Changing epidemiology of parvovirus B19 in the Netherlands since 1990, including its re-emergence after the COVID-19 pandemic.

Parvovirus B19V (B19V) infection during pregnancy can be complicated by potentially life-threatening fetal hydrops, which can be managed by intrauterine transfusion (IUT). This study investigates the long-term temporal patterns in the epidemiology of B19V and evaluates the impact on fetal hydrops, by combining data on B19V infections from the Dutch Sentinel Surveillance system in the period 1990 to 2023, Dutch blood banking data and hospital data on fetal hydrops. Using wavelet analysis, we identified annual epidemic cycles in the Netherlands in the period 1990-2019 and we identified superimposed multiannual cycles in the period 1990-2009. After 2009, no multiannual cycle could be identified, although the incidence fluctuated and correlates with number of IUT performed. As of 2020, weekly reports of B19V infection demonstrated a historically low incidence and B19V-DNA positive blood donors were nearly absent. From May 2020 to May 2023, no IUT for B19V-related hydrops was performed. In the spring of 2023, B19V infections re-emerged, reaching pre-pandemic epidemic levels. Due to the changes in B19V epidemiology over the last 30 years and the near-absence of B19V during the COVID-19 pandemic, the resulting low immunity levels may lead to rebound outbreaks. Alertness to severe complications such as fetal hydrops is warranted.

Estimation of the infection attack rate of mumps in an outbreak among college students using paired serology.

Mumps virus is a highly transmissible pathogen that is effectively controlled in countries with high vaccination coverage. Nevertheless, outbreaks have occurred worldwide over the past decades in vaccinated populations. Here we analyse an outbreak of mumps virus genotype G among college students in the Netherlands over the period 2009-2012 using paired serological data. To identify infections in the presence of preexisting antibodies we compared mumps specific serum IgG concentrations in two consecutive samples (n=746), whereby the first sample was taken when students started their study prior to the outbreaks, and the second sample was taken 2-5 years later. We fit a binary mixture model to the data. The two mixing distributions represent uninfected and infected classes. Throughout we assume that the infection probability increases with the ratio of antibody concentrations of the second to first sample. The estimated infection attack rate in this study is higher than reported earlier (0.095 versus 0.042). The analyses yield probabilistic classifications of participants, which are mostly quite precise owing to the high intraclass correlation of samples in uninfected participants (0.85, 95%CrI: 0.82-0.87). The estimated probability of infection increases with decreasing antibody concentration in the pre-outbreak sample, such that the probability of infection is 0.12 (95%CrI: 0.10-0.13) for the lowest quartile of the pre-outbreak samples and 0.056 (95%CrI: 0.044-0.068) for the highest quartile. We discuss the implications of these insights for the design of booster vaccination strategies.

Wastewater-based reproduction numbers and projections of COVID-19 cases in three areas in Japan, November 2021 to December 2022.

BackgroundWastewater surveillance has expanded globally as a means to monitor spread of infectious diseases. An inherent challenge is substantial noise and bias in wastewater data because of the sampling and quantification process, limiting the applicability of wastewater surveillance as a monitoring tool.AimTo present an analytical framework for capturing the growth trend of circulating infections from wastewater data and conducting scenario analyses to guide policy decisions.MethodsWe developed a mathematical model for translating the observed SARS-CoV-2 viral load in wastewater into effective reproduction numbers. We used an extended Kalman filter to infer underlying transmissions by smoothing out observational noise. We also illustrated the impact of different countermeasures such as expanded vaccinations and non-pharmaceutical interventions on the projected number of cases using three study areas in Japan during 2021-22 as an example.ResultsObserved notified cases were matched with the range of cases estimated by our approach with wastewater data only, across different study areas and virus quantification methods, especially when the disease prevalence was high. Estimated reproduction numbers derived from wastewater data were consistent with notification-based reproduction numbers. Our projections showed that a 10-20% increase in vaccination coverage or a 10% reduction in contact rate may suffice to initiate a declining trend in study areas.ConclusionOur study demonstrates how wastewater data can be used to track reproduction numbers and perform scenario modelling to inform policy decisions. The proposed framework complements conventional clinical surveillance, especially when reliable and timely epidemiological data are not available.

Estimation of introduction and transmission rates of SARS-CoV-2 in a prospective household study.

