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BACKGROUND: Spatial modeling of disease risk using primary care registry data is promising for public health surveillance. However, it remains unclear to which extent challenges such as spatially disproportionate sampling and practice-specific reporting variation affect statistical inference. METHODS: Using lower respiratory tract infection data from the INTEGO registry, modeled with a logistic model incorporating patient characteristics, a spatially structured random effect at municipality level, and an unstructured random effect at practice level, we conducted a case and simulation study to assess the impact of these challenges on spatial trend estimation. RESULTS: Even with spatial imbalance and practice-specific reporting variation, the model performed well. Performance improved with increasing spatial sample balance and decreasing practice-specific variation. CONCLUSION: Our findings indicate that, with correction for reporting efforts, primary care registries are valuable for spatial trend estimation. The diversity of patient locations within practice populations plays an important role.
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Atenção Primária à Saúde , Sistema de Registros , Humanos , Atenção Primária à Saúde/estatística & dados numéricos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Análise Espacial , Infecções Respiratórias/epidemiologia , Idoso , Adolescente , Modelos Logísticos , Criança , Modelos Estatísticos , Adulto Jovem , Pré-EscolarRESUMO
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.
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Vacinas contra COVID-19 , COVID-19 , Anos de Vida Ajustados por Qualidade de Vida , SARS-CoV-2 , Humanos , COVID-19/prevenção & controle , COVID-19/epidemiologia , COVID-19/mortalidade , Bélgica/epidemiologia , Criança , Vacinas contra COVID-19/administração & dosagem , Pré-Escolar , Adulto , Fatores Etários , Modelos Teóricos , Adolescente , Programas de Imunização , Pessoa de Meia-Idade , Vacinação/estatística & dados numéricos , Idoso , Adulto JovemRESUMO
While Reinforcement Learning (RL) has already proven successful in performing complex tasks, such as controlling large-scale epidemics, mitigating influenza and playing computer games beyond expert level, it is currently largely unexplored in the field of separation sciences. This paper therefore aims to introduce RL, specifically proximal policy optimization (PPO), in liquid chromatography, and evaluate whether it can be trained to optimize separations directly, based solely on the outcome of a single generic separation as input, and a reward signal based on the resolution between peak pairs (taking a value between [-1,1]). More specifically, PPO algorithms or agents were trained to select linear (1-segment) or multi-segment (2-, 3-, or 16-segment) gradients in 1 experiment, based on the outcome of an initial, generic linear gradient (Ïstart=0.3, Ïend=1.0, and tg=20min), to improve separations. The size of the mixtures to be separated varied between 10 and 20 components. Furthermore, two agents, selecting 16-segment gradients, were trained to perform this optimization using either 2 or 3 experiments, in sequence, to investigate whether the agents could improve separations further, based on previous outcomes. Results showed that the PPO agent can improve separations given the outcome of one generic scouting run as input, by selecting Ï-programs tailored to the mixture under consideration. Allowing agents more freedom in selecting multi-segment gradients increased the reward from 0.891 to 0.908 on average; and allowing the agents to perform an additional experiment increased the reward from 0.908 to 0.918 on average. Finally, the agent outperformed random experiments as well as standard experiments (Ïstart=0.0, Ïend=1.0, and tg=20min) significantly; as random experiments resulted in average rewards between 0.220 and 0.283, and standard experiments resulted in average rewards of 0.840. In conclusion, while there is room for improvement, the results demonstrate the potential of RL in chromatography and present an interesting future direction for the automated optimization of separations.
