Lack of functional TCR-epitope interaction is associated with herpes zoster through reduced downstream T cell activation.

The role of T cell receptor (TCR) diversity in infectious disease susceptibility is not well understood. We use a systems immunology approach on three cohorts of herpes zoster (HZ) patients and controls to investigate whether TCR diversity against varicella-zoster virus (VZV) influences the risk of HZ. We show that CD4+ T cell TCR diversity against VZV glycoprotein E (gE) and immediate early 63 protein (IE63) after 1-week culture is more restricted in HZ patients. Single-cell RNA and TCR sequencing of VZV-specific T cells shows that T cell activation pathways are significantly decreased after stimulation with VZV peptides in convalescent HZ patients. TCR clustering indicates that TCRs from HZ patients co-cluster more often together than TCRs from controls. Collectively, our results suggest that not only lower VZV-specific TCR diversity but also reduced functional TCR affinity for VZV-specific proteins in HZ patients leads to lower T cell activation and consequently affects the susceptibility for viral reactivation.

Characterising information gains and losses when collecting multiple epidemic model outputs.

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.

Multimorbidity healthcare expenditure in Belgium: a 4-year analysis (COMORB study).

BACKGROUND: The complex management of health needs in multimorbid patients, alongside limited cost data, presents challenges in developing cost-effective patient-care pathways. We estimated the costs of managing 171 dyads and 969 triads in Belgium, taking into account the influence of morbidity interactions on costs. METHODS: We followed a retrospective longitudinal study design, using the linked Belgian Health Interview Survey 2018 and the administrative claim database 2017-2020 hosted by the Intermutualistic Agency. We included people aged 15 and older, who had complete profiles (N = 9753). Applying a system costing perspective, the average annual direct cost per person per dyad/triad was presented in 2022 Euro and comprised mainly direct medical costs. We developed mixed models to analyse the impact of single chronic conditions, dyads and triads on healthcare costs, considering two-/three-way interactions within dyads/triads, key cost determinants and clustering at the household level. RESULTS: People with multimorbidity constituted nearly half of the study population and their total healthcare cost constituted around three quarters of the healthcare cost of the study population. The most common dyad, arthropathies + dorsopathies, with a 14% prevalence rate, accounted for 11% of the total national health expenditure. The most frequent triad, arthropathies + dorsopathies + hypertension, with a 5% prevalence rate, contributed 5%. The average annual direct costs per person with dyad and triad were €3515 (95% CI 3093-3937) and €4592 (95% CI 3920-5264), respectively. Dyads and triads associated with cancer, diabetes, chronic fatigue, and genitourinary problems incurred the highest costs. In most cases, the cost associated with multimorbidity was lower or not substantially different from the combined cost of the same conditions observed in separate patients. CONCLUSION: Prevalent morbidity combinations, rather than high-cost ones, made a greater contribution to total national health expenditure. Our study contributes to the sparse evidence on this topic globally and in Europe, with the aim of improving cost-effective care for patients with diverse needs.

A Comparison of Items and Constructs of Standardized Health-Related Quality of Life and Mental Well-Being Measures.

