Feasibility of SARS-CoV-2 Surveillance Testing Among Children and Childcare Workers at German Day Care Centers

Key Points Question Is continuous SARS-CoV-2 testing accepted by children, parents, and childcare workers and can it prevent viral spreading in day care centers? Findings In this nonrandomized controlled trial, surveillance testing for SARS-CoV-2 among 954 eligible individuals was well accepted by children, parents, and childcare workers if saliva sampling at home was used. Mathematical modeling based on study and literature data identified biweekly testing of at least 50% of children and childcare workers as minimal requirements to limit secondary infections. Meaning These findings suggest that SARS-CoV-2 surveillance testing is feasible and allows for continued day care attendance for children during the COVID-19 pandemic.


Introduction
The global COVID-19 pandemic has resulted in substantial public health measures, including closure of schools and day care centers (DCCs). 1 The latter was mainly based on evidence showing that children are associated with transmission of influenza and that DCC closure can be effective in limiting viral spread. [2][3][4] In addition, effective nonpharmaceutical interventions, such as medical masks or physical distancing, cannot be applied for preschool children. Despite differences between influenza viruses and SARS-CoV-2, 5 modeling studies [6][7][8] have suggested that closure of schools and DCCs might be beneficial in limiting the dissemination of SARS-CoV-2. However, other models 9,10 support reopening of childcare facilities, suggesting that they have only a minor impact on viral spreading in the population or disproportionate negative effects. Diminished educational, psychosocial, and nutritional opportunities are negative consequences of DCC closures, 11 especially for children with special educational needs, chronic disease, and poor socioeconomic status. 12 Closure of childcare facilities also poses a substantial risk of parenting-related exhaustion, 13 which is a factor associated with increased risk of child abuse. Indeed, violence against children has been addressed as "a hidden crisis of the COVID-19 pandemic" by the World Health Organization. 14 Closure of DCCs and schools mainly benefits the society at large, because children are mostly mildly affected by SARS-CoV-2 and complications are rare. 15,16 Up to now, children have had a very low seroprevalence for SARS-CoV-2, 17 and a longitudinal testing study 18 revealed no relevant number of hidden cases among children in kindergarten or schools. Prospective contact tracing indicated a very low risk of secondary transmission in DCCs, and childcare exposure was not associated with SARS-CoV-2 infection. 19,20 Surveillance testing to prevent viral spread in DCCs could offer an alternative to complete closure. Therefore, we conducted a feasibility study addressing acceptance of different surveillance protocols among children, parents, and childcare workers (CCWs) and performed mathematical modeling to identify feasible and effective testing approaches for DCCs.

Methods Feasibility Study Wü-KiTa-CoV Design and Conduct
The full protocol of this nonrandomized controlled trial is available in Supplement 1; for an overview of the study design, see Figure 1. The study protocol was approved by the ethics committee of the of Evaluations With Nonrandomized Designs (TREND) reporting guideline for nonrandomized controlled trials.
In brief, 9 DCCs within the study region of Wuerzburg, Germany, participated in the study from October 2020 to March 2021. Wuerzburg (approximately 130 000 inhabitants) is a city in the north of the German state of Bavaria and is the administrative seat of the district Lower Franconia. Each participating DCC was assigned nonrandomly to 1 of 4 testing approaches (modules 1-4) for 12 weeks.
Continuous testing of asymptomatic children and CCWs was done by midturbinate nasal swabbing twice weekly (module 1) or once weekly (module 2) performed by trained test teams in the DCC or by self-sampled mouth-rinsing fluid (ie, saliva testing) sampled by parents or CCWs after initial online video instruction at home twice a week (module 3). In module 4, we instructed children, CCWs, and their household members about SARS-CoV-2-associated symptoms and tested on demand by oropharyngeal swabbing. Parents of children aged 1 year or older and CCWs were asked for informed consent in modules 1, 2, and 4. For module 3, the minimum age was 2 years with regard to the children's ability to participate in sample acquisition. Before and after the testing period, SARS-CoV-2 antibody testing was performed. SARS-CoV-2 polymerase chain reaction and antibody testing are described in eAppendix 1 in Supplement 2.

Questionnaires and Interviews
Before the start of the screening and at weeks 1, 6, and 12, CCWs, children, and their parents answered questionnaires and online surveys on personal data, general attitudes, perception of the pandemic and experience of the specific surveillance method applied. For detailed information see eAppendix 1 in Supplement 2.

End Points
The primary end points for modules 1, 2, and 3 were the acceptance rate of the respective surveillance protocol, defined as the proportion of children or CCWs with successful participation (at least 60% of all scheduled samples collected successfully) among all eligible children and CCWs in the DCC estimated via 95% CI according to Wilson score. The primary end point for module 4 is the proportion of cases with successful sampling (ie, completed diagnostic analysis, or receipt of test

wk
Children and childcare workers (CCWs) from day care centers (DCCs) were allocated (per DCC) to 1 of 4 surveillance modules, with respiratory sampling (laboratory analysis by polymerase chain reaction) planned for a period of 12 weeks. Blood sampling (finger prick test) for seroprevalence was conducted before and after the sampling period. Respiratory sampling was accompanied by psychosocial questionnaires at weeks 1, 6, and 12, and qualitative interviews were performed for a representative subsample of participants. As an additional service outside the regular testing schedule, on-demand testing was offered also for symptomatic DCC children and CCWs from modules 1, 2, and 3. result in the case of external testing, within 72 hours after first telephone contact with the study center) among all cases of sample collection recommended for symptomatic children, CCWs, or household members, estimated via 95% CI according to Wilson score.

