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In the course of its evolution, a black hole (BH) accretes gas from a wide range of directions. Given a random accretion event, the typical angular momentum of an accretion disc would be tilted by $\sim$60$^\circ$ relative to the BH spin. Misalignment causes the disc to precess at a rate that increases with BH spin and tilt angle. We present the first general-relativistic magnetohydrodynamic (GRMHD) simulations spanning a full precession period of highly tilted (60$^\circ$), moderately thin ($h/r=0.1$) accretion discs around a rapidly spinning ($a\simeq0.9$) BH. While the disc and jets precess in phase, we find that the corona, sandwiched between the two, lags behind by $\gtrsim 10^{\circ}$. For spectral models of BH accretion, the implication is that hard non-thermal (corona) emission lags behind the softer (disc) emission, thus potentially explaining some properties of the hard energy lags seen in Type-C low frequency quasi-periodic oscillations in X-Ray binaries. While strong jets are unaffected by this disc-corona lag, weak jets stall when encountering the lagging corona at distances $r \sim 100$ black hole radii. This interaction may quench large-scale jet formation., 6 pages, 4 figures, Accepted in New Astronomy, see YouTube playlist for 3D renderings: https://www.youtube.com/playlist?list=PLDO1oeU33GwmwOV_Hp9s7572JdU8JPSSK

Background Meningococcal serogroup C (MenC) vaccination was introduced for 14-month-olds in the Netherlands in 2002, alongside a mass campaign for 1–18 year-olds. Due to an outbreak of serogroup W disease, MenC vaccination was replaced for MenACWY vaccination in 2018, next to introduction of a booster at 14 years of age and a catch-up campaign for 14–18 year-olds. We assessed meningococcal ACWY antibodies across the Dutch population in 2016/17 and 2020. Methods In a nationwide cross-sectional serosurvey in 2016/17, sera from participants aged 0–89 years (n = 6886) were tested for MenACWY-polysaccharide-specific (PS) serum IgG concentrations, and functional MenACWY antibody titers were determined in subsets. Moreover, longitudinal samples collected in 2020 (n = 1782) were measured for MenACWY-PS serum IgG concentrations. Results MenC antibody levels were low, except in recently vaccinated 14–23 month-olds and individuals who were vaccinated as teenagers in 2002, with seroprevalence of 59% and 20–46%, respectively. Meningococcal AWY antibody levels were overall low both in 2016/17 and in 2020. Naturally-acquired MenW immunity was limited in 2020 despite the recent serogroup W outbreak. Conclusions This study demonstrates waning of MenC immunity 15 years after a mass campaign in the Netherlands. Furthermore, it highlights the lack of meningococcal AWY immunity across the population and underlines the importance of the recently introduced MenACWY (booster) vaccination.

Background Gastric acid-suppressive therapy has been suggested to increase the risk for intestinal carriage of MDR Enterobacterales, but there is scarce community-based evidence substantiating this risk. Objectives To investigate if acid-suppressant use is associated with a risk of intestinal carriage of ESBL and carbapenemase-producing Enterobacterales (ESBL-E) in the open population, and to assess possible modifying factors. Methods Within the framework of a nationwide seroprevalence study, we identified a population-based cross-sectional cohort comprising 2746 adults (≥18 years), who provided stool specimens between February 2016 and June 2017. Specimens were tested by phenotypic assays and confirmatory genotype analysis to detect carriage of ESBL-E. Covariate data were extracted from self-administered questionnaires. ORs and 95% CIs were estimated using multivariable multilevel logistic regression, controlling for confounders informed by directed acyclic graphs. Results Among 2746 participants, 316 (11.5%) used acid suppressants; the prevalence of ESBL-E carriage was 7.4% (95% CI, 6.1%–8.6%). Current use of acid suppressants was not associated with ESBL-E carriage (adjusted OR [aOR], 1.05; 95% CI, 0.64–1.74); lifestyle and comorbidity did not modify this association. A higher BMI (≥25 kg/m2) (aOR, 1.42 [95% CI, 1.02–1.98]), non-Western ethnic origin (aOR, 1.96 [95% CI, 1.34–2.87]), travel to Eastern-Mediterranean, Western-Pacific or South-East Asia regions (aOR, 3.16 [95% CI, 1.71–5.83]) were associated with ESBL-E carriage. Sensitivity analyses confirmed these results; spline analysis supported a BMI-associated risk. Conclusions In this open population study, current use of acid suppressants was not associated with ESBL-E carriage. Travel to high-endemic regions and non-Western ethnicity were confirmed as risk factors, while a higher BMI emerged as a potential new risk for ESBL-E carriage.