Household studies provide an efficient means to study transmission of infectious diseases, enabling estimation of susceptibility and infectivity by person-type. A main inclusion criterion in such studies is usually the presence of an infected person. This precludes estimation of the hazards of pathogen introduction into the household. Here we estimate age- and time-dependent household introduction hazards together with within household transmission rates using data from a prospective household-based study in the Netherlands. A total of 307 households containing 1,209 persons were included from August 2020 until March 2021. Follow-up of households took place between August 2020 and August 2021 with maximal follow-up per household mostly limited to 161 days. Almost 1 out of 5 households (59/307) had evidence of an introduction of SARS-CoV-2. We estimate introduction hazards and within-household transmission rates in our study population with penalized splines and stochastic epidemic models, respectively. The estimated hazard of introduction of SARS-CoV-2 in the households was lower for children (0-12 years) than for adults (relative hazard: 0.62; 95%CrI: 0.34-1.0). Estimated introduction hazards peaked in mid October 2020, mid December 2020, and mid April 2021, preceding peaks in hospital admissions by 1-2 weeks. Best fitting transmission models included increased infectivity of children relative to adults and adolescents, such that the estimated child-to-child transmission probability (0.62; 95%CrI: 0.40-0.81) was considerably higher than the adult-to-adult transmission probability (0.12; 95%CrI: 0.057-0.19). Scenario analyses indicate that vaccination of adults can strongly reduce household infection attack rates and that adding adolescent vaccination offers limited added benefit.

Inferring hospital admissions from SARS-CoV-2 virus loads in wastewater in The Netherlands, August 2020 - February 2022.

Wastewater-based surveillance enables tracking of SARS-CoV-2 circulation at a local scale in near-real time. Here we investigate the relation between virus loads and the number of hospital admissions in the Netherlands. Inferred virus loads from August 2020 until February 2022 in each of the 344 Dutch municipalities are analysed in a Bayesian multilevel Poisson regression to relate virus loads to daily age-stratified (in groups of 20 years) hospital admissions. Covariates include municipal vaccination coverages stratified by age and dose (first, second, and booster) and prevalence of the circulating coronavirus variants (wildtype, Alpha, Delta, and Omicron (BA.1 and BA.2)). Our model captures the relation between hospital admissions and virus loads well. Estimated hospitalisation rates per 1,000,000 persons per day at a virus load of 1013 particles range from 0.18 (95 % Prediction Interval (PI): 0.046-0.48) in children (0-19 years) to 20.1 (95 % PI: 9.46-36.8) in the oldest age group (80 years and older) in an unvaccinated population with only wildtype SARS-CoV-2 circulation. The analyses indicate a nearly twofold (1.92 (95 % PI: 1.78-2.05)) decrease in the expected number of hospitalisations at a given virus load between the Alpha and the Omicron variant. Our analyses show that virus load estimates in wastewater are closely related to the expected number of hospitalisations and provide an attractive tool to detect increased SARS-CoV-2 circulation at a local scale, even when there are few hospital admissions. Our analyses enable integration of data at the municipality level into meaningful conversion rates to translate virus loads at a local level into expected numbers of hospital admissions, which would allow for a better interpretation of virus loads detected in wastewater.

Impact of Subgroup Distribution on Seasonality of Human Respiratory Syncytial Virus: A Global Systematic Analysis.

BACKGROUND: Previous studies reported inconsistent findings regarding the association between respiratory syncytial virus (RSV) subgroup distribution and timing of RSV season. We aimed to further understand the association by conducting a global-level systematic analysis. METHODS: We compiled published data on RSV seasonality through a systematic literature review, and unpublished data shared by international collaborators. Using annual cumulative proportion (ACP) of RSV-positive cases, we defined RSV season onset and offset as ACP reaching 10% and 90%, respectively. Linear regression models accounting for meteorological factors were constructed to analyze the association of proportion of RSV-A with the corresponding RSV season onset and offset. RESULTS: We included 36 study sites from 20 countries, providing data for 179 study-years in 1995-2019. Globally, RSV subgroup distribution was not significantly associated with RSV season onset or offset globally, except for RSV season offset in the tropics in 1 model, possibly by chance. Models that included RSV subgroup distribution and meteorological factors explained only 2%-4% of the variations in timing of RSV season. CONCLUSIONS: Year-on-year variations in RSV season onset and offset are not well explained by RSV subgroup distribution or meteorological factors. Factors including population susceptibility, mobility, and viral interference should be examined in future studies.

