Effect of school reopening on SARS-CoV-2 incidence in a low-prevalence region: Prospective SARS-CoV-2 testing in healthcare workers with primary school-attending children versus without children living at home

Coronavirus disease 2019 (COVID-19) often presents asymptomatically or milder in children compared to adults. The role of young children in the transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) remains largely unknown. In the Netherlands, the first action of loosening the partial lockdown that had been implemented to reduce SARS-CoV-2 transmission was the reopening of primary schools on 1 May 2020. We subsequently conducted a prospective cohort study among healthcare workers (HCWs) with primary school-attending children versus HCWs without children living at home. We tested each HCW three times for SARS-CoV-2 from May 20 to June 15 2020 at 1-week intervals. In total, 832 nasopharyngeal swabs were taken from 283 HCWs with primary school-attending children living at home and 864 nasopharyngeal swabs from 285 HCWs without children living at home. All nasopharyngeal swabs tested negative for SARS-CoV-2. In our region with a low population density and low SARS-CoV-2 prevalence, reopening of primary schools did not lead to an increase in infections. The results of this study may serve as an example for the implementation of regional strategies to reduce SARS-CoV-2 transmission in countries with large variations in both population density and SARS-CoV-2 prevalence.

Structured observation has been found to be the best indicator to assess handwashing practices in Indian households (Biran et al., 2008).

Outcome variable
The outcome variable considered for the analysis was 'the use of soap/detergent and water for handwashing'. It is defined as the presence of soap/detergent along with water in the usual place of handwashing among the households, where the place of handwashing was observed.

Predictor variables
The predictor variables used in the analysis were chosen based on the extensive literature review and available information in the NFHS-4. Specifically, the predictor variables used were the schooling of the household head (< 5 years including the illiterates, 5-9 years, 10-11 years, ⩾ 12 years), sex of the household head (male, female), religion of the household head (Hindu, Muslim, Christian and Others), caste/tribe of the household head (scheduled caste [SC], scheduled tribe [ST], other backward classes [OBC] or non-SC/ST/OBC), household size (< 5 members, ⩾ 5 members), house type (kuccha, semi-pucca, pucca), location of water source (in own dwelling, elsewhere), ownership of the house (not own house, own house), wealth index (poorest, poorer, middle, richer, richest), place of residence (urban, rural) and region (north, central, east, northeast, west, south).

Statistical analysis
In the present study, cross-tabulations between the outcome and predictor variables were done using the appropriate sample weights. The binary logistic regression was carried out to understand the predictors of handwashing practices. For this regression analysis, the dependent variable 'Soap/ detergent and water used for handwashing' was categorised into two, i.e. 1 = yes, 0 = no. The variables 'house type' and 'ownership of house' were dropped from the regression analysis to avoid multicollinearity. The Statistical Package for Social Sciences (SPSS-25, IBM Corp., Armonk, NY, USA) was used for analysis. The choropleth map was prepared at the district level using the ArcMap (version 10.4) to assess the regional scenario. The local indicators of spatial association (LISA) cluster map and Moran's I scatter plot were calculated through GeoDa (version 1.14) to understand the spatial clustering in the use of soap/detergent and water for handwashing.

Type of handwashing elements observed at the usual place of handwashing
Soap/detergent and water were observed in the usual place of handwashing in three-fifths (60%) of the households ( Figure 1). In 16% of the households, only water was observed in the usual place of handwashing. Seven out of every ten households were observed to have water and any cleansing element in their regular handwashing place. Nine percent of the households were found to have no water, no soap or any other cleansing agent at their usual place for handwashing. Table 1 presents the bivariate analyses to understand the individual association between the predictors and outcome variable. Of the male-headed households, 61% use soap and water for handwashing compared with 55% of the female-headed households. Use of soap and water for handwashing was found to increase with increasing education of  Journal of Infection Prevention 00 (0) medical attention and thus be counted in the number of infected cases (Mehta et al, 2020;Viner et al, 2021). Information regarding the circulation of SARS-CoV-2 among children and the role of SARS-CoV-2 transmission from children to adults remains limited (Kelvin and Halperin, 2020). On 11 May 2020, primary schools reopened in the Netherlands, as a first action of loosening up the partial lockdown that had been implemented in order to reduce SARS-CoV-2 transmission (Supplementary material) (Government of the Netherlands, 2020). To answer the question on potential transmission by children, the BackToSchool-study was initiated to investigate whether healthcare workers (HCWs) with primary school-attending children were more likely to become infected with SARS-CoV-2 compared to HCWs without children living at home. This cohort study started after a period of active case finding among HCWs at the University Medical Center Groningen (UMCG). In the northern Netherlands, the first case of COVID-19 was diagnosed in the last week of February 2020 (National Institute for Public Health and the Environment, 2020). As of 10 March 2020, the UMCG actively tested all symptomatic UMCG-HCWs to prevent further transmission at work and within the community. We also present the results of this testing policy.

