacts per person per day and lowest in CH at 6.0 (95 % CI 5.4-6.6). Contacts at work were lowest in the UK (1.4 contacts per person per day) and highest in NL at 2.8 contacts per person per day. Other contacts were also lower in the UK at 1.6 per person per day (95 % CI 1.4-1.9) and highest in NL at 3.4 recorded per person per day (95 % CI 43.0-4.0). The next-generation approach suggests that R 0 for a close-contact disease would be roughly half pre-pandemic levels in the UK, 80 % in NL and intermediate in the other two countries. The pandemic appears to have resulted in lasting changes in contact patterns expected to have an impact on the epidemiology of many different pathogens. Further post-pandemic surveys are necessary to confirm this finding., Competing Interests: Declaration of Competing Interest None to declare., (Crown Copyright © 2024. Published by Elsevier B.V. All rights reserved.)

Open surveys complementing surveillance programs often yield opportunistically sampled data characterised by spatio-temporal imbalance. We set up our study to understand to what extent spatio-temporal statistical models using such data achieve in describing epidemiological trends. We used self-reported symptomatic COVID-19 data from two Belgian regions, Flanders and the Brussels-Capital Region. These data were collected in a large-scale open survey with spatio-temporally imbalanced participation rates. We compared incidence estimates of both self-reported symptoms and test-confirmed COVID-19 cases obtained through generalised linear mixed models correcting for spatio-temporal correlation. We additionally simulated symptom incidences under different sampling strategies to explore the impact of sample imbalance, sample size and disease incidence, on trend detection. Our study shows that spatio-temporal sample imbalance generally does not lead to bad model performances in spatio-temporal trend estimation and high-risk area detection. Except for low-incidence diseases, collecting large samples will often be more essential than ensuring spatio-temporally sample balance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Estimating the instantaneous reproduction number ( ) in near real time is crucial for monitoring and responding to epidemic outbreaks on a daily basis. However, such estimates often suffer from bias due to reporting delays inherent in surveillance systems. We propose a fast and flexible Bayesian methodology to overcome this challenge by estimating while taking into account reporting delays. Furthermore, the method naturally takes into account the uncertainty associated with the nowcasting of cases to get a valid uncertainty estimation of the nowcasted reproduction number. We evaluate the proposed methodology through a simulation study and apply it to COVID-19 incidence data in Belgium., Competing Interests: Disclosure: The authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: Belgium experienced multiple COVID-19 waves that hit various groups in the population, which changed the mortality pattern compared to periods before the pandemic. In this study, we investigated the geographical excess mortality trend in Belgium during the first year of the COVID-19 pandemic., Methods: We retrieved the number of deaths and population data in 2020 based on gender, age, and municipality of residence, and we made a comparison with the mortality data in 2017-2019 using a spatially discrete model., Results: Excess mortality was significantly associated with age, gender, and COVID-19 incidence, with larger effects in the second half of 2020. Most municipalities had higher risks of mortality with a number of exceptions in the northeastern part of Belgium. Some discrepancies in excess mortality were observed between the north and south regions., Conclusions: This study offers useful insight into excess mortality and will aid local and regional authorities in monitoring mortality trends., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Collaborative comparisons and combinations of epidemic models are used as policy-relevant evidence during epidemic outbreaks. In the process of collecting multiple model projections, such collaborations may gain or lose relevant information. Typically, modellers contribute a probabilistic summary at each time-step. We compared this to directly collecting simulated trajectories. We aimed to explore information on key epidemic quantities; ensemble uncertainty; and performance against data, investigating potential to continuously gain information from a single cross-sectional collection of model results., Methods: We compared projections from the European COVID-19 Scenario Modelling Hub. Five teams modelled incidence in Belgium, the Netherlands, and Spain. We compared July 2022 projections by incidence, peaks, and cumulative totals. We created a probabilistic ensemble drawn from all trajectories, and compared to ensembles from a median across each model's quantiles, or a linear opinion pool. We measured the predictive accuracy of individual trajectories against observations, using this in a weighted ensemble. We repeated this sequentially against increasing weeks of observed data. We evaluated these ensembles to reflect performance with varying observed data., Results: By collecting modelled trajectories, we showed policy-relevant epidemic characteristics. Trajectories contained a right-skewed distribution well represented by an ensemble of trajectories or a linear opinion pool, but not models' quantile intervals. Ensembles weighted by performance typically retained the range of plausible incidence over time, and in some cases narrowed this by excluding some epidemic shapes., Conclusions: We observed several information gains from collecting modelled trajectories rather than quantile distributions, including potential for continuously updated information from a single model collection. The value of information gains and losses may vary with each collaborative effort's aims, depending on the needs of projection users. Understanding the differing information potential of methods to collect model projections can support the accuracy, sustainability, and communication of collaborative infectious disease modelling efforts., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: In Flanders, general practitioners (GPs) were among the first ones to collect data regarding COVID-19 cases. Intego is a GPs' morbidity registry in primary care with data collected from the electronic medical records from a sample of general practices. The Intego database contain elaborate information regarding patient characteristics, such as comorbidities. At the national level, the Belgian Public Health Institute (Sciensano) recorded all test-confirmed COVID-19 cases, but without other patient characteristics., Methods: Spatio and spatio-temporal analyses were used to analyse the spread of COVID-19 incidence at two levels of spatial aggregation: the municipality and the health sector levels. Our study goal was to compare spatio-temporal modelling results based on the Intego and Sciensano data, in order to see whether the Intego database is capable of detecting epidemiological trends similar to those in the Sciensano data. Comparable results would allow researchers to use these Intego data, and their wealth of patient information, to model COVID-19-related processes., Results: The two data sources provided comparable results. Being a male decreased the odds of having COVID-19 disease. The odds for the age categories (17,35], (35,65] and (65,110] of being a confirmed COVID-19 case were significantly higher than the odds for the age category [0,17]. In the Intego data, having one of the following comorbidities, i.e., chronic kidney disease, heart and vascular disease, and diabetes, was significantly associated with being a COVID-19 case, increasing the odds of being diagnosed with COVID-19., Conclusion: We were able to show how an alternative data source, the Intego data, can be used in a pandemic situation. We consider our findings useful for public health officials who plan intervention strategies aimed at monitor and control disease outbreaks such as that of COVID-19., (© 2024. The Author(s).)