Vaccine value profile for cytomegalovirus.

Cytomegalovirus (CMV) is the most common infectious cause of congenital malformation and a leading cause of developmental disabilities such as sensorineural hearing loss (SNHL), motor and cognitive deficits. The significant disease burden from congenital CMV infection (cCMV) led the US National Institute of Medicine to rank CMV vaccine development as the highest priority. An average of 6.7/1000 live births are affected by cCMV, but the prevalence varies across and within countries. In contrast to other congenital infections such as rubella and toxoplasmosis, the prevalence of cCMV increases with CMV seroprevalence rates in the population. The true global burden of cCMV disease is likely underestimated because most infected infants (85-90 %) have asymptomatic infection and are not identified. However, about 7-11 % of those with asymptomatic infection will develop SNHL throughout early childhood. Although no licensed CMV vaccine exists, several candidate vaccines are in development, including one currently in phase 3 trials. Licensure of one or more vaccine candidates is feasible within the next five years. Various models of CMV vaccine strategies employing different target populations have shown to provide substantial benefit in reducing cCMV. Although CMV can cause end-organ disease with significant morbidity and mortality in immunocompromised individuals, the focus of this vaccine value profile (VVP) is on preventing or reducing the cCMV disease burden. This CMV VVP provides a high-level, comprehensive assessment of the currently available data to inform the potential public health, economic, and societal value of CMV vaccines. The CMV VVP was developed by a working group of subject matter experts from academia, public health groups, policy organizations, and non-profit organizations. All contributors have extensive expertise on various elements of the CMV VVP and have described the state of knowledge and identified the current gaps. The VVP was developed using only existing and publicly available information.

Estimation of introduction and transmission rates of SARS-CoV-2 in a prospective household study.

Household studies provide an efficient means to study transmission of infectious diseases, enabling estimation of individual susceptibility and infectivity. A main inclusion criterion in such studies is often the presence of an infected person. This precludes estimation of the hazards of pathogen introduction into the household. Here we use data from a prospective household-based study to estimate SARS-CoV-2 age- and time-dependent household introduction hazards together with within household transmission rates in the Netherlands from August 2020 to August 2021. Introduction hazards and within-household transmission rates are estimated with penalized splines and stochastic epidemic models, respectively. The estimated hazard of introduction of SARS-CoV-2 in the households was lower for children (0-12 years) than for adults (relative hazard: 0.62; 95%CrI: 0.34-1.0). Estimated introduction hazards peaked in mid October 2020, mid December 2020, and mid April 2021, preceding peaks in hospital admissions by 1-2 weeks. The best fitting transmission models include increased infectivity of children relative to adults and adolescents, such that the estimated child-to-child transmission probability (0.62; 95%CrI: 0.40-0.81) was considerably higher than the adult-to-adult transmission probability (0.12; 95%CrI: 0.057-0.19). Scenario analyses show that vaccination of adults could have strongly reduced infection attack rates in households and that adding adolescent vaccination would have offered limited added benefit.

Patterns of SARS-CoV-2 circulation revealed by a nationwide sewage surveillance programme, the Netherlands, August 2020 to February 2022.

BackgroundSurveillance of SARS-CoV-2 in wastewater offers a near real-time tool to track circulation of SARS-CoV-2 at a local scale. However, individual measurements of SARS-CoV-2 in sewage are noisy, inherently variable and can be left-censored.AimWe aimed to infer latent virus loads in a comprehensive sewage surveillance programme that includes all sewage treatment plants (STPs) in the Netherlands and covers 99.6% of the Dutch population.MethodsWe applied a multilevel Bayesian penalised spline model to estimate time- and STP-specific virus loads based on water flow-adjusted SARS-CoV-2 qRT-PCR data for one to four sewage samples per week for each of the more than 300 STPs.ResultsThe model captured the epidemic upsurges and downturns in the Netherlands, despite substantial day-to-day variation in the measurements. Estimated STP virus loads varied by more than two orders of magnitude, from ca 1012 virus particles per 100,000 persons per day in the epidemic trough in August 2020 to almost 1015 per 100,000 in many STPs in January 2022. The timing of epidemics at the local level was slightly shifted between STPs and municipalities, which resulted in less pronounced peaks and troughs at the national level.ConclusionAlthough substantial day-to-day variation is observed in virus load measurements, wastewater-based surveillance of SARS-CoV-2 that is performed at high sampling frequency can track long-term progression of an epidemic at a local scale in near real time.

