Membrane-Electrolyte System Approach to Understanding Ionic Conductivity and Crossover in Alkaline Flow Cells.

Membrane transport properties are crucial for electrochemical devices, and these properties are influenced by the composition and concentration of the electrolyte in contact with the membrane. We apply this general membrane-electrolyte system approach to alkaline flow batteries, studying the conductivity and ferricyanide crossover of Nafion and E-620. We report undetectable crossover for as-received Nafion and E-620 after both sodium and potassium exchange but high ferricyanide permeability of 10-7 to 10-8 cm2 s-1 for Nafion subjected to pretreatment prevalent in the flow battery literature. We show how the electrolyte mass fraction in hydrated membranes regulates the influence of ion concentration on membrane conductivity, identifying that increasing electrolyte concentration may not increase membrane conductivity even when it increases electrolyte conductivity. To illustrate this behavior, we introduce a new metric, the membrane penalty, as the ratio of the conductivity of the electrolyte to that of the membrane equilibrated with the electrolyte. We discuss the trade-off between flow battery volumetric capacity and areal power density that arises from these findings. Finally, we apply insights from this approach to provide recommendations for use of membranes in alkaline flow cells and electrochemical reactors in general.

Non-response bias in the analysis of the association between mental health and the urban environment: a cross-sectional study in Brussels, Belgium.

BACKGROUND: This paper aims at analysing the impact of partial non-response in the association between urban environment and mental health in Brussels. The potential threats of the partial non-response are biases in survey estimates and statistics. The effect of non-response on statistical associations is often overlooked and evidence in the research literature is lacking. METHODS: Data from the Belgian Health Interview Survey 2008 and 2013 were used. The association between non-response and potential determinants was explored through logistic regressions. RESULTS: Participants with low income, low educational levels, lower or higher age or in households with children were less likely to respond. When adjusting for socio-economic variables, non-response was higher in areas which are less vegetated, more polluted or more urbanised. Because the determinants of non-response and depressive disorders were similar, it is reasonable to assume that there will be more people with mental health problems among the non-respondents. And because more non-responses were found in low vegetation areas, the protective association between green spaces and mental health may be underestimated. CONCLUSION: Our capacity to measure the association between the urban environment and health is affected by non-response in surveys. The non-random spatial and socio-economic distribution of this bias affects the research findings.

Targeting lysyl-oxidase (LOX) may facilitate intramural periarterial drainage for the treatment of Alzheimer's disease.

Alzheimer's disease is the commonest form of dementia. It is likely that a lack of clearance of amyloid beta (Aß) results in its accumulation in the parenchyma as Aß oligomers and insoluble plaques, and within the walls of blood vessels as cerebral amyloid angiopathy (CAA). The drainage of Aß along the basement membranes of blood vessels as intramural periarterial drainage (IPAD), could be improved if the driving force behind IPAD could be augmented, therefore reducing Aß accumulation. There are alterations in the composition of the vascular basement membrane in Alzheimer's disease. Lysyl oxidase (LOX) is an enzyme involved in the remodelling of the extracellular matrix and its expression and function is altered in various disease states. The expression of LOX is increased in Alzheimer's disease, but it is unclear whether this is a contributory factor in the impairment of IPAD in Alzheimer's disease. The pharmacological inhibition of LOX may be a strategy to improve IPAD and reduce the accumulation of Aß in the parenchyma and within the walls of blood vessels.

Influenza versus other respiratory viruses - assessing severity among hospitalised children, Belgium, 2011 to 2020.