OBJECTIVES: This study aimed to explore the internal constructs of the concepts being measured by EQ-5D-5L (a health-related quality of life measure that can produce preference-based utility values) and the 12-item General Health Questionnaire (GHQ-12, a mental well-being measure) and to understand to what extent the items of EQ-5D-5L and GHQ-12 associate with each other. METHODS: We used data from 12 701 respondents participating in a Belgian survey in 2022. Correlation coefficients between GHQ-12 and EQ-5D-5L were calculated at both the aggregate and item levels. Multidimensional scaling, exploratory factor analysis, and regression models were performed to investigate the underlying constructs that are associated with the items. RESULTS: Despite a moderate correlation (0.39) between the EQ-5D-5L and GHQ-12 total scores, only a trivial or weak correlation (<0.3) was observed between the first 4 EQ-5D-5L items and any GHQ-12 item. Multidimensional scaling and exploratory factor analysis showed the first 4 EQ-5D-5L dimensions were clustered together with EuroQol visual analog scale and positively phrased GHQ-12 items were close to each other, whereas EQ-anxiety/depression and negatively phrased GHQ-12 items were grouped with overall life satisfaction. In the regression models, not all GHQ-12 items had a significant coefficient to predict EQ-5D-5L responses. CONCLUSIONS: To the best of our knowledge, we present the first comparison of items and underlying constructs of GHQ-12 and EQ-5D-5L. The results showed that GHQ-12 can only partially predict the responses of EQ-5D-5L and the 2 instruments measure different constructs. Researchers should carefully consider conceptual legitimacy while applying the mapping technique and consider sensitivity analyses for the mapping estimates.

COVID-19-related health utility values and changes in COVID-19 patients and the general population: a scoping review.

PURPOSE: To summarise the diverse literature reporting the impact of COVID-19 on health utility in COVID-19 patients as well as in general populations being affected by COVID-19 control policies. METHODS: A literature search up to April 2023 was conducted to identify papers reporting health utility in COVID-19 patients or in COVID-19-affected general populations. We present a narrative synthesis of the health utility values/losses of the retained studies to show the mean health utility values/losses with 95% confidence intervals. Mean utility values/losses for categories defined by medical attendance and data collection time were calculated using random-effects models. RESULTS: In total, 98 studies-68 studies on COVID-19 patients and 30 studies on general populations-were retained for detailed review. Mean (95% CI) health utility values were 0.83 (0.81, 0.86), 0.78 (0.73, 0.83), 0.82 (0.78, 0.86) and 0.71 (0.65, 0.78) for general populations, non-hospitalised, hospitalised and ICU patients, respectively, irrespective of the data collection time. Mean utility losses in patients and general populations ranged from 0.03 to 0.34 and from 0.02 to 0.18, respectively. CONCLUSIONS: This scoping review provides a summary of the health utility impact of COVID-19 and COVID-19 control policies. COVID-19-affected populations were reported to have poor health utility, while a high degree of heterogeneity was observed across studies. Population- and/or country-specific health utility is recommended for use in future economic evaluation on COVID-19-related interventions.

Diagnosing Viral Infections Through T-Cell Receptor Sequencing of Activated CD8+ T Cells.

T-cell-based diagnostic tools identify pathogen exposure but lack differentiation between recent and historical exposures in acute infectious diseases. Here, T-cell receptor (TCR) RNA sequencing was performed on HLA-DR+/CD38+CD8+ T-cell subsets of hospitalized coronavirus disease 2019 (COVID-19) patients (n = 30) and healthy controls (n = 30; 10 of whom had previously been exposed to severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]). CDR3α and CDR3ß TCR regions were clustered separately before epitope specificity annotation using a database of SARS-CoV-2-associated CDR3α and CDR3ß sequences corresponding to >1000 SARS-CoV-2 epitopes. The depth of the SARS-CoV-2-associated CDR3α/ß sequences differentiated COVID-19 patients from the healthy controls with a receiver operating characteristic area under the curve of 0.84 ± 0.10. Hence, annotating TCR sequences of activated CD8+ T cells can be used to diagnose an acute viral infection and discriminate it from historical exposure. In essence, this work presents a new paradigm for applying the T-cell repertoire to accomplish TCR-based diagnostics.

Population age and household structures shape transmission dynamics of emerging infectious diseases: a longitudinal microsimulation approach.

