Catalonia is an autonomous region in north-eastern Spain with 7,653,845 inhabitants (1,384,382 under 18 years of age). We obtained public data on the total tested and confirmed SARS-CoV-2 cases in Catalonia, provided by the Catalan Agency for Quality and Health Assessment (AQuAS) that had downloaded the original data from the Catalan Epidemiological Surveillance Network's clinical microbiological laboratories (18). No additional data were available.

A confirmed COVID-19 case was defined as any individual testing SARS-CoV-2 positive by molecular assays [polymerase chain reaction (PCR) or transcription-mediated amplification (TMA)] or rapid antigen testing (RAT) (PANBIO COVID-19 by ABBOTT©) in a respiratory specimen which has a sensitivity of 98.1% (95% CI: 93.2–99.8%) and a specificity of 99.8% (95% CI: 98.6–100.0%) in symptomatic patients, according to the company information. RAT has only been available since 23^rd October 2020 (7th week of the school-course) in primary care settings. All the close contacts of the confirmed cases were tested, mainly with PCR. Nevertheless, in the schools, all the classroom contacts were tested by PCR and not by RAT.

This study used aggregated public health data from the health surveillance system to investigate the risk of SARS-CoV-2 among children. No personal or identifiable data were collected; thus, the institutional research board waived the requirement for parental and/or patient informed consent. This information was critical for supporting health-policy recommendations on easing COVID-19 lockdown measures and allowing children to return to school safely. This was identified as a public health priority and as part of the public health response to the COVID-19 pandemic in Catalonia. The results have been used to provide an evidence base for informing national guidance and public health policy to help protect children and staff in educational settings.

In Spain, the educational system for those under 18 years has four educational levels. A first non-compulsory stage that corresponds to nursery education (0–5 years) is divided into two cycles, kindergarten (0–3 years) and pre-school (3–5 years). The second stage is the elementary education (6–11 years), which is compulsory, and it is followed by secondary education (12–16 years). The fourth stage is non-compulsory and comprises the high-school education (16–18 years), intermediate vocational training, intermediate professional plastic arts and design courses, and intermediate sports courses (19). According to these stages, and including adults as an independent control group, we focused our research on age-group incidence (cases per 10⁵ population), diagnostic effort (tests per 10⁵ population), and positivity, defined as the quotient between positive SARS-CoV-2 tests (cases) and the total of SARS-CoV-2 tests performed, given as a percentage:

If an individual was tested at different times for the same clinical episode, delimited by the maximum incubation period for the SARS-CoV-2 infection, we defined the following dates: when all the tests were negative, we considered the date of the first test performed in the clinical episode; and when a test was positive, we relied on the date of that test regardless of the previous negative results in the same episode. Each episode counted once to analyze the dynamics of the epidemic. For each of the variables (i.e., incidence, diagnostic effort, and positivity) and age-groups, we assessed its relative value with regards to that of the general population. These relative variables allow for a rapid identification of those values above the average (<1) and those below (<1).

In addition, we performed a one-way analysis of variance (ANOVA) test to explore differences in the number of the diagnostic tests performed per 10⁵ population, incidence of cases (cases per 10⁵ population), and positivity between the different age-groups. The one-way ANOVA returns the p-value for a group of data. It tests the hypothesis that the different samples tested are drawn from populations with the same mean. A p-value below 0.05 indicates that the hypothesis is rejected with a 95% significance level.

Holidays and school periods were shared by children of all educational stages until higher education (20). The vacation periods considered for testing were between 21^st December 2021 and 10^th January 2021 for Christmas, and between 27^th March and 5^th April 2021 for Easter holidays. To analyze the infections associated with the school-closure periods for holidays, and considering an average period of 7 days between the infection and the diagnosis (approximately 5 days until symptoms onset and 2 days from symptoms onset to the doctor's appointment in Catalonia) (21, 22), the incidence and positivity were defined between 28^th December 2020 (i.e., one week after the beginning of the Christmas holidays) and 17^th January 2021 (i.e., one week after returning to school). For the Easter holidays this period was defined as between 3^rd and 12^th April 2021.