BackgroundKnowledge on the burden attributed to influenza viruses vs other respiratory viruses in children hospitalised with severe acute respiratory infections (SARI) in Belgium is limited.AimThis observational study aimed at describing the epidemiology and assessing risk factors for severe disease.MethodsWe retrospectively analysed data from routine national sentinel SARI surveillance in Belgium. Respiratory specimens collected during winter seasons 2011 to 2020 were tested by multiplex real-time quantitative PCR (RT-qPCR) for influenza and other respiratory viruses. Demographic data and risk factors were collected through questionnaires. Patients were followed-up for complications or death during hospital stay. Analysis focused on children younger than 15 years. Binomial logistic regression was used to identify risk factors for severe disease in relation to infection status.ResultsDuring the winter seasons 2011 to 2020, 2,944 specimens met the study case definition. Complications were more common in children with underlying risk factors, especially asthma (adjusted risk ratio (aRR): 1.87; 95% confidence interval (CI): 1.46-2.30) and chronic respiratory disease (aRR: 1.88; 95% CI: 1.44-2.32), regardless of infection status and age. Children infected with non-influenza respiratory viruses had a 32% higher risk of complications (aRR: 1.32; 95% CI: 1.06-1.66) compared with children with influenza only.ConclusionMulti-virus testing in children with SARI allows a more accurate assessment of the risk of complications and attribution of burden to respiratory viruses beyond influenza. Children with asthma and respiratory disease should be prioritised for clinical care, regardless of their virological test result and age, and targeted for prevention campaigns.

Effect of neuraminidase inhibitor (oseltamivir) treatment on outcome of hospitalised influenza patients, surveillance data from 11 EU countries, 2010 to 2020.

BackgroundTimely treatment with neuraminidase inhibitors (NAI) can reduce severe outcomes in influenza patients.AimWe assessed the impact of antiviral treatment on in-hospital deaths of laboratory-confirmed influenza patients in 11 European Union countries from 2010/11 to 2019/20.MethodsCase-based surveillance data from hospitalised patients with known age, sex, outcome, ward, vaccination status, timing of antiviral treatment, and hospitalisation were obtained. A mixed effect logistic regression model using country as random intercept was applied to estimate the adjusted odds ratio (aOR) for in-hospital death in patients treated with NAIs vs not treated.ResultsOf 19,937 patients, 31% received NAIs within 48 hours of hospital admission. Older age (60-79 years aOR 3.0, 95% CI: 2.4-3.8; 80 years 8.3 (6.6-10.5)) and intensive care unit admission (3.8, 95% CI: 3.4-4.2) increased risk of dying, while early hospital admission after symptom onset decreased risk (aOR 0.91, 95% CI: 0.90-0.93). NAI treatment initiation within 48 hours and up to 7 days reduced risk of dying (0-48 hours aOR 0.51, 95% CI: 0.45-0.59; 3-4 days 0.59 (0.51-0.67); 5-7 days 0.64 (0.56-0.74)), in particular in patients 40 years and older (e.g. treatment within 48 hours: 40-59 years aOR 0.43, 95% CI: 0.28-0.66; 60-79 years 0.50 (0.39-0.63); ≥80 years 0.51 (0.42-0.63)).ConclusionNAI treatment given within 48 hours and possibly up to 7 days after symptom onset reduced risk of in-hospital death. NAI treatment should be considered in older patients to prevent severe outcomes.

A general approach to identify low-frequency variants within influenza samples collected during routine surveillance.

Influenza viruses exhibit considerable diversity between hosts. Additionally, different quasispecies can be found within the same host. High-throughput sequencing technologies can be used to sequence a patient-derived virus population at sufficient depths to identify low-frequency variants (LFV) present in a quasispecies, but many challenges remain for reliable LFV detection because of experimental errors introduced during sample preparation and sequencing. High genomic copy numbers and extensive sequencing depths are required to differentiate false positive from real LFV, especially at low allelic frequencies (AFs). This study proposes a general approach for identifying LFV in patient-derived samples obtained during routine surveillance. Firstly, validated thresholds were determined for LFV detection, whilst balancing both the cost and feasibility of reliable LFV detection in clinical samples. Using a genetically well-defined population of influenza A viruses, thresholds of at least 104 genomes per microlitre and AF of ≥5 % were established as detection limits. Secondly, a subset of 59 retained influenza A (H3N2) samples from the 2016-2017 Belgian influenza season was composed. Thirdly, as a proof of concept for the added value of LFV for routine influenza monitoring, potential associations between patient data and whole genome sequencing data were investigated. A significant association was found between a high prevalence of LFV and disease severity. This study provides a general methodology for influenza LFV detection, which can also be adopted by other national influenza reference centres and for other viruses such as SARS-CoV-2. Additionally, this study suggests that the current relevance of LFV for routine influenza surveillance programmes might be undervalued.