Host population demographics and patterns of host-to-host interactions are important drivers of heterogeneity in infectious disease transmission. To improve our understanding of how population structures and changes therein influence disease transmission dynamics at the individual and population level, we model a dynamic age- and household-structured population using longitudinal microdata drawn from Belgian census and population registers. At different points in time, we simulate the spread of a close-contact infectious disease and vary the age profiles of infectiousness and susceptibility to reflect specific infections (e.g. influenza and SARS-CoV-2) using a two-level mixing model, which distinguishes between exposure to infection in the household and exposure in the community. We find that the strong relationship between age and household structures, in combination with social mixing patterns and epidemiological parameters, shape the spread of an emerging infection. Disease transmission in the adult population in particular is to a large degree explained by differential household compositions and not just household size. Moreover, we highlight how demographic processes alter population structures in an ageing population and how these in turn affect disease transmission dynamics across population groups.

Reflections On Epidemiological Modeling To Inform Policy During The COVID-19 Pandemic In Western Europe, 2020-23.

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.

Assessing the impact of COVID-19 passes and mandates on disease transmission, vaccination intention, and uptake: a scoping review.

PURPOSE: Policymakers have struggled to maintain SARS-CoV-2 transmission at levels that are manageable to contain the COVID-19 disease burden while enabling a maximum of societal and economic activities. One of the tools that have been used to facilitate this is the so-called "COVID-19 pass". We aimed to document current evidence on the effectiveness of COVID-19 passes, distinguishing their indirect effects by improving vaccination intention and uptake from their direct effects on COVID-19 transmission measured by the incidence of cases, hospitalizations, and deaths. METHODS: We performed a scoping review on the scientific literature of the proposed topic covering the period January 2021 to September 2022, in accordance with the PRISMA-ScR guidelines for scoping reviews. RESULTS: Out of a yield of 4,693 publications, 45 studies from multiple countries were retained for full-text review. The results suggest that implementing COVID-19 passes tends to reduce the incidence of cases, hospitalizations, and deaths due to COVID-19. The use of COVID-19 passes was also shown to improve overall vaccination uptake and intention, but not in people who hold strong anti-COVID-19 vaccine beliefs. CONCLUSION: The evidence from the literature we reviewed tends to indicate positive direct and indirect effects from the use of COVID-19 passes. A major limitation to establishing this firmly is the entanglement of individual effects of multiple measures being implemented simultaneously.

Exploring the impact of population ageing on the spread of emerging respiratory infections and the associated burden of mortality.

BACKGROUND: Increasing life expectancy and persistently low fertility levels have led to old population age structures in most high-income countries, and population ageing is expected to continue or even accelerate in the coming decades. While older adults on average have few interactions that potentially could lead to disease transmission, their morbidity and mortality due to infectious diseases, respiratory infections in particular, remain substantial. We aim to explore how population ageing affects the future transmission dynamics and mortality burden of emerging respiratory infections. METHODS: Using longitudinal individual-level data from population registers, we model the Belgian population with evolving age and household structures, and explicitly consider long-term care facilities (LTCFs). Three scenarios are presented for the future proportion of older adults living in LTCFs. For each demographic scenario, we simulate outbreaks of SARS-CoV-2 and a novel influenza A virus in 2020, 2030, 2040 and 2050 and distinguish between household and community transmission. We estimate attack rates by age and household size/type, as well as disease-related deaths and the associated quality-adjusted life-years (QALYs) lost. RESULTS: As the population is ageing, small households and LTCFs become more prevalent. Additionally, families with children become smaller (i.e. low fertility, single-parent families). The overall attack rate slightly decreases as the population is ageing, but to a larger degree for influenza than for SARS-CoV-2 due to differential age-specific attack rates. Nevertheless, the number of deaths and QALY losses per 1,000 people is increasing for both infections and at a speed influenced by the share living in LTCFs. CONCLUSION: Population ageing is associated with smaller outbreaks of COVID-19 and influenza, but at the same time it is causing a substantially larger burden of mortality, even if the proportion of LTCF residents were to decrease. These relationships are influenced by age patterns in epidemiological parameters. Not only the shift in the age distribution, but also the induced changes in the household structures are important to consider when assessing the potential impact of population ageing on the transmission and burden of emerging respiratory infections.