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Algoritmos , Cromatografia Líquida/métodosRESUMO
Background: Serological surveys for SARS-CoV-2 were used early in the COVID-19 pandemic to assess epidemiological scenarios. In the municipality of Cascais (Portugal), serological testing combined with a comprehensive socio-demographic, clinical and behavioral questionnaire was offered to residents between May 2020 and beginning of 2021. In this study, we analyze the factors associated with adherence to this municipal initiative, as well as the sociodemographic profile and chronic diseases clinical correlates associated to seropositivity. We aim to contribute with relevant information for future pandemic preparedness efforts. Methods: This was a cross-sectional study with non-probabilistic sampling. Citizens residing in Cascais Municipality went voluntarily to blood collection centers to participate in the serological survey. The proportion of participants, stratified by socio-demographic variables, was compared to the census proportions to identify the groups with lower levels of adherence to the survey. Univariate and multivariate logistic regression were used to identify socio-demographic, clinical and behavioral factors associated with seropositivity. Results: From May 2020 to February 2021, 19,608 participants (9.2% of the residents of Cascais) were included in the study. Based on the comparison to census data, groups with lower adherence to this survey were men, the youngest and the oldest age groups, individuals with lower levels of education and unemployed/inactive. Significant predictors of a reactive (positive) serological test were younger age, being employed or a student, and living in larger households. Individuals with chronic diseases generally showed lower seroprevalence. Conclusion: The groups with low adherence to this voluntary study, as well as the socio-economic contexts identified as more at risk of viral transmission, may be targeted in future pandemic situations. We also found that the individuals with chronic diseases, perceiving higher risk of serious illness, adopted protective behaviors that limited infection rates, revealing that health education on preventive measures was effective for these patients.
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COVID-19 , Masculino , Humanos , Feminino , COVID-19/epidemiologia , SARS-CoV-2 , Portugal/epidemiologia , Pandemias , Estudos Transversais , Preparação para Pandemia , Estudos Soroepidemiológicos , Doença CrônicaRESUMO
AIMS: Brugada syndrome (BrS) is a hereditary arrhythmic disease, associated with sudden cardiac death. To date, little is known about the psychosocial correlates and impacts associated with this disease. The aim of this study was to assess a set of patient-reported psychosocial outcomes, to better profile these patients, and to propose a tailored psychosocial care. METHODS AND RESULTS: Patients were recruited at the European reference Centre for BrS at Universitair Ziekenhuis Brussel, Belgium. Recruitment was undertaken in two phases: phase 1 (retrospective), patients with confirmed BrS, and phase 2 (prospective), patients referred for ajmaline testing who had an either positive or negative diagnosis. BrS patients were compared to controls from the general population. Two hundred and nine questionnaires were analysed (144 retrospective and 65 prospective). Collected patient-reported outcomes were on mental health (12 item General Health Questionnaire; GHQ-12), social support (Oslo Social Support Scale), health-related quality of life, presence of Type-D personality (Type-D Scale; DS14), coping styles (Brief-COPE), and personality dimensions (Ten Item Personality Inventory). Results showed higher mental distress (GHQ-12) in BrS patients (2.53 ± 3.03) than in the general population (P < 0.001) and higher prevalence (32.7%) of Type D personality (P < 0.001) in patients with confirmed Brugada syndrome (BrS +). A strong correlation was found in the BrS + group (0.611, P < 0.001) between DS14 negative affectivity subscale and mental distress (GHQ-12). CONCLUSION: Mental distress and type D personality are significantly more common in BrS patients compared to the general population. This clearly illustrates the necessity to include mental health screening and care as standard for BrS.
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Síndrome de Brugada , Humanos , Síndrome de Brugada/diagnóstico , Síndrome de Brugada/terapia , Síndrome de Brugada/complicações , Saúde Mental , Estudos Prospectivos , Estudos Retrospectivos , Qualidade de Vida , Medidas de Resultados Relatados pelo Paciente , Eletrocardiografia/métodosRESUMO