Estimation of the Number of Respiratory Syncytial Virus-Associated Hospitalizations in Adults in the European Union.

BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections in adults that can result in hospitalizations. Estimating RSV-associated hospitalization is critical for planning RSV-related healthcare across Europe. METHODS: We gathered RSV-associated hospitalization estimates from the RSV Consortium in Europe (RESCEU) for adults in Denmark, England, Finland, Norway, Netherlands, and Scotland from 2006 to 2017. We extrapolated these estimates to 28 European Union (EU) countries using nearest-neighbor matching, multiple imputations, and 2 sets of 10 indicators. RESULTS: On average, 158 229 (95% confidence interval [CI], 140 865-175 592) RSV-associated hospitalizations occur annually among adults in the EU (≥18 years); 92% of these hospitalizations occur in adults ≥65 years. Among 75-84 years, the annual average is estimated at 74 519 (95% CI, 69 923-79 115) at a rate of 2.24 (95% CI, 2.10-2.38) per 1000. Among ≥85 years, the annual average is estimated at 37 904 (95% CI, 32 444-43 363) at a rate of 2.99 (95% CI, 2.56-3.42). CONCLUSIONS: Our estimates of RSV-associated hospitalizations in adults are the first analysis integrating available data to provide the disease burden across the EU. Importantly, for a condition considered in the past to be primarily a disease of young children, the average annual hospitalization estimate in adults was lower but of a similar magnitude to the estimate in young children (0-4 years): 158 229 (95% CI, 140 865-175 592) versus 245 244 (95% CI, 224 688-265 799).

Age-Specific Estimates of Respiratory Syncytial Virus-Associated Hospitalizations in 6 European Countries: A Time Series Analysis.

BACKGROUND: Knowledge on age-specific hospitalizations associated with RSV infection is limited due to limited testing, especially in older children and adults in whom RSV infections are not expected to be severe. Burden estimates based on RSV coding of hospital admissions are known to underestimate the burden of RSV. We aimed to provide robust and reliable age-specific burden estimates of RSV-associated hospital admissions based on data on respiratory infections from national health registers and laboratory-confirmed cases of RSV. METHODS: We conducted multiseason regression analysis of weekly hospitalizations with respiratory infection and weekly laboratory-confirmed cases of RSV and influenza as covariates, based on national health registers and laboratory databases across 6 European countries. The burden of RSV-associated hospitalizations was estimated by age group, clinical diagnosis, and presence of underlying medical conditions. RESULTS: Across the 6 European countries, hospitalizations of children with respiratory infections were clearly associated with RSV, with associated proportions ranging from 28% to 60% in children younger than 3 months and we found substantial proportions of admissions to hospital with respiratory infections associated with RSV in children younger than 3 years. Associated proportions were highest among hospitalizations with ICD-10 codes of "bronchitis and bronchiolitis." In all 6 countries, annual incidence of RSV-associated hospitalizations was >40 per 1000 persons in the age group 0-2 months. In age group 1-2 years the incidence rate ranged from 1.3 to 10.5 hospitalizations per 1000. Adults older than 85 years had hospitalizations with respiratory infection associated to RSV in all 6 countries although incidence rates were low. CONCLUSIONS: Our findings highlight the substantial proportion of RSV infections among hospital admissions across different ages and may help public health professionals and policy makers when planning prevention and control strategies. In addition, our findings provide valuable insights for health care professionals attending to both children and adults presenting with symptoms of viral respiratory infections.

SARS-CoV-2 Spike S1-specific IgG kinetic profiles following mRNA or vector-based vaccination in the general Dutch population show distinct kinetics.

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. In adults 18-64 years old (n = 2412), the median vaccination interval between the two doses was 77 days for Vaxzevria (interquartile range, IQR: 69-77), 35 days (28-35) for Comirnaty and 33 days (28-35) for Spikevax. mRNA vaccines induced faster inclines and higher S1 antibodies compared to vector-based vaccines. 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, IQR: 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.

A Systematic Review of European Clinical Practice Guidelines for Respiratory Syncytial Virus Prophylaxis.