Statistical Analysis
To determine the module's association with consent into surveillance, we performed univariable and multivariable logistic regression analysis on the attitude of the parents toward SARS-CoV-2 variables and sociodemographic factors, such as age, sex, and school. Secondary end points included initial consent rates to respiratory surveillance (modules 1-4), dropout rates (modules 1-3), and acceptance of finger-prick blood sampling, stratified by children and CCWs. For details see the study protocol in

Study Setting
Nine large DCCs (approximately 20% of preschool DCC places in Wuerzburg) were selected for study participation, with 812 registered children and 182 CCWs. Of these, 772 of 812 children (95%) and all CCWs were eligible for the study; 40 children younger than 2 years were excluded in module 3 (eFigure 1A in Supplement 2). Of 954 eligible persons, 592 (62%) participated in the surveillance modules ( The study took place from October 2020 to March 2021, before any vaccine availability for study participants, and included 12 weeks of regular respiratory surveillance (Figure 2 and eFigure 2 in Supplement 2). The regional 7-day incidence during the study period was 20 to 152 cases per 100 000 population ( Figure 2). As the result of a national lockdown, the study was paused from December 14, 2020, to February 14, 2021.  for weekly nasal swabbing. In all modules, CCW acceptance rates were higher than those of children (

Identification of SARS-CoV-2 Imports Into DCCs
In total, 4755 tests for SARS-CoV-2 were conducted during the regular study period. In DCCs with Overall, 72% (559 of 772) of eligible participants initially agreed to serological testing. For 78% (435 of 559 participants), data were available for both time points. At study start, antibodies against workers who were initially considered eligible and had given informed consent to respiratory sampling were excluded from primary end point analysis, because they could not participate in respiratory sampling for reasons unrelated to the respiratory surveillance measures (eg, seropositivity for SARS-CoV-2 at the beginning of the study, maternity leave, and change of day care center).

Modeling an Optimal Surveillance Protocol for DCCs
Although our study estimates feasibility of SARS-CoV-2 surveillance in DCCs, it does not address efficiency. Thus, we developed an SBM based on parameters identified in our study and literature data (eTable 5, eTable 6, and eTable 7 in Supplement 2) to estimate infection spread in DCCs (Figure 3). This model includes the applied test frequencies and participation rates reached in the feasibility study but also reports expected efficacy in altered settings. We considered 3 different scenarios, with the index patient being an infected child randomly chosen to be symptomatic or asymptomatic and to participate or not in testing (scenario 1), an infected asymptomatic child who does not participate in testing (scenario 2), and an infected CCW who is randomly symptomatic or asymptomatic and participates in testing (scenario 3 Supplement 2). ASI also depended on the specific days that are selected for regular testing, with Monday being an optimal testing day. Importantly, for all scenarios, an ASI less than 1 could be realized independently of the quarantine policy with a test frequency of twice per week (including Monday as testing day) and a test participation rate of at least 50% (eFigure 5 in Supplement 2).

Discussion
To avoid complete DCC closures, alternative approaches that enable safe childcare in a pandemic are urgently required. Combining a real-life feasibility study with mathematical modeling, the results of this nonrandomized controlled trial allow us to define important parameters enabling effective SARS-CoV-2 surveillance in DCCs. Importantly, we can show that long-term surveillance testing is feasible and well accepted by children, parents, and CCWs, with long-term acceptance rates greater than 65% when using noninvasive saliva sampling. Efforts for collecting saliva specimens at home were negligible and conceived as unproblematic by a large majority of parents. Although a symptomatic testing approach identifies more cases compared with continuous testing of asymptomatic individuals, our data suggest that continuous testing of asymptomatic individuals is better suited to detect cases early and avoid transmission within DCCs. Importantly, continuous testing but not on-demand symptomatic testing significantly improved the parents' sense of security and avoided an increase of anxiety and depression. Despite a regional 7-day incidence of 20 to 152 cases per 100 000 population, the frequency of SARS-CoV-2 infections found in DCCs was very low and comparable to other studies. 18,19,[24][25][26][27] During our study, introduction of SARS-CoV-2 into DCCs occurred mainly via adult index cases. This observation supports early vaccination of CCWs, as has been prioritized in many countries including Germany. Importantly, serological testing before and after surveillance indicated that few or no infections occurred unnoticed.
Although our study clearly shows that surveillance testing is feasible, it is very difficult to evaluate effectiveness thoroughly in a real-life study. Thus, we developed a mathematical model that specifically addresses viral spread in DCCs. Because the number of individuals in DCCs is generally low, and, thus, stochastic variation is high, we used an SBM to account for the stochasticity of the ...

Limitations
Limitations of our study include a nonrandomized design, a lack of control for saliva sampling at home, and the exclusion of children younger than 2 years in module 3. Furthermore, the feasibility study was performed in only 1 city and was largely conducted before the emergence of highly transmittable SARS-CoV-2 variants. 32 We cannot exclude clustering of households and DCCs in the different modules; to minimize its effect, only 1 person per household was included in the descriptive and multivariable models.

Conclusions
In this nonrandomized controlled trial combined with mathematical modeling, we explored avenues for continuous and safe preschool childcare during the SARS-CoV-2 pandemic. Our findings suggest that evidence-based continuous surveillance can help to avoid the negative impact of closure of DCCs.