Methods
The UMCG is the sole tertiary care centre in the northern part of the Netherlands supplying care for the provinces of Groningen, Friesland and Drenthe, a population of approximately 1.7 million inhabitants. As of 10 March 2020, HCWs of the UMCG were routinely tested by the occupational health service when showing symptoms compatible with COVID-19. If transmission within a department was likely, asymptomatic HCWs on the department were also tested. The number of HCWs tested and the numbers of positive and negative results were recorded.
The BackToSchool-study was a prospective cohort study among UMCG employees. A recruiting advertisement was posted in the daily digital newsletter. HCWs were eligible for inclusion if they were 18 years or older, had at least one primary school-attending child (study group) or had no children living at home (control group). An exclusion criterion was a previous positive test result for SARS-CoV-2 for the participant or their family members. Only one HCW per family could be enrolled. After reopening of primary schools on 11 May, from 20 May to 15 June 2020, participants were tested for SARS-CoV-2 by real-time polymerase chain reaction (RT-PCR) on nasopharyngeal and throat swabs (Supplementary material). Each participant was tested three times, at 1-week intervals. If symptoms compatible with COVID-19 occurred between two testing moments, an extra test was scheduled (Supplementary material). A baseline questionnaire was filled out prior to the first testing moment. An additional questionnaire regarding daily contacts, travel history and symptoms was filled out every testing day (Supplementary material).
To achieve 80% power with an α of 0.05, the minimum sample size per group was 270 including a 5% dropout. This was based on the incidence of HCWs testing positive for SARS-CoV-2 at the time of design of this study (<1%) and the estimation of a difference between groups of 3%. Statistical analyses were performed using IBM SPSS 23.0. Figure 1 shows the number of UMCG-HCWs tested per week, the number of positive and negative results and the test positivity rate from 10 March to 15 June 2020 (study samples not included). A peak in positive results was seen in March 2020, and declined afterwards. For the BackToSchool-study, 283 HCWs with primary schoolattending children (mean age 42.1 years) and 285 HCWs without children living at home (mean age 45.7 years) were included. A total of 1696 nasopharyngeal swabs were taken (832 in the study group and 864 in the control group), and all tested negative for SARS-CoV-2. Thus, no difference in infection rates was detected between groups. Sociodemographic characteristics and questionnaire data are shown in Table 1.