Background: When formulating and evaluating COVID-19 vaccination strategies, an emphasis has been placed on preventing severe disease that overburdens healthcare systems and leads to mortality. However, more conventional outcomes such as quality-adjusted life years (QALYs) and inequality indicators are warranted as additional information for policymakers., Methods: We adopted a mathematical transmission model to describe the infectious disease dynamics of SARS-COV-2, including disease mortality and morbidity, and to evaluate (non)pharmaceutical interventions. Therefore, we considered temporal immunity levels, together with the distinct transmissibility of variants of concern (VOCs) and their corresponding vaccine effectiveness. We included both general and age-specific characteristics related to SARS-CoV-2 vaccination. Our scenario study is informed by data from Belgium, focusing on the period from August 2021 until February 2022, when vaccination for children aged 5-11 years was initially not yet licensed and first booster doses were administered to adults. More specifically, we investigated the potential impact of an earlier vaccination programme for children and increased or reduced historical adult booster dose uptake., Results: Through simulations, we demonstrate that increasing vaccine uptake in children aged 5-11 years in August-September 2021 could have led to reduced disease incidence and ICU occupancy, which was an essential indicator for implementing non-pharmaceutical interventions and maintaining healthcare system functionality. However, an enhanced booster dose regimen for adults from November 2021 onward could have resulted in more substantial cumulative QALY gains, particularly through the prevention of elevated levels of infection and disease incidence associated with the emergence of Omicron VOC. In both scenarios, the need for non-pharmaceutical interventions could have decreased, potentially boosting economic activity and mental well-being., Conclusions: When calculating the impact of measures to mitigate disease spread in terms of life years lost due to COVID-19 mortality, we highlight the impact of COVID-19 on the health-related quality of life of survivors. Our study underscores that disease-related morbidity could constitute a significant part of the overall health burden. Our quantitative findings depend on the specific setup of the interventions under review, which is open to debate or should be contextualised within future situations., (© 2024. The Author(s).)

The COVID-19 pandemic led to sustained surveillance efforts, which made unprecedented volumes and types of data available. In Belgium, these data were used to conduct a targeted and regular assessment of the epidemiological situation. In addition, management tools were developed, incorporating key indicators and thresholds, to define risk levels and offer guidance to policy makers. Categorizing risk into various levels provided a stable framework to monitor the COVID-19 epidemiological situation and allowed for clear communication to authorities. Although translating risk levels into specific public health measures has remained challenging, this experience was foundational for future evaluation of the situation for respiratory infections in general, which, in Belgium, is now based on a management tool combining different data sources., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 De Muylder, Laisnez, Stefani, Boulouffe, Faes, Hammami, Hubin, Molenberghs, Sans, van de Konijnenburg, Van der Borght, Brondeel, Stassijns and Lernout.)

We reflect on epidemiological modeling conducted throughout the COVID-19 pandemic in Western Europe, specifically in Belgium, France, Italy, the Netherlands, Portugal, Switzerland, and the United Kingdom. Western Europe was initially one of the worst-hit regions during the COVID-19 pandemic. Western European countries deployed a range of policy responses to the pandemic, which were often informed by mathematical, computational, and statistical models. Models differed in terms of temporal scope, pandemic stage, interventions modeled, and analytical form. This diversity was modulated by differences in data availability and quality, government interventions, societal responses, and technical capacity. Many of these models were decisive to policy making at key junctures, such as during the introduction of vaccination and the emergence of the Alpha, Delta, and Omicron variants. However, models also faced intense criticism from the press, other scientists, and politicians around their accuracy and appropriateness for decision making. Hence, evaluating the success of models in terms of accuracy and influence is an essential task. Modeling needs to be supported by infrastructure for systems to collect and share data, model development, and collaboration between groups, as well as two-way engagement between modelers and both policy makers and the public.

Introduction: COVID-19 remains a major concern globally. Therefore, it is important to evaluate COVID-19's rapidly changing trends. The fractal dimension has been proposed as a viable method to characterize COVID-19 curves since epidemic data is often subject to considerable heterogeneity. In this study, we aim to investigate the association between various socio-demographic factors and the complexity of the COVID-19 curve as quantified through its fractal dimension., Methods: We collected population indicators data (ethnic composition, socioeconomic status, number of inhabitants, population density, the older adult population proportion, vaccination rate, satisfaction, and trust in the government) at the level of the statistical sector in Belgium. We compared these data with fractal dimension indicators of COVID-19 incidence between 1 January - 31 December 2021 using canonical correlation analysis., Results: Our results showed that these population indicators have a significant association with COVID-19 incidences, with the highest explanatory and predictive power coming from the number of inhabitants, population density, and ethnic composition., Conclusion: It is important to monitor these population indicators during a pandemic, especially when dealing with targeted interventions for a specific population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Natalia, Faes, Neyens, Hammami and Molenberghs.)