Sagittarius A* exhibits regular variability in its multiwavelength emission, including daily X-ray flares and roughly continuous near-infrared (NIR) flickering. The origin of this variability is still ambiguous since both inverse Compton and synchrotron emission are possible radiative mechanisms. The underlying particle distributions are also not well constrained, particularly the non-thermal contribution. In this work, we employ the GPU-accelerated general relativistic magnetohydrodynamics (GRMHD) code H-AMR perform a study of flare flux distributions, including the effect of particle acceleration for the first time in high-resolution 3D simulations of Sgr A*. For the particle acceleration, we use the general relativistic ray-tracing (GRRT) code BHOSS to perform the radiative transfer, assuming a hybrid thermal+non-thermal electron energy distribution. We extract ~60 h lightcurves in the sub-millimetre, NIR and X-ray wavebands, and compare the power spectra and the cumulative flux distributions of the lightcurves to statistical descriptions for Sgr A* flares. Our results indicate that non-thermal populations of electrons arising from turbulence-driven reconnection in weakly magnetised accretion flows lead to moderate NIR and X-ray flares and reasonably describe the X-ray flux distribution while fulfilling multiwavelength flux constraints. These models exhibit high rms% amplitudes, >~150% both in the NIR and the X-rays, with changes in the accretion rate driving the 230~GHz flux variability, in agreement with Sgr A* observations., Accepted by MNRAS

Luminous active galactic nuclei (AGN) and X-Ray binaries (XRBs) often contain geometrically thin, radiatively cooled accretion discs. According to theory, these are -- in many cases -- initially highly misaligned with the black hole equator. In this work, we present the first general relativistic magnetohydrodynamic simulations of very thin (h/r~0.015-0.05) accretion discs around rapidly spinning (a~0.9) black holes and tilted by 45-65 degrees. We show that the inner regions of the discs with h/r, 8 pages, 5 figures, accompanying animations included in YouTube playlist: https://www.youtube.com/playlist?list=PLDO1oeU33GwlaPSME1TdCto1Y3P6yG91L

Background: Gut colonisation by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli is a risk factor for developing overt infection. The gut microbiome can provide colonisation resistance against enteropathogens, but it remains unclear whether it confers resistance against ESBL-producing E coli. We aimed to identify a potential role of the microbiome in controlling colonisation by this antibiotic-resistant bacterium.Methods: For this matched case-control study, we used faeces from 2751 individuals in a Dutch cross-sectional population study (PIENTER-3) to culture ESBL-producing bacteria. Of these, we selected 49 samples that were positive for an ESBL-producing E coli (ESBL-positive) and negative for several variables known to affect microbiome composition. These samples were matched 1:1 to ESBL-negative samples on the basis of individuals' age, sex, having been abroad or not in the past 6 months, and ethnicity. Shotgun metagenomic sequencing was done and taxonomic species composition and functional annotations (ie, microbial metabolism and carbohydrate-active enzymes) were determined. Targeted quantitative metabolic profiling (proton nuclear magnetic resonance spectroscopy) was done to investigate metabolomic profiles and combinations of univariate (t test and Wilcoxon test), multivariate (principal coordinates analysis, permutational multivariate analysis of variance, and partial least-squares discriminant analysis) and machine-learning approaches (least absolute shrinkage and selection operator and random forests) were used to analyse all the molecular data.Findings: No differences in diversity parameters or in relative abundance were observed between ESBL-positive and ESBL-negative groups based on bacterial species-level composition. Machine-learning approaches using microbiota composition did not accurately predict ESBL status (area under the receiver operating characteristic curve [AUROC]=0.41) when using either microbiota composition or any of the functional profiles. The metabolome also did not differ between ESBL groups, as assessed by various methods including random forest (AUROC=0- 61).Interpretation: By combining multiomics and machine-learning approaches, we conclude that asymptomatic gut carriage of ESBL-producing E. coli is not associated with an altered microbiome composition or function. This finding might suggest that microbiome-mediated colonisation resistance against ESBL-producing E, coli is not as relevant as it is against other enteropathogens and antibiotic-resistant bacteria. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd.

