Spatio-temporal dynamic of the COVID-19 epidemic and the impact of imported cases in Rwanda.

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.

Social contact patterns during the COVID-19 pandemic in 21 European countries - evidence from a two-year study.

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.

A linear mixed model to estimate COVID-19-induced excess mortality.

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.

Fractal dimension based geographical clustering of COVID-19 time series data.

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.

Spatio-Temporal Bayesian Models for Malaria Risk Using Survey and Health Facility Routine Data in Rwanda.

INTRODUCTION: Malaria is a life-threatening disease ocuring mainly in developing countries. Almost half of the world's population was at risk of malaria in 2020. Children under five years age are among the population groups at considerably higher risk of contracting malaria and developing severe disease. Most countries use Demographic and Health Survey (DHS) data for health programs and evaluation. However, malaria elimination strategies require a real-time, locally-tailored response based on malaria risk estimates at the lowest administrative levels. In this paper, we propose a two-step modeling framework using survey and routine data to improve estimates of malaria risk incidence in small areas and enable quantifying malaria trends. METHODS: To improve estimates, we suggest an alternative approach to modeling malaria relative risk by combining information from survey and routine data through Bayesian spatio-temporal models. We model malaria risk using two steps: (1) fitting a binomial model to the survey data, and (2) extracting fitted values and using them in the Poison model as nonlinear effects in the routine data. We modeled malaria relative risk among under-five-year old children in Rwanda. RESULTS: The estimation of malaria prevalence among children who are under five years old using Rwanda demographic and health survey data for the years 2019-2020 alone showed a higher prevalence in the southwest, central, and northeast of Rwanda than the rest of the country. Combining with routine health facility data, we detected clusters that were undetected based on the survey data alone. The proposed approach enabled spatial and temporal trend effect estimation of relative risk in local/small areas in Rwanda. CONCLUSIONS: The findings of this analysis suggest that using DHS combined with routine health services data for active malaria surveillance may provide provide more precise estimates of the malaria burden, which can be used toward malaria elimination targets. We compared findings from geostatistical modeling of malaria prevalence among under-five-year old children using DHS 2019-2020 and findings from malaria relative risk spatio-temporal modeling using both DHS survey 2019-2020 and health facility routine data. The strength of routinely collected data at small scales and high-quality data from the survey contributed to a better understanding of the malaria relative risk at the subnational level in Rwanda.

A spatial model to jointly analyze self-reported survey data of COVID-19 symptoms and official COVID-19 incidence data.

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.

Spatio-temporal model to investigate COVID-19 spread accounting for the mobility amongst municipalities.

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.

The doubling effect of COVID-19 cases on key health indicators.

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.

EpiLPS: A fast and flexible Bayesian tool for estimation of the time-varying reproduction number.

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.

Pregnancy during COVID-19: social contact patterns and vaccine coverage of pregnant women from CoMix in 19 European countries.

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.

Variation in smoking attributable all-cause mortality across municipalities in Belgium, 2018: application of a Bayesian approach for small area estimations.

