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1.
medrxiv; 2024.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2024.03.06.24303851

ABSTRACT

Background: The first wave of the COVID-19 pandemic in 2020 was largely mitigated by reducing contacts in the general population. In 2022 most contact-reducing measures were lifted. Aim We assess whether the population has reverted to pre-pandemic contact behaviour and how this would affect the transmission potential of a newly emerging pathogen. Methods The PIENTER Corona study was held every 2-6 months in the Netherlands from April 2020, as a follow-up on the 2016-2017 PIENTER3 study. In both studies, participants (ages 1-85) reported the number and age group of all face-to-face persons contacted on the previous day. The contact behaviour during and after the COVID-19 pandemic was compared to the pre-pandemic baseline. Results We found an average of 15.2 (13.3-16.9, 95% CI) community contacts per person per day in the post-pandemic period, which is 14% lower than the baseline value of 17.6 (16.3-18.9). Children have the highest number of contacts as before the pandemic. Mainly adults aged 20-59 have not reverted to their pre-pandemic behaviour, possibly because this age group works more often from home. Although the number of contacts is structurally lower compared to the pre-pandemic period, the effect on the potential spread of a newly emerging respiratory pathogen is limited if all age groups were equally susceptible. If younger age groups were less susceptible, as observed during the first COVID-19 wave, the transmission potential as well as the required control effort would be lower. Conclusion Continuous monitoring of contacts is needed to be prepared for a future pandemic.


Subject(s)
COVID-19
2.
medrxiv; 2024.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2024.01.24.24301644

ABSTRACT

SARS-CoV-2 infections elicit antibodies against the viral spike (S) and nucleocapsid (N) proteins; COVID-19 vaccines against the S-protein only. The BCG-Corona trial, initiated in March 2020 in SARS-CoV-2-naive Dutch healthcare workers, captured several epidemic peaks and the introduction of COVID-19 vaccines during the one-year follow-up. We assessed determinants of systemic anti-S1 and anti-N immunoglobulin type G (IgG) responses using trial data. Participants were randomized to BCG or placebo vaccination, reported daily symptoms, SARS-CoV-2 test results, and COVID-19 vaccinations, and donated blood for SARS-CoV-2 serology at two time points. In the 970 participants, anti-S1 geometric mean antibody concentrations (GMCs) were much higher than anti-N GMCs. Anti-S1 GMCs significantly increased with increasing number of immune events (SARS-CoV-2 infection or COVID-19 vaccination): 104.7 international units (IU)/ml, 955.0 IU/ml, and 2290.9 IU/ml for one, two, and three immune events, respectively (p<0.001). In adjusted multivariable linear regression models, anti-S1 and anti-N log10 concentrations were significantly associated with infection severity, and anti-S1 log10 concentration with COVID-19 vaccine type/dose. In univariable models, anti-N log10 concentration was also significantly associated with acute infection duration, and severity and duration of individual symptoms. Antibody concentrations were not associated with Long COVID or long-term loss of smell/taste.


Subject(s)
Acute Disease , Severe Acute Respiratory Syndrome , COVID-19
3.
medrxiv; 2023.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2023.02.09.23285703

ABSTRACT

Background: Severity of SARS-CoV-2 infection may vary over time. Here, we estimate age-specific risks of hospitalization, ICU admission and death given infection in the Netherlands from February 2020 - June 2021. Methods: A nationwide longitudinal serology study was used to estimate numbers of infections in three epidemic periods (February 2020 - June 2020, July 2020 - February 2021, March 2021 - June 2021). We accounted for reinfections and, as vaccination started in January 2021, breakthrough infections among vaccinated persons. Severity estimates were inferred by combining numbers of infections with aligned numbers of hospitalizations and ICU admissions from a national hospital-based registry, and aligned numbers of deaths based on national excess all-cause mortality estimates. Results: In each period there was a nearly consistent pattern of accelerating, almost exponential, increase in severity of infection with age. The rate of increase with age was highest for death and lowest for hospitalization. In the first period, the overall risk of hospitalization, ICU admission and death were 1.5% (95%-confidence interval [CI] 1.3-1.8%), 0.36% (95%-CI: 0.31-0.42%) and 1.2% (95%-CI: 1.0-1.4), respectively. The risk of hospitalization was higher in the following periods, while the risk of ICU admission remained stable. The risk of death decreased over time, with a substantial drop among [≥]70-years-olds in February 2021 - June 2021. Conclusion: The accelerating increase in severity of SARS-CoV-2 with age remained intact during the first three epidemic periods in the Netherlands. The substantial drop in risk of death among elderly in the third period coincided with the introduction of COVID-19 vaccination.