Discussion
After reopening primary schools, we found no increased SARS-CoV-2 incidence among HCWs compared to previous weeks. Nor did we find a difference in SARS-CoV-2 incidences between HCWs with primary school-attending children versus HCWs without children living at home. In fact, no infections were detected at all. To put these findings in perspective, the epidemic in the Netherlands evolved from the beginning of March, peaked in April and stabilised at low frequency in May and June (Supplementary Figure  1). The epidemic started in the south of the Netherlands and before it had reached the northern provinces, the partial lockdown was introduced country-wide.
Despite the early implementation of the partial lockdown in our region, infections did occur (Supplementary Figure 2). However, the cumulative prevalence in our region until July 21 2020 was 91/100,000 inhabitants, compared to the Dutch total of 299/100,000 inhabitants (National Institute for Public Health and the Environment, 2020).
Nationwide screening of all symptomatic persons was introduced in the Netherlands on 1 June 2020, with a nationwide positivity rate during the BackToSchool-study of 1.6% (1880/116,764) and of 0.5% (41/7703) for the three northern provinces (National Institute for Public Health and the Environment, 2020). We did not expect the incidence to 2015). Globally, only 19% of people wash their hands after contact with excreta (Freeman et al., 2014).
Handwashing is practised by washing hands using the several combinations of water, solid or liquid soap, sanitiser, alcohol-based components, sand, ash and mud. Although mostly water is used for handwashing, water alone is an inefficient skin cleanser because fats and proteins are not readily dissolved in water. People in lowincome countries such as India, Bangladesh and sub-Saharan Africa use ash, mud or sand for handwashing as zero-cost alternatives to soap (Bloomfield and Nath, 2009). Although there is potential for infection transmission by using contaminated soil/mud/ash for handwashing, ash or mud is perceived to clean hands as effectively as soap (Nizame et al., 2015). Handwashing with soap can dramatically reduce the rates of common diseases, including pneumonia and diarrhoea, two of the leading causes of deaths in children. Handwashing with soap and water is a simple and efficient method for reducing the risk of infectious diseases (Burton et al., 2011). Handwashing with soap can reduce childhood mortality rates related to respiratory and diarrheal diseases by almost 50% in developing countries (Curtis and Cairncross, 2003). Handwashing with soap prevents the two clinical syndromes that cause the most significant number of childhood deaths globally; namely, diarrhoea and acute lower respiratory infections (Luby et al., 2005).
Effective national programs for changes in handwashing behaviour can be expected to reduce diarrhoea and pneumonia caused by lack of handwashing by 25% (Townsend et al., 2017). A large number of people do not wash their hands regularly or do not know how to wash their hands properly (Ali et al., 2014). Education, socioeconomic status, availability of a water source in the house, ownership of the house and rural residence are associated with handwashing (Al-Khatib et al., 2015;Halder et al., 2010;Kumar et al., 2017;Ray et al., 2010;Schmidt et al., 2009;Ssemugabo et al., 2020). Handwashing is also related to knowledge of hand hygiene and non-availability of handwashing spaces or soap among school children (Mane et al., 2016).
India, with a cumulative number of 2,905,823 cases of COVID-19, is the third-worst affected country after the USA and Brazil as of 21 August 2020 (WHO, 2020b). Experts differ on the future trend of the COVID-19 in the country, amid rapidly growing cases across the states (Application Programming Interface, 2020), and the disease transmission stage being classified as 'cluster of cases' (WHO, 2020b). Appropriate handwashing (handwashing with alcohol-based agent or soap and water for a minimum of 20 s) is recommended as one of the most important ways to prevent person-to-person transmission of COVID 19. Nevertheless, evidence suggests poor hand hygiene in hospitals /healthcare providers (Mani et al., 2010;Sureshkumar et al., 2011;Tyagi et al., 2018) and the role of hands in spreading infections in the country (Taneja et al., 2003). Handwashing through alcohol-based agent/soap and water at the household level again seems not universal, as millions of Indians do not have access to basic amenities (Kumar, 2015). With several parts of India being water-stressed, and as much as 70% of the surface water resources being contaminated (Niti Aayog, 2019), is further perceived to worsen the recommended handwashing practices. Empirical evidence on existing handwashing practices is crucial to combat infectious diseases like COVID-19. There is, however, no scientific study exploring handwashing practices, spatial clustering and its determinants at the household level using the nationally representative sample in India. The aims of the present study were to: (1) understand the pattern and predictors of handwashing using soap/detergent and water; and (2) assess the spatial clustering of handwashing through soap/detergent and water at the district level in India.

Data
The study used data from the fourth round of the National Family Health Survey (NFHS), 2015-2016. The NFHS-4 is a nationally representative survey of 601,509 households that provides information for a wide range of monitoring and impact evaluation indicators of health, nutrition and women's empowerment. The sampling design of the NFHS-4 is a stratified two-stage sample with an overall response rate of 98%. The Primary Sampling Unit (PSUs), i.e. the survey villages in rural areas and Census Enumeration Blocks (CEBs) in urban areas, were selected using probability proportional to size (PPS) sampling. Data collection was conducted in two phases from January 2015 to December 2016. The data were gathered using computer-assisted personal interviewing (CAPI) by trained research investigators. Only those respondents who gave oral/written consent were interviewed in the survey. A more detailed description of survey design, questionnaire and quality control measures can be obtained elsewhere (Paswan et al., 2017).
The NFHS-4 asked a specific question: 'Please show me where members of your household most often wash their hands'. In the households where the place of handwashing was observed, research investigators were instructed to observe the presence of water, soap/detergent (bar, liquid, powder, paste) or other cleansing agents (ash, mud, sand) or absence of any cleansing agent. The present analysis is restricted to 582,064 households where the usual place for handwashing was observed. The availability of specific handwashing materials at the usual place of handwashing is assumed to be used by the household for handwashing. There is no consensus on a gold standard for identifying handwashing behaviour (Manun'Ebo et al., 1997), though handwashing behaviour can be assessed using questionnaires, by handwashing demonstration and by direct/indirect observation.