Background: In the Netherlands, bivalent human papillomavirus (HPV) vaccination was included in the National Immunization Program for 12-year-old girls in 2010 (vaccination coverage, 45%–60%). We examined possible changes in HPV seroprevalence in the HPV-unvaccinated Dutch population aged 0–89 years, comparing prevaccination data with data of approximately 6 years after implementation of national vaccination. Methods: Serum samples of men and women were used from two cross-sectional population-based serosurveillance studies performed before (2006–07, n = 6,384) and after (2016–17, n = 5,645) implementation of HPV vaccination in the Netherlands. Seven high-risk HPV-specific antibodies (HPV16, 18, 31, 33, 45, 52, and 58) were tested in a virus-like particle-based multiplex immunoassay. Results: Type-specific HPV seroprevalence increased in women between 2006–07 and 2016–17. Also, a higher seroprevalence for at least one type in women >15 years was found in 2016–17 (31.7%) compared with 2006–07 (25.2%). In men, overall HPV seroprevalence remained similar; however, a lower seroprevalence was found for HPV16 in 2016–17 (7.5%) compared with 2006–07 (10.6%). Conclusions: Our results indicate an increase in high-risk HPV types in women and a rather stable exposure in men. No clear effects of the strategy of girls-only vaccination were observed in men, probably because of the short time after introduction combined with suboptimal coverage. Impact: No herd immunity has been observed yet in a population with suboptimal HPV vaccination coverage.

Background Respiratory syncytial virus (RSV) generally causes mild disease but can cause severe infections in (premature) infants and elderly adults. Here, we studied RSV-specific antibody concentrations throughout life with emphasis on infants and chronic obstructive pulmonary disease (COPD) patients. Methods Sera (N = 2655) from 2 nationwide cross-sectional studies in the Netherlands including individuals aged 0–90 years were analyzed for IgG and IgA antibodies to RSV prefusion F, postfusion F, N, Ga, and Gb proteins and for antibody avidity in 42 COPD patients. Results Maternal IgG concentrations declined to age 10–12 months. After the first year of life, approximately 40% of children lacked infection-induced IgA antibodies and may therefore be uninfected. All Dutch children showed serological evidence of RSV infection by age 3 years. Antibody concentrations reached a plateau by age 5–9 years and remains constant throughout life. COPD patients had similar levels and avidity of RSV-specific IgG antibodies compared with age-matched healthy controls. Conclusions RSV-IgG antibody patterns throughout life can be used to estimate the degree of immunity acquisition to RSV and to identify groups at increased risk of infection. Seroprevalence of IgA could be a proxy to determine RSV infection in children younger than 1 year., RSV-IgG antibody patterns throughout life can be used to estimate the degree of immunity to RSV and identify groups at increased risk of infection while IgA seroprevalence could be used as proxy for RSV infection in children < 1 year.