BACKGROUND: Since 2014, Belgium's Superior Health Council has recommended pneumococcal vaccination for adults aged 19-85 years at increased risk for pneumococcal diseases with a specific vaccine administration sequence and timing. Currently, Belgium has no publicly funded adult pneumococcal vaccination program. This study investigated the seasonal pneumococcal vaccination trends, evolution of vaccination coverage and adherence to the 2014 recommendations. METHODS: INTEGO is a general practice morbidity registry in Flanders (Belgium) that represents 102 general practice centres and comprised over 300.000 patients in 2021. A repeated cross-sectional study was performed for the period between 2017 and 2021. Using adjusted odds ratios computed via multiple logistic regression, the association between an individual's characteristics (gender, age, comorbidities, influenza vaccination status and socioeconomic status) and schedule-adherent pneumococcal vaccination status was assessed. RESULTS: Pneumococcal vaccination coincided with seasonal flu vaccination. The vaccination coverage in the population at risk decreased from 21% in 2017 to 18.2% in 2018 and then started to increase to 23.6% in 2021. Coverage in 2021 was highest for high-risk adults (33.8%) followed by 50- to 85-year-olds with comorbidities (25.5%) and healthy 65- to 85-year-olds (18.7%). In 2021, 56.3% of the high-risk adults, 74.6% of the 50+ with comorbidities persons, and 74% of the 65+ healthy persons had an adherent vaccination schedule. Persons with a lower socioeconomic status had an adjusted odds ratio of 0.92 (95% Confidence Interval (CI) 0.87-0.97) for primary vaccination, 0.67 (95% CI 0.60-0.75) for adherence to the recommended second vaccination if the 13-valent pneumococcal conjugate vaccine was administered first and 0.86 (95% CI 0.76-0.97) if the 23-valent pneumococcal polysaccharide vaccine was administered first. CONCLUSION: Pneumococcal vaccine coverage is slowly increasing in Flanders, displaying seasonal peaks in sync with influenza vaccination campaigns. However, with less than one-fourth of the target population vaccinated, less than 60% high-risk and approximately 74% of 50 + with comorbidities and 65+ healthy persons with an adherent schedule, there is still much room for improvement. Furthermore, adults with poor socioeconomic status had lower odds of primary vaccination and schedule adherence, demonstrating the need for a publicly funded program in Belgium to ensure equitable access.
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Influenza Humana , Infecções Pneumocócicas , Humanos , Adulto , Cobertura Vacinal , Estudos Transversais , Influenza Humana/prevenção & controle , Vacinação , Vacinas Pneumocócicas , Streptococcus pneumoniae , Infecções Pneumocócicas/prevenção & controle , Infecções Pneumocócicas/epidemiologia , Morbidade , Sistema de RegistrosRESUMO
Mathematical modelling studies have shown that repetitive screening can be used to mitigate SARS-CoV-2 transmission in primary schools while keeping schools open. However, not much is known about how transmission progresses within schools and whether there is a risk of importation to households. During the academic year 2020-2021, a prospective surveillance study using repetitive screening was conducted in a primary school and associated households in Liège (Belgium). SARS-CoV-2 screening was performed via throat washing either once or twice a week. We used genomic and epidemiological data to reconstruct the observed school outbreaks using two different models. The outbreaker2 model combines information on the generation time and contact patterns with a model of sequence evolution. For comparison we also used SCOTTI, a phylogenetic model based on the structured coalescent. In addition, we performed a simulation study to investigate how the accuracy of estimated positivity rates in a school depends on the proportion of a school that is sampled in a repetitive screening strategy. We found no difference in SARS-CoV-2 positivity between children and adults and children were not more often asymptomatic compared to adults. Both models for outbreak reconstruction revealed that transmission occurred mainly within the school environment. Uncertainty in outbreak reconstruction was lowest when including genomic as well as epidemiological data. We found that observed weekly positivity rates are a good approximation to the true weekly positivity rate, especially in children, even when only 25% of the school population is sampled. These results indicate that, in addition to reducing infections as shown in modelling studies, repetitive screening in school settings can lead to a better understanding of the extent of transmission in schools during a pandemic and importation risk at the community level.
