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OBJECTIVES: A decrease in community antibiotic consumption in Europe has been observed during the COVID-19 pandemic. The magnitude of this decrease, how fast after the outbreak it occurred, whether it was sustained during the pandemic and whether the seasonal variation in antibiotic consumption was affected, have not yet been evaluated in detail. METHODS: Data on community antibiotic consumption were available from the European Surveillance of Antimicrobial Consumption Network for 28 EU/European Economic Area (EEA) countries between 2010 and 2021. Antibiotic consumption was expressed as DDDs per 1000 inhabitants per day (DID). The impact of the pandemic on antibiotic consumption was investigated using descriptive statistics and non-linear mixed changepoint models for quarterly and yearly data. RESULTS: The decrease in overall antibiotic consumption between 2019 and 2020 (-3.4 DID; -18.6%) was mainly due to a decrease in the consumption of penicillins [Anatomical Therapeutic Chemical (ATC) code J01C] (-1.9 DID; -23.0%), other ß-lactam antibacterials (J01D) (-0.6 DID; -25.8%) and macrolides, lincosamides and streptogramins (J01F) (-0.5 DID; -17.4%) and was sustained during 2021. The changepoint analysis of yearly data (28 countries) estimated a decrease of 3.3 DID in overall antibiotic consumption (J01) between 2019 and 2020. The analysis of quarterly data (16 countries) estimated a decrease in overall antibiotic consumption (J01) of 4.0 DID and a decrease in seasonal variation of 1.2 DID between the first and second quarters of 2020. CONCLUSIONS: The changepoint analysis indicated a significant, sudden and steep decrease in community antibiotic consumption in the EU/EEA immediately after the start of the COVID-19 outbreak in Europe, as well as a decrease in its seasonal variation.
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Antibacterianos , COVID-19 , Humanos , Antibacterianos/uso terapêutico , Pandemias , Uso de Medicamentos , COVID-19/epidemiologia , Estreptograminas , Europa (Continente)/epidemiologiaRESUMO
BackgroundThe Belgian COVID-19 vaccination campaign aimed to reduce disease spread and severity.AimWe estimated SARS-CoV-2 variant-specific vaccine effectiveness against symptomatic infection (VEi) and hospitalisation (VEh), given time since vaccination and prior infection.MethodsNationwide healthcare records from July 2021 to May 2022 on testing and vaccination were combined with a clinical hospital survey. We used a test-negative design and proportional hazard regression to estimate VEi and VEh, controlling for prior infection, time since vaccination, age, sex, residence and calendar week of sampling.ResultsWe included 1,932,546 symptomatic individuals, of whom 734,115 tested positive. VEi against Delta waned from an initial estimate of 80% (95%â¯confidence interval (CI):â¯80-81) to 55% (95%â¯CI:â¯54-55) 100-150 days after the primary vaccination course. Booster vaccination increased initial VEi to 85% (95%â¯CI:â¯84-85). Against Omicron, an initial VEi of 33% (95%â¯CI:â¯30-36) waned to 17% (95%â¯CI:â¯15-18), while booster vaccination increased VEi to 50% (95%â¯CI:â¯49-50), which waned to 20% (95%â¯CI:â¯19-21) 100-150 days after vaccination. Initial VEh for booster vaccination decreased from 96% (95%â¯CI:â¯95-96) against Delta to 87% (95%â¯CI:â¯86-89) against Omicron. VEh against Omicron waned to 73% (95%â¯CI:â¯71-75) 100-150 days after booster vaccination. While recent prior infections conferred higher protection, infections occurring before 2021 remained associated with significant risk reduction against symptomatic infection. Vaccination and prior infection outperformed vaccination or prior infection only.ConclusionWe report waning and a significant decrease in VEi and VEh from Delta to Omicron-dominant periods. Booster vaccination and prior infection attenuated these effects.