BACKGROUND: Smoking is one of the leading causes of preventable mortality and morbidity worldwide, with the European Region having the highest prevalence of tobacco smoking among adults compared to other WHO regions. The Belgian Health Interview Survey (BHIS) provides a reliable source of national and regional estimates of smoking prevalence; however, currently there are no estimates at a smaller geographical resolution such as the municipality scale in Belgium. This hinders the estimation of the spatial distribution of smoking attributable mortality at small geographical scale (i.e., number of deaths that can be attributed to tobacco). The objective of this study was to obtain estimates of smoking prevalence in each Belgian municipality using BHIS and calculate smoking attributable mortality at municipality level. METHODS: Data of participants aged 15 + on smoking behavior, age, gender, educational level and municipality of residence were obtained from the BHIS 2018. A Bayesian hierarchical Besag-York-Mollie (BYM) model was used to model the logit transformation of the design-based Horvitz-Thompson direct prevalence estimates. Municipality-level variables obtained from Statbel, the Belgian statistical office, were used as auxiliary variables in the model. Model parameters were estimated using Integrated Nested Laplace Approximation (INLA). Deviance Information Criterion (DIC) and Conditional Predictive Ordinate (CPO) were computed to assess model fit. Population attributable fractions (PAF) were computed using the estimated prevalence of smoking in each of the 589 Belgian municipalities and relative risks obtained from published meta-analyses. Smoking attributable mortality was calculated by multiplying PAF with age-gender standardized and stratified number of deaths in each municipality. RESULTS: BHIS 2018 data included 7,829 respondents from 154 municipalities. Smoothed estimates for current smoking ranged between 11% [Credible Interval 3;23] and 27% [21;34] per municipality, and for former smoking between 4% [0;14] and 34% [21;47]. Estimates of smoking attributable mortality constituted between 10% [7;15] and 47% [34;59] of total number of deaths per municipality. CONCLUSIONS: Within-country variation in smoking and smoking attributable mortality was observed. Computed estimates should inform local public health prevention campaigns as well as contribute to explaining the regional differences in mortality.

On the timing of interventions to preserve hospital capacity: lessons to be learned from the Belgian SARS-CoV-2 pandemic in 2020.

Using publicly available data on the number of new hospitalisations we use a newly developed statistical model to produce a phase portrait to monitor the epidemic allowing for assessing whether or not intervention measures are needed to keep hospital capacity under control. The phase portrait is called a cliquets' diagram, referring to the discrete alarm phases it points to. Using this cliquets' diagram we show that intervention measures were associated with an effective mitigation of a Summer resurgence but that too little too late was done to prevent a large autumn wave in Belgium.

Inferring age-specific differences in susceptibility to and infectiousness upon SARS-CoV-2 infection based on Belgian social contact data.

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.

The influence of risk perceptions on close contact frequency during the SARS-CoV-2 pandemic.

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.

COVID-19 mortality, excess mortality, deaths per million and infection fatality ratio, Belgium, 9 March 2020 to 28 June 2020.

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.

The COVID-19 wave in Belgium during the Fall of 2020 and its association with higher education.

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.

Leveraging of SARS-CoV-2 PCR Cycle Thresholds Values to Forecast COVID-19 Trends.

Introduction: We assessed the usefulness of SARS-CoV-2 RT-PCR cycle thresholds (Ct) values trends produced by the LHUB-ULB (a consolidated microbiology laboratory located in Brussels, Belgium) for monitoring the epidemic's dynamics at local and national levels and for improving forecasting models. Methods: SARS-CoV-2 RT-PCR Ct values produced from April 1, 2020, to May 15, 2021, were compared with national COVID-19 confirmed cases notifications according to their geographical and time distribution. These Ct values were evaluated against both a phase diagram predicting the number of COVID-19 patients requiring intensive care and an age-structured model estimating COVID-19 prevalence in Belgium. Results: Over 155,811 RT-PCR performed, 12,799 were positive and 7,910 Ct values were available for analysis. The 14-day median Ct values were negatively correlated with the 14-day mean daily positive tests with a lag of 17 days. In addition, the 14-day mean daily positive tests in LHUB-ULB were strongly correlated with the 14-day mean confirmed cases in the Brussels-Capital and in Belgium with coinciding start, peak, and end of the different waves of the epidemic. Ct values decreased concurrently with the forecasted phase-shifts of the diagram. Similarly, the evolution of 14-day median Ct values was negatively correlated with daily estimated prevalence for all age-classes. Conclusion: We provide preliminary evidence that trends of Ct values can help to both follow and predict the epidemic's trajectory at local and national levels, underlining that consolidated microbiology laboratories can act as epidemic sensors as they gather data that are representative of the geographical area they serve.

SOCRATES-CoMix: a platform for timely and open-source contact mixing data during and in between COVID-19 surges and interventions in over 20 European countries.

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.

Transmission of SARS-CoV-2 After COVID-19 Screening and Mitigation Measures for Primary School Children Attending School in Liège, Belgium.

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.