The direct disease burden of COVID-19 in Belgium in 2020 and 2021.

BACKGROUND: Burden of disease estimates have become important population health metrics over the past decade to measure losses in health. In Belgium, the disease burden caused by COVID-19 has not yet been estimated, although COVID-19 has emerged as one of the most important diseases. Therefore, the current study aims to estimate the direct COVID-19 burden in Belgium, observed despite policy interventions, during 2020 and 2021, and compare it to the burden from other causes. METHODS: Disability-adjusted life years (DALYs) are the sum of Years Lived with Disability (YLDs) and Years of Life Lost (YLLs) due to disease. DALYs allow comparing the burden of disease between countries, diseases, and over time. We used the European Burden of Disease Network consensus disease model for COVID-19 to estimate DALYs related to COVID-19. Estimates of person-years for (a) acute non-fatal disease states were calculated from a compartmental model, using Belgian seroprevalence, social contact, hospital, and intensive care admission data, (b) deaths were sourced from the national COVID-19 mortality surveillance, and (c) chronic post-acute disease states were derived from a Belgian cohort study. RESULTS: In 2020, the total number of COVID-19 related DALYs was estimated at 253,577 [252,541 - 254,739], which is higher than in 2021, when it was 139,281 [136,704 - 142,306]. The observed COVID-19 burden was largely borne by the elderly, and over 90% of the burden was attributable to premature mortality (i.e., YLLs). In younger people, morbidity (i.e., YLD) contributed relatively more to the DALYs, especially in 2021, when vaccination was rolled out. Morbidity was mainly attributable to long-lasting post-acute symptoms. CONCLUSION: COVID-19 had a substantial impact on population health in Belgium, especially in 2020, when COVID-19 would have been the main cause of disease burden if all other causes had maintained their 2019 level.

Determinants of life-expectancy and disability-adjusted life years (DALYs) in European and Organisation for Economic Co-operation and Development (OECD) countries: A longitudinal analysis (1990-2019).

•We relate 68 factors to population health observed in 61 countries over 30 years.•Using random forests, multiple imputation and generalized estimating equations.•GDP per capita and demographics are key; income inequality is not.•Health and social expenditure are more influential than freedom and corruption.•On the macro-level, life-style effects appear to be mediated by cultural context.

The influence of COVID-19 risk perception and vaccination status on the number of social contacts across Europe: insights from the CoMix study.

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.

The age profile of respiratory syncytial virus burden in preschool children of low- and middle-income countries: A semi-parametric, meta-regression approach.

BACKGROUND: Respiratory syncytial virus (RSV) infections are among the primary causes of death for children under 5 years of age worldwide. A notable challenge with many of the upcoming prophylactic interventions against RSV is their short duration of protection, making the age profile of key interest to the design of prevention strategies. METHODS AND FINDINGS: We leverage the RSV data collected on cases, hospitalizations, and deaths in a systematic review in combination with flexible generalized additive mixed models (GAMMs) to characterize the age burden of RSV incidence, hospitalization, and hospital-based case fatality rate (hCFR). Due to the flexible nature of GAMMs, we estimate the peak, median, and mean incidence of infection to inform discussions on the ideal "window of protection" of prophylactic interventions. In a secondary analysis, we reestimate the burden of RSV in all low- and middle-income countries. The peak age of community-based incidence is 4.8 months, and the mean and median age of infection is 18.9 and 14.7 months, respectively. Estimating the age profile using the incidence coming from hospital-based studies yields a slightly younger age profile, in which the peak age of infection is 2.6 months and the mean and median age of infection are 15.8 and 11.6 months, respectively. More severe outcomes, such as hospitalization and in-hospital death have a younger age profile. Children under 6 months of age constitute 10% of the population under 5 years of age but bear 20% to 29% of cases, 28% to 39% of hospitalizations, and 38% to 50% of deaths. On an average year, we estimate 28.23 to 31.34 million cases of RSV, between 2.95 to 3.35 million hospitalizations, and 16,835 to 19,909 in-hospital deaths in low, lower- and upper middle-income countries. In addition, we estimate 17,254 to 23,875 deaths in the community, for a total of 34,114 to 46,485 deaths. Globally, evidence shows that community-based incidence may differ by World Bank Income Group, but not hospital-based incidence, probability of hospitalization, or the probability of in-hospital death (p ≤ 0.01, p = 1, p = 0.86, 0.63, respectively). Our study is limited mainly due to the sparsity of the data, especially for low-income countries (LICs). The lack of information for some populations makes detecting heterogeneity between income groups difficult, and differences in access to care may impact the reported burden. CONCLUSIONS: We have demonstrated an approach to synthesize information on RSV outcomes in a statistically principled manner, and we estimate that the age profile of RSV burden depends on whether information on incidence is collected in hospitals or in the community. Our results suggest that the ideal prophylactic strategy may require multiple products to avert the risk among preschool children.

