Vaccine effectiveness against COVID-19 related hospital admission in the Netherlands by medical risk condition: A test-negative case-control study.

INTRODUCTION: Vaccination remains crucial in reducing COVID-19 hospitalizations and mitigating the strain on healthcare systems. We conducted a multicenter study to assess vaccine effectiveness (VE) of primary and booster vaccination against hospitalization and to identify subgroups with reduced VE. METHODS: From March to July 2021 and October 2021 to January 2022, a test-negative case-control study was conducted in nine Dutch hospitals. The study included adults eligible for COVID-19 vaccination who were hospitalized with respiratory symptoms. Cases tested positive for SARS-CoV-2 within 14 days prior to or 48 h after admission, while controls tested negative. Logistic regression was used to calculate VE, adjusting for calendar week, sex, age, nursing home residency and comorbidity. We explored COVID-19 case characteristics and whether there are subgroups with less effective protection by vaccination against COVID-19 hospitalization. RESULTS: Between October 2021 to January 2022, when the Delta variant was dominant, 335 cases and 277 controls were included. VE of primary and booster vaccination was 78 % (95 % CI: 65-86), and 89 % (95 % CI: 69-96), respectively. Using data from both study periods, including 700 cases and 511 controls, VE of primary vaccination was significantly reduced in those aged 60+ and patients with malignancy, chronic cardiac disease or an immunocompromising condition. CONCLUSION: Although VE against hospitalization was 78% and increased to 89% after boosting during the Delta-dominant study period, VE was lower in certain high risk groups, for which indirect protection or other protective measures might be of added importance.

SARS-CoV-2 incidence in secondary schools; the role of national and school-initiated COVID-19 measures.

INTRODUCTION: Our aim was to gain insight into the effect of COVID-19 measures on SARS-CoV-2 incidence in secondary schools and the association with classroom CO2 concentration and airborne contamination. METHODS: Between October 2020-June 2021, 18 schools weekly reported SARS-CoV-2 incidence and completed surveys on school-initiated COVID-19 measures (e.g. improving hygiene or minimizing contacts). CO2 was measured in occupied classrooms twice, and SARS-CoV-2 air contamination longitudinally using electrostatic dust collectors (EDC) and analyzed using RT-qPCR. National COVID-19 policy measures varied during pre-lockdown, lockdown and post-lockdown periods. During the entire study, schools were recommended to improve ventilation. SARS-CoV-2 incidence rate ratios (IRR) were estimated by Generalized Estimating Equation (GEE) models. RESULTS: During 18 weeks follow-up (range: 10-22) SARS-CoV-2 school-incidence decreased during national lockdown (adjusted IRR: 0.41, 95%CI: 0.21-0.80) and post-lockdown (IRR: 0.60, 0.39-0.93) compared to pre-lockdown. School-initiated COVID-19 measures had no additional effect. Pre-lockdown, IRRs per 10% increase in time CO2 exceeded 400, 550 and 800 ppm above outdoor level respectively, were 1.08 (1.00-1.16), 1.10 (1.02-1.19), and 1.08 (0.95-1.22). Post-lockdown, CO2-concentrations were considerably lower and not associated with SARS-CoV-2 incidence. No SARS-CoV-2 RNA was detected in any of the EDC samples. CONCLUSION: During a period with low SARS-CoV-2 population immunity and increased attention to ventilation, with CO2 levels most of the time below acceptable thresholds, only the national policy during and post-lockdown of reduced class-occupancy, stringent quarantine, and contact testing reduced SARS-CoV-2 incidence in Dutch secondary schools. Widespread SARS-CoV-2 air contamination could not be demonstrated in schools under the prevailing conditions during the study.

Vaccine effectiveness against COVID-19 related hospital admission in the Netherlands: A test-negative case-control study.