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COVID-19 , SARS-CoV-2 , Adulto , Criança , Humanos , SARS-CoV-2/genética , Filogenia , Estudos Prospectivos , COVID-19/epidemiologia , Genômica , Surtos de Doenças , Instituições AcadêmicasRESUMO
Superspreading events play an important role in the spread of several pathogens, such as SARS-CoV-2. While the basic reproduction number of the original Wuhan SARS-CoV-2 is estimated to be about 3 for Belgium, there is substantial inter-individual variation in the number of secondary cases each infected individual causes-with most infectious individuals generating no or only a few secondary cases, while about 20% of infectious individuals is responsible for 80% of new infections. Multiple factors contribute to the occurrence of superspreading events: heterogeneity in infectiousness, individual variations in susceptibility, differences in contact behavior, and the environment in which transmission takes place. While superspreading has been included in several infectious disease transmission models, research into the effects of different forms of superspreading on the spread of pathogens remains limited. To disentangle the effects of infectiousness-related heterogeneity on the one hand and contact-related heterogeneity on the other, we implemented both forms of superspreading in an individual-based model describing the transmission and spread of SARS-CoV-2 in a synthetic Belgian population. We considered its impact on viral spread as well as on epidemic resurgence after a period of social distancing. We found that the effects of superspreading driven by heterogeneity in infectiousness are different from the effects of superspreading driven by heterogeneity in contact behavior. On the one hand, a higher level of infectiousness-related heterogeneity results in a lower risk of an outbreak persisting following the introduction of one infected individual into the population. Outbreaks that did persist led to fewer total cases and were slower, with a lower peak which occurred at a later point in time, and a lower herd immunity threshold. Finally, the risk of resurgence of an outbreak following a period of lockdown decreased. On the other hand, when contact-related heterogeneity was high, this also led to fewer cases in total during persistent outbreaks, but caused outbreaks to be more explosive in regard to other aspects (such as higher peaks which occurred earlier, and a higher herd immunity threshold). Finally, the risk of resurgence of an outbreak following a period of lockdown increased. We found that these effects were conserved when testing combinations of infectiousness-related and contact-related heterogeneity.
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COVID-19 , SARS-CoV-2 , Número Básico de Reprodução , COVID-19/epidemiologia , Controle de Doenças Transmissíveis/métodos , Surtos de Doenças , HumanosRESUMO
SARS-CoV-2 remains a worldwide emergency. While vaccines have been approved and are widely administered, there is an ongoing debate whether children should be vaccinated or prioritized for vaccination. Therefore, in order to mitigate the spread of more transmissible SARS-CoV-2 variants among children, the use of non-pharmaceutical interventions is still warranted. We investigate the impact of different testing strategies on the SARS-CoV-2 infection dynamics in a primary school environment, using an individual-based modelling approach. Specifically, we consider three testing strategies: (1) symptomatic isolation, where we test symptomatic individuals and isolate them when they test positive, (2) reactive screening, where a class is screened once one symptomatic individual was identified, and (3) repetitive screening, where the school in its entirety is screened on regular time intervals. Through this analysis, we demonstrate that repetitive testing strategies can significantly reduce the attack rate in schools, contrary to a reactive screening or a symptomatic isolation approach. However, when a repetitive testing strategy is in place, more cases will be detected and class and school closures are more easily triggered, leading to a higher number of school days lost per child. While maintaining the epidemic under control with a repetitive testing strategy, we show that absenteeism can be reduced by relaxing class and school closure thresholds.
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COVID-19 , SARS-CoV-2 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Criança , Humanos , Instituições AcadêmicasRESUMO
Emerging infectious diseases are one of the main threats to public health, with the potential to cause a pandemic when the infectious agent manages to spread globally. The first major pandemic to appear in the 20th century was the influenza pandemic of 1918, caused by the influenza A H1N1 strain that is characterized by a high fatality rate. Another major pandemic was caused by the human immunodeficiency virus (HIV), that started early in the 20th century and remained undetected until 1981. The ongoing HIV pandemic demonstrated a high mortality and morbidity rate, with discrepant impacts in different regions around the globe. The most recent major pandemic event, is the ongoing pandemic of COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has caused over 5.7 million deaths since its emergence, 2 years ago. The aim of this work is to highlight the main determinants of the emergence, epidemic response and available countermeasures of these three pandemics, as we argue that such knowledge is paramount to prepare for the next pandemic. We analyse these pandemics' historical and epidemiological contexts and the determinants of their emergence. Furthermore, we compare pharmaceutical and non-pharmaceutical interventions that have been used to slow down these three pandemics and zoom in on the technological advances that were made in the progress. Finally, we discuss the evolution of epidemiological modelling, that has become an essential tool to support public health policy making and discuss it in the context of these three pandemics. While these pandemics are caused by distinct viruses, that ignited in different time periods and in different regions of the globe, our work shows that many of the determinants of their emergence and countermeasures used to halt transmission were common. Therefore, it is important to further improve and optimize such approaches and adapt it to future threatening emerging infectious diseases.