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Vacinas contra COVID-19 , COVID-19 , Humanos , SARS-CoV-2 , Bélgica/epidemiologia , COVID-19/epidemiologia , COVID-19/prevenção & controle , Eficácia de Vacinas , HospitalizaçãoRESUMO
BACKGROUND: Differences in the genetic material of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants may result in altered virulence characteristics. Assessing the disease severity caused by newly emerging variants is essential to estimate their impact on public health. However, causally inferring the intrinsic severity of infection with variants using observational data is a challenging process on which guidance is still limited. We describe potential limitations and biases that researchers are confronted with and evaluate different methodological approaches to study the severity of infection with SARS-CoV-2 variants. METHODS: We reviewed the literature to identify limitations and potential biases in methods used to study the severity of infection with a particular variant. The impact of different methodological choices is illustrated by using real-world data of Belgian hospitalized COVID-19 patients. RESULTS: We observed different ways of defining coronavirus disease 2019 (COVID-19) disease severity (e.g., admission to the hospital or intensive care unit versus the occurrence of severe complications or death) and exposure to a variant (e.g., linkage of the sequencing or genotyping result with the patient data through a unique identifier versus categorization of patients based on time periods). Different potential selection biases (e.g., overcontrol bias, endogenous selection bias, sample truncation bias) and factors fluctuating over time (e.g., medical expertise and therapeutic strategies, vaccination coverage and natural immunity, pressure on the healthcare system, affected population groups) according to the successive waves of COVID-19, dominated by different variants, were identified. Using data of Belgian hospitalized COVID-19 patients, we were able to document (i) the robustness of the analyses when using different variant exposure ascertainment methods, (ii) indications of the presence of selection bias and (iii) how important confounding variables are fluctuating over time. CONCLUSIONS: When estimating the unbiased marginal effect of SARS-CoV-2 variants on the severity of infection, different strategies can be used and different assumptions can be made, potentially leading to different conclusions. We propose four best practices to identify and reduce potential bias introduced by the study design, the data analysis approach, and the features of the underlying surveillance strategies and data infrastructure.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/epidemiologia , Bélgica/epidemiologia , Unidades de Terapia IntensivaRESUMO
Leaves of Vitellaria paradoxa, also called "Shea butter tree", are used in traditional medicine to treat various symptoms including malaria fever, dysentery, or skin infections. Composition of the dichloromethane extract of V. paradoxa leaves possessing antiparasitic activities was investigated. Five pentacyclic triterpenic acids together with 6 ester derivatives were isolated and identified by standards comparison, MS and 1H-NMR analysis. Corosolic, maslinic, and tormentic coumaroyl esters and their corresponding triterpenic acids were isolated from this plant for the first time. The antiparasitic activities of the 11 isolated compounds were evaluated in vitro on Plasmodium falciparum, Trypanosoma brucei brucei, and Leishmania mexicana mexicana and their selectivity determined by cytotoxicity evaluation on WI38 cells. None of the isolated compounds showed good antiplasmodial activity. The antitrypanosomal activity of individual compounds was in general higher than their antileishmanial one. One isolated triterpenic ester mixture in equilibrium, 3-O-p-E/Z-coumaroyltormentic acids, showed an attractive promising antitrypanosomal activity (IC50 = 0.7 µM) with low cytotoxicity (IC50= 44.5 µM) compared to the corresponding acid. Acute toxicity test on this ester did not show any toxicity at the maximal cumulative dose of 100 mg/kg intraperitoneally on mice. In vivo efficacy evaluation of this compound, at 50 mg/kg by intraperitoneal route on a T.âb. brucei-infected mice model, showed a significant parasitemia reduction on day 4 post-infection together with 33.3% survival improvement. Further bioavailability and PK studies are needed along with mode of action investigations to further assess the potential of this molecule.