INTRODUCTION: Real-world vaccine effectiveness (VE) estimates are essential to identify potential groups at higher risk of break-through infections and to guide policy. We assessed the VE of COVID-19 vaccination against COVID-19 hospitalization, while adjusting and stratifying for patient characteristics. METHODS: We performed a test-negative case-control study in six Dutch hospitals. The study population consisted of adults eligible for COVID-19 vaccination hospitalized between May 1 and June 28, 2021 with respiratory symptoms. Cases were defined as patients who tested positive for SARS-CoV-2 by PCR during the first 48 h of admission or within 14 days prior to hospital admission. Controls were patients tested negative at admission and did not have a positive test during the 2 weeks prior to hospitalization. VE was calculated using multivariable logistic regression, adjusting for calendar week, sex, age, comorbidity and nursing home residency. Subgroup analysis was performed for age, sex and different comorbidities. Secondary endpoints were ICU-admission and mortality. RESULTS: 379 cases and 255 controls were included of whom 157 (18%) were vaccinated prior to admission. Five cases (1%) and 40 controls (16%) were fully vaccinated (VE: 93%; 95% CI: 81 - 98), and 40 cases (11%) and 70 controls (27%) were partially vaccinated (VE: 70%; 95% CI: 50-82). A strongly protective effect of vaccination was found in all comorbidity subgroups. No ICU-admission or mortality were reported among fully vaccinated cases. Of unvaccinated cases, mortality was 10% and 19% was admitted at the ICU. CONCLUSION: COVID-19 vaccination provides a strong protective effect against COVID-19 related hospital admission, in patients with and without comorbidity.

Impact analysis of rotavirus vaccination in various geographic regions in Western Europe.

BACKGROUND: Universal mass vaccination (UMV) against rotavirus has been implemented in many but not all European countries. This study investigated the impact of UMV on rotavirus incidence trends by comparing European countries with UMV: Belgium, England/Wales and Germany versus countries without UMV: Denmark and the Netherlands. METHODS: For this observational retrospective cohort study, time series data (2001-2016) on rotavirus detections, meteorological factors and population demographics were collected. For each country, several meteorological and population factors were investigated as possible predictors of rotavirus incidence. The final set of predictors were incorporated in negative binomial models accounting for seasonality and serial autocorrelation, and time-varying incidence rate ratios (IRR) were calculated for each age group and country separately. The overall vaccination impact two years after vaccine implementation was estimated by pooling the results using a random effects meta-analyses. Independent t-tests were used to compare annual epidemics in the pre-vaccination and post-vaccination era to explore any changes in the timing of rotavirus epidemics. RESULTS: The population size and several meteorological factors were predictors for the rotavirus epidemiology. Overall, we estimated a 42% (95%-CI 23;56%) reduction in rotavirus incidence attributable to UMV. Strongest reductions were observed for age-groups 0-, 1- and 2-years (IRR 0.47, 0.48 and 0.63, respectively). No herd effect induced by UMV in neighbouring countries was observed. In all UMV countries, the start and/or stop and corresponding peak of the rotavirus season was delayed by 4-7 weeks. CONCLUSIONS: The introduction of rotavirus UMV resulted in an overall reduction of 42% in rotavirus incidence in Western European countries two years after vaccine introduction and caused a change in seasonal pattern. No herd effect induced by UMV neighbouring countries was observed for Denmark and the Netherlands.

Universal risk assessment upon hospital admission for screening of carriage with multidrug-resistant micro-organisms in a Dutch tertiary care centre.