The goal of tracing, testing, and quarantining contacts of infected individuals is to contain the spread of infectious diseases, a strategy widely used during the COVID-19 pandemic. However, limited research exists on the effectiveness of contact tracing, especially with regard to key performance indicators (KPIs), such as the proportion of cases arising from previously identified contacts. In our study, we analyzed contact tracing data from Belgium collected between September 2020 and December 2021 to assess the impact of contact tracing on SARS-CoV-2 transmission and understand its characteristics. Among confirmed cases involved in contact tracing in the Flemish and Brussels-Capital regions, 19.1% were previously identified as close contacts and were aware of prior exposure. These cases, referred to as 'known' to contact tracing operators, reported on average fewer close contacts compared to newly identified individuals (0.80 versus 1.05), resulting in fewer secondary cases (0.23 versus 0.28). Additionally, we calculated the secondary attack rate, representing infections per contact, which was on average lower for the 'known' cases (0.22 versus 0.25) between December 2020 and August 2021. These findings indicate the effectiveness of contact tracing in Belgium in reducing SARS-CoV-2 transmission. Although we were unable to quantify the exact number of prevented cases, our findings emphasize the importance of contact tracing as a public health measure. In addition, contact tracing data provide indications of potential shifts in transmission patterns among different age groups associated with emerging variants of concern and increasing vaccination rates., Competing Interests: Naima Hammami is an employee of the the Flemish Government’s Department of Care and Jorden Boone has been working as a consultant for this agency during the COVID-19 pandemic. Niel Hens declares that the Universities of Antwerp and Hasselt have received funding for advisory boards and research projects of MSD, GSK, JnJ, Pfizer outside the proposed work. Niel Hens has not received any personal remuneration related to this work. The other authors declare that they have no competing interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Kremer et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The SARS-CoV-2 transmission dynamics have been greatly modulated by human contact behaviour. To curb the spread of the virus, global efforts focused on implementing both Non-Pharmaceutical Interventions (NPIs) and pharmaceutical interventions such as vaccination. This study was conducted to explore the influence of COVID-19 vaccination status and risk perceptions related to SARS-CoV-2 on the number of social contacts of individuals in 16 European countries., Methods: We used data from longitudinal surveys conducted in the 16 European countries to measure social contact behaviour in the course of the pandemic. The data consisted of representative panels of participants in terms of gender, age and region of residence in each country. The surveys were conducted in several rounds between December 2020 and September 2021 and comprised of 29,292 participants providing a total of 111,103 completed surveys. We employed a multilevel generalized linear mixed effects model to explore the influence of risk perceptions and COVID-19 vaccination status on the number of social contacts of individuals., Results: The results indicated that perceived severity played a significant role in social contact behaviour during the pandemic after controlling for other variables (p-value < 0.001). More specifically, participants who had low or neutral levels of perceived severity reported 1.25 (95% Confidence intervals (CI) 1.13 - 1.37) and 1.10 (95% CI 1.00 - 1.21) times more contacts compared to those who perceived COVID-19 to be a serious illness, respectively. Additionally, vaccination status was also a significant predictor of contacts (p-value < 0.001), with vaccinated individuals reporting 1.31 (95% CI 1.23 - 1.39) times higher number of contacts than the non-vaccinated. Furthermore, individual-level factors played a more substantial role in influencing contact behaviour than country-level factors., Conclusion: Our multi-country study yields significant insights on the importance of risk perceptions and vaccination in behavioral changes during a pandemic emergency. The apparent increase in social contact behaviour following vaccination would require urgent intervention in the event of emergence of an immune escaping variant., (© 2023. The Author(s).)

Background: During the COVID-19 pandemic, the CoMix study, a longitudinal behavioral survey, was designed to monitor social contacts and public awareness in multiple countries, including Belgium. As a longitudinal survey, it is vulnerable to participants' "survey fatigue", which may impact inferences., Methods: A negative binomial generalized additive model for location, scale, and shape (NBI GAMLSS) was adopted to estimate the number of contacts reported between age groups and to deal with under-reporting due to fatigue within the study. The dropout process was analyzed with first-order auto-regressive logistic regression to identify factors that influence dropout. Using the so-called next generation principle, we calculated the effect of under-reporting due to fatigue on estimating the reproduction number., Results: Fewer contacts were reported as people participated longer in the survey, which suggests under-reporting due to survey fatigue. Participant dropout is significantly affected by household size and age categories, but not significantly affected by the number of contacts reported in any of the two latest waves. This indicates covariate-dependent missing completely at random (MCAR) in the dropout pattern, when missing at random (MAR) is the alternative. However, we cannot rule out more complex mechanisms such as missing not at random (MNAR). Moreover, under-reporting due to fatigue is found to be consistent over time and implies a 15-30% reduction in both the number of contacts and the reproduction number ([Formula: see text]) ratio between correcting and not correcting for under-reporting. Lastly, we found that correcting for fatigue did not change the pattern of relative incidence between age groups also when considering age-specific heterogeneity in susceptibility and infectivity., Conclusions: CoMix data highlights the variability of contact patterns across age groups and time, revealing the mechanisms governing the spread/transmission of COVID-19/airborne diseases in the population. Although such longitudinal contact surveys are prone to the under-reporting due to participant fatigue and drop-out, we showed that these factors can be identified and corrected using NBI GAMLSS. This information can be used to improve the design of similar, future surveys., (© 2023. The Author(s).)

Background: The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has rapidly spread over the world and caused tremendous impacts on global health. Understanding the mechanism responsible for the spread of this pathogen and the impact of specific factors, such as human mobility, will help authorities to tailor interventions for future SARS-CoV-2 waves or newly emerging airborne infections. In this study, we aim to analyze the spatio-temporal transmission of SARS-CoV-2 in Belgium at municipality level between January and December 2021 and explore the effect of different levels of human travel on disease incidence through the use of counterfactual scenarios., Methods: We applied the endemic-epidemic modelling framework, in which the disease incidence decomposes into endemic, autoregressive and neighbourhood components. The spatial dependencies among areas are adjusted based on actual connectivity through mobile network data. We also took into account other important factors such as international mobility, vaccination coverage, population size and the stringency of restriction measures., Results: The results demonstrate the aggravating effect of international travel on the incidence, and simulated counterfactual scenarios further stress the alleviating impact of a reduction in national and international travel on epidemic growth. It is also clear that local transmission contributed the most during 2021, and municipalities with a larger population tended to attract a higher number of cases from neighboring areas., Conclusions: Although transmission between municipalities was observed, local transmission was dominant. We highlight the positive association between the mobility data and the infection spread over time. Our study provides insight to assist health authorities in decision-making, particularly when the disease is airborne and therefore likely influenced by human movement., (© 2023. The Author(s).)