Efficacy and safety of camostat mesylate in early COVID-19 disease in an ambulatory setting: a randomized placebo-controlled phase II trial.

OBJECTIVES: This study aimed to assess the efficacy and safety of 300 mg camostat mesylate three times daily in a fasted state to treat early phase COVID-19 in an ambulatory setting. METHODS: We conducted a phase II randomized controlled trial in symptomatic (maximum 5 days) and asymptomatic patients with confirmed COVID-19 infection. Patients were randomly assigned in a 2:1 ratio to receive either camostat mesylate or a placebo. Outcomes included change in nasopharyngeal viral load, time to clinical improvement, the presence of neutralizing antibodies, and safety. RESULTS: Of 96 participants randomized between November 2020 and June 2021, analyses were performed on the data of 90 participants who completed treatment (N = 61 camostat mesylate, N = 29 placebo). The estimated mean change in cycle threshold between day 1 and day 5 between the camostat and placebo group was 1.183 (P = 0.511). The unadjusted hazard ratio for clinical improvement in the camostat group was 0.965 (95% confidence interval, 0.480-1.942, P = 0.921 by Cox regression). The percentage distribution of the 50% neutralizing antibody titer at day 28 visit and frequency of adverse events were similar between the two groups. CONCLUSION: Under this protocol, camostat mesylate was not found to be effective as an antiviral drug against SARS-CoV-2. TRIAL REGISTRATION: ClinicalTrials.gov NCT04625114; November 12, 2020.

Metronomic Cyclophosphamide With Cisplatin and Bevacizumab for Refractory Anaplastic Ependymoma: A Retrospective Study.

BACKGROUND/AIM: Anaplastic ependymoma is a rare cancer of the central nervous system. The treatment includes optimal resection with focal radiotherapy. Some case reports or retrospective studies have suggested efficacy of regimens containing platinum or bevacizumab. We describe the feasibility and clinical benefit of the cisplatin-bevacizumab-cyclophosphamide treatment of anaplastic ependymoma. PATIENTS AND METHODS: Patients were identified through the Adolescent and Young Adults (AYAS) brain tumor national Web conference. We estimated the median progression-free (PFS) and overall survival (OS). RESULTS: There were eight patients with anaplastic ependymoma, with a median age of 36 years. The median OS was 19.9 months and median PFS was 12.3 months. Three patients obtained partial response, four stable disease, and one patient had disease progression during induction. Six patients received maintenance with a median duration of 224 days. CONCLUSION: This study confirms the tolerance of bevacizumab-cyclophosphamide-cisplatin treatment of anaplastic ependymoma. The clinical benefit seems even superior to that described in the literature.

Whole-Genome Sequence Approach and Phylogenomic Stratification Improve the Association Analysis of Mutations With Patient Data in Influenza Surveillance.

Each year, seasonal influenza results in high mortality and morbidity. The current classification of circulating influenza viruses is mainly focused on the hemagglutinin gene. Whole-genome sequencing (WGS) enables tracking mutations across all influenza segments allowing a better understanding of the epidemiological effects of intra- and inter-seasonal evolutionary dynamics, and exploring potential associations between mutations across the viral genome and patient's clinical data. In this study, mutations were identified in 253 Influenza A (H3N2) clinical isolates from the 2016-2017 influenza season in Belgium. As a proof of concept, available patient data were integrated with this genomic data, resulting in statistically significant associations that could be relevant to improve the vaccine and clinical management of infected patients. Several mutations were significantly associated with the sampling period. A new approach was proposed for exploring mutational effects in highly diverse Influenza A (H3N2) strains through considering the viral genetic background by using phylogenetic classification to stratify the samples. This resulted in several mutations that were significantly associated with patients suffering from renal insufficiency. This study demonstrates the usefulness of using WGS data for tracking mutations across the complete genome and linking these to patient data, and illustrates the importance of accounting for the viral genetic background in association studies. A limitation of this association study, especially when analyzing stratified groups, relates to the number of samples, especially in the context of national surveillance of small countries. Therefore, we investigated if international databases like GISAID may help to verify whether observed associations in the Belgium A (H3N2) samples, could be extrapolated to a global level. This work highlights the need to construct international databases with both information of viral genome sequences and patient data.