Background The COVID-19 pandemic necessitates better understanding of the kinetics of antibody production induced by infection with SARS-CoV-2. We aimed to develop a high-throughput multiplex assay to detect antibodies to SARS-CoV-2 to assess immunity to the virus in the general population. Methods Spike protein subunits S1 and receptor binding domain, and nucleoprotein were coupled to microspheres. Sera collected before emergence of SARS-CoV-2 (n = 224) and of non-SARS-CoV-2 influenza-like illness (n = 184), and laboratory-confirmed cases of SARS-CoV-2 infection (n = 115) with various severities of COVID-19 were tested for SARS-CoV-2–specific IgG concentrations. Results Our assay discriminated SARS-CoV-2–induced antibodies and those induced by other viruses. The assay specificity was 95.1%–99.0% with sensitivity 83.6%–95.7%. By merging the test results for all 3 antigens a specificity of 100% was achieved with a sensitivity of at least 90%. Hospitalized COVID-19 patients developed higher IgG concentrations and the rate of IgG production increased faster compared to nonhospitalized cases. Conclusions The bead-based serological assay for quantitation of SARS-CoV-2–specific antibodies proved to be robust and can be conducted in many laboratories. We demonstrated that testing of antibodies against multiple antigens increases sensitivity and specificity compared to single-antigen–specific IgG determination., Detection of SARS-CoV-2–specific antibodies is instrumental to study seroprevalence and immune protection to the virus. We validated a multiplex assay to detect antibodies to SARS-CoV-2 N, S1, and RBD, and provide a framework to perform accurate serosurveys for COVID-19.

Objectives Varicella zoster virus (VZV) infection is reported regularly among adolescents and adults in Caribbean island populations. The disease more often runs a severe course among these populations, causing a substantial burden. The aim of this sero-epidemiological study was to obtain an insight into VZV susceptibility and its determinants in island populations of the Caribbean Netherlands (CN). Methods Participants from Bonaire, St. Eustatius, and Saba (n = 1829, aged 0–90 years) donated a blood sample and completed a questionnaire. VZV-specific IgG antibodies were determined using a bead-based multiplex immunoassay. Risk factors were analysed using a logistic regression model. Results Overall seroprevalence in CN was 78%, being lowest on St. Eustatius (73%) and highest on Bonaire and Saba (79%). Seropositivity increased gradually with age, with 60% and 80% at ages 10 years and 30 years, respectively, and ranging between 80% and 90% thereafter. Higher odds for VZV seronegativity were seen among persons who were born in CN or had resided there since early childhood, and among single-person households. Conclusions VZV susceptibility is relatively high among adolescents and adults in CN. In order to reduce the burden of VZV-related disease in these populations, routine varicella vaccination is recommended. As data are scarce, the study findings can serve as a blueprint for the epidemiology in tropical regions.

This large, nationwide, population-based, seroepidemiological study provides evidence of the effectiveness of physical distancing (>1.5 m) and indoor group size reductions in reducing severe acute respiratory syndrome coronavirus 2 infection. Additionally, young adults may play an important role in viral spread, contrary to children up until age 12 years with whom close contact is permitted. Clinical Trials Registration NTR8473.

mRNA- and vector-based vaccines are used at a large scale to prevent COVID-19. We compared Spike S1-specific (S1) IgG antibodies after vaccination with mRNA-based (Comirnaty, Spikevax) or vector-based (Janssen, Vaxzevria) vaccines, using samples from a Dutch nationwide cohort. mRNA vaccines induced faster inclines and higher S1 antibodies compared to vector-based vaccines in adults 18-64 years old (n=2,412). For all vaccines, one dose resulted in boosting of S1 antibodies in adults with a history of SARS-CoV-2 infection. For Comirnaty, two to four months following the second dose (n=196), S1 antibodies in adults aged 18-64 years old (436 BAU/mL, interquartile range: 328-891) were less variable and median concentrations higher compared to those in persons ≥80 years old (366, 177-743), but differences were not statistically significant (p>0.100). Nearly all participants seroconverted following COVID-19 vaccination, including the aging population. These data confirm results from controlled vaccine trials in a general population, including vulnerable groups.