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Antiprotozoários , Ésteres , Animais , Antiprotozoários/farmacologia , Camundongos , Extratos Vegetais/farmacologia , Folhas de Planta , Plasmodium falciparumRESUMO
Combining antibiotics with resistance reversing agents is a key strategy to overcome bacterial resistance. Upon screening antimicrobial activities of plants used in traditional medicine, we found that a leaf dichloromethane extract from the shea butter tree (Vitellaria paradoxa) had antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA) with further evidence of synergy when combined with ß-lactams. Using HPLC-MS, we identified ursolic (UA) and oleanolic acids (OA) in leaves and twigs of this species, and quantified them by HPLC-UV as the major constituents in leaf extracts (21% and 6% respectively). Both pure triterpenic acids showed antimicrobial activity against reference and clinical strains of MRSA, with MICs ranging from 8-16 mg/L for UA to 32-128 mg/L for OA. They were highly synergistic with ß-lactams (ampicillin and oxacillin) at subMIC concentrations. Reversion of MRSA phenotype was attributed to their capacity to delocalize PBP2 from the septal division site, as observed by fluorescence microscopy, and to disturb thereby peptidoglycan synthesis. Moreover, both compounds also inhibited ß-lactamases activity of living bacteria (as assessed by inhibition of nitrocefin hydrolysis), but not in bacterial lysates, suggesting an indirect mechanism for this inhibition. In a murine model of subcutaneous MRSA infection, local administration of UA was synergistic with nafcillin to reduce lesion size and inflammatory cytokine (IL-1ß) production. Thus, these data highlight the potential interest of triterpenic acids as resistance reversing agents in combination with ß-lactams against MRSA.
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Antibacterianos/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Antibacterianos/isolamento & purificação , Antibacterianos/uso terapêutico , Proteínas de Bactérias/metabolismo , Farmacorresistência Bacteriana , Sinergismo Farmacológico , Ericales/química , Feminino , Hidrólise , Staphylococcus aureus Resistente à Meticilina/enzimologia , Camundongos Endogâmicos C57BL , Testes de Sensibilidade Microbiana , Ácido Oleanólico , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/uso terapêutico , Folhas de Planta/química , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Triterpenos , beta-Lactamases/metabolismo , beta-Lactamas/farmacologia , Ácido UrsólicoRESUMO
Vaccination has played a major role in overcoming the COVID-19 pandemic. However, vaccination status can be influenced by demographic and socio-economic factors at individual and area level. In the context of the LINK-VACC project, the Belgian vaccine register for the COVID-19 vaccination campaign was linked at individual level with other registers, notably the COVID-19 laboratory test results and demographic and socio-economic variables from the DEMOBEL database. The present article aims at investigating to which extent COVID-19 vaccination status is associated with area level and/or individual level demographic and socio-economic factors. From a sample of all individuals tested for SARS-CoV-2 (LINK-VACC sample) demographic and socio-economic indicators are derived and their impact on vaccination coverages at an aggregated geographical level (municipality) is quantified. The same indicators are calculated for the full Belgian population, allowing to assess the representativeness of the LINK-VACC sample with respect to the impact of demographic and socio-economic disparities on vaccination uptake. In a second step, hierarchical models are fitted to the individual level LINK-VACC data to disentangle the individual and municipality effects allowing to evaluate the added value of the availability of individual level data in this context. The most important effects observed at the individual level are reflected in the aggregated data at the municipality level. Multilevel analyses show that most of the demographic and socio-economic impacts on vaccination are captured at the individual level, although accounting for area level in individual level analyses improve the overall description.
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Methicillin-resistant Staphylococcus epidermidis (MRSE) endocarditis failing conventional therapy has been successfully treated with nafcillin plus daptomycin in the clinic. In vitro studies showed that nafcillin enhanced daptomycin killing of MRSE in both planktonic cells and biofilm. Nafcillin exposure also sensitized MRSE to killing by human neutrophils and cathelicidin antimicrobial peptide LL-37. Fluorescent microscopy showed increased daptomycin and LL-37 binding to the MRSE bacterial surface upon nafcillin treatment. Ceftaroline also increased MRSE killing by daptomycin in planktonic cultures and biofilms, as well as daptomycin and LL-37 binding on the bacterial surface. Nafcillin, ceftaroline, and possibly other ß-lactams, may serve an important role in the therapy of MRSE endocarditis through augmentation of cationic peptide, the innate immune system, and daptomycin killing. Clinical studies will be needed to determine how early these regimens should be deployed to optimize clinical outcome.