Background: Non-pharmaceutical interventions (NPIs) were adopted in Belgium in order to decrease social interactions between people and as such decrease viral transmission of SARS-CoV-2. With the aim to better evaluate the impact of NPIs on the evolution of the pandemic, an estimation of social contact patterns during the pandemic is needed when social contact patterns are not available yet in real time., Methods: In this paper we use a model-based approach allowing for time varying effects to evaluate whether mobility and pre-pandemic social contact patterns can be used to predict the social contact patterns observed during the COVID-19 pandemic between November 11, 2020 and July 4, 2022., Results: We found that location-specific pre-pandemic social contact patterns are good indicators for estimating social contact patterns during the pandemic. However, the relationship between both changes with time. Considering a proxy for mobility, namely the change in the number of visitors to transit stations, in interaction with pre-pandemic contacts does not explain the time-varying nature of this relationship well., Conclusion: In a situation where data from social contact surveys conducted during the pandemic are not yet available, the use of a linear combination of pre-pandemic social contact patterns could prove valuable. However, translating the NPIs at a given time into appropriate coefficients remains the main challenge of such an approach. In this respect, the assumption that the time variation of the coefficients can somehow be related to aggregated mobility data seems unacceptable during our study period for estimating the number of contacts at a given time., (© 2023. The Author(s).)

The rapid spread of COVID-19 worldwide led to the implementation of various non-pharmaceutical interventions to limit transmission and hence reduce the number of infections. Using telecom-operator-based mobility data and a spatio-temporal dynamic model, the impact of mobility on the evolution of the pandemic at the level of the 581 Belgian municipalities is investigated. By decomposing incidence, particularly into within- and between-municipality components, we noted that the global epidemic component is relatively more important in larger municipalities (e.g., cities), while the local component is more relevant in smaller (rural) municipalities. Investigation of the effect of mobility on the pandemic spread showed that reduction of mobility has a significant impact in reducing the number of new infections., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: Africa was threatened by the coronavirus disease 2019 (COVID-19) due to the limited health care infrastructure. Rwanda has consistently used non-pharmaceutical strategies, such as lockdown, curfew, and enforcement of prevention measures to control the spread of COVID-19. Despite the mitigation measures taken, the country has faced a series of outbreaks in 2020 and 2021. In this paper, we investigate the nature of epidemic phenomena in Rwanda and the impact of imported cases on the spread of COVID-19 using endemic-epidemic spatio-temporal models. Our study provides a framework for understanding the dynamics of the epidemic in Rwanda and monitoring its phenomena to inform public health decision-makers for timely and targeted interventions., Results: The findings provide insights into the effects of lockdown and imported infections in Rwanda's COVID-19 outbreaks. The findings showed that imported infections are dominated by locally transmitted cases. The high incidence was predominant in urban areas and at the borders of Rwanda with its neighboring countries. The inter-district spread of COVID-19 was very limited due to mitigation measures taken in Rwanda., Conclusion: The study recommends using evidence-based decisions in the management of epidemics and integrating statistical models in the analytics component of the health information system., (© 2023. The Author(s).)

Background: Most countries have enacted some restrictions to reduce social contacts to slow down disease transmission during the COVID-19 pandemic. For nearly two years, individuals likely also adopted new behaviours to avoid pathogen exposure based on personal circumstances. We aimed to understand the way in which different factors affect social contacts - a critical step to improving future pandemic responses., Methods: The analysis was based on repeated cross-sectional contact survey data collected in a standardized international study from 21 European countries between March 2020 and March 2022. We calculated the mean daily contacts reported using a clustered bootstrap by country and by settings (at home, at work, or in other settings). Where data were available, contact rates during the study period were compared with rates recorded prior to the pandemic. We fitted censored individual-level generalized additive mixed models to examine the effects of various factors on the number of social contacts., Results: The survey recorded 463,336 observations from 96,456 participants. In all countries where comparison data were available, contact rates over the previous two years were substantially lower than those seen prior to the pandemic (approximately from over 10 to < 5), predominantly due to fewer contacts outside the home. Government restrictions imposed immediate effect on contacts, and these effects lingered after the restrictions were lifted. Across countries, the relationships between national policy, individual perceptions, or personal circumstances determining contacts varied., Conclusions: Our study, coordinated at the regional level, provides important insights into the understanding of the factors associated with social contacts to support future infectious disease outbreak responses., (© 2023. The Author(s).)

Understanding the local dynamics of COVID-19 transmission calls for an approach that characterizes the incidence curve in a small geographical unit. Given that incidence curves exhibit considerable day-to-day variation, the fractal structure of the time series dynamics is investigated for the Flanders and Brussels Regions of Belgium. For each statistical sector, the smallest administrative geographical entity in Belgium, fractal dimensions of COVID-19 incidence rates, based on rolling time spans of 7, 14, and 21 days were estimated using four different estimators: box-count, Hall-Wood, variogram, and madogram. We found varying patterns of fractal dimensions across time and location. The fractal dimension is further summarized by its mean, variance, and autocorrelation over time. These summary statistics are then used to cluster regions with different incidence rate patterns using k-means clustering. Fractal dimension analysis of COVID-19 incidence thus offers important insight into the past, current, and arguably future evolution of an infectious disease outbreak., (© 2023. The Author(s).)