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The Zika virus (ZIKV) disease caused a public health emergency of international concern that started in February 2016. The overall number of ZIKV-related cases increased until November 2016, after which it declined sharply. While the evaluation of the potential risk and impact of future arbovirus epidemics remains challenging, intensified surveillance efforts along with a scale-up of ZIKV whole-genome sequencing provide an opportunity to understand the patterns of genetic diversity, evolution, and spread of ZIKV. However, a classification system that reflects the true extent of ZIKV genetic variation is lacking. Our objective was to characterize ZIKV genetic diversity and phylodynamics, identify genomic footprints of differentiation patterns, and propose a dynamic classification system that reflects its divergence levels. We analysed a curated dataset of 762 publicly available sequences spanning the full-length coding region of ZIKV from across its geographical span and collected between 1947 and 2021. The definition of genetic groups was based on comprehensive evolutionary dynamics analyses, which included recombination and phylogenetic analyses, within- and between-group pairwise genetic distances comparison, detection of selective pressure, and clustering analyses. Evidence for potential recombination events was detected in a few sequences. However, we argue that these events are likely due to sequencing errors as proposed in previous studies. There was evidence of strong purifying selection, widespread across the genome, as also detected for other arboviruses. A total of 50 sites showed evidence of positive selection, and for a few of these sites, there was amino acid (AA) differentiation between genetic clusters. Two main genetic clusters were defined, ZA and ZB, which correspond to the already characterized 'African' and 'Asian' genotypes, respectively. Within ZB, two subgroups, ZB.1 and ZB.2, represent the Asiatic and the American (and Oceania) lineages, respectively. ZB.1 is further subdivided into ZB.1.0 (a basal Malaysia sequence sampled in the 1960s and a recent Indian sequence), ZB.1.1 (South-Eastern Asia, Southern Asia, and Micronesia sequences), and ZB.1.2 (very similar sequences from the outbreak in Singapore). ZB.2 is subdivided into ZB.2.0 (basal American sequences and the sequences from French Polynesia, the putative origin of South America introduction), ZB.2.1 (Central America), and ZB.2.2 (Caribbean and North America). This classification system does not use geographical references and is flexible to accommodate potential future lineages. It will be a helpful tool for studies that involve analyses of ZIKV genomic variation and its association with pathogenicity and serve as a starting point for the public health surveillance and response to on-going and future epidemics and to outbreaks that lead to the emergence of new variants.
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Model comparisons have been widely used to guide intervention strategies to control infectious diseases. Agreement between different models is crucial for providing robust evidence for policy-makers because differences in model properties can influence their predictions. In this study, we compared models implemented by two individual-based model simulators for HIV epidemiology in a heterosexual population with Herpes simplex virus type-2 (HSV-2). For each model simulator, we constructed four models, starting from a simplified basic model and stepwise including more model complexity. For the resulting eight models, the predictions of the impact of behavioural interventions on the HIV epidemic in Yaoundé-Cameroon were compared. The results show that differences in model assumptions and model complexity can influence the size of the predicted impact of the intervention, as well as the predicted qualitative behaviour of the HIV epidemic after the intervention. These differences in predictions of an intervention were also observed for two models that agreed in their predictions of the HIV epidemic in the absence of that intervention. Without additional data, it is impossible to determine which of these two models is the most reliable. These findings highlight the importance of making more data available for the calibration and validation of epidemiological models.
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Infecções por HIV/epidemiologia , Herpes Genital/epidemiologia , Modelos Estatísticos , Adolescente , Adulto , Camarões/epidemiologia , Coinfecção/epidemiologia , Simulação por Computador , Estudos Transversais , Feminino , HIV-1/fisiologia , Herpesvirus Humano 2/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Fatores Socioeconômicos , Adulto JovemRESUMO
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.
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COVID-19/epidemiologia , COVID-19/prevenção & controle , Modelos Teóricos , Pandemias , Bélgica/epidemiologia , Controle de Doenças Transmissíveis , Hospitalização , Humanos , Distanciamento Físico , Instituições Acadêmicas , Local de TrabalhoRESUMO
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.