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Daptomicina , Endocardite , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Humanos , Daptomicina/farmacologia , Daptomicina/uso terapêutico , Nafcilina/uso terapêutico , Catelicidinas , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Staphylococcus epidermidis , Resistência a Meticilina , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Endocardite/tratamento farmacológico , Testes de Sensibilidade Microbiana , CeftarolinaRESUMO
OBJECTIVE: This study aimed to investigate factors influencing the uptake of first and second COVID-19 booster vaccines among adults in Belgium, particularly age, sex, region of residence and laboratory confirmed COVID-19 infection history. RESULTS: A binomial regression model was used with having received the first or second booster as outcome and age, sex, region of residence and infection history as fixed variables. Among adults, there was generally a higher uptake to receive the first booster among older age groups compared to younger ones. Females, individuals residing in Flanders and those with no previous COVID-19 infection were more likely to receive the first booster. For the second booster, the same age trend was seen as for the first booster. Males, individuals residing in Flanders and those who tested positive for COVID-19 once after first booster were more likely to receive the second booster. Individuals with multiple positive COVID-19 tests before and after primary course or first booster were less likely to receive the subsequent booster dose compared to COVID-naïve individuals. This information could be used to guide future vaccination campaigns during a pandemic and can provide valuable insights into booster uptake patterns.
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Vacinas contra COVID-19 , COVID-19 , Feminino , Masculino , Adulto , Humanos , Idoso , COVID-19/epidemiologia , COVID-19/prevenção & controle , Bélgica/epidemiologia , Transporte Biológico , Programas de Imunização , VacinaçãoRESUMO
COVID-19 severely affected nursing home residents from March 2020 onwards in Belgium. This study aimed to model the impact of vaccination and facility characteristics on cluster occurrence, duration and severity in this setting. Possible clusters were identified between June 2020 and January 2022, based on the Belgian COVID-19 surveillance in nursing homes. Median attack rates (AR) among residents and staff, case hospitalization rates (CHR) and case fatality rates (CFR) were calculated. A negative binomial model was used to identify the association between nursing home characteristics and the number of cases, hospital admissions and deaths and the duration of the cluster. A total of 2239 clusters were detected in more than 80% of nursing homes. Most of these (62%) occurred before the start of COVID-19 vaccination (end of December 2020). After vaccination, the number of clusters, the AR among residents and staff, the CHR and the CFR dropped. Previous cluster(s) and vaccination decreased the number of cases, hospital admissions and deaths among residents. Previous cluster experience and having started vaccination were protective factors. We recommend continued implementation of targeted interventions such as vaccination, large-scale screening and immediate implementation of additional infection prevention and control measures.
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COVID-19 , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Bélgica/epidemiologia , Vacinas contra COVID-19 , Casas de Saúde , VacinaçãoRESUMO
OBJECTIVES: Vaccine effectiveness against transmission (VET) of SARS-CoV-2-infection can be estimated from secondary attack rates observed during contact tracing. We estimated VET, the vaccine-effect on infectiousness of the index case and susceptibility of the high-risk exposure contact (HREC). METHODS: We fitted RT-PCR-test results from HREC to immunity status (vaccine schedule, prior infection, time since last immunity-conferring event), age, sex, calendar week of sampling, household, background positivity rate and dominant VOC using a multilevel Bayesian regression-model. We included Belgian data collected between January 2021 and January 2022. RESULTS: For primary BNT162b2-vaccination we estimated initial VET at 96% (95%CI 95-97) against Alpha, 87% (95%CI 84-88) against Delta and 31% (95%CI 25-37) against Omicron. Initial VET of booster-vaccination (mRNA primary and booster-vaccination) was 87% (95%CI 86-89) against Delta and 68% (95%CI 65-70) against Omicron. The VET-estimate against Delta and Omicron decreased to 71% (95%CI 64-78) and 55% (95%CI 46-62) respectively, 150-200 days after booster-vaccination. Hybrid immunity, defined as vaccination and documented prior infection, was associated with durable and higher or comparable (by number of antigen exposures) protection against transmission. CONCLUSIONS: While we observed VOC-specific immune-escape, especially by Omicron, and waning over time since immunization, vaccination remained associated with a reduced risk of SARS-CoV-2-transmission.