Outcome variable
The outcome variable considered for the analysis was 'the use of soap/detergent and water for handwashing'. It is defined as the presence of soap/detergent along with water in the usual place of handwashing among the households, where the place of handwashing was observed.

Predictor variables
The predictor variables used in the analysis were chosen based on the extensive literature review and available information in the NFHS-4. Specifically, the predictor variables used were the schooling of the household head (< 5 years including the illiterates, 5-9 years, 10-11 years, ⩾ 12 years), sex of the household head (

Statistical analysis
In the present study, cross-tabulations between the outcome and predictor variables were done using the appropriate sample weights. The binary logistic regression was carried out to understand the predictors of handwashing practices. For this regression analysis, the dependent variable 'Soap/ detergent and water used for handwashing' was categorised into two, i.e. 1 = yes, 0 = no. The variables 'house type' and 'ownership of house' were dropped from the regression analysis to avoid multicollinearity. The Statistical Package for Social Sciences (SPSS-25, IBM Corp., Armonk, NY, USA) was used for analysis. The choropleth map was prepared at the district level using the ArcMap (version 10.4) to assess the regional scenario. The local indicators of spatial association (LISA) cluster map and Moran's I scatter plot were calculated through GeoDa (version 1.14) to understand the spatial clustering in the use of soap/detergent and water for handwashing.

Type of handwashing elements observed at the usual place of handwashing
Soap/detergent and water were observed in the usual place of handwashing in three-fifths (60%) of the households (Figure 1). In 16% of the households, only water was observed in the usual place of handwashing. Seven out of every ten households were observed to have water and any cleansing element in their regular handwashing place. Nine percent of the households were found to have no water, no soap or any other cleansing agent at their usual place for handwashing. Table 1 presents the bivariate analyses to understand the individual association between the predictors and outcome variable. Of the male-headed households, 61% use soap and water for handwashing compared with 55% of the female-headed households. Use of soap and water for handwashing was found to increase with increasing education of  Handwashing is practised by washing hands using the several combinations of water, solid or liquid soap, sanitiser, alcohol-based components, sand, ash and mud. Although mostly water is used for handwashing, water alone is an inefficient skin cleanser because fats and proteins are not readily dissolved in water. People in lowincome countries such as India, Bangladesh and sub-Saharan Africa use ash, mud or sand for handwashing as zero-cost alternatives to soap (Bloomfield and Nath, 2009). Although there is potential for infection transmission by using contaminated soil/mud/ash for handwashing, ash or mud is perceived to clean hands as effectively as soap (Nizame et al., 2015). Handwashing with soap can dramatically reduce the rates of common diseases, including pneumonia and diarrhoea, two of the leading causes of deaths in children. Handwashing with soap and water is a simple and efficient method for reducing the risk of infectious diseases (Burton et al., 2011). Handwashing with soap can reduce childhood mortality rates related to respiratory and diarrheal diseases by almost 50% in developing countries (Curtis and Cairncross, 2003). Handwashing with soap prevents the two clinical syndromes that cause the most significant number of childhood deaths globally; namely, diarrhoea and acute lower respiratory infections (Luby et al., 2005).

