We conducted a population-based cohort study using primary care data from the Information System for Research in Primary Care (SIDIAP; www.sidiap.org) database, which contains pseudo-anonymized electronic health records of approximately 75% of the Catalan population and is representative in geography, age, and sex (15). This database has been standardized to the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM), and the provenance of the data, specifically for capturing COVID-19 vaccination and infection has been well documented (16).

We followed children aged 5–11 years and adolescents aged 12–15 years during two time periods (1) a pre-vaccination period, three months before the start of the vaccination rollout in Spain, from the 26th of September to the 26th of December 2020 (17); and (2) a vaccination period, three months after the start of the vaccination rollout among adolescents [from the 1st August to the 1st November 2021 (18)] and children [from the 15th of December 2021 to the 15th of March 2022 (19)]. Thus, four cohorts were followed, one for each age group and time period (Figure 1), with the follow-up of all cohorts starting on the first day of each time period (index date). The vaccination period for children was set to three months, and, to ensure consistency across cohorts, the same time window was applied to the other cohorts (20, 21).

We included all children and adolescents registered in the SIDIAP database as of 26 September 2020 (index date for all participants). We excluded those with less than 1 year of prior medical history available at the index date and those with missing data on deprivation or living in rural areas (defined as municipalities with <10,000 inhabitants and a population density <150 habitants/km2) as this information was unavailable in these areas (Figure 2).

When analyzing COVID-19 infection, we excluded those individuals with an infection ≤6 weeks before the start of the study period. When analyzing COVID-19 vaccine uptake, we excluded those vaccinated before the vaccination period, and those who tested positive for COVID-19 within the previous 8 weeks, since Spanish policies required 8-week delay between infection and vaccination (22). Additionally, participants who had been infected before vaccination were censored at the date of infection due to infections being considered a competing risk for vaccination (23–25). Figure 2 shows the flow chart of inclusion and exclusion criteria.

For each period, children and adolescents were followed until the occurrence of the outcome of interest, end of the study period, exit from the SIDIAP database, or death, whichever occurred first.

Our study was conducted against the backdrop of the evolving COVID-19 pandemic in Catalonia, Spain. The region experienced distinct phases of the pandemic, each marked by unique challenges and responses.

During the pre-vaccination period, Catalonia was experiencing the second wave of the COVID-19 pandemic, with incidence rates ranging from 120 to over 400 cases per 100,000 inhabitants (26, 27). In September 2020, educational settings reopened for in-person activities after closing in March 2020 and enforced stringent non-pharmaceutical interventions to mitigate the virus transmission. These measures consisted of handwashing, mandatory mask use for children over 5 years old, social distancing, organization of children and teachers into bubble groups to maintain the same groups of individuals and therefore facilitate contact tracing, and the improvement of ventilation of classrooms. Other public health measures such as mass testing were implemented in schools located in areas with high incidence of COVID-19 to reduce transmission (28, 29). In the event of a confirmed case, testing of all classmates was performed and, regardless of the PCR test result, the whole group was quarantined for 10 days (30).

In late July 2021, pharmacies began selling antigen tests following a surge of COVID-19 cases that coincided with the emergence of the Delta variant (31, 32). When the academic year 2021–2022 started in September after a two-month break, school protocols were revised. In the event of a confirmed infection, close contacts were required to undergo testing, which was provided free of charge through the public health system. Those who had previously been infected within the last 6 months or were fully vaccinated, were directed to obtain a supervised antigen test at authorized pharmacies. Individuals who did not meet these criteria were instructed to undergo a PCR test at a primary healthcare center (33). Between October and November 2021, COVID-19 incidence rates decreased from 1,630 to 716 cases per 100,000 inhabitants (26).

In the vaccination period for children, the incidence of COVID-19 in Catalonia increased sharply due to the higher transmissibility rate of the Omicron variant, rising from 551 cases in December 2021 to 3,285 cases per 100,000 inhabitants in January 2022, but then rapidly decreased to 300 cases per 100,000 inhabitants by mid-March when most of the population had been infected (26, 32). In January 2022, the government regulated the price of antigen tests to improve accessibility and offered free antigen tests to fully vaccinated children and adolescents when a positive case appeared in their social bubble (34, 35). Testing was restricted to unvaccinated children and adolescents without prior history of infection over the last three months. This measure ended in February 2022, along with mass testing and quarantines in schools (36–38).

Deprivation was assessed using a Socioeconomic Deprivation Index (SDI) score based on the place of residence, the Mortalidad en áreas pequeñas españolas y desigualdades socioeconómicas y ambientales deprivation index (39). This index was calculated at census tract areas using data from the 2001 national census