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COVID-19 , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , SARS-CoV-2 , Vacina BNT162 , Teorema de Bayes , Bélgica/epidemiologia , Busca de Comunicante , Eficácia de Vacinas , Imunização SecundáriaRESUMO
We investigated effectiveness of (1) mRNA booster vaccination versus primary vaccination only and (2) heterologous (viral vector-mRNA) versus homologous (mRNA-mRNA) prime-boost vaccination against severe outcomes of BA.1, BA.2, BA.4 or BA.5 Omicron infection (confirmed by whole genome sequencing) among hospitalized COVID-19 patients using observational data from national COVID-19 registries. In addition, it was investigated whether the difference between the heterologous and homologous prime-boost vaccination was homogenous across Omicron sub-lineages. Regression standardization (parametric g-formula) was used to estimate counterfactual risks for severe COVID-19 (combination of severity indicators), intensive care unit (ICU) admission, and in-hospital mortality under exposure to different vaccination schedules. The estimated risk for severe COVID-19 and in-hospital mortality was significantly lower with an mRNA booster vaccination as compared to only a primary vaccination schedule (RR = 0.59 [0.33; 0.85] and RR = 0.47 [0.15; 0.79], respectively). No significance difference was observed in the estimated risk for severe COVID-19, ICU admission and in-hospital mortality with a heterologous compared to a homologous prime-boost vaccination schedule, and this difference was not significantly modified by the Omicron sub-lineage. Our results support evidence that mRNA booster vaccination reduced the risk of severe COVID-19 disease during the Omicron-predominant period.
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BACKGROUND: Recent studies have identified important social inequalities in SARS-CoV-2 infections and related COVID-19 outcomes in the Belgian population. The aim of our study was to investigate the sociodemographic and socioeconomic characteristics associated with the uptake of COVID-19 vaccine in Belgium. METHODS: We conducted a cross-sectional analysis of the uptake of a first COVID-19 vaccine dose among 5 342 110 adults (≥18 years) in Belgium on 31 August 2021. We integrated data from four national data sources: the Belgian vaccine register (vaccination status), COVID-19 Healthdata (laboratory test results), DEMOBEL (sociodemographic/socioeconomic data) and the Common Base Register for HealthCare Actors (individuals licensed to practice a healthcare profession in Belgium). We used multivariable logistic regression analysis for identifying characteristics associated with not having obtained a first COVID-19 vaccine dose in Belgium and for each of its three regions (Flanders, Brussels and Wallonia). RESULTS: During the study period, 10% (536 716/5 342 110) of the Belgian adult population included in our study sample was not vaccinated with a first COVID-19 vaccine dose. A lower COVID-19 vaccine uptake was found among young individuals, men, migrants, single parents, one-person households and disadvantaged socioeconomic groups (with lower levels of income and education, unemployed). Overall, the sociodemographic and socioeconomic disparities were comparable for all regions. CONCLUSIONS: The identification of sociodemographic and socioeconomic disparities in COVID-19 vaccination uptake is critical to develop strategies guaranteeing a more equitable vaccination coverage of the Belgian adult population.
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INTRODUCTION: The pathogenesis of COVID-19 depends on the interplay between host characteristics, viral characteristics and contextual factors. Here, we compare COVID-19 disease severity between hospitalized patients in Belgium infected with the SARS-CoV-2 variant B.1.1.7 and those infected with previously circulating strains. METHODS: The study is conducted within a causal framework to study the severity of SARS-CoV-2 variants by merging surveillance registries in Belgium. Infection with SARS-CoV-2 B.1.1.7 ('exposed') was compared to infection with previously circulating strains ('unexposed') in terms of the manifestation of severe COVID-19, intensive care unit (ICU) admission, or in-hospital mortality. The exposed and unexposed group were matched based on the hospital and the mean ICU occupancy rate during the patient's hospital stay. Other variables identified as confounders in a Directed Acyclic Graph (DAG) were adjusted for using regression analysis. Sensitivity analyses were performed to assess the influence of selection bias, vaccination rollout, and unmeasured confounding. RESULTS: We observed no difference between the exposed and unexposed group in severe COVID-19 disease or in-hospital mortality (RR = 1.15, 95% CI [0.93-1.38] and RR = 0.92, 95% CI [0.62-1.23], respectively). The estimated standardized risk to be admitted in ICU was significantly higher (RR = 1.36, 95% CI [1.03-1.68]) when infected with the B.1.1.7 variant. An age-stratified analysis showed that among the younger age group (≤65 years), the SARS-CoV-2 variant B.1.1.7 was significantly associated with both severe COVID-19 progression and ICU admission. CONCLUSION: This matched observational cohort study did not find an overall increased risk of severe COVID-19 or death associated with B.1.1.7 infection among patients already hospitalized. There was a significant increased risk to be transferred to ICU when infected with the B.1.1.7 variant, especially among the younger age group. However, potential selection biases advocate for more systematic sequencing of samples from hospitalized COVID-19 patients.