The Corona Virus Disease (COVID-19) pandemic has increased mortality in countries worldwide. To evaluate the impact of the pandemic on mortality, the use of excess mortality rather than reported COVID-19 deaths has been suggested. Excess mortality, however, requires estimation of mortality under nonpandemic conditions. Although many methods exist to forecast mortality, they are either complex to apply, require many sources of information, ignore serial correlation, and/or are influenced by historical excess mortality. We propose a linear mixed model that is easy to apply, requires only historical mortality data, allows for serial correlation, and down-weighs the influence of historical excess mortality. Appropriateness of the linear mixed model is evaluated with fit statistics and forecasting accuracy measures for Belgium and the Netherlands. Unlike the commonly used 5-year weekly average, the linear mixed model is forecasting the year-specific mortality, and as a result improves the estimation of excess mortality for Belgium and the Netherlands., (© 2021 The International Biometric Society.)

This work presents a joint spatial modeling framework to improve estimation of the spatial distribution of the latent COVID-19 incidence in Belgium, based on test-confirmed COVID-19 cases and crowd-sourced symptoms data as reported in a large-scale online survey. Correction is envisioned for stochastic dependence between the survey's response rate and spatial COVID-19 incidence, commonly known as preferential sampling, but not found significant. Results show that an online survey can provide valuable auxiliary data to optimize spatial COVID-19 incidence estimation based on confirmed cases in situations with limited testing capacity. Furthermore, it is shown that an online survey on COVID-19 symptoms with a sufficiently large sample size per spatial entity is capable of pinpointing the same locations that appear as test-confirmed clusters, approximately 1 week earlier. We conclude that a large-scale online study provides an inexpensive and flexible method to collect timely information of an epidemic during its early phase, which can be used by policy makers in an early phase of an epidemic and in conjunction with other monitoring systems., (© 2022 Wiley-VCH GmbH.)

From the beginning of the COVID-19 pandemic, researchers advised policy makers to make informed decisions towards the adoption of mitigating interventions. Key easy-to-interpret metrics applied over time can measure the public health impact of epidemic outbreaks. We propose a novel method which quantifies the effect of hospitalizations or mortality when the number of COVID-19 cases doubles. Two analyses are used, a country-by-country analysis and a multi-country approach which considers all countries simultaneously. The new measure is applied to several European countries, where the presence of different variants, vaccination rates and intervention measures taken over time leads to a different risk. Based on our results, the vaccination campaign has a clear effect for all countries analyzed, reducing the risk over time. However, the constant emergence of new variants combined with distinct intervention measures impacts differently the risk per country., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Petrof et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In infectious disease epidemiology, the instantaneous reproduction number [Formula: see text] is a time-varying parameter defined as the average number of secondary infections generated by an infected individual at time t. It is therefore a crucial epidemiological statistic that assists public health decision makers in the management of an epidemic. We present a new Bayesian tool (EpiLPS) for robust estimation of the time-varying reproduction number. The proposed methodology smooths the epidemic curve and allows to obtain (approximate) point estimates and credible intervals of [Formula: see text] by employing the renewal equation, using Bayesian P-splines coupled with Laplace approximations of the conditional posterior of the spline vector. Two alternative approaches for inference are presented: (1) an approach based on a maximum a posteriori argument for the model hyperparameters, delivering estimates of [Formula: see text] in only a few seconds; and (2) an approach based on a Markov chain Monte Carlo (MCMC) scheme with underlying Langevin dynamics for efficient sampling of the posterior target distribution. Case counts per unit of time are assumed to follow a negative binomial distribution to account for potential overdispersion in the data that would not be captured by a classic Poisson model. Furthermore, after smoothing the epidemic curve, a "plug-in'' estimate of the reproduction number can be obtained from the renewal equation yielding a closed form expression of [Formula: see text] as a function of the spline parameters. The approach is extremely fast and free of arbitrary smoothing assumptions. EpiLPS is applied on data of SARS-CoV-1 in Hong-Kong (2003), influenza A H1N1 (2009) in the USA and on the SARS-CoV-2 pandemic (2020-2021) for Belgium, Portugal, Denmark and France., Competing Interests: The authors have declared that no competing interests exist.

Background: Evidence and advice for pregnant women evolved during the COVID-19 pandemic. We studied social contact behaviour and vaccine uptake in pregnant women between March 2020 and September 2021 in 19 European countries., Methods: In each country, repeated online survey data were collected from a panel of nationally-representative participants. We calculated the adjusted mean number of contacts reported with an individual-level generalized additive mixed model, modelled using the negative binomial distribution and a log link function. Mean proportion of people in isolation or quarantine, and vaccination coverage by pregnancy status and gender were calculated using a clustered bootstrap., Findings: We recorded 4,129 observations from 1,041 pregnant women, and 115,359 observations from 29,860 non-pregnant individuals aged 18-49. Pregnant women made slightly fewer contacts (3.6, 95%CI = 3.5-3.7) than non-pregnant women (4.0, 95%CI = 3.9-4.0), driven by fewer work contacts but marginally more contacts in non-essential social settings. Approximately 15-20% pregnant and 5% of non-pregnant individuals reported to be in isolation and quarantine for large parts of the study period. COVID-19 vaccine coverage was higher in pregnant women than in non-pregnant women between January and April 2021. Since May 2021, vaccination in non-pregnant women began to increase and surpassed that in pregnant women., Interpretation: Limited social contact to avoid pathogen exposure during the COVID-19 pandemic has been a challenge to many, especially women going through pregnancy. More recognition of maternal social support desire is needed in the ongoing pandemic. As COVID-19 vaccination continues to remain an important pillar of outbreak response, strategies to promote correct information can provide reassurance and facilitate informed pregnancy vaccine decisions in this vulnerable group., (© 2022. The Author(s).)