BackgroundWith COVID-19 vaccine roll-out ongoing in many countries globally, monitoring of breakthrough infections is of great importance. Antibodies persist in the blood after a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Since COVID-19 vaccines induce immune response to the Spike protein of the virus, which is the main serosurveillance target to date, alternative targets should be explored to distinguish infection from vaccination.MethodsMultiplex immunoassay data from 1,513 SARS-CoV-2 RT-qPCR-tested individuals (352 positive and 1,161 negative) with a primary infection and no vaccination history were used to determine the accuracy of Nucleoprotein-specific immunoglobulin G (IgG) in detecting past SARS-CoV-2 infection. We also described Spike S1 and Nucleoprotein-specific IgG responses in 230 COVID-19 vaccinated individuals (Pfizer/BioNTech).ResultsThe sensitivity of Nucleoprotein seropositivity was 85% (95% confidence interval: 80-90%) for mild COVID-19 in the first two months following symptom onset. Sensitivity was lower in asymptomatic individuals (67%, 50-81%). Participants who had experienced a SARS-CoV-2 infection up to 11 months preceding vaccination, as assessed by Spike S1 seropositivity or RT-qPCR, produced 2.7-fold higher median levels of IgG to Spike S1 ≥14 days after the first dose as compared to those unexposed to SARS-CoV-2 at ≥7 days after the second dose (p=0.011). Nucleoprotein-specific IgG concentrations were not affected by vaccination in naïve participants.ConclusionsSerological responses to Nucleoprotein may prove helpful in identifying SARS-CoV-2 infections after vaccination. Furthermore, it can help interpret IgG to Spike S1 after COVID-19 vaccination as particularly high responses shortly after vaccination could be explained by prior exposure history.

For more than a decade human papillomavirus (HPV) vaccine have been implemented in most high-income countries, and more recently also in several low- and middle-income countries. The vaccines are safe and their impact and effectiveness in preventing HPV vaccine type infection and associated diseases has been thoroughly established. Currently, the primary recommended cohorts for immunisation are adolescents, 9–15 years of age but HPV is an ubiquitous infection that is mainly (but not exclusively) sexually transmitted. Sexually active adults remain susceptible to infection and continued transmission of the virus, representing a reservoir of infection in the population. A recent meeting, conducted by the HPV Prevention and Control Board (HPV-PCB), reviewed the current status of HPV vaccination of adults, discussed limitations, challenges and benefits of HPV vaccination of adults, evaluated the effectiveness of HPV vaccination after treatment of post cervical cancer and precancerous lesions, and discussed the potential impact of adult vaccination on cervical cancer elimination strategies in light of the current and future HPV vaccine shortage. HPV-PCB is an independent multidisciplinary board of international experts that disseminates relevant information on HPV to a broad array of stakeholders and provides guidance on strategic, technical and policy issues in the implementation of HPV prevention and control programs. The HPV-PCB concluded that, given the current data available on adult HPV vaccination and the ongoing vaccine supply constraints, it is too early to implement routine vaccination of adults. Many research gaps need to be filled before we have a better understanding of the efficacy and broader public health impact of HPV vaccination in adult women.

Objectives Pertussis is a respiratory infectious disease caused by Bordetella pertussis. In the Caribbean Netherlands (CN), comprising the islands Bonaire, St Eustatius, and Saba, registration of cases is mandatory for disease surveillance. However, insufficient laboratory facilities hamper case confirmation, and circulation persists. The aim of this seroepidemiological study was to gain insight into B. pertussis circulation in CN, and to investigate what factors contribute to the risk of infection. Methods Blood samples and questionnaires were collected for 1829 participants aged 0–90 years. Concentrations of B. pertussis toxin-specific IgG antibodies (anti-Pt) were determined using a bead-based immunoassay to indicate infections within the previous 12 months (based on anti-Pt ≥ 50 IU/mL) in participants without detectable vaccine-induced humoral immunity. Risk factors for recent infection were analyzed using logistic regression models. Results An estimated 8.2% (95% CI 6.6–10.1) of CN residents aged ≥ 9 years were found to have been recently infected by B. pertussis. Risk factors for a recent infection were age 12–29 years (13.8–14.6%) and Dutch Caribbean or Surinamese origin (10.7%). Conclusions B. pertussis infections occur frequently among CN residents aged ≥ 9 years, although few clinical pertussis cases are reported. Transmission to vulnerable individuals seems likely and should be taken into account in optimizing vaccination programs.