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COVID-19 , SARS-CoV-2 , Idoso , Bélgica/epidemiologia , COVID-19/epidemiologia , Hospitalização , HumanosRESUMO
We aimed to investigate vaccine effectiveness against progression to severe COVID-19 (acute respiratory distress syndrome (ARDS), intensive care unit (ICU) admission and/or death) and in-hospital death in a cohort of hospitalized COVID-19 patients. Mixed effects logistic regression analyses were performed to estimate the association between receiving a primary COVID-19 vaccination schedule and severe outcomes after adjusting for patient, hospital, and vaccination characteristics. Additionally, the effects of the vaccine brands including mRNA vaccines mRNA-1273 and BNT162b2, and adenovirus-vector vaccines ChAdOx1 (AZ) and Ad26.COV2.S (J&J) were compared to each other. This retrospective, multicenter cohort study included 2493 COVID-19 patients hospitalized across 73 acute care hospitals in Belgium during the time period 15 August 2021-14 November 2021 when the Delta variant (B1.617.2) was predominant. Hospitalized COVID-19 patients that received a primary vaccination schedule had lower odds of progressing to severe disease (OR (95% CI); 0.48 (0.38; 0.60)) and in-hospital death (OR (95% CI); 0.49 (0.36; 0.65)) than unvaccinated patients. Among the vaccinated patients older than 75 years, mRNA vaccines and AZ seemed to confer similar protection, while one dose of J&J showed lower protection in this age category. In conclusion, a primary vaccination schedule protects against worsening of COVID-19 to severe outcomes among hospitalized patients.
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The objective of this study was to investigate the incidence and risk factors associated with COVID-19 vaccine breakthrough infections. We included all persons ≥18 years that had been fully vaccinated against COVID-19 for ≥14 days, between 1 February 2021 and 5 December 2021, in Belgium. The incidence of breakthrough infections (laboratory confirmed SARS-CoV-2-infections) was determined. Factors associated with breakthrough infections were analyzed using COX proportional hazard models. Among 8,062,600 fully vaccinated adults, we identified 373,070 breakthrough infections with an incidence of 11.2 (95%CI 11.2-11.3)/100 person years. Vaccination with Ad26.COV2.S (HR1.54, 95%CI 1.52-1.56) or ChAdOx1 (HR1.68, 95%CI 1.66-1.69) was associated with a higher risk of a breakthrough infection compared to BNT162b2, while mRNA-1273 was associated with a lower risk (HR0.68, 95%CI 0.67-0.69). A prior COVID-19-infection was protective against a breakthrough infection (HR0.23, 95%CI 0.23-0.24), as was an mRNA booster (HR0.44, 95%CI 0.43-0.45). During a breakthrough infection, those who had a prior COVID-19 infection were less likely to have COVID-19 symptoms of almost all types than naïve persons. We identified risk factors associated with breakthrough infections, such as vaccination with adenoviral-vector vaccines, which could help inform future decisions on booster vaccination strategies. A prior COVID-19 infection lowered the risk of breakthrough infections and of having symptoms, highlighting the protective effect of hybrid immunity.