Validity of self-reported air pollution annoyance to assess long-term exposure to air pollutants in Belgium.

In epidemiological studies, assessment of long term exposure to air pollution is often estimated using air pollution measurements at fixed monitoring stations, and interpolated to the residence of survey participants through Geographical Information Systems (GIS). However, obtaining georeferenced address data from national registries requires a long and cumbersome administrative procedure, since this kind of personal data is protected by privacy regulations. This paper aims to assess whether information collected in health interview surveys, including air pollution annoyance, could be used to build prediction models for assessing individual long term exposure to air pollution, removing the need for data on personal residence address. Analyses were carried out based on data from the Belgian Health Interview Survey (BHIS) 2013 linked to GIS-modelled air pollution exposure at the residence place of participants older than 15 years (n = 9347). First, univariate linear regressions were performed to assess the relationship between air pollution annoyance and modelled exposure to each air pollutant. Secondly, a multivariable linear regression was performed for each air pollutant based on a set of variables selected with elastic net cross-validation, including variables related to environmental annoyance, socio-economic and health status of participants. Finally, the performance of the models to classify individuals in three levels of exposure was assessed by means of a confusion matrix. Our results suggest a limited validity of self-reported air pollution annoyance as a direct proxy for air pollution exposure and a weak contribution of environmental annoyance variables in prediction models. Models using variables related to the socio-economic status, region, urban level and environmental annoyance allow to predict individual air pollution exposure with a percentage of error ranging from 8% to 18%. Although these models do not provide very accurate predictions in terms of absolute exposure to air pollution, they do allow to classify individuals in groups of relative exposure levels, ranking participants from low over medium to high air pollution exposure. This model represents a rapid assessment tool to identify groups within the BHIS participants undergoing the highest levels of environmental stress.

Poor Antibody Response to BioNTech/Pfizer Coronavirus Disease 2019 Vaccination in Severe Acute Respiratory Syndrome Coronavirus 2-Naive Residents of Nursing Homes.

BACKGROUND: Residents of nursing homes (NHs) are at high risk of coronavirus disease 2019 (COVID-19)-related disease and death and may respond poorly to vaccination because of old age and frequent comorbid conditions. METHODS: Seventy-eight residents and 106 staff members, naive to infection or previously infected with severe acute respiratory syndrome coronavirus (SARS-CoV-2), were recruited in NHs in Belgium before immunization with 2 doses of 30 µg BNT162b2 messenger RNA (mRNA) vaccine at days 0 and 21. Binding antibodies (Abs) to SARS-CoV-2 receptor-binding domain (RBD), spike domains S1 and S2, RBD Ab avidity, and neutralizing Abs against SARS-CoV-2 wild type and B.1.351 were assessed at days 0, 21, 28, and 49. RESULTS: SARS-CoV-2-naive residents had lower Ab responses to BNT162b2 mRNA vaccination than naive staff. These poor responses involved lower levels of immunoglobulin (Ig) G to all spike domains, lower avidity of RBD IgG, and lower levels of Abs neutralizing the vaccine strain. No naive residents had detectable neutralizing Abs to the B.1.351 variant. In contrast, SARS-CoV-2-infected residents had high responses to mRNA vaccination, with Ab levels comparable to those in infected staff. Cluster analysis revealed that poor vaccine responders included not only naive residents but also naive staff, emphasizing the heterogeneity of responses to mRNA vaccination in the general population. CONCLUSIONS: The poor Ab responses to mRNA vaccination observed in infection-naive NH residents and in some naive staff members suggest suboptimal protection against breakthrough infection, especially with variants of concern. These data support the administration of a third dose of mRNA vaccine to further improve protection of NH residents against COVID-19.