Subject(s)
COVID-19 , Breakthrough Pain , Death
4.
medrxiv; 2022.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2022.12.12.22283282

ABSTRACT

Background. Bacillus Calmette-Guerin (BCG) vaccination has been hypothesised to reduce SARS-CoV-2 infection, severity, and/or duration via trained immunity induction. Methods. Healthcare workers (HCWs) in 9 Dutch hospitals were randomised to BCG or placebo vaccination (1:1) in March/April 2020 and followed for one year. They reported daily symptoms, SARS-CoV-2 test results, and healthcare-seeking behaviour via a smartphone application, and donated blood for SARS-CoV-2 serology at two time points. Results. 1,511 HCWs were randomised and 1,309 analysed (665 BCG and 644 placebo). Of the 298 infections detected during the trial, 74 were detected by serology only. The SARS-CoV-2 incidence rates were 0.25 and 0.26 per person-year in the BCG and placebo groups, respectively (incidence rate ratio=0.95; 95% confidence interval 0.76-1.21; p=0.732). Only three participants required hospitalisation for COVID-19. The proportions of participants with asymptomatic, mild, or mild-to-moderate infections, and the mean infection durations, did not differ between randomisation groups. Unadjusted and adjusted logistic regression and Cox proportional hazards models showed no differences between BCG and placebo vaccination for any of these outcomes either. The percentage of participants with seroconversion (7.8% versus 2.8%; p=0.006) and mean anti-S1 antibody concentration (13.1 versus 4.3 IU/ml; p=0.023) were higher in the BCG than placebo group at 3 months but not at 6 or 12 months post-vaccination. Conclusions. BCG vaccination of HCWs did not reduce SARS-CoV-2 infections nor infection duration or severity (on a scale from asymptomatic to moderate). In the first 3 months after vaccination, BCG vaccination may enhance SARS-CoV-2 antibody production during SARS-CoV-2 infection.


Subject(s)
COVID-19 , Severe Acute Respiratory Syndrome
5.
medrxiv; 2020.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2020.05.20.20108126

ABSTRACT

ImportanceThe degree to which children and young people are infected by and transmit the SARS-CoV-2 virus is unclear. The role of children and young people in transmission of SARS-CoV-2 is dependent on susceptibility, symptoms, viral load, social contact patterns and behaviour. ObjectiveWe undertook a rapid systematic review to address the question "What is the susceptibility to and transmission of SARS-CoV-2 by children and adolescents compared with adults?" Data sourcesWe searched PubMed and medRxiv up to 28 July 2020 and identified 13,926 studies, with additional studies identified through handsearching of cited references and professional contacts. Study SelectionWe included studies which provided data on the prevalence of SARS-CoV-2 in children and young people (<20 years) compared with adults derived from contact-tracing or population-screening. We excluded single household studies. Data extraction and SynthesisWe followed PRISMA guidelines for abstracting data, independently by 2 reviewers. Quality was assessed using a critical appraisal checklist for prevalence studies. Random effects meta-analysis was undertaken. Main OutcomesSecondary infection rate (contact-tracing studies) or prevalence or seroprevalence (population-screening studies) amongst children and young people compared with adults. Results32 studies met inclusion criteria; 18 contact-tracing and 14 population-screening. The pooled odds ratio of being an infected contact in children compared with adults was 0.56 (0.37, 0.85) with substantial heterogeneity (95%). Three school contact tracing studies found minimal transmission by child or teacher index cases. Findings from population-screening studies were heterogenous and were not suitable for meta-analysis. The majority of studies were consistent with lower seroprevalence in children compared with adults, although seroprevalence in adolescents appeared similar to adults. ConclusionsThere is preliminary evidence that children and young people have lower susceptibility to SARS-CoV-2, with a 43% lower odds of being an infected contact. There is weak evidence that children and young people play a lesser role in transmission of SARS-CoV-2 at a population level. Our study provides no information on the infectivity of children. Key pointsO_ST_ABSQuestionC_ST_ABSWhat is the evidence on the susceptibility and transmission of children and young people to SARS-CoV-2 in comparison with adults? FindingsIn this systematic review and meta-analysis, children and young people under 18-20 years had an 435 lower odds of secondary infection of with SARS-CoV-2 compared to adults 20 years plus, a significant difference. This finding was most marked in children under 12-14 years. Data were insufficient to conclude whether transmission of SARS-CoV-2 by children is lower than by adults. MeaningWe found preliminary evidence that children have a lower susceptibility for SARS-CoV-2 infection compared with adults, although data for adolescents is less clear. The role that children and young people play in transmission of this pandemic remains unclear.


Subject(s)
COVID-19
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