BACKGROUND: Since the widespread adoption of palivizumab prophylaxis in Europe, there have been a number of clinical practice guidelines (CPGs) published for the prevention of respiratory syncytial virus (RSV) infection in children. The aim of this systematic review was to identify CPGs for the prevention of RSV infection across Europe. METHODS: We performed a systematic literature search and contacted European influenza and respiratory virus networks and public health institutions, to identify national CPGs for the prevention of RSV infection. The Reporting Items for practice Guidelines in Healthcare (RIGHT) Statement checklist was applied to extract data and review the quality of reporting. RESULTS: A total of 20 national CPGs were identified, all published between 2000 and 2018. The greatest discrepancy between guidelines was the recommendations for palivizumab prophylaxis for premature infants, with recommendations varying by gestational age. All guidelines recommended or considered the use of palivizumab in infants with bronchopulmonary dysplasia, 85% (n = 17) in children with congenital heart disease (CHD), and 60% (n = 12) in children with severe combined immunodeficiency. CONCLUSIONS: We recommend that agencies publishing RSV prevention guidelines adopt the RIGHT reporting requirements when updating these guidelines to improve the presentation of the evidence-base for decisions.

Seropositivity to Nucleoprotein to detect mild and asymptomatic SARS-CoV-2 infections: A complementary tool to detect breakthrough infections after COVID-19 vaccination?

BACKGROUND: With 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. METHODS: Multiplex immunoassay data from 1,513 SARS-CoV-2 RT-qPCR-tested individuals (352 positive and 1,161 negative) without COVID-19 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). RESULTS: The 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 infection-naïve participants. CONCLUSIONS: Serological 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.

Respiratory Syncytial Virus-Associated Hospital Admissions and Bed Days in Children <5 Years of Age in 7 European Countries.

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of respiratory tract infections (RTIs) in young children. High-quality country-specific estimates of bed days and length of stay (LOS) show the population burden of RSV-RTI on secondary care services and the burden among patients, and can be used to inform RSV immunization implementation decisions. METHODS: We estimated the hospital burden of RSV-associated RTI (RSV-RTI) in children under 5 years in 7 European countries (Finland, Denmark, Norway, Scotland, England, the Netherlands, and Italy) using routinely collected hospital databases during 2001-2018. We described RSV-RTI admission rates during the first year of life by birth month and assessed their correlation with RSV seasonality in 5 of the countries (except for England and Italy). We estimated average annual numbers and rates of bed days for RSV-RTI and other-pathogen RTI, as well as the hospital LOS. RESULTS: We found that infants born 2 months before the peak month of RSV epidemics more frequently had the highest RSV-RTI hospital admission rate. RSV-RTI hospital episodes accounted for 9.9-21.2 bed days per 1000 children aged <5 years annually, with the median (interquartile range) LOS ranging from 2 days (0.5-4 days) to 4 days (2-6 days) between countries. Between 70% and 89% of these bed days were in infants aged <1 year, representing 40.3 (95% confidence interval [CI], 40.1-40.4) to 91.2 (95% CI, 90.6-91.8) bed days per 1000 infants annually. The number of bed days for RSV-RTI was higher than that for RTIs associated with other pathogens in infants aged <1 year, especially in those <6 months. CONCLUSIONS: RSV disease prevention therapies (monoclonal antibodies and maternal vaccines) for infants could help prevent a substantial number of bed days due to RSV-RTI. "High-risk" birth months should be considered when developing RSV immunization schedules. Variation in LOS between countries might reflect differences in hospital care practices.

Increasing burden of viral bronchiolitis in the pediatric intensive care unit; an observational study.

PURPOSE: Viral bronchiolitis is a major cause of pediatric intensive care unit (PICU) admission. Insight in the trends of bronchiolitis-associated PICU admissions is limited, but imperative for future PICU resource and capacity planning. MATERIALS AND METHODS: We retrospectively studied trends in PICU admissions for bronchiolitis in six European sites, including three full national registries, between 2000 and 2019 and calculated population-based estimates per 100,000 children where appropriate. Information concerning risk factors for severe disease and use of invasive mechanical ventilation was also collected when available. RESULTS: In total, there were 15,606 PICU admissions for bronchiolitis. We observed an increase in the annual number, rate and estimates per 100,000 children of PICU admissions for bronchiolitis at all sites over the last two decades, while the proportion of patients at high risk for severe disease remained relatively stable. CONCLUSIONS: The international increased burden of bronchiolitis for the PICU is concerning, and warrants further international attention and investigation.

