The Impact of School and Family Networks on COVID-19 Infections Among Dutch Students: A Study Using Population-Level Registry Data (preprint)

Understanding the impact of different social interactions is key to improving epidemic models. Here, we use extensive registry data -- including PCR test results and population-level networks -- to investigate the impact of school, family, and other social contacts on SARS-CoV-2 transmission in the Netherlands (June 2020--October 2021). We isolate and compare different contexts of potential SARS-CoV-2 transmission by matching pairs of students based on their attendance at the same or different primary school (in 2020) and secondary school (in 2021) and their geographic proximity. We then calculated the probability of temporally associated infections -- i.e. the probability of both students testing positive within a 14-day period. Our results highlight the relative importance of household and family transmission in the spread of SARS-CoV-2 compared to school settings. The probability of temporally associated infections for siblings and parent-child pairs living in the same household was 22.6--23.2\%, and 4.7--7.9\% for family members living in different household. In contrast, the probability of temporally associated infections was 0.52\% for pairs of students living nearby but not attending the same primary or secondary school, 0.66\% for pairs attending different secondary schools but having attended the same primary school, and 1.65\% for pairs attending the same secondary school. Finally, we used multilevel regression analyses to examine how individual, school, and geographic factors contribute to transmission risk. We found that the largest differences in transmission probabilities were due to unobserved individual (60\%) and school-level (34\%) factors. Only a small proportion (3\%) could be attributed to geographic proximity of students or to school size, denomination, or the median income of the school area.

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.

Lower prevalence of Post-Covid-19 Condition following Omicron SARS-CoV-2 infection. (preprint)

Background: Different SARS-CoV-2 variants can differentially affect the prevalence of Post Covid-19 Condition (PCC). This prospective study assesses prevalence and severity of symptoms three months after an Omicron infection, compared to Delta, test-negative and population controls. This study also assesses symptomology after reinfection and breakthrough infections . Methods: After a positive SARS-CoV-2 test, cases were classified as Omicron or Delta based on [≥] 85% surveillance prevalence. Population controls were representatively invited and symptomatic test-negative controls enrolled after a negative SARS-CoV-2 test. Three months after enrolment, participants indicated point prevalence for 41 symptoms and severity of four symptoms. Permutation tests identified significantly elevated symptoms in cases compared to controls. PCC prevalence was estimated as the difference in prevalence of at least one elevated symptom in cases compared to population controls. Findings: At three months follow-up, five symptoms and severe dyspnea were significantly elevated in Omicron cases (n = 4138) compared to test-negative (n= 1672) and population controls (n= 2762). PCC prevalence was 10.4% for Omicron cases and 17.7% for Delta cases (n = 6855). Prevalence of severe fatigue and dyspnea were higher in reinfected compared to primary infected Omicron cases, while severity of symptoms did not significantly differ between Omicron cases with a booster or primary vaccination course. Interpretation: Three months after Omicron, prevalence of PCC is 41% lower than after Delta. Reinfection seems associated with more prevalent severe long-term symptoms compared to a first infection. A booster prior to infection does not seem to improve the outcome of long-term symptoms. Funding: The study is executed by the National Institute for Public Health and the Environment by order of the Ministry of Health, Welfare and Sport.

Prevalence and severity of symptoms 3 months after infection with SARS-CoV-2 compared to test-negative and population controls in the Netherlands (preprint)

Background: More information is needed on prevalence of long-term symptoms after SARS-CoV-2-infection. This prospective study assesses symptoms three months after SARS-CoV-2-infection compared to test-negative and population controls, and the effect of vaccination prior to infection. Methods: Participants enrolled after a positive (cases) or negative (test-negative controls) SARS-CoV-2-test, or after invitation from the general population (population controls). After three months, participants indicated presence of 41 symptoms, and severity of four symptoms. Permutation tests were used to select symptoms significantly elevated in cases compared to controls and to compare symptoms between cases that were vaccinated or unvaccinated prior to infection. Findings: Between May 19th and December 13th 2021 9166 cases, 1698 symptomatic but test-negative controls, and 3708 population controls enrolled. At three months, 13 symptoms, and severity of fatigue, cognitive impairment and dyspnoea, were significantly elevated between cases and controls. Of cases, 48.5% reported [≥]1 significantly elevated symptom, compared to 29.8% of test-negative controls and 26.0% of population controls. Effect of vaccination could only be determined for cases <65yrs, and was found to be significantly protective for loss of smell and taste but not for other symptoms. Interpretation: Three months after SARS-CoV-2 infection, almost half of the cases still report symptoms, which is higher than the background prevalence and prevalence in test-negative controls. Vaccination prior to infection was protective against loss of smell and taste as assessed in cases aged <65.