Several important aspects related to SARS-CoV-2 transmission are not well known due to a lack of appropriate data. However, mathematical and computational tools can be used to extract part of this information from the available data, like some hidden age-related characteristics. In this paper, we present a method to investigate age-specific differences in transmission parameters related to susceptibility to and infectiousness upon contracting SARS-CoV-2 infection. More specifically, we use panel-based social contact data from diary-based surveys conducted in Belgium combined with the next generation principle to infer the relative incidence and we compare this to real-life incidence data. Comparing these two allows for the estimation of age-specific transmission parameters. Our analysis implies the susceptibility in children to be around half of the susceptibility in adults, and even lower for very young children (preschooler). However, the probability of adults and the elderly to contract the infection is decreasing throughout the vaccination campaign, thereby modifying the picture over time., Competing Interests: The authors have declared that no competing interests exist.

Human behaviour is known to be crucial in the propagation of infectious diseases through respiratory or close-contact routes like the current SARS-CoV-2 virus. Intervention measures implemented to curb the spread of the virus mainly aim at limiting the number of close contacts, until vaccine roll-out is complete. Our main objective was to assess the relationships between SARS-CoV-2 perceptions and social contact behaviour in Belgium. Understanding these relationships is crucial to maximize interventions' effectiveness, e.g. by tailoring public health communication campaigns. In this study, we surveyed a representative sample of adults in Belgium in two longitudinal surveys (survey 1 in April 2020 to August 2020, and survey 2 in November 2020 to April 2021). Generalized linear mixed effects models were used to analyse the two surveys. Participants with low and neutral perceptions on perceived severity made a significantly higher number of social contacts as compared to participants with high levels of perceived severity after controlling for other variables. Our results highlight the key role of perceived severity on social contact behaviour during a pandemic. Nevertheless, additional research is required to investigate the impact of public health communication on severity of COVID-19 in terms of changes in social contact behaviour., (© 2022. The Author(s).)

Soon after SARS-CoV-2 emerged in late 2019, Belgium was confronted with a first COVID-19 wave in March-April 2020. SARS-CoV-2 circulation declined in the summer months (late May to early July 2020). Following a successfully trumped late July-August peak, COVID-19 incidence fell slightly, to then enter two successive phases of rapid incline: in the first half of September, and then again in October 2020. The first of these coincided with the peak period of returning summer travelers; the second one coincided with the start of higher education's academic year. The largest observed COVID-19 incidence occurred in the period 16-31 October, particularly in the Walloon Region, the southern, French-speaking part of Belgium. We examine the potential association of the higher education population with spatio-temporal spread of COVID-19, using Bayesian spatial Poisson models for confirmed test cases, accounting for socio-demographic heterogeneity in the population. We find a significant association between the number of COVID-19 cases in the age groups 18-29 years and 30-39 years and the size of the higher education student population at the municipality level. These results can be useful towards COVID-19 mitigation strategies, particularly in areas where virus transmission from higher education students into the broader community could exacerbate morbidity and mortality of COVID-19 among populations with prevalent underlying conditions associated with more severe outcomes following infection., Competing Interests: The authors have declared that no competing interests exist.

BackgroundCOVID-19 mortality, excess mortality, deaths per million population (DPM), infection fatality ratio (IFR) and case fatality ratio (CFR) are reported and compared for many countries globally. These measures may appear objective, however, they should be interpreted with caution.AimWe examined reported COVID-19-related mortality in Belgium from 9 March 2020 to 28 June 2020, placing it against the background of excess mortality and compared the DPM and IFR between countries and within subgroups.MethodsThe relation between COVID-19-related mortality and excess mortality was evaluated by comparing COVID-19 mortality and the difference between observed and weekly average predictions of all-cause mortality. DPM were evaluated using demographic data of the Belgian population. The number of infections was estimated by a stochastic compartmental model. The IFR was estimated using a delay distribution between infection and death.ResultsIn the study period, 9,621 COVID-19-related deaths were reported, which is close to the excess mortality estimated using weekly averages (8,985 deaths). This translates to 837 DPM and an IFR of 1.5% in the general population. Both DPM and IFR increase with age and are substantially larger in the nursing home population.DiscussionDuring the first pandemic wave, Belgium had no discrepancy between COVID-19-related mortality and excess mortality. In light of this close agreement, it is useful to consider the DPM and IFR, which are both age, sex, and nursing home population-dependent. Comparison of COVID-19 mortality between countries should rather be based on excess mortality than on COVID-19-related mortality.