High Infection Secondary Attack Rates of Severe Acute Respiratory Syndrome Coronavirus 2 in Dutch Households Revealed by Dense Sampling.

BACKGROUND: Indoor environments are considered one of the main settings for transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Households in particular represent a close-contact environment with high probability of transmission between persons of different ages and roles in society. METHODS: Households with a laboratory-confirmed SARS-CoV-2 positive case in the Netherlands (March-May 2020) were included. At least 3 home visits were performed during 4-6 weeks of follow-up, collecting naso- and oropharyngeal swabs, oral fluid, feces and blood samples from all household members for molecular and serological analyses. Symptoms were recorded from 2 weeks before the first visit through to the final visit. Infection secondary attack rates (SAR) were estimated with logistic regression. A transmission model was used to assess household transmission routes. RESULTS: A total of 55 households with 187 household contacts were included. In 17 households no transmission took place; in 11 households all persons were infected. Estimated infection SARs were high, ranging from 35% (95% confidence interval [CI], 24%-46%) in children to 51% (95% CI, 39%-63%) in adults. Estimated transmission rates in the household were high, with reduced susceptibility of children compared with adolescents and adults (0.67; 95% CI, .40-1.1). CONCLUSION: Estimated infection SARs were higher than reported in earlier household studies, presumably owing to our dense sampling protocol. Children were shown to be less susceptible than adults, but the estimated infection SAR in children was still high. Our results reinforce the role of households as one of the main multipliers of SARS-CoV-2 infection in the population.

Estimating the asymptomatic proportion of SARS-CoV-2 infection in the general population: Analysis of nationwide serosurvey data in the Netherlands.

BACKGROUND: The 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. METHODS: Based on two rounds of a large population-based serological study comprising test results on seropositivity and self-reported symptom history conducted in April/May and June/July 2020 in the Netherlands (n = 7517), 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. RESULTS: Using age-aggregated data, the 'crude' AP was 37% but the model-estimated AP was 65% (95% CI 63-68%). The estimated AP varied with age, from 74% (95% CI 65-90%) for < 20 years, to 61% (95% CI 57-65%) for the 50-59 years age-group. CONCLUSION: Whereas 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.

Controlling the pandemic during the SARS-CoV-2 vaccination rollout.

There is a consensus that mass vaccination against SARS-CoV-2 will ultimately end the COVID-19 pandemic. However, it is not clear when and which control measures can be relaxed during the rollout of vaccination programmes. We investigate relaxation scenarios using an age-structured transmission model that has been fitted to age-specific seroprevalence data, hospital admissions, and projected vaccination coverage for Portugal. Our analyses suggest that the pressing need to restart socioeconomic activities could lead to new pandemic waves, and that substantial control efforts prove necessary throughout 2021. Using knowledge on control measures introduced in 2020, we anticipate that relaxing measures completely or to the extent as in autumn 2020 could launch a wave starting in April 2021. Additional waves could be prevented altogether if measures are relaxed as in summer 2020 or in a step-wise manner throughout 2021. We discuss at which point the control of COVID-19 would be achieved for each scenario.

Population-based serology reveals risk factors for RSV infection in children younger than 5 years.

Respiratory syncytial virus (RSV) infection is a leading cause of hospitalization in infants. Underlying risk factors for RSV infection in the general population are not well understood, as previous work has focused on severe outcomes of infection in a clinical setting. Here we use RSV-specific IgG and IgA antibody measurements from two population-based cross-sectional serosurveys carried out in the Netherlands (n = 682) to classify children up to 5 years as seronegative or seropositive. We employ a generalized additive model to estimate the probability of prior RSV infection as function of age, date of birth within the year, and other risk factors. The analyses show that the majority of children have experienced a RSV infection before the age of 2 years. Age and birthdate are strong predictors of RSV infection in the first years of life, and children born in summer have higher estimated probability of infection than those born in winter [e.g., 0.56 (95% CI 0.45-0.66) vs. 0.32 (0.21-0.45) at age 1 year]. Our analyses reveal that the mean age at infection depends on date of birth, which has implications for the design of vaccination programmes and prioritisation schemes for the prophylactic use of monoclonal antibodies.