The prior infection with SARS-CoV-2 study (PICOV) in nursing home residents and staff - study protocol description and presentation of preliminary findings on symptoms.

BACKGROUND: The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has presented itself as one of the most important health concerns of the 2020's, and hit the geriatric population the hardest. The presence of co-morbidities and immune ageing in the elderly lead to an increased susceptibility to COVID-19, as is the case for other influenza-like illnesses (ILI) or acute respiratory tract infections (ARI). However, little is known, about the impact of a previous or current infection on the other in terms of susceptibility, immune response, and clinical course. The aim of the "Prior Infection with SARS-COV-2" (PICOV) study is to compare the time to occurrence of an ILI or ARI between participants with a confirmed past SARS-CoV-2 infection (previously infected) and those without a confirmed past infection (naïve) in residents and staff members of nursing homes. This paper describes the study design and population characteristics at baseline. METHODS: In 26 Belgian nursing homes, all eligible residents and staff members were invited to participate, resulting in 1,226 participants. They were classified as naïve or previously infected based on the presence of detectable SARS-CoV-2 antibodies and/or a positive RT-qPCR result before participation in the study. Symptoms from a prior SARS-CoV-2 infection between March and August 2020 were compared between previously infected residents and staff members. RESULTS: Infection naïve nursing home residents reported fewer symptoms than previously infected residents: on average 1.9 and 3.1 symptoms, respectively (p = 0.016). The same effect was observed for infection naïve staff members and previously infected staff members (3.1 and 6.1 symptoms, respectively; p <0.0001). Moreover, the antibody development after a SARS-CoV-2 infection differs between residents and staff members, as previously infected residents tend to have a higher rate of asymptomatic cases compared to previously infected staff members (20.5% compared to 12.4%; p <0.0001). CONCLUSIONS: We can postulate that COVID-19 disease development and symptomatology are different between a geriatric and younger population. Therefore, the occurrence and severity of a future ILI and/or ARI might vary from resident to staff.

Spotlight influenza: Extending influenza surveillance to detect non-influenza respiratory viruses of public health relevance: analysis of surveillance data, Belgium, 2015 to 2019.

BackgroundSeasonal influenza-like illness (ILI) affects millions of people yearly. Severe acute respiratory infections (SARI), mainly influenza, are a leading cause of hospitalisation and mortality. Increasing evidence indicates that non-influenza respiratory viruses (NIRV) also contribute to the burden of SARI. In Belgium, SARI surveillance by a network of sentinel hospitals has been ongoing since 2011.AimWe report the results of using in-house multiplex qPCR for the detection of a flexible panel of viruses in respiratory ILI and SARI samples and the estimated incidence rates of SARI associated with each virus.MethodsWe defined ILI as an illness with onset of fever and cough or dyspnoea. SARI was defined as an illness requiring hospitalisation with onset of fever and cough or dyspnoea within the previous 10 days. Samples were collected in four winter seasons and tested by multiplex qPCR for influenza virus and NIRV. Using catchment population estimates, we calculated incidence rates of SARI associated with each virus.ResultsOne third of the SARI cases were positive for NIRV, reaching 49.4% among children younger than 15 years. In children younger than 5 years, incidence rates of NIRV-associated SARI were twice that of influenza (103.5 vs 57.6/100,000 person-months); co-infections with several NIRV, respiratory syncytial viruses, human metapneumoviruses and picornaviruses contributed most (33.1, 13.6, 15.8 and 18.2/100,000 person-months, respectively).ConclusionEarly testing for NIRV could be beneficial to clinical management of SARI patients, especially in children younger than 5 years, for whom the burden of NIRV-associated disease exceeds that of influenza.

Whole-genome-based phylogenomic analysis of the Belgian 2016-2017 influenza A(H3N2) outbreak season allows improved surveillance.