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COVID-19/epidemiologia , Previsões/métodos , Modelos Estatísticos , Teorema de Bayes , Bélgica/epidemiologia , COVID-19/mortalidade , COVID-19/prevenção & controle , Controle de Doenças Transmissíveis , Hospitalização , Humanos , SARS-CoV-2/imunologia , Estudos SoroepidemiológicosRESUMO
Outbreaks of SARS-CoV-2 are threatening the health care systems of several countries around the world. The initial control of SARS-CoV-2 epidemics relied on non-pharmaceutical interventions, such as social distancing, teleworking, mouth masks and contact tracing. However, as pre-symptomatic transmission remains an important driver of the epidemic, contact tracing efforts struggle to fully control SARS-CoV-2 epidemics. Therefore, in this work, we investigate to what extent the use of universal testing, i.e., an approach in which we screen the entire population, can be utilized to mitigate this epidemic. To this end, we rely on PCR test pooling of individuals that belong to the same households, to allow for a universal testing procedure that is feasible with the limited testing capacity. We evaluate two isolation strategies: on the one hand pool isolation, where we isolate all individuals that belong to a positive PCR test pool, and on the other hand individual isolation, where we determine which of the individuals that belong to the positive PCR pool are positive, through an additional testing step. We evaluate this universal testing approach in the STRIDE individual-based epidemiological model in the context of the Belgian COVID-19 epidemic. As the organisation of universal testing will be challenging, we discuss the different aspects related to sample extraction and PCR testing, to demonstrate the feasibility of universal testing when a decentralized testing approach is used. We show through simulation, that weekly universal testing is able to control the epidemic, even when many of the contact reductions are relieved. Finally, our model shows that the use of universal testing in combination with stringent contact reductions could be considered as a strategy to eradicate the virus.
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Teste de Ácido Nucleico para COVID-19/métodos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Epidemias/prevenção & controle , SARS-CoV-2 , Bélgica/epidemiologia , COVID-19/transmissão , Teste de Ácido Nucleico para COVID-19/estatística & dados numéricos , Teste de Ácido Nucleico para COVID-19/tendências , Biologia Computacional , Simulação por Computador , Busca de Comunicante/métodos , Busca de Comunicante/estatística & dados numéricos , Busca de Comunicante/tendências , Reações Falso-Negativas , Características da Família , Estudos de Viabilidade , Humanos , Programas de Rastreamento/métodos , Programas de Rastreamento/estatística & dados numéricos , Programas de Rastreamento/tendências , Modelos Estatísticos , Quarentena/métodos , Quarentena/estatística & dados numéricos , Quarentena/tendências , ViagemRESUMO
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.
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COVID-19/epidemiologia , COVID-19/prevenção & controle , Modelos Estatísticos , Pandemias/prevenção & controle , SARS-CoV-2 , Infecções Assintomáticas/epidemiologia , Número Básico de Reprodução/estatística & dados numéricos , COVID-19/transmissão , Biologia Computacional , Simulação por Computador , Humanos , Incidência , Prevalência , Processos Estocásticos , Fatores de TempoRESUMO
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.
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COVID-19/transmissão , Busca de Comunicante , Transmissão de Doença Infecciosa/prevenção & controle , Características da Família , Quarentena , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bélgica/epidemiologia , COVID-19/epidemiologia , Criança , Pré-Escolar , Controle de Doenças Transmissíveis/métodos , Política de Saúde , Hospitalização , Humanos , Lactente , Recém-Nascido , Pessoa de Meia-Idade , Modelos Teóricos , Pandemias , SARS-CoV-2/isolamento & purificação , Instituições Acadêmicas , Adulto JovemRESUMO
SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is a novel virus of the family Coronaviridae. The virus causes the infectious disease COVID-19. The biology of coronaviruses has been studied for many years. However, bioinformatics tools designed explicitly for SARS-CoV-2 have only recently been developed as a rapid reaction to the need for fast detection, understanding and treatment of COVID-19. To control the ongoing COVID-19 pandemic, it is of utmost importance to get insight into the evolution and pathogenesis of the virus. In this review, we cover bioinformatics workflows and tools for the routine detection of SARS-CoV-2 infection, the reliable analysis of sequencing data, the tracking of the COVID-19 pandemic and evaluation of containment measures, the study of coronavirus evolution, the discovery of potential drug targets and development of therapeutic strategies. For each tool, we briefly describe its use case and how it advances research specifically for SARS-CoV-2. All tools are free to use and available online, either through web applications or public code repositories. Contact:evbc@unj-jena.de.