Introduction: Immunisation during pregnancy to protect infants against tetanus, pertussis and influenza is recommended in many countries. However, maternal antibodies can interfere with infant vaccine responses. We investigated the effect of antenatal diphtheria-tetanus-acellular pertussis (dTpa) and trivalent inactivated influenza (TIV) immunisation on specific and heterologous antibody responses to routine immunisations given in the first year of life. Methods: In total, 471 healthy infants were included. At 7 and 13 months of age, antibodies to the primary course of routine vaccines given at 6 weeks, 4 and 6 months of age (pertussis (pertussis toxin (PT), filamentous haemagglutinin (FHA), pertactin (PRN)), polio (type 1, 2, 3), Haemophilus influenzae type b (Hib), pneumococcus (serotype 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F)) were measured, and at 13 months of age, antibodies to the 12-month routine vaccines (Hib, meningococcus C, measles, mumps and rubella). The seroprotection rates for each vaccine and the geometric mean concentrations (GMC) of antibodies were compared between infants whose mothers did or did not receive dTpa or TIV immunisation during pregnancy. Results: A total of 369 infants were included in the final analysis. Maternal dTpa immunisation was associated with reduced antibody responses to both specific (diphtheria and pertussis) and heterologous (polio and pneumococcus) vaccine antigens. This effect was stronger for persistence of antibodies at 13 months of age than it was at 7 months of age. At 7 months of age, adjusted average antibody concentrations were significantly lower for diphtheria, pertussis (PT, FHA, PRN) and polio type 2, and at 13 months of age, for diphtheria, pertussis (PT, FHA, PRN), polio type 1–3 and pneumococcal serotypes 1, 4, 5, 6A, 6B, 7F, 18C and 23F. Additionally, at 13 months of age, seroprotection rates for diphtheria, PT, pneumococcal serotype 1, 6A and 6B were significantly lower in infants after maternal dTpa immunisation. In contrast, for Hib, in infants with maternal dTpa immunisation, the adjusted average antibody concentration and the seroprotection rate were higher, particularly at 7 months of age. Maternal TIV immunisation had minimal effect on infant vaccine responses. Conclusion: Whilst maternal immunisation protects infants in the first few months of life, it might interfere with both specific and heterologous (unrelated) vaccines responses in infants. Research in context: Evidence before this study: Maternal immunisation during pregnancy helps to protect infants during the period before they complete their primary immunisations. It has been proven to be safe and beneficial. However, pre-existing maternal antibodies can influence antibody responses following infant immunisation, an effect called ‘blunting’. Previous studies have investigated the influence of dTpa but not influenza immunisation during pregnancy on infant vaccine responses. The majority of studies investigated antibody concentrations only to the specific vaccine antigens included in the maternal immunisation, and there is scarce data available on heterologous vaccine responses, particularly pneumococcal responses.Added value of this study: In this study, we have shown that maternal dTpa immunisation during pregnancy is associated with reduced antibody responses to both specific (diphtheria and pertussis) and heterologous (polio and pneumococcus) vaccine antigens. This effect is stronger for persistence of antibodies at 13 months of age than after primary immunisation at 7 months of age. In contrast, for Hib, in infants with maternal dTpa immunisation, antibody concentrations are higher, particularly at 7 months of age. Maternal TIV immunisation has minimal effect on infant vaccine responses.Implications of all the available evidence: Whilst maternal immunisation protects infants in the first few months of life, it might interfere with both specific and heterologous (unrelated) vaccines responses in infants. As most vaccines induce very high antibody responses, small differences in antibody concentrations may not be of clinical significance. However, since maternal immunisation during pregnancy also influences seroprotection rates, strategies, such as additional booster doses in the second year of life, particularly for pertussis and pneumococcus, might need to be considered to address this. Keywords: Adacel, Boostrix, dTpa, Flu, Influenza, Vaccination, Antibodies, Humoral, Immunoglobulin, Immunisation, Titre, Heterologous, Non-specific