Seasonal influenza epidemics are associated with high mortality and morbidity in the human population. Influenza surveillance is critical for providing information to national influenza programmes and for making vaccine composition predictions. Vaccination prevents viral infections, but rapid influenza evolution results in emerging mutants that differ antigenically from vaccine strains. Current influenza surveillance relies on Sanger sequencing of the haemagglutinin (HA) gene. Its classification according to World Health Organization (WHO) and European Centre for Disease Prevention and Control (ECDC) guidelines is based on combining certain genotypic amino acid mutations and phylogenetic analysis. Next-generation sequencing technologies enable a shift to whole-genome sequencing (WGS) for influenza surveillance, but this requires laboratory workflow adaptations and advanced bioinformatics workflows. In this study, 253 influenza A(H3N2) positive clinical specimens from the 2016-2017 Belgian season underwent WGS using the Illumina MiSeq system. HA-based classification according to WHO/ECDC guidelines did not allow classification of all samples. A new approach, considering the whole genome, was investigated based on using powerful phylogenomic tools including beast and Nextstrain, which substantially improved phylogenetic classification. Moreover, Bayesian inference via beast facilitated reassortment detection by both manual inspection and computational methods, detecting intra-subtype reassortants at an estimated rate of 15 %. Real-time analysis (i.e. as an outbreak is ongoing) via Nextstrain allowed positioning of the Belgian isolates into the globally circulating context. Finally, integration of patient data with phylogenetic groups and reassortment status allowed detection of several associations that would have been missed when solely considering HA, such as hospitalized patients being more likely to be infected with A(H3N2) reassortants, and the possibility to link several phylogenetic groups to disease severity indicators could be relevant for epidemiological monitoring. Our study demonstrates that WGS offers multiple advantages for influenza monitoring in (inter)national influenza surveillance, and proposes an improved methodology. This allows leveraging all information contained in influenza genomes, and allows for more accurate genetic characterization and reassortment detection.

Improved potency of pyridin-2(1H)one derivatives for the treatment of mechanical allodynia.

Mechanical allodynia, a painful sensation caused by innocuous touch, is a major chronic pain symptom, which often remains without an effective treatment. There is thus a need for new anti-allodynic treatments based on new drug classes. We recently synthetized new 3,5-disubstituted pyridin-2(1H)-one derivatives. By substituting the pyridinone at the 3-position by various aryl/heteroaryl moieties and at the 5-position by a phenylamino group, we discovered that some derivatives exhibited a strong anti-allodynic potency in rats. Here, we report that varying the substitution of the pyridinone 5-position, the 3-position being substituted by an indol-4-yl moiety, further improves such anti-allodynic potency. Compared with 2, one of the two most active compounds of the first series, eleven out of nineteen newly synthetized compounds showed higher anti-allodynic potency, with two of them completely preventing mechanical allodynia. In the first series, hit compounds 1 and 2 appeared to be inhibitors of p38α MAPK, a protein kinase known to underlie pain hypersensitivity in animal models. Depending on the substitution at the 5-position, some newly synthetized compounds were also stronger p38α MAPK inhibitors. Surprisingly, though, anti-allodynic effects and p38α MAPK inhibitory potencies were not correlated, suggesting that other biological target(s) is/are involved in the analgesic activity in this series. Altogether, these results confirm that 3,5-disubstituted pyridine-2(1H)-one derivatives are of high interest for the development of new treatment of mechanical allodynia.

Evaluation of the added value of viral genomic information for predicting severity of influenza infection.

BACKGROUND: The severity of an influenza infection is influenced by both host and viral characteristics. This study aims to assess the relevance of viral genomic data for the prediction of severe influenza A(H3N2) infections among patients hospitalized for severe acute respiratory infection (SARI), in view of risk assessment and patient management. METHODS: 160 A(H3N2) influenza positive samples from the 2016-2017 season originating from the Belgian SARI surveillance were selected for whole genome sequencing. Predictor variables for severity were selected using a penalized elastic net logistic regression model from a combined host and genomic dataset, including patient information and nucleotide mutations identified in the viral genome. The goodness-of-fit of the model combining host and genomic data was compared using a likelihood-ratio test with the model including host data only. Internal validation of model discrimination was conducted by calculating the optimism-adjusted area under the Receiver Operating Characteristic curve (AUC) for both models. RESULTS: The model including viral mutations in addition to the host characteristics had an improved fit ([Formula: see text]=12.03, df = 3, p = 0.007). The optimism-adjusted AUC increased from 0.671 to 0.732. CONCLUSIONS: Adding genomic data (selected season-specific mutations in the viral genome) to the model containing host characteristics improved the prediction of severe influenza infection among hospitalized SARI patients, thereby offering the potential for translation into a prospective strategy to perform early season risk assessment or to guide individual patient management.