Assuntos
COVID-19/prevenção & controle , Biologia Computacional , SARS-CoV-2/isolamento & purificação , Pesquisa Biomédica , COVID-19/epidemiologia , COVID-19/virologia , Genoma Viral , Humanos , Pandemias , SARS-CoV-2/genéticaRESUMO
INTRODUCTION: Treatment for All recommendations have allowed access to antiretroviral (ARV) treatment for an increasing number of patients. This minimizes the transmission of infection but can potentiate the risk of transmitted (TDR) and acquired drug resistance (ADR). OBJECTIVE: To study the trends of TDR and ADR in patients followed up in Portuguese hospitals between 2001 and 2017. METHODS: In total, 11,911 patients of the Portuguese REGA database were included. TDR was defined as the presence of one or more surveillance drug resistance mutation according to the WHO surveillance list. Genotypic resistance to ARV was evaluated with Stanford HIVdb v7.0. Patterns of TDR, ADR and the prevalence of mutations over time were analyzed using logistic regression. RESULTS AND DISCUSSION: The prevalence of TDR increased from 7.9% in 2003 to 13.1% in 2017 (p < 0.001). This was due to a significant increase in both resistance to nucleotide reverse transcriptase inhibitors (NRTIs) and non-nucleotide reverse transcriptase inhibitors (NNRTIs), from 5.6% to 6.7% (p = 0.002) and 2.9% to 8.9% (p < 0.001), respectively. TDR was associated with infection with subtype B, and with lower viral load levels (p < 0.05). The prevalence of ADR declined from 86.6% in 2001 to 51.0% in 2017 (p < 0.001), caused by decreasing drug resistance to all antiretroviral (ARV) classes (p < 0.001). CONCLUSIONS: While ADR has been decreasing since 2001, TDR has been increasing, reaching a value of 13.1% by the end of 2017. It is urgently necessary to develop public health programs to monitor the levels and patterns of TDR in newly diagnosed patients.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Farmacorresistência Viral , Infecções por HIV/epidemiologia , Infecções por HIV/transmissão , HIV-1/efeitos dos fármacos , Adolescente , Adulto , Fármacos Anti-HIV/farmacologia , Feminino , Genótipo , Infecções por HIV/tratamento farmacológico , HIV-1/genética , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Filogenia , Portugal/epidemiologia , Prevalência , Saúde Pública/métodos , Inibidores da Transcriptase Reversa/farmacologia , Inibidores da Transcriptase Reversa/uso terapêutico , Adulto JovemRESUMO
BACKGROUND: Current outbreaks of COVID-19 are threatening the health care systems of several countries around the world. Control measures, based on isolation, contact tracing, and quarantine, can decrease and delay the burden of the ongoing epidemic. With respect to the ongoing COVID-19 epidemic, recent modeling work shows that these interventions may be inadequate to control local outbreaks, even when perfect isolation is assumed. The effect of infectiousness prior to symptom onset combined with asymptomatic infectees further complicates the use of contact tracing. We aim to study whether antivirals, which decrease the viral load and reduce infectiousness, could be integrated into control measures in order to augment the feasibility of controlling the epidemic. METHODS: Using a simulation-based model of viral transmission, we tested the efficacy of different intervention measures to control local COVID-19 outbreaks. For individuals that were identified through contact tracing, we evaluate two procedures: monitoring individuals for symptoms onset and testing of individuals. Additionally, we investigate the implementation of an antiviral compound combined with the contact tracing process. RESULTS: For an infectious disease in which asymptomatic and presymptomatic infections are plausible, an intervention measure based on contact tracing performs better when combined with testing instead of monitoring, provided that the test is able to detect infections during the incubation period. Antiviral drugs, in combination with contact tracing, quarantine, and isolation, result in a significant decrease of the final size and the peak incidence, and increase the probability that the outbreak will fade out. CONCLUSION: In all tested scenarios, the model highlights the benefits of control measures based on the testing of traced individuals. In addition, the administration of an antiviral drug, together with quarantine, isolation, and contact tracing, is shown to decrease the spread of the epidemic. This control measure could be an effective strategy to control local and re-emerging outbreaks of COVID-19.