BACKGROUND: In Dutch hospitals a six-point questionnaire is currently mandatory for risk assessment to identify carriers of multidrug-resistant organisms (MDROs) at the time of hospitalization. Presence of one or more risk factors is followed by pre-emptive isolation and microbiological culturing. AIM: To evaluate the yield of the universal risk assessment in identifying MDRO carriers upon hospitalization. METHODS: A cross-sectional study was performed using routine healthcare data in a Dutch tertiary hospital between January 1st, 2015 and August 1st, 2019. MDRO risk assessment upon hospitalization included assessment of: known MDRO carriage, previous hospitalization in another Dutch hospital during an outbreak or a foreign hospital, living in an asylum centre, exposure to livestock farming, and household membership of a meticillin-resistant Staphylococcus aureus carrier. FINDINGS: In total, 144,051 admissions of 84,485 unique patients were included; 4480 (3.1%) admissions had a positive MDRO risk assessment. In 1516 (34%) admissions microbiological screening was performed, of which 341 (23%) yielded MDRO. Eighty-one patients were categorized as new MDRO carriers, as identified through MDRO risk assessment, reflecting 0.06% (95% confidence interval: 0.04-0.07) of all admissions and 1.8% (1.4-2.2) of those with positive risk assessment. As a result, the number of 'MDRO risk assessments needed to perform' and individual 'MDRO questions needed to ask' to detect one new MDRO carrier upon hospitalization were 1778 and 10,420, respectively. CONCLUSION: The yield of the current strategy of MDRO risk assessment upon hospitalization is limited and it needs thorough reconsideration.

Childhood infections and common carotid intima media thickness in adolescence.

Atherosclerotic changes can be measured as changes in common carotid intima media thickness (CIMT). It is hypothesised that repeated infection-associated inflammatory responses in childhood contribute to the atherosclerotic process. We set out to determine whether the frequency of infectious diseases in childhood is associated with CIMT in adolescence. The study is part of the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) population-based birth cohort. At age 16 years, common CIMT was measured. We collected general practitioner (GP) diagnosed infections and prescribed antibiotics. Parent-reported infections were retrieved from annual questionnaires. Linear regression analysis assessed the association between number of infections during the first 4 years of life and common CIMT. Common CIMT measurement, GP and questionnaire data were available for 221 participants. No association was observed between the infection measures and CIMT. In a subgroup analysis, significant positive associations with CIMT were observed in participants with low parental education for 2-3 or ⩾7 GP diagnosed infections (+26.4 µm, 95% CI 0.4-52.4 and +26.8 µm, 95% CI 3.6-49.9, respectively) and ⩾3 antibiotic prescriptions (+35.5 µm, 95%CI 15.8-55.3). Overall, early childhood infections were not associated with common CIMT in adolescence. However, a higher number of childhood infections might contribute to the inflammatory process of atherosclerosis in subgroups with low education, this needs to be confirmed in future studies.

Updated cost-effectiveness and risk-benefit analysis of two infant rotavirus vaccination strategies in a high-income, low-endemic setting.

BACKGROUND AND OBJECTIVE: Since 2013, a biennial rotavirus pattern has emerged in the Netherlands with alternating high and low endemic years and a nearly 50% reduction in rotavirus hospitalization rates overall, while infant rotavirus vaccination has remained below 1% throughout. As the rotavirus vaccination cost-effectiveness and risk-benefit ratio in high-income settings is highly influenced by the total rotavirus disease burden, we re-evaluated two infant vaccination strategies, taking into account this recent change in rotavirus epidemiology. METHODS: We used updated rotavirus disease burden estimates derived from (active) surveillance to evaluate (1) a targeted strategy with selective vaccination of infants with medical risk conditions (prematurity, low birth weight, or congenital conditions) and (2) universal vaccination including all infants. In addition, we added herd protection as well as vaccine-induced intussusception risk to our previous cost-effectiveness model. An age- and risk-group structured, discrete-time event, stochastic multi-cohort model of the Dutch pediatric population was used to estimate the costs and effects of each vaccination strategy. RESULTS: The targeted vaccination was cost-saving under all scenarios tested from both the healthcare payer and societal perspective at rotavirus vaccine market prices (€135/child). The cost-effectiveness ratio for universal vaccination was €51,277 at the assumed vaccine price of €75/child, using a societal perspective and 3% discount rates. Universal vaccination became cost-neutral at €32/child. At an assumed vaccine-induced intussusception rate of 1/50,000, an estimated 1707 hospitalizations and 21 fatal rotavirus cases were averted by targeted vaccination per vaccine-induced intussusception case. Applying universal vaccination, an additional 571 hospitalizations and <  1 additional rotavirus death were averted in healthy children per vaccine-induced intussusception case. CONCLUSION: While universal infant rotavirus vaccination results in the highest reductions in the population burden of rotavirus, targeted vaccination should be considered as a cost-saving alternative with a favorable risk-benefit ratio for high-income settings where universal implementation is unfeasible because of budget restrictions, low rotavirus endemicity, and/or public acceptance.