Prevalence and incidence of anti-SARS-CoV-2 antibodies among healthcare workers in Belgian hospitals before vaccination: a prospective cohort study.

OBJECTIVES: To describe prevalence and incidence of anti-SARS-CoV-2 antibodies among Belgian hospital healthcare workers (HCW) in April-December 2020. DESIGN: Prospective cohort study. Follow-up was originally planned until September and later extended. SETTING: Multicentre study, 17 hospitals. PARTICIPANTS: 50 HCW were randomly selected per hospital. HCW employed beyond the end of the study and whose profession involved contact with patients were eligible. 850 HCW entered the study in April-May 2020, 673 HCW (79%) attended the September visit and 308 (36%) the December visit. OUTCOME MEASURES: A semiquantitative ELISA was used to detect IgG against SARS-CoV-2 in serum (Euroimmun) at 10 time points. In seropositive samples, neutralising antibodies were measured using a virus neutralisation test. Real-time reverse transcription PCR (RT-qPCR) was performed to detect SARS-CoV-2 on nasopharyngeal swabs. Participant characteristics and the presence of symptoms were collected via an online questionnaire. RESULTS: Among all participants, 80% were women, 60% nurses and 21% physicians. Median age was 40 years. The seroprevalence remained relatively stable from April (7.7% (95% CI: 4.8% to 12.1%) to September (8.2% (95% CI: 5.7% to 11.6%)) and increased thereafter, reaching 19.7% (95% CI: 12.0% to 30.6%) in December 2020. 76 of 778 initially seronegative participants seroconverted during the follow-up (incidence: 205/1000 person-years). Among all seropositive individuals, 118/148 (80%) had a positive neutralisation test, 83/147 (56%) presented or reported a positive RT-qPCR, and 130/147 (88%) reported COVID-19-compatible symptoms at least once. However, only 46/73 (63%) of the seroconverters presented COVID-19-compatible symptoms in the month prior to seroconversion. CONCLUSIONS: The seroprevalence among hospital HCW was slightly higher than that of the general Belgian population but followed a similar evolution, suggesting that infection prevention and control measures were effective and should be strictly maintained. After two SARS-CoV-2 waves, 80% of HCW remained seronegative, justifying their prioritisation in the vaccination strategy. TRIAL REGISTRATION NUMBER: NCT04373889.

Monitoring of human coronaviruses in Belgian primary care and hospitals, 2015-20: a surveillance study.