Schools re-opened in Catalonia on 14^th September 2020 after a long closure period, starting 13^th March 2020. This reopening occurred in a context in which the average 14-day cumulative incidence was around 180–190 cases per 10⁵ population, and the most prevalent SARS-CoV-2 Pangolin lineage was B.1.177 with other minor lineages. To mitigate the risk of transmission, a set of NPIs was established: (1) face masks were mandatory in all educational centers for children older than 5, (2) natural ventilation and hand hygiene in the classrooms and common spaces were recommended, (3) infants and adolescents were clustered into bubble-groups (mainly restricted to classmates) in all educational centers with no interactions with other groups in the center, and (4) whenever a positive case was detected, the whole group was screened and, whatever the result of the SARS-CoV-2 tests, the whole group was quarantined for 10 days. In addition, several mass screening campaigns were carried out in educational centers located in high incidence areas. Furthermore, during the analyzed period, the regional government introduced other community NPIs to reduce the global incidence of COVID-19, as shown in Supplementary Table 1 (23). Eventually, on 9^th May 2021, the Spanish Government relaxed some of the previous interventions and allowed mobility throughout the country.

During the study period, 1,654,099 SARS-CoV-2 tests were performed in the population <18 years, representing 1.2 tests per person, and 91,857 of them were positive (5.5%). RAT was used for testing in the 34.4% of the 0–5 year-old children, 20.2% of the 6–11 y-old, and 19.6% of 12–17 y-old. Furthermore, 5,554,060 SARS-CoV-2 tests were performed in the adult population, representing less than one test performed per person (0.9), and 400,506 of them were positive (7.2%). The diagnostic effort during the analyzed period was generally greater in children than in adults (yellow and black lines in Figure 1A, respectively), with a difference of 1,335 tests per 10⁵ population between children and adults. For the three different waves of the pandemic occurring since mid-September 2020 (weeks of the school-year: 1–11, 14–24, and 26-35), the mean children/adults test ratios per 10⁵ population per week were: 1.87 (3,910/2,086), 0.97 (3,228/3,326), and 1.63 (2,995/1,839), respectively. However, this diagnostic effort largely varied, especially among children, during the study period (see Figure 1A). Apart from vacation time, the diagnostic effort was clearly greater in all the children's age groups, particularly for the 12–17 years old with a mean of 4,925 tests per 10⁵ population (light blue line of Figure 1A) vs. 2,355 tests per 10⁵ population for adults. Only during 14 weeks of the study period (between week 11 and 23, and during week 30) was the diagnostic effort among the 0-5 years-old lower than for the adults, with a mean of−1,051 tests per 10⁵ population. Four of these 14 weeks were holidays. At Christmas (approximately weeks 15–17), tests were mainly performed on adults, with this the period having the lowest number of tests for children, and yielding a mean difference of−806 tests per 10⁵ population compared to adults.

Sars-CoV-2 incidence in children was slightly higher than the incidence in adults for most of the study-period, with a mean difference of 21 cases per 10⁵ population (yellow and black lines in Figure 1B, respectively). This difference was above the mean during the third wave (weeks 30–34), with a difference of 27 cases per 10⁵ population. However, during these weeks, just after the Easter holidays, the diagnostic effort difference between children and adults was higher, as shown in Figure 1A (a mean difference of 1154 tests per 10⁵ population between children and adults in this period). SARS-CoV-2 incidence was directly associated with the age of the children: averages of 248, 175, and 118 cases per 10⁵ population for the group of 12–17, 6–11, and 0–5 years old, respectively, for the study-period. Otherwise, the evolution of incidence for all age-groups followed a similar pattern.