Empirical evidence of transmission over a school-household network for SARS-CoV-2; exploration of transmission pairs stratified by primary and secondary school. (preprint)

Background Children play a key role in the transmission of many infectious diseases. They have many of their close social encounters at home or at school. We hypothesized that most of the transmission of respiratory infections among children occur in these two settings and that transmission patterns can be predicted by a bipartite network of schools and households. Aim and methods To confirm transmission over a school-household network, SARS-CoV-2 transmission pairs in children aged 4-17 years were analyzed by study year and primary/secondary school. Cases with symptom onset between the 1st of March 2021 and the 4th of April 2021 identified by source and contact-tracing in the Netherlands were included. In this period, primary schools were open and secondary school students attended class at least once per week. Within pairs, spatial distance between the postcodes was calculated as the Euclidean distance. Results A total of 4,059 transmission pairs were identified; 51.9% between primary schoolers; 19.6% between primary and secondary schoolers; 28.5% between secondary schoolers. Most (68.5%) of the transmission for children in the same study year occurred at school. In contrast, most of the transmission of children from different study years (64.3%) and most primary-secondary transmission (81.7%) occurred at home. The average spatial distance between infections was 1.2km (median 0.4) for primary school pairs, 1.6km (median 0) for primary-secondary school pairs and 4.1km (median 1.2) for secondary school pairs. Conclusion The results provide evidence of transmission on a bipartite school-household network. Schools play an important role in transmission within study years, and households play an important role in transmission between study years and between primary and secondary schools. Spatial distance between infections in a transmission pair reflects the smaller school catchment area of primary schools versus secondary schools. Many of these observed patterns likely hold for other respiratory pathogens.

Prevalence and determinants of persistent symptoms after infection with SARS-CoV-2: Protocol for an observational cohort study (LongCOVID-study) (preprint)

Background: A substantial proportion of individuals infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) report persisting symptoms weeks and months following acute infection. Estimates on prevalence vary due to differences in study designs, populations, heterogeneity of symptoms and the way symptoms are measured. Common symptoms include fatigue, cognitive impairment and dyspnea. However, knowledge regarding the nature and risk factors for developing persisting symptoms is still limited. Hence in this study we aim to determine the prevalence, severity, risk factors and impact on quality of life of persisting symptoms in the first year following acute SARS-CoV-2 infection. Methods: The LongCOVID-study is both a prospective and retrospective cohort study with a one year follow up. Participants aged 5 years and above with self-reported positive or negative tests for SARS-CoV-2 will be included in the study. The primary outcome is the prevalence and severity of persistent symptoms in participants that tested positive for SARS-CoV-2 compared to controls. Symptom severity will be assessed for fatigue using the Checklist Individual Strength (CIS subscale fatigue severity), pain (Rand-36/SF-36 subscale bodily pain), dyspnea (Medical Research Council (mMRC)) and cognitive impairment using the Cognitive Failure Questionnaire (CFQ). Secondary outcomes include loss of health-related quality of life (HRQoL) and risk factors for persisting symptoms following infection with SARS-CoV-2. Discussion: A better understanding regarding the nature of persisting symptoms following SARS-CoV-2 infection will enable better diagnosis, management and will consequently minimize negative consequences on quality of life. Keywords: SARS-CoV-2, post COVID-19 condition, LongCovid, prevalence, HRQoL, risk factors

The impact of vaccinating adolescents and children on COVID-19 disease outcomes (preprint)