BACKGROUND: Seasonal human coronaviruses (hCoVs) broadly circulate in humans. Their epidemiology and effect on the spread of emerging coronaviruses has been neglected thus far. We aimed to elucidate the epidemiology and burden of disease of seasonal hCoVs OC43, NL63, and 229E in patients in primary care and hospitals in Belgium between 2015 and 2020. METHODS: We retrospectively analysed data from the national influenza surveillance networks in Belgium during the winter seasons of 2015-20. Respiratory specimens were collected through the severe acute respiratory infection (SARI) and the influenza-like illness networks from patients with acute respiratory illness with onset within the previous 10 days, with measured or reported fever of 38°C or greater, cough, or dyspnoea; and for patients admitted to hospital for at least one night. Potential risk factors were recorded and patients who were admitted to hospital were followed up for the occurrence of complications or death for the length of their hospital stay. All samples were analysed by multiplex quantitative RT-PCRs for respiratory viruses, including seasonal hCoVs OC43, NL63, and 229E. We estimated the prevalence and incidence of seasonal hCoV infection, with or without co-infection with other respiratory viruses. We evaluated the association between co-infections and potential risk factors with complications or death in patients admitted to hospital with seasonal hCoV infections by age group. Samples received from week 8, 2020, were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). FINDINGS: 2573 primary care and 6494 hospital samples were included in the study. 161 (6·3%) of 2573 patients in primary care and 371 (5·7%) of 6494 patients admitted to hospital were infected with a seasonal hCoV. OC43 was the seasonal hCoV with the highest prevalence across age groups and highest incidence in children admitted to hospital who were younger than 5 years (incidence 9·0 [95% CI 7·2-11·2] per 100 000 person-months) and adults older than 65 years (2·6 [2·1-3·2] per 100 000 person-months). Among 262 patients admitted to hospital with seasonal hCoV infection and with complete information on potential risk factors, 66 (73·3%) of 90 patients who had complications or died also had at least one potential risk factor (p=0·0064). Complications in children younger than 5 years were associated with co-infection (24 [36·4%] of 66; p=0·017), and in teenagers and adults (≥15 years), more complications arose in patients with a single hCoV infection (49 [45·0%] of 109; p=0·0097). In early 2020, the Belgian SARI surveillance detected the first SARS-CoV-2-positive sample concomitantly with the first confirmed COVID-19 case with no travel history to China. INTERPRETATION: The main burden of severe seasonal hCoV infection lies with children younger than 5 years with co-infections and adults aged 65 years and older with pre-existing comorbidities. These age and patient groups should be targeted for enhanced observation when in medical care and in possible future vaccination strategies, and co-infections in children younger than 5 years should be considered during diagnosis and treatment. Our findings support the use of national influenza surveillance systems for seasonal hCoV monitoring and early detection, and monitoring of emerging coronaviruses such as SARS-CoV-2. FUNDING: Belgian Federal Public Service Health, Food Chain Safety, and Environment; Belgian National Insurance Health Care (Institut national d'assurance maladie-invalidité/Rijksinstituut voor ziekte-en invaliditeitsverzekering); and Regional Health Authorities (Flanders Agentschap zorg en gezondheid, Brussels Commission communautaire commune, Wallonia Agence pour une vie de qualité).

Efficacy comparison of three rapid antigen tests for SARS-CoV-2 and how viral load impact their performance.

More and more rapid antigen tests for the diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) appear in the market with varying performance. The sensitivity of these tests heavily depends on the viral load, extrapolated by the threshold cycle (Ct). It is therefore essential to verify their performance before their inclusion in routine. The Coronavirus Ag Rapid Test Cassette Bio-Rad, the GSD NovaGen SARS-CoV-2 (COVID-19) Antigen Rapid Test, and the Aegle Coronavirus Ag Rapid Test Cassette were evaluated on 199 samples: 150 fresh samples from the routine and positive in quantitative reverse-transcription polymerase chain reaction (RT-qPCR), nine fresh samples negative in RT-qPCR, and 40 frozen samples, taken before the discovery of SARS-CoV-2 but positive for other respiratory viruses. Positive RT-qPCR samples were categorized according to their Ct: Ct < 20 (18.7%), ≥ 20-< 25 (27.3%), ≥ 25-< 30 (18.7%), ≥ 30-35 (17.3%), and > 35 (18.0%). Sensitivities (95% confidence interval) for Ct below 25 were 95.7% (92.4-98.9), 97.1% (94.4-99.8), and 97.1% (94.4-99.8) for GSD NovaGen, Bio-Rad, and Aegle, respectively but drastically dropped when Ct exceeded 27. Among samples with previously diagnosed viruses, seven false-positive results were found with GSD NovaGen only (specificity 85.7%). Equivalent, high sensitivities were observed with the highest viral load samples. The GSD NovaGen assay showed less specificity. Although the three kits tested in this study are inadequate for routine testing in a high throughput laboratory, they can help to quickly identify the most infectious patients and screen their close contacts in an environment where molecular tests are not readily available.