Handwashing through soap and water by background characteristics of the households
Effective national programs for changes in handwashing behaviour can be expected to reduce diarrhoea and pneumonia caused by lack of handwashing by 25% (Townsend et al., 2017). A large number of people do not wash their hands regularly or do not know how to wash their hands properly (Ali et al., 2014). Education, socioeconomic status, availability of a water source in the house, ownership of the house and rural residence are associated with handwashing (Al-Khatib et al., 2015;Halder et al., 2010;Kumar et al., 2017;Ray et al., 2010;Schmidt et al., 2009;Ssemugabo et al., 2020). Handwashing is also related to knowledge of hand hygiene and non-availability of handwashing spaces or soap among school children (Mane et al., 2016).
India, with a cumulative number of 2,905,823 cases of COVID-19, is the third-worst affected country after the USA and Brazil as of 21 August 2020 (WHO, 2020b). Experts differ on the future trend of the COVID-19 in the country, amid rapidly growing cases across the states (Application Programming Interface, 2020), and the disease transmission stage being classified as 'cluster of cases' (WHO, 2020b). Appropriate handwashing (handwashing with alcohol-based agent or soap and water for a minimum of 20 s) is recommended as one of the most important ways to prevent person-to-person transmission of COVID 19. Nevertheless, evidence suggests poor hand hygiene in hospitals /healthcare providers (Mani et al., 2010;Sureshkumar et al., 2011;Tyagi et al., 2018) and the role of hands in spreading infections in the country (Taneja et al., 2003). Handwashing through alcohol-based agent/soap and water at the household level again seems not universal, as millions of Indians do not have access to basic amenities (Kumar, 2015). With several parts of India being water-stressed, and as much as 70% of the surface water resources being contaminated (Niti Aayog, 2019), is further perceived to worsen the recommended handwashing practices. Empirical evidence on existing handwashing practices is crucial to combat infectious diseases like COVID-19. There is, however, no scientific study exploring handwashing practices, spatial clustering and its determinants at the household level using the nationally representative sample in India. The aims of the present study were to: (1) understand the pattern and predictors of handwashing using soap/detergent and water; and (2) assess the spatial clustering of handwashing through soap/detergent and water at the district level in India.

Data
The study used data from the fourth round of the National Family Health Survey (NFHS), 2015-2016. The NFHS-4 is a nationally representative survey of 601,509 households that provides information for a wide range of monitoring and impact evaluation indicators of health, nutrition and women's empowerment. The sampling design of the NFHS-4 is a stratified two-stage sample with an overall response rate of 98%. The Primary Sampling Unit (PSUs), i.e. the survey villages in rural areas and Census Enumeration Blocks (CEBs) in urban areas, were selected using probability proportional to size (PPS) sampling. Data collection was conducted in two phases from January 2015 to December 2016. The data were gathered using computer-assisted personal interviewing (CAPI) by trained research investigators. Only those respondents who gave oral/written consent were interviewed in the survey. A more detailed description of survey design, questionnaire and quality control measures can be obtained elsewhere (Paswan et al., 2017).
The NFHS-4 asked a specific question: 'Please show me where members of your household most often wash their hands'. In the households where the place of handwashing was observed, research investigators were instructed to observe the presence of water, soap/detergent (bar, liquid, powder, paste) or other cleansing agents (ash, mud, sand) or absence of any cleansing agent. The present analysis is restricted to 582,064 households where the usual place for handwashing was observed. The availability of specific handwashing materials at the usual place of handwashing is assumed to be used by the household for handwashing. There is no consensus on a gold standard for identifying handwashing behaviour (Manun'Ebo et al., 1997), though handwashing behaviour can be assessed using questionnaires, by handwashing demonstration and by direct/indirect observation. Education categories were defined as: low = high school graduate or lower; middle = college education but no college degree; high = college degree or higher. b The three northern provinces of the Netherlands include the provinces of Friesland, Groningen, and Drenthe. c Defined as having contact with others for 15 minutes or longer, at a distance less than 1.5 metres, without wearing protective facial mask, glasses or comparable protective clothing. d Coronavirus-like symptoms included symptoms of fever, shortness of breath, muscle ache, (dry) cough, sore throat, runny nose, fatigue, loss of taste or smell, headache or (unexplained) diarrhoea. HCWs: healthcare workers; SD: standard deviation; IQR: interquartile range; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; NA: not applicable. drop so low that comparison between study groups would be hampered. Postponing the study to a later moment in time, e.g. in autumn or during a regional outbreak, might have increased our statistical power as a result of a higher background incidence. However, the moment of opportunity of only schools being reopened after a period of partial lockdown made us decide not to postpone. Antibody testing prior to the study was not performed as we believe that only a very small percentage of the HCWs included in this study will have unknowingly been infected, due to the active testing strategy in the preceding months and the low seroprevalence in our region (Slot et al, 2020). The majority of positive cases in the UMCG were UMCG-HCWs (69%). By very early and active testing of all symptomatic HCWs, and excluding those with a positive test from working, we were able to reduce transmission of SARS-CoV-2 in our hospital. This service was promptly extended to all HCWs in critical professions in the provinces of Groningen and Drenthe, in cooperation with the Municipal Health Services and regional laboratories. In this collaboration, we also offered testing to symptomatic family members of HCWs, before the nationwide screening was initiated. This contributed amongst many other factors to a very low reproductive number in the northern Netherlands.
A cross-sectional study conducted in the southern province of Noord-Brabant showed that 6% out of 1353 symptomatic HCWs tested positive for SARS-CoV-2 and that the majority only experienced mild symptoms (Kluytmans-van den Bergh et al, 2020). It is of importance to actively test HCWs for SARS-CoV-2 even if only very mild symptoms are being reported and even more so when policies allow HCWs to work with mild symptoms. Furthermore, testing pre-/asymptomatic HCWs after Structured observation has been found to be the best indicator to assess handwashing practices in Indian households (Biran et al., 2008).