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Vacinas contra COVID-19 , COVID-19 , Ad26COVS1 , Adulto , Vacina BNT162 , Bélgica/epidemiologia , COVID-19/epidemiologia , COVID-19/prevenção & controle , Humanos , Incidência , Estudos Prospectivos , Fatores de Risco , SARS-CoV-2/genéticaRESUMO
BACKGROUND: During the first half of 2021, we observed high vaccine effectiveness (VE) against SARS-CoV2-infection. The replacement of the alpha-'variant of concern' (VOC) by the delta-VOC and uncertainty about the time course of immunity called for a re-assessment. METHODS: We estimated VE against transmission of infection (VET) from Belgian contact tracing data for high-risk exposure contacts between 26/01/2021 and 14/12/2021 by susceptibility (VEs) and infectiousness of breakthrough cases (VEi) for a complete schedule of Ad26.COV2.S, ChAdOx1, BNT162b2, mRNA-1273 as well as infection-acquired and hybrid immunity. We used a multilevel Bayesian model and adjusted for personal characteristics (age, sex, household), background exposure, calendar week, VOC and time since immunity conferring-event. FINDINGS: VET-estimates were higher for mRNA-vaccines, over 90%, compared to viral vector vaccines: 66% and 80% for Ad26COV2.S and ChAdOx1 respectively (Alpha, 0-50 days after vaccination). Delta was associated with a 40% increase in odds of transmission and a decrease of VEs (72-64%) and especially of VEi (71-46% for BNT162b2). Infection-acquired and hybrid immunity were less affected by Delta. Waning further reduced VET-estimates: from 81% to 63% for BNT162b2 (Delta, 150-200 days after vaccination). We observed lower initial VEi in the age group 65-84 years (32% vs 46% in the age group 45-64 years for BNT162b2) and faster waning. Hybrid immunity waned slower than vaccine-induced immunity. INTERPRETATION: VEi and VEs-estimates, while remaining significant, were reduced by Delta and waned over time. We observed faster waning in the oldest age group. We should seek to improve vaccine-induced protection in older persons and those vaccinated with viral-vector vaccines.
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COVID-19 , Vacinas , Ad26COVS1 , Idoso , Idoso de 80 Anos ou mais , Vacina BNT162 , Teorema de Bayes , Bélgica/epidemiologia , COVID-19/prevenção & controle , Busca de Comunicante , Humanos , Pessoa de Meia-Idade , RNA Viral , SARS-CoV-2 , Vacinação , Eficácia de VacinasRESUMO
This retrospective multi-center matched cohort study assessed the risk for severe COVID-19 (combination of severity indicators), intensive care unit (ICU) admission, and in-hospital mortality in hospitalized patients when infected with the Omicron variant compared to when infected with the Delta variant. The study is based on a causal framework using individually-linked data from national COVID-19 registries. The study population consisted of 954 COVID-19 patients (of which, 445 were infected with Omicron) above 18 years old admitted to a Belgian hospital during the autumn and winter season 2021-2022, and with available viral genomic data. Patients were matched based on the hospital, whereas other possible confounders (demographics, comorbidities, vaccination status, socio-economic status, and ICU occupancy) were adjusted for by using a multivariable logistic regression analysis. The estimated standardized risk for severe COVID-19 and ICU admission in hospitalized patients was significantly lower (RR = 0.63; 95% CI (0.30; 0.97) and RR = 0.56; 95% CI (0.14; 0.99), respectively) when infected with the Omicron variant, whereas in-hospital mortality was not significantly different according to the SARS-CoV-2 variant (RR = 0.78, 95% CI (0.28-1.29)). This study demonstrates the added value of integrated genomic and clinical surveillance to recognize the multifactorial nature of COVID-19 pathogenesis.
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COVID-19 , SARS-CoV-2 , Adolescente , Bélgica/epidemiologia , COVID-19/epidemiologia , Estudos de Coortes , Humanos , Estudos Retrospectivos , SARS-CoV-2/genética , Estações do AnoRESUMO
The national vaccination campaign against SARS-CoV-2 started in January 2021 in Belgium. In the present study, we aimed to use national hospitalisation surveillance data to investigate the recent evolution of vaccine impact on the risk of COVID-19 hospitalisation. We analysed aggregated data from 27,608 COVID-19 patients hospitalised between October 2021 and February 2022, stratified by age category and vaccination status. For each period, vaccination status, and age group, we estimated risk ratios (RR) corresponding to the ratio between the probability of being hospitalised following SARS-CoV-2 infection if belonging to the vaccinated population and the same probability if belonging to the unvaccinated population. In October 2021, a relatively high RR was estimated for vaccinated people > 75 years old, possibly reflecting waning immunity within this group, which was vaccinated early in 2021 and invited to receive the booster vaccination at that time. In January 2022, a RR increase was observed in all age categories coinciding with the dominance of the Omicron variant. Despite the absence of control for factors like comorbidities, previous infections, or time since the last administered vaccine, we showed that such real-time aggregated data make it possible to approximate trends in vaccine impact over time.