Impact of infant pneumococcal conjugate vaccination on community acquired pneumonia hospitalization in all ages in the Netherlands.

BACKGROUND: The long-term impact of pneumococcal conjugate vaccines on pneumonia hospitalizations in all age-groups varies between countries. In the Netherlands, the 7-valent pneumococcal conjugate vaccine (PCV7) was implemented for newborns in 2006 and replaced by PCV10 in 2011. We assessed the impact of PCVs on community-acquired pneumonia (CAP) hospitalization rates in all age-groups. METHODS: A time series analysis using Poisson regression was performed on 155,994 CAP hospitalizations. Hospitalization rates were calculated using the total number of hospitalizations as denominator. The time trend in the pre-PCV period (1999-2006) was extrapolated to predict the hospitalization rate in the post-PCV period (2006-2014) if PCV had not been implemented. Rate ratios over time were calculated by comparing observed and predicted time trends. RESULTS: In children <5 years of age, the observed hospitalization rates during the post-PCV period were significantly lower than predicted if PCV had not been implemented (0-6 months: 0.62, 95% CI: 0.41-0.96; 6 months - 1 year: 0.67, 95% CI: 0.50-0.90; 2-4 years: 0.78, 95% CI: 0.61-0.97). In all other age-groups, rate ratios declined over time but did not reach statistical significance. CONCLUSIONS: After introduction of PCV, CAP hospitalizations declined in young children but no clear impact of PCV on CAP hospitalizations was seen in other age-groups.

Rotavirus disease course among immunocompromised patients; 5-year observations from a tertiary care medical centre.

Rotavirus (RV) is highly endemic inside and outside hospital-settings. Immunocompromised children and adults are at risk of complicated rotavirus gastroenteritis (RVGE), but general rotavirus disease severity in this group remains poorly described and rotavirus testing is not routinely performed beyond infancy. We assessed rotavirus disease among immunocompromised hospitalized patients. METHODS: Rotavirus infections at a Dutch tertiary-care centre were identified from 5-year laboratory records. Rotavirus disease course was evaluated by chart review for each immunocompromised patient. In a matched case-control analysis, we assessed whether being immunocompromised predisposed to RVGE. Rotavirus testing practice for suspected infectious gastroenteritis in our hospital was determined over a 3-years period. RESULTS: Out of 4584 RV tests performed, 294 were positive among hospitalized patients. Immunocompromised patients represented 57% (N = 20) of adult, and 12% (N = 32) of paediatric RVGE. A complicated disease course occurred in 81% of them and 33% required adaptations in underlying disease management. Immunocompromised adults were 7.4 times more likely todevelop RVGE compared to non-immunocompromised matched hospital-controls. Rotavirus testing in adult patients with suspected infectious gastroenteritis was uncommon (12% tested). CONCLUSIONS: In our hospital, most adults with RVGE are immunocompromised compared to a much smaller proportion in children. RVGE in immunocompromised patients is associated with significant morbidity. Routine rotavirus testing beyond infancy should be recommended for immunocompromised patients with suspected infectious gastroenteritis.

Exceptionally low rotavirus incidence in the Netherlands in 2013/14 in the absence of rotavirus vaccination.

An unexpected drop in rotavirus (RV) detections was observed in the Netherlands in 2014, without RV vaccination. The estimated decrease in RV detections and gastroenteritis consultations in under five year-olds, in January-April 2014, compared to the same months in previous years, was 72% and 36%, respectively. The low birth rate, mild winter, high RV incidence in the previous year and the introduction of RV vaccination in neighbouring countries may have contributed to this decrease.