The impact of wildtype SARS-CoV-2 on fatigue and quality of life: prevalence of post COVID-19 condition in a Dutch population-based serosurveillance cohort. (preprint)

Background: Our aim was to assess the relationship between (time since) wild-type SARS-CoV-2 infection and health-related quality of life (HRQoL) and fatigue as endpoints linked to Post COVID-19 condition (PCC). Methods: Participants [≥]15 years were selected from the February 2021 round of the population-based PIENTER Corona study. We investigated the association between (time since) SARS-COV-2 infection and health outcomes: HRQoL (health utility (SF-6D); physical health and mental health (both SF-12)) and fatigue (CIS-fatigue) using multivariable logistic regression analyses adjusted for age, sex, educational level, number of comorbidities, COVID-19 vaccination status, and the intensity of restrictions. For each outcome, multivariable logistic regression models were fitted at cut-off points selected based on the cumulative distribution of those uninfected. Results: Results shown correspond to the cut-off point related to the worst off 15% of each outcome. Significant differences between those uninfected (n=4,614) and cases infected [≤]4 months ago (n=368) were observed for health utility (OR [95%CI]: 1.6 [1.2-2.2]), physical health (OR [95%CI]: 1.7 [1.3-2.3]) and fatigue (OR [95%CI]: 1.6 [1.2-2.0]), but not for mental health. There were no significant differences between uninfected and cases infected >4 months ago (n=345) for all outcomes. Conclusions: In a Dutch population-based cohort of seroconverted individuals, those infected with wild-type SARS-CoV-2 [≤]4 months ago more often reported poor health utility and physical health and were more often severely fatigued compared to those uninfected (at the 15% cut-off). HRQoL and fatigue remained below the detection limit for those infected >4 months ago, suggesting a relatively low prevalence of PCC.

Contact behaviour before, during and after the COVID-19 pandemic in the Netherlands: evidence from contact surveys in 2016-2017 and 2020-2023 (preprint)

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.

Nationwide SARS-CoV-2 Seroprevalence Trends in the Netherlands in the Variant of Concern Era, 2021-2022: an Ongoing Prospective Cohort Study (preprint)

BackgroundRepeated population-based SARS-CoV-2 serosurveillance is key in complementing other surveillance tools. AimAssessing trends in infection- and/or vaccine-induced immunity, including breakthrough infections, among (sub)groups and regions in the Dutch population during the Variant of Concern (VOC)-era whilst varying levels of stringency, to evaluate population immunity dynamics and inform future pandemic response planning. MethodsIn this prospective population-based cohort, randomly-selected participants (n=9,985) aged 1-92 years (recruited since early-2020) donated home-collected fingerstick blood samples at six timepoints in 2021-2022, covering waves dominated by Alpha, Delta, and Omicron (BA.1, BA.2, BA.5). IgG antibody assessments against Spike-S1 and Nucleoprotein were combined with vaccination- and testing data to estimate infection-induced (inf) and total (infection- and vaccination-induced) seroprevalence. ResultsIn 2021, nationwide inf-seroprevalence rose modestly from 12% since Alpha to 26% amidst Delta, while total seroprevalence increased rapidly to nearly 90%, particularly fast in vulnerable groups (i.e., elderly and those with comorbidities). Highest infection rates were noticeable in adolescents and young adults, low/middle educated elderly, non-Western, contact professions (other than healthcare), and low-vaccination coverage regions. In 2022, following Omicron emergence, inf-seroprevalence elevated sharply to 62% and further to 86%, with frequent breakthrough infections and reduction of seroprevalence dissimilarities between most groups. Whereas >90% of <60-year-olds had been infected, 30% of vaccinated vulnerable individuals had not acquired hybrid immunity. ConclusionAlthough total SARS-CoV-2 seroprevalence had increased rapidly, infection rates were unequally distributed within the Dutch population. Ongoing tailored vaccination efforts and (sero-)monitoring of vulnerable groups remain important given their lowest rate of hybrid immunity and highest susceptibility to severe disease.

Age-specific severity of SARS-CoV-2 in February 2020 - June 2021 in the Netherlands (preprint)

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.

Dynamics of non-household contacts during the COVID-19 pandemic in 2020 and 2021 in the Netherlands (preprint)

The COVID-19 pandemic was in 2020 and 2021 for a large part mitigated by reducing contacts in the general population. To monitor how these contacts changed over the course of the pandemic in the Netherlands, a longitudinal survey was conducted where participants reported on their at-risk contacts every two weeks, as part of the European CoMix survey. The survey included 1659 participants from April to August 2020 and 2514 participants from December 2020 to September 2021. We categorized the number of unique contacted persons excluding household members, reported per participant per day into six activity levels, defined as 0, 1, 2, 3-4, 5-9 and 10 or more reported contacts. After correcting for age, vaccination status, risk status for severe outcome of infection, and frequency of participation, activity levels increased over time, coinciding with relaxation of COVID-19 control measures.

Estimating the asymptomatic proportion of SARS-CoV-2 infection in the general population: Analysis of a nationwide serosurvey in the Netherlands (preprint)

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 <20 years age-group, to 55% (95% CI: 48-68%) for the 70+ years age-group. 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.

Associations between measures of social distancing and SARS-CoV-2 seropositivity: a nationwide population-based study in the Netherlands (preprint)

ABSTRACT 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.

The impact of physical distancing measures against COVID-19 transmission on contacts and mixing patterns in the Netherlands: repeated cross-sectional surveys (preprint)

BackgroundDuring the current pandemic of coronavirus (COVID-19) many countries have taken drastic measures to reduce transmission of SARS-CoV2. The measures often include physical distancing that aims to reduce the number of contacts in the population. Little is known about the actual reduction in number of contacts as a consequence of physical distancing measures. MethodsIn the Netherlands, a cross-sectional survey was carried out in 2016/2017 in which 8179 participants retrospectively reported the number, age and gender of different persons they had contacted (spoken to in person or touched) during the previous day. The survey was repeated among 2830 of the original participants, using the same questionnaire, in March and April 2020 after physical distancing measures had been implemented. ResultsThe average number of contacts in the community was reduced from on average 12.5 (interquartile range: 2-17) to 3.7 (interquartile range: 0-4) different persons per participant, a reduction of 71% (95% confidence interval: 71-71). The reduction in the number of community contacts was highest for children and adolescents (between 5 and 20 years) and smallest for elderly persons of 80 years and older. The reduction in the effective number of total contacts, measured as the largest eigenvalue of the matrix with community and household contacts, was 62% (95% confidence interval: 48 - 72). ConclusionThe substantial reduction in contacts has contributed greatly in halting the COVID-19 epidemic. This reduction was unevenly distributed over age groups, household sizes and occupations. These findings offer guidance for the lifting of age-group targeted measures.