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Vacinas contra COVID-19 , COVID-19 , Idoso , Bélgica/epidemiologia , COVID-19/epidemiologia , COVID-19/prevenção & controle , Hospitalização , Humanos , SARS-CoV-2 , VacinaçãoRESUMO
Staphylococcus aureus is an opportunistic pathogen and the major causative agent of life-threatening hospital- and community-acquired infections. A combination of antibiotics could be an opportunity to address the widespread emergence of antibiotic-resistant strains, including Methicillin-Resistant S. aureus (MRSA). We here investigated the potential synergy between ampicillin and plant-derived antibiotics (pentacyclic triterpenes, ursolic acid (UA) and oleanolic acid (OA)) towards MRSA (ATCC33591 and COL) and the mechanisms involved. We calculated the Fractional Inhibitory Concentration Index (FICI) and demonstrated synergy. We monitored fluorescence of Bodipy-TR-Cadaverin, propidium iodide and membrane potential-sensitive probe for determining the ability of UA and OA to bind to lipoteichoic acids (LTA), and to induce membrane permeabilization and depolarization, respectively. Both pentacyclic triterpenes were able to bind to LTA and to induce membrane permeabilization and depolarization in a dose-dependent fashion. These effects were not accompanied by significant changes in cellular concentration of pentacyclic triterpenes and/or ampicillin, suggesting an effect mediated through lipid membranes. We therefore focused on membranous effects induced by UA and OA, and we investigated on models of membranes, the role of specific lipids including phosphatidylglycerol and cardiolipin. The effect induced on membrane fluidity, permeability and ability to fuse were studied by determining changes in fluorescence anisotropy of DPH/generalized polarization of Laurdan, calcein release from liposomes, fluorescence dequenching of octadecyl-rhodamine B and liposome-size, respectively. Both UA and OA showed a dose-dependent effect with membrane rigidification, increase of membrane permeabilization and fusion. Except for the effect on membrane fluidity, the effect of UA was consistently higher compared with that obtained with OA, suggesting the role of methyl group position. All together the data demonstrated the potential role of compounds acting on lipid membranes for enhancing the activity of other antibiotics, like ampicillin and inducing synergy. Such combinations offer an opportunity to explore a larger antibiotic chemical space.
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BACKGROUND: SARS-CoV-2 strains evolve continuously and accumulate mutations in their genomes over the course of the pandemic. The severity of a SARS-CoV-2 infection could partly depend on these viral genetic characteristics. Here, we present a general conceptual framework that allows to study the effect of SARS-CoV-2 variants on COVID-19 disease severity among hospitalized patients. METHODS: A causal model is defined and visualized using a Directed Acyclic Graph (DAG), in which assumptions on the relationship between (confounding) variables are made explicit. Various DAGs are presented to explore specific study design options and the risk for selection bias. Next, the data infrastructure specific to the COVID-19 surveillance in Belgium is described, along with its strengths and weaknesses for the study of clinical impact of variants. DISCUSSION: A well-established framework that provides a complete view on COVID-19 disease severity among hospitalized patients by combining information from different sources on host factors, viral factors, and healthcare-related factors, will enable to assess the clinical impact of emerging SARS-CoV-2 variants and answer questions that will be raised in the future. The framework shows the complexity related to causal research, the corresponding data requirements, and it underlines important limitations, such as unmeasured confounders or selection bias, inherent to repurposing existing routine COVID-19 data registries. TRIAL REGISTRATION: Each individual research project within the current conceptual framework will be prospectively registered in Open Science Framework (OSF identifier: https://doi.org/10.17605/OSF.IO/UEF29 ). OSF project created on 18 May 2021.