Background The majority of infants will not be protected by maternal antibodies until their first measles vaccination, between 12 and 15 months of age. This provides incentive to reduce the age at measles vaccination, but immunological consequences are insufficiently understood, and long-term effects are largely unknown. Methods A total of 79 infants who received early measles vaccination between 6 and 12 months age and a second dose at 14 months of age were compared to 44 children in a control group who received 1 dose at 14 months of age. Measles virus–specific neutralizing antibody concentrations and avidity were determined up to 4 years of age. Results Infants who first received measles vaccination before 12 months of age had a long-term decrease in the concentration and avidity of measles virus–specific neutralizing antibodies, compared with infants in the control group. For 11.1% of children with a first dose before 9 months of age, antibody levels at 4 years of age had dropped below the cutoff for clinical protection. Conclusions Early measles vaccination provides immediate protection in the majority of infants but yields a long-term decrease in neutralizing antibody responses, compared to vaccination at a later age. Additional vaccination at 14 months of age does not improve this. Over the long term, this may result in an increasing number of children susceptible to measles., Measles vaccination before 9 months of age results in reduced levels of measles virus neutralizing antibodies. Additional vaccination only leads to a short-term increase in antibody levels. Among children who received early vaccination, the number with nonprotective antibody levels increased over the long term.

BackgroundThe proportion of SARS-CoV-2 positive persons who are asymptomatic – and whether this proportion is age-dependent – are still open research questions. Because an unknown proportion of reported symptoms among SARS-CoV-2 positives will be attributable to another infection or affliction, the observed, or ‘crude’ proportion without symptoms may underestimate the proportion of persons without symptoms that are caused by SARS-CoV-2 infection.MethodsBased on a large population-based serological study comprising test results on seropositivity and self-reported symptom history conducted in April/May 2020 in the Netherlands (n=3147), we estimated the proportion of reported symptoms among those persons infected with SARS-CoV-2 that is attributable to this infection, where the set of relevant symptoms fulfills the ECDC case definition of COVID-19, using inferential methods for the attributable risk (AR). Generalised additive regression modelling was used to estimate the age-dependent relative risk (RR) of reported symptoms, and the AR and asymptomatic proportion (AP) were calculated from the fitted RR.ResultsUsing age-aggregated data, the estimated AP was 70% (95% CI: 65-77%). The estimated AP decreased with age, from 80% (95% CI: 67-100%) for the ConclusionWhereas the ‘crude’ AP represents a lower bound for the proportion of persons infected with SARS-CoV-2 without COVID-19 symptoms, the AP as estimated via an attributable risk approach represents an upper bound. Age-specific AP estimates can inform the implementation of public health actions such as targetted virological testing and therefore enhance containment strategies.

Serosurveys are important tools for estimating population immunity and providing immunization activity guidance. The measles and rubella multiplex bead assay (MBA) offers multiple advantages over standard serological assays and was validated by comparison with the enzyme-linked immunosorbent assay (ELISA) and the measles plaque reduction neutralization (PRN) assay. Results from a laboratory-produced purified measles virus whole-virus antigen MBA (MeV WVA(L)) correlated better with ELISA and PRN than results from the baculovirus-expressed measles nucleoprotein (N) MBA. Therefore, a commercially produced whole-virus antigen (MeV WVA(C)) was evaluated. Serum IgG antibody concentrations correlated significantly with a strong linear relationship between the MeV WVA(C) and MeV WVA(L) MBAs (R = 0.962 and R(2) = 0.926). IgG concentrations from the MeV WVA(C) MBA showed strong correlation with PRN titers (R = 0.846), with a linear relationship comparable to values obtained with the MeV WVA(L) MBA and PRN assay (R(2) = 0.716 and R(2) = 0.768, respectively). Receiver operating characteristic (ROC) curve analysis of the MeV WVA(C) using PRN titer as the comparator resulted in a seroprotection cutoff of 153 mIU/ml, similar to the established correlate of protection of 120 mIU/ml, with a sensitivity of 98% and a specificity of 83%. IgG concentrations correlated strongly between the rubella WVA MBA and ELISA (R = 0.959 and R(2) = 0.919). ROC analysis of the rubella MBA using ELISA as the comparator yielded a cutoff of 9.36 IU/ml, similar to the accepted cutoff of 10 IU/ml for seroprotection, with a sensitivity of 99% and a specificity of 100%. These results support use of the MBA for multiantigen serosurveys assessing measles and rubella population immunity.