Figure 2 shows that relative values of tests per 10⁵ population among children with respect to the value among the general population were higher compared to the adult relative values during the entire period (mean difference of 0.37), except during weeks 12-18. In fact, relative diagnostic effort among children was almost twice that among adults (means 1.61/0.86) in the first 11 weeks of the school year. Older children (12-17 years) were the most tested age-group (mean of 1.9 relative diagnostic effort) in contrast to pre-school children (1.1), children in elementary school (1.3), and adults (0.9). However, during holiday periods these figures were completely different, with an average of 1.03 relative diagnostic effort in the group of 12–17, compared to 0.62, 0.66, and 1.05 for children aged 0–5, 6–11, and adults, respectively. Regarding the relative SARS-CoV-2 incidence (Figure 2B), this was slightly higher in children than in adults with a mean difference of 0.15, except during the holiday periods (−0.19 relative incidence). Adolescents (12–17 years) had the highest relative incidence throughout the study period, with, on average, 1.5 and 1.1 relative values for the school period and holidays, respectively. Among children of less than 5 years of age, despite the higher relative diagnostic effort, with a mean of 1, incidence was clearly lower than for the general population (on average, 0.69 relative incidence).

During the first 11 weeks of the school year, positivity among children (yellow line) remained clearly below the positivity among adults (black line), with percentages around 5% or even lower for younger children. This indicates, at least in part, that the higher incidence for the 12–17 years-old age group could be explained by a greater effort at diagnosis. In contrast, after a long weekend (week 12) and during the Christmas holidays (weeks 15-17), the positivity rate for all childhood age groups increased substantially, as shown in Figure 3, because of a lower diagnosis effort (see Figures 1A, 2A).

Figure 4 shows the relative diagnostic effort, incidence cases, and positivity among the childhood age groups and adults vs. general population during the entire study period and separating school periods and holidays. Even though the relative number of daily tests among children was significantly higher (p < 0.001) than among adults during the study period (Figure 4A, with a mean value of 1.19 and 0.96 for <18 years and adults, respectively), the relative incidence presented similar values, being on average 1.03 for children and 0.99 for adults (Figure 4B). As a consequence, positivity was lower (p < 0.001) among children (Figure 4C, with a mean of 0.94 and 1.04 for <18 years and adults, respectively).

We also analyzed separately the school period and the holidays and different age-groups among children. Relative tests decreased considerably for all the children's age groups when the schools were closed (mean values for school period/holidays: 0.97/0.67, 1.09/0.69, 1.62/0.99 for 0–5, 6–11, 12–17 years, respectively), but this was not observed in the adults, who had a similar relative number of tests in the two periods (0.95/1.05, Figures 4D,G). On the other hand, there was a significant difference (p < 0.001) between the tests performed within the different age groups during the school period, except for children 0–5 years old when compared to adults (p = 0.37). In contrast, during the holidays, there was a significant difference (p < 0.001) between the tests performed within the different age groups during the school period, except for children aged 0–5 compared to children 6–11 years old (p = 0.83), and for older children (12–17 years) in comparison to adults (p = 0.45).

Moreover, the relative incidence among children increased considerably with the age of the cohort in both analyzed periods, being clearly lower than that observed in adults (mean values 0.97 and 1.05 in average during the school period and holidays, respectively) among kindergarten children (0.70 and 0.55, Figures 4E,H). Evidently, during the holidays, the lower number of tests performed substantially decreased the relative incidence among children. Furthermore, it is noteworthy that incidence within different age groups during the school period was significantly different (p < 0.005). Nevertheless, performing the same analysis for the holidays, children aged 12–17 showed a non-significant difference when compared to adults (p = 0.2).

Finally, relative positivity was smaller for all the children's age groups when compared to the relative positivity among adults during the school period (averages of 0.76, 0.98, 0.91, 1.05 for each age group represented in Figure 4F from left to right), but it was clearly higher among children when the schools were closed (1.09, 1.49, 1.28, 0.97) mainly due to a decrease in the diagnostic effort (Figure 4I). It is of note that, during both the school period and holidays, positivity in all groups differed from each other significantly (p < 0.001).