Multi-View Learning to Unravel the Different Levels Underlying Hepatitis B Vaccine Response.

The immune system acts as an intricate apparatus that is dedicated to mounting a defense and ensures host survival from microbial threats. To engage this faceted immune response and provide protection against infectious diseases, vaccinations are a critical tool to be developed. However, vaccine responses are governed by levels that, when interrogated, separately only explain a fraction of the immune reaction. To address this knowledge gap, we conducted a feasibility study to determine if multi-view modeling could aid in gaining actionable insights on response markers shared across populations, capture the immune system's diversity, and disentangle confounders. We thus sought to assess this multi-view modeling capacity on the responsiveness to the Hepatitis B virus (HBV) vaccination. Seroconversion to vaccine-induced antibodies against the HBV surface antigen (anti-HBs) in early converters (n = 21; <2 months) and late converters (n = 9; <6 months) and was defined based on the anti-HBs titers (>10IU/L). The multi-view data encompassed bulk RNA-seq, CD4+ T-cell parameters (including T-cell receptor data), flow cytometry data, and clinical metadata (including age and gender). The modeling included testing single-view and multi-view joint dimensionality reductions. Multi-view joint dimensionality reduction outperformed single-view methods in terms of the area under the curve and balanced accuracy, confirming the increase in predictive power to be gained. The interpretation of these findings showed that age, gender, inflammation-related gene sets, and pre-existing vaccine-specific T-cells could be associated with vaccination responsiveness. This multi-view dimensionality reduction approach complements clinical seroconversion and all single modalities. Importantly, this modeling could identify what features could predict HBV vaccine response. This methodology could be extended to other vaccination trials to identify the key features regulating responsiveness.

Longitudinal social contact data analysis: insights from 2 years of data collection in Belgium during the COVID-19 pandemic.

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.

The estimated disease burden of COVID-19 in Japan from 2020 to 2021.

BACKGROUND: To date, it is not fully understood to what extent COVID-19 has burdened society in Japan. This study aimed to estimate the total disease burden due to COVID-19 in Japan during 2020-2021. METHODS: We stratify disease burden estimates by age group and present it as absolute Quality Adjusted Life Years (QALYs) lost and QALYs lost per 100,000 persons. The total estimated value of QALYs lost consists of (1) QALYs lost brought by deaths due to COVID-19, (2) QALYs lost brought by inpatient cases, (3) QALYs lost brought by outpatient cases, and (4) QALYs lost brought by long-COVID. RESULTS: The total QALYs lost due to COVID-19 was estimated as 286,782 for two years, 114.0 QALYs per 100,000 population per year. 71.3% of them were explained by the burden derived from deaths. Probabilistic sensitivity analysis showed that the burden of outpatient cases was the most sensitive factor. CONCLUSIONS: The large part of disease burden due to COVID-19 in Japan from the beginning of 2020 to the end of 2021 was derived from Wave 3, 4, and 5 and the proportion of QALYs lost due to morbidity in the total burden increased gradually. The estimated disease burden was smaller than that in other high-income countries. It will be our future challenge to take other indirect factors into consideration.