Outcome variable
The outcome variable considered for the analysis was 'the use of soap/detergent and water for handwashing'. It is defined as the presence of soap/detergent along with water in the usual place of handwashing among the households, where the place of handwashing was observed.

Predictor variables
The predictor variables used in the analysis were chosen based on the extensive literature review and available information in the NFHS-4. Specifically, the predictor variables used were the schooling of the household head (< 5 years including the illiterates, 5-9 years, 10-11 years, ⩾ 12 years), sex of the household head (male, female), religion of the household head (Hindu, Muslim, Christian and Others), caste/tribe of the household head (scheduled caste [SC], scheduled tribe [ST], other backward classes [OBC] or non-SC/ST/OBC), household size (< 5 members, ⩾ 5 members), house type (kuccha, semi-pucca, pucca), location of water source (in own dwelling, elsewhere), ownership of the house (not own house, own house), wealth index (poorest, poorer, middle, richer, richest), place of residence (urban, rural) and region (north, central, east, northeast, west, south).

Statistical analysis
In the present study, cross-tabulations between the outcome and predictor variables were done using the appropriate sample weights. The binary logistic regression was carried out to understand the predictors of handwashing practices. For this regression analysis, the dependent variable 'Soap/ detergent and water used for handwashing' was categorised into two, i.e. 1 = yes, 0 = no. The variables 'house type' and 'ownership of house' were dropped from the regression analysis to avoid multicollinearity. The Statistical Package for Social Sciences (SPSS-25, IBM Corp., Armonk, NY, USA) was used for analysis. The choropleth map was prepared at the district level using the ArcMap (version 10.4) to assess the regional scenario. The local indicators of spatial association (LISA) cluster map and Moran's I scatter plot were calculated through GeoDa (version 1.14) to understand the spatial clustering in the use of soap/detergent and water for handwashing.

Type of handwashing elements observed at the usual place of handwashing
Soap/detergent and water were observed in the usual place of handwashing in three-fifths (60%) of the households (Figure 1). In 16% of the households, only water was observed in the usual place of handwashing. Seven out of every ten households were observed to have water and any cleansing element in their regular handwashing place. Nine percent of the households were found to have no water, no soap or any other cleansing agent at their usual place for handwashing. Table 1 presents the bivariate analyses to understand the individual association between the predictors and outcome variable. Of the male-headed households, 61% use soap and water for handwashing compared with 55% of the female-headed households. Use of soap and water for handwashing was found to increase with increasing education of  Journal of Infection Prevention 00(0) being exposed to a COVID-19-infected person is crucial in a preventive search-and-contain policy within healthcare institutions. The findings of this study suggest that reopening primary schools in areas with a low population density and low SARS-CoV-2 incidences will not cause disproportional SARS-CoV-2 transmission in this area. However, it is important to state that our study does not exclude that in another epidemiological context, with a higher incidence, introduction of positive cases into schools could have led to enhanced transmission of SARS-CoV-2.