Importance: Recent data suggest a relatively low incidence of COVID-19 among children. The possible role that children attending primary school may play in the transmission of SARS-CoV-2 remains poorly understood., Objective: To gain a better understanding of the possible role of children in the transmission of SARS-CoV-2., Design, Setting, and Participants: This prospective cohort study was conducted from September 21 to December 31, 2020, in a primary school in Liège, Belgium, among a volunteer sample of 181 children, parents, and school employees., Exposures: Participants were tested for SARS-CoV-2 infection once a week for 15 weeks through throat washing, performed with 5 mL of saline and collected in a sterile tube after approximately 30 seconds of gargling. Quantitative reverse transcription-polymerase chain reaction was performed to detect SARS-CoV-2 infection., Main Outcomes and Measures: In case of test positivity, participants were asked to complete a questionnaire aimed at determining the timing of symptom onset and symptom duration. SARS-CoV-2 genetic sequencing was also performed. Confirmed cases were linked based on available information on known contacts and viral sequences., Results: A total of 181 individuals participated in this study, including 63 children (34 girls [54.0%]; mean [SD] age, 8.6 [1.9] years [range, 5-13 years]) and 118 adults (75 women [63.6%]; mean [SD] age, 42.5 [5.7] years [range, 30-59 years]). Forty-five individuals (24.9%) tested positive: 13 children (20.6%; 95% CI, 10.6%-30.6%) and 32 adults (27.1%; 95% CI, 19.1%-35.7%) (P = .34). Children were more often asymptomatic compared with adults (6 [46.2%; 95% CI, 19.1%-73.3%] vs 4 of 31 [12.9%; 95% CI, 1.3%-24.5%]; P = .04). The median duration of symptoms was shorter in children than in adults (0.00 days [IQR, 0.00-1.00 days] vs 15.00 days [IQR, 7.00-22.00 days]). A reconstruction of the outbreak revealed that most transmission events occurred between teachers and between children within the school. Of the observed household transmission events, most seemed to have originated from a child or teacher who acquired the infection at school., Conclusions and Relevance: Despite the implementation of several mitigation measures, the incidence of COVID-19 among children attending primary school in this study was comparable to that observed among teachers and parents. Transmission tree reconstruction suggests that most transmission events originated from within the school. Additional measures should be considered to reduce the transmission of SARS-CoV-2 at school, including intensified testing.

Background: SARS-CoV-2 dynamics are driven by human behaviour. Social contact data are of utmost importance in the context of transmission models of close-contact infections., Methods: Using online representative panels of adults reporting on their own behaviour as well as parents reporting on the behaviour of one of their children, we collect contact mixing (CoMix) behaviour in various phases of the COVID-19 pandemic in over 20 European countries. We provide these timely, repeated observations using an online platform: SOCRATES-CoMix. In addition to providing cleaned datasets to researchers, the platform allows users to extract contact matrices that can be stratified by age, type of day, intensity of the contact and gender. These observations provide insights on the relative impact of recommended or imposed social distance measures on contacts and can inform mathematical models on epidemic spread., Conclusion: These data provide essential information for policymakers to balance non-pharmaceutical interventions, economic activity, mental health and wellbeing, during vaccine rollout., (© 2021. The Author(s).)

The number of secondary cases, i.e. the number of new infections generated by an infectious individual, is an important parameter for the control of infectious diseases. When individual variation in disease transmission is present, like for COVID-19, the distribution of the number of secondary cases is skewed and often modeled using a negative binomial distribution. However, this may not always be the best distribution to describe the underlying transmission process. We propose the use of three other offspring distributions to quantify heterogeneity in transmission, and we assess the possible bias in estimates of the mean and variance of this distribution when the data generating distribution is different from the one used for inference. We also analyze COVID-19 data from Hong Kong, India, and Rwanda, and quantify the proportion of cases responsible for 80% of transmission, [Formula: see text], while acknowledging the variation arising from the assumed offspring distribution. In a simulation study, we find that variance estimates may be biased when there is a substantial amount of heterogeneity, and that selection of the most accurate distribution from a set of distributions is important. In addition we find that the number of secondary cases for two of the three COVID-19 datasets is better described by a Poisson-lognormal distribution.

Introduction: COVID-19 has shown an exceptionally high spread rate across and within countries worldwide. Understanding the dynamics of such an infectious disease transmission is critical for devising strategies to control its spread. In particular, Rwanda was one of the African countries that started COVID-19 preparedness early in January 2020, and a total lockdown was imposed when the country had only 18 COVID-19 confirmed cases known. Using intensive contact tracing, several infections were identified, with the majority of them being returning travellers and their close contacts. We used the contact tracing data in Rwanda for understanding the geographic patterns of COVID-19 to inform targeted interventions., Methods: We estimated the attack rates and identified risk factors associated to COVID-19 spread. We used Bayesian disease mapping models to assess the spatial pattern of COVID-19 and to identify areas characterised by unusually high or low relative risk. In addition, we used multiple variable conditional logistic regression to assess the impact of the risk factors., Results: The results showed that COVID-19 cases in Rwanda are localised mainly in the central regions and in the southwest of Rwanda and that some clusters occurred in the northeast of Rwanda. Relationship to the index case, being male and coworkers are the important risk factors for COVID-19 transmission in Rwanda., Conclusion: The analysis of contact tracing data using spatial modelling allowed us to identify high-risk areas at subnational level in Rwanda. Estimating risk factors for infection with SARS-CoV-2 is vital in identifying the clusters in low spread of SARS-CoV-2 subnational level. It is imperative to understand the interactions between the index case and contacts to identify superspreaders, risk factors and high-risk places. The findings recommend that self-isolation at home in Rwanda should be reviewed to limit secondary cases from the same households and spatiotemporal analysis should be introduced in routine monitoring of COVID-19 in Rwanda for policy making decision on real time., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Following the onset of the ongoing COVID-19 pandemic throughout the world, a large fraction of the global population is or has been under strict measures of physical distancing and quarantine, with many countries being in partial or full lockdown. These measures are imposed in order to reduce the spread of the disease and to lift the pressure on healthcare systems. Estimating the impact of such interventions as well as monitoring the gradual relaxing of these stringent measures is quintessential to understand how resurgence of the COVID-19 epidemic can be controlled for in the future. In this paper we use a stochastic age-structured discrete time compartmental model to describe the transmission of COVID-19 in Belgium. Our model explicitly accounts for age-structure by integrating data on social contacts to (i) assess the impact of the lockdown as implemented on March 13, 2020 on the number of new hospitalizations in Belgium; (ii) conduct a scenario analysis estimating the impact of possible exit strategies on potential future COVID-19 waves. More specifically, the aforementioned model is fitted to hospital admission data, data on the daily number of COVID-19 deaths and serial serological survey data informing the (sero)prevalence of the disease in the population while relying on a Bayesian MCMC approach. Our age-structured stochastic model describes the observed outbreak data well, both in terms of hospitalizations as well as COVID-19 related deaths in the Belgian population. Despite an extensive exploration of various projections for the future course of the epidemic, based on the impact of adherence to measures of physical distancing and a potential increase in contacts as a result of the relaxation of the stringent lockdown measures, a lot of uncertainty remains about the evolution of the epidemic in the next months., (Copyright © 2021. Published by Elsevier B.V.)