Impact of tiered measures on social contact and mixing patterns of in Italy during the second wave of COVID-19.

BACKGROUND: Most countries around the world enforced non-pharmaceutical interventions against COVID-19. Italy was one of the first countries to be affected by the pandemic, imposing a hard lockdown, in the first epidemic wave. During the second wave, the country implemented progressively restrictive tiers at the regional level according to weekly epidemiological risk assessments. This paper quantifies the impact of these restrictions on contacts and on the reproduction number. METHODS: Representative (with respect to age, sex, and region of residence) longitudinal surveys of the Italian population were undertaken during the second epidemic wave. Epidemiologically relevant contact patterns were measured and compared with pre-pandemic levels and according to the level of interventions experienced by the participants. Contact matrices were used to quantify the reduction in the number of contacts by age group and contact setting. The reproduction number was estimated to evaluate the impact of restrictions on the spread of COVID-19. RESULTS: The comparison with the pre-pandemic baseline shows a significant decrease in the number of contacts, independently from the age group or contact settings. This decrease in the number of contacts significantly depends on the strictness of the non-pharmaceutical interventions. For all levels of strictness considered, the reduction in social mixing results in a reproduction number smaller than one. In particular, the impact of the restriction on the number of contacts decreases with the severity of the interventions. CONCLUSIONS: The progressive restriction tiers implemented in Italy reduced the reproduction number, with stricter interventions associated with higher reductions. Readily collected contact data can inform the implementation of mitigation measures at the national level in epidemic emergencies to come.

Haemophilus influenzae carriage and antibiotic resistance profile in Belgian infants over a three-year period (2016-2018).

Background: Non-typeable Haemophilus influenzae has become increasingly important as a causative agent of invasive diseases following vaccination against H. influenzae type b. The emergence of antibiotic resistance underscores the necessity to investigate typeable non-b carriage and non-typeable H. influenzae (NTHi) in children. Methods: Nasopharyngeal swab samples were taken over a three-year period (2016-2018) from 336 children (6-30 months of age) attending daycare centers (DCCs) in Belgium, and from 218 children with acute otitis media (AOM). Biotype, serotype, and antibiotic resistance of H. influenzae strains were determined phenotypically. Mutations in the ftsI gene were explored in 129 strains that were resistant or had reduced susceptibility to beta-lactam antibiotics. Results were compared with data obtained during overlapping time periods from 94 children experiencing invasive disease. Results: Overall, NTHi was most frequently present in both carriage (DCC, AOM) and invasive group. This was followed by serotype "f" (2.2%) and "e" (1.4%) in carriage, and "b" (16.0%), "f" (11.7%), and "a" (4.3%) in invasive strains. Biotype II was most prevalent in all studied groups, followed by biotype III in carriage and I in invasive strains. Strains from both groups showed highest resistance to ampicillin (26.7% in carriage vs. 18.1% in invasive group). A higher frequency of ftsI mutations were found in the AOM group than the DCC group (21.6 vs. 14.9% - p = 0.056). Even more so, the proportion of biotype III strains that carried a ftsI mutation was higher in AOM compared to DCC (50.0 vs. 26.3% - p < 0.01) and invasive group. Conclusion: In both groups, NTHi was most frequently circulating, while specific encapsulated serotypes for carriage and invasive group were found. Biotypes I, II and III were more frequently present in the carriage and invasive group. The carriage group had a higher resistance-frequency to the analyzed antibiotics than the invasive group. Interestingly, a higher degree of ftsI mutations was found in children with AOM compared to DCC and invasive group. This data helps understanding the H. influenzae carriage in Belgian children, as such information is scarce.