Introduction: Despite the high COVID-19 vaccination coverage among adults, there is concern over a peak in SARS-CoV-2 infections in the coming months. To help ensure that healthcare systems are not overwhelmed in the event of a new wave of SARS-CoV-2 infections, many countries have extended vaccination to adolescents (those aged 12-17 years) and may consider further extending to children aged 5-11 years. However, there is considerable debate about whether or not to vaccinate healthy adolescents and children against SARS-CoV-2 because, while vaccination of children and adolescents may limit transmission from these groups to other, more vulnerable groups, adolescents and children themselves have limited risk of severe disease if infected and may experience adverse events from vaccination. To quantify the benefits of extending COVID-19 vaccination beyond adults we compare daily cases, hospital admissions, and intensive care (IC) admissions for vaccination in adults only, those 12 years and above, and those 5 years and above. Methods and Findings: We developed a deterministic, age-structured susceptible-exposed-infectious-recovered (SEIR) model to simulate disease outcomes (e.g., cases, hospital admissions, IC admissions) under different vaccination scenarios. The model is partitioned into 10-year age bands (0-9, 10-19, ..., 70-79, 80+) and accounts for differences in susceptibility and infectiousness by age group, seasonality in transmission rate, modes of vaccine protection (e.g., infection, transmission), and vaccine characteristics (e.g., vaccine effectiveness). Model parameters are estimated by fitting the model piecewise to daily cases from the Dutch notification database Osiris from 01 January 2020 to 22 June 2021. Forward simulations are performed from 22 June 2021 to 31 March 2022. We performed sensitivity analyses in which vaccine-induced immunity waned. We found that upon relaxation of all non-pharmaceutical control measures a large wave occurred regardless of vaccination strategy. We found overall reductions of 5.7% (4.4%, 6.9%) of cases, 2.0% (0.7%, 3.2%) of hospital admissions, and 1.7% (0.6%, 2.8%) of IC admissions when those 12 years and above were vaccinated compared to vaccinating only adults. When those 5 years and above were vaccinated we observed reductions of 8.7% (7.5%, 9.9%) of cases, 3.2% (2.0%, 4.5%) of hospital admissions, and 2.4% (1.2%, 3.5%) of IC admissions compared to vaccination in adults only. Benefits of extending vaccination were larger within the age groups included in the vaccination program extension than in other age groups. The benefits of vaccinating adolescents and children were smaller if vaccine protection against infection, hospitalization, and transmission (once infected) wanes. Discussion: Our results highlight the benefits of extending COVID-19 vaccination programs beyond adults to reduce infections and severe outcomes in adolescents and children and in the wider population. A reduction of infections in school-aged children/adolescents may have the added benefit of reducing the need for school closures during a new wave. Additional control measures may be required in future to prevent a large wave despite vaccination program extensions. While the results presented here are based on population characteristics and the COVID-19 vaccination program in The Netherlands, they may provide valuable insights for other countries who are considering COVID-19 vaccination program extensions.

Testing behaviour and positivity for SARS-CoV-2 infection: Insights from web-based participatory surveillance (preprint)

BackgroundVoluntary testing for SARS-CoV-2 infection is an integral component of an effective response to the COVID-19 pandemic. It is essential to identify populations at a high risk for infection but who are less likely to present for testing. Here, we use internet-based participatory surveillance data from the Netherlands to identify sociodemographic and household factors that are associated with a lower propensity to be tested and, if tested, with a higher risk of a positive test result.MethodsMultivariable analyses using generalised estimating equations for binomial outcomes were conducted to estimate the adjusted odds ratios of testing and of positivity associated with participant and household characteristics.ResultsBased on five months (17 November 2020 to 18 April 2021) of weekly surveys obtained from 12,026 participants, males (adjusted odds ratio for testing (ORt): 0.92; adjusted odds ratio for positivity (ORp): 1.30, age-groups <20 (ORt: 0.89; ORp: 1.27) 50-64 years (ORt: 0.94; ORp: 1.06) and 65+ years (ORt: 0.78; ORp: 1.24), diabetics (ORt: 0.97; ORp: 1.06), and sales/administrative employees (ORt: 0.93; ORp: 1.90) were distinguished as lower propensity/higher positivity factors.ConclusionsThe factors identified using this approach can help identify potential target groups for improving communication and encouraging testing among those with symptoms and thus increase the effectiveness of testing, which is essential for the response to the COVID-19 pandemic and for public health strategies in the longer term.

Implications of the school-household network structure on SARS-CoV-2 transmission under different school reopening strategies in England (preprint)

Background School closures are a well-established non-pharmaceutical intervention in the event of infectious disease outbreaks, and have been implemented in many countries across the world, including the UK, to slow down the spread of SARS-CoV-2. As governments begin to relax restrictions on public life there is a need to understand the potential impact that reopening schools may have on transmission. Methods We used data provided by the UK Department for Education to construct a network of English schools, connected through pairs of pupils resident at the same address. We used the network to evaluate the potential for transmission between schools, and for long range propagation across the network, under different reopening scenarios. Results Amongst the options evaluated we found that reopening only Reception, Year 1 and Year 6 (4-6 and 10-11 year olds) resulted in the lowest risk of transmission between schools, with outbreaks within a single school unlikely to result in outbreaks in adjacent schools in the network. The additional reopening of Years 10 and 12 (14-15 and 16-17 year olds) resulted in an increase in the risk of transmission between schools comparable to reopening all primary school years (4-11 year olds). However, the majority of schools presented low risk of initiating widespread transmission through the school system. Reopening all secondary school years (11-18 year olds) resulted in large potential outbreak clusters putting up to 50% of households connected to schools at risk of infection if sustained transmission within schools was possible. Conclusions Reopening secondary school years is likely to have a greater impact on community transmission than reopening primary schools in England. Keeping transmission within schools limited is essential for reducing the risk of large outbreaks amongst school-aged children and their household members.