Background: In response to the ongoing COVID-19 pandemic, several countries adopted measures of social distancing to a different degree. For many countries, after successfully curbing the initial wave, lockdown measures were gradually lifted. In Belgium, such relief started on May 4th with phase 1, followed by several subsequent phases over the next few weeks., Methods: We analysed the expected impact of relaxing stringent lockdown measures taken according to the phased Belgian exit strategy. We developed a stochastic, data-informed, meta-population model that accounts for mixing and mobility of the age-structured population of Belgium. The model is calibrated to daily hospitalization data and is able to reproduce the outbreak at the national level. We consider different scenarios for relieving the lockdown, quantified in terms of relative reductions in pre-pandemic social mixing and mobility. We validate our assumptions by making comparisons with social contact data collected during and after the lockdown., Results: Our model is able to successfully describe the initial wave of COVID-19 in Belgium and identifies interactions during leisure/other activities as pivotal in the exit strategy. Indeed, we find a smaller impact of school re-openings as compared to restarting leisure activities and re-openings of work places. We also assess the impact of case isolation of new (suspected) infections, and find that it allows re-establishing relatively more social interactions while still ensuring epidemic control. Scenarios predicting a second wave of hospitalizations were not observed, suggesting that the per-contact probability of infection has changed with respect to the pre-lockdown period., Conclusions: Contacts during leisure activities are found to be most influential, followed by professional contacts and school contacts, respectively, for an impending second wave of COVID-19. Regular re-assessment of social contacts in the population is therefore crucial to adjust to evolving behavioral changes that can affect epidemic diffusion.

The SARS-CoV-2 pathogen is currently spreading worldwide and its propensity for presymptomatic and asymptomatic transmission makes it difficult to control. The control measures adopted in several countries aim at isolating individuals once diagnosed, limiting their social interactions and consequently their transmission probability. These interventions, which have a strong impact on the disease dynamics, can affect the inference of the epidemiological quantities. We first present a theoretical explanation of the effect caused by non-pharmaceutical intervention measures on the mean serial and generation intervals. Then, in a simulation study, we vary the assumed efficacy of control measures and quantify the effect on the mean and variance of realized generation and serial intervals. The simulation results show that the realized serial and generation intervals both depend on control measures and their values contract according to the efficacy of the intervention strategies. Interestingly, the mean serial interval differs from the mean generation interval. The deviation between these two values depends on two factors. First, the number of undiagnosed infectious individuals. Second, the relationship between infectiousness, symptom onset and timing of isolation. Similarly, the standard deviations of realized serial and generation intervals do not coincide, with the former shorter than the latter on average. The findings of this study are directly relevant to estimates performed for the current COVID-19 pandemic. In particular, the effective reproduction number is often inferred using both daily incidence data and the generation interval. Failing to account for either contraction or mis-specification by using the serial interval could lead to biased estimates of the effective reproduction number. Consequently, this might affect the choices made by decision makers when deciding which control measures to apply based on the value of the quantity thereof., Competing Interests: The authors have declared that no competing interests exist.

The COVID-19 pandemic caused many governments to impose policies restricting social interactions. A controlled and persistent release of lockdown measures covers many potential strategies and is subject to extensive scenario analyses. Here, we use an individual-based model (STRIDE) to simulate interactions between 11 million inhabitants of Belgium at different levels including extended household settings, i.e., "household bubbles". The burden of COVID-19 is impacted by both the intensity and frequency of physical contacts, and therefore, household bubbles have the potential to reduce hospital admissions by 90%. In addition, we find that it is crucial to complete contact tracing 4 days after symptom onset. Assumptions on the susceptibility of children affect the impact of school reopening, though we find that business and leisure-related social mixing patterns have more impact on COVID-19 associated disease burden. An optimal deployment of the mitigation policies under study require timely compliance to physical distancing, testing and self-isolation.

Starting from historic reflections, the current SARS-CoV-2 induced COVID-19 pandemic is examined from various perspectives, in terms of what it implies for the implementation of non-pharmaceutical interventions, the modeling and monitoring of the epidemic, the development of early-warning systems, the study of mortality, prevalence estimation, diagnostic and serological testing, vaccine development, and ultimately clinical trials. Emphasis is placed on how the pandemic had led to unprecedented speed in methodological and clinical development, the pitfalls thereof, but also the opportunities that it engenders for national and international collaboration, and how it has simplified and sped up procedures. We also study the impact of the pandemic on clinical trials in other indications. We note that it has placed biostatistics, epidemiology, virology, infectiology, and vaccinology, and related fields in the spotlight in an unprecedented way, implying great opportunities, but also the need to communicate effectively, often amidst controversy., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The clinical frailty scale (CFS) was used as a triage tool for medical decision making during the COVID-19 pandemic. The CFS has been posed as a suitable risk marker for in-hospital mortality in COVID-19 patients. We evaluated whether the CFS is associated with mortality 24 months after hospitalisation for COVID-19. Methods: The COvid MEdicaTion (COMET) study is an international, multicentre, observational cohort study, including adult patients hospitalised for COVID-19 between March 2020–July 2020. Patients’ characteristics, prescribed medication, clinical characteristics, and CFS were collected at admission, survival data were collected 24 months after hospitalisation. Multivariable cox proportional hazard models stratified by age (