This large nationwide population-based seroepidemiological study provides evidence on the effectiveness of physical distancing (>1.5m) and indoor group size reductions on SARS-CoV-2 infection. Additionally, young adults seem to play a significant role in viral spread, opposed to children up until the primary school age with whom close contact is permitted.

Background Assessing the duration of immunity following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a first priority to gauge the degree of protection following infection. Such knowledge is lacking, especially in the general population. Here, we studied changes in immunoglobulin isotype seropositivity and immunoglobulin G (IgG) binding strength of SARS-CoV-2–specific serum antibodies up to 7 months following onset of symptoms in a nationwide sample. Methods Participants from a prospective representative serological study in the Netherlands were included based on IgG seroconversion to the spike S1 protein of SARS-CoV-2 (N = 353), with up to 3 consecutive serum samples per seroconverted participant (N = 738). Immunoglobulin M (IgM), immunoglobulin A (IgA), and IgG antibody concentrations to S1, and increase in IgG avidity in relation to time since onset of disease symptoms, were determined. Results While SARS-CoV-2–specific IgM and IgA antibodies declined rapidly after the first month after disease onset, specific IgG was still present in 92% (95% confidence interval [CI], 89%–95%) of the participants after 7 months. The estimated 2-fold decrease of IgG antibodies was 158 days (95% CI, 136–189 days). Concentrations were sustained better in persons reporting significant symptoms compared to asymptomatic persons or those with mild upper respiratory complaints only. Similarly, avidity of IgG antibodies for symptomatic persons showed a steeper increase over time compared with persons with mild or no symptoms (P = .022). Conclusions SARS-CoV-2–specific IgG antibodies persist and show increasing avidity over time, indicative of underlying immune maturation. These data support development of immune memory against SARS-CoV-2, providing insight into protection of the general unvaccinated part of the population. Clinical Trials Registration NL8473 (the Dutch trial registry).

Additional file 3. Age-adjusted immunity simulations with proportion immune greater than herd immunity threshold.

Additional file 4. Outbreak probability for different scenarios of reduction in measles transmissibility.

Additional file 2. Age stratified population immunity profiles for age-adjusted immunity.

Additional file 6. Impact of delayed vaccination on outbreak probability.

Additional file 5. Impact of SIA on outbreak probability for different scenarios of reduction in measles transmissibility.

Additional file 8. Crude immunity simulations with proportion immune greater than herd immunity threshold.

Additional file 1. Serological data used in the analysis.

Additional file 7. Monthly projected crude versus age-adjusted immunity profiles from September 2019 to December 2021.

Background Bronchiolitis caused by respiratory syncytial virus (RSV) is a major cause of mortality and morbidity in infants. Aim To describe RSV epidemiology in children in the community in a high-income setting. Methods We used stored blood samples from the United Kingdom Born in Bradford cohort study that had been collected at birth, age 1 and 2 years old, tested for IgG RSV postfusion F antibody and linked to questionnaires and primary and hospital care records. We used finite mixture models to classify children as RSV infected/not infected according to their antibody concentrations at age 1 and 2 years. We assessed risk factors for primary RSV infection at each age using Poisson regression models. Results The study cohort included 700 children with cord blood samples; 490 had additional blood samples taken at both ages 1 and 2 years old. Of these 490 children, 258 (53%; 95% confidence interval (CI): 48–57%) were first infected with RSV at age 1, 99 of whom (38%; 95% CI: 33–43%) had been in contact with healthcare during peak RSV season (November–January). Having older siblings, birth in October–June and attending formal childcare were associated with risk of RSV infection in infancy. By age 2, a further 164 of 490 children (33%; 95% CI: 29–38%) had been infected. Conclusion Over half of children experienced RSV infection in infancy, a further one third had evidence of primary RSV infection by age 2, and one in seven remained seronegative by their second birthday. These findings will inform future analyses to assess the cost-effectiveness of RSV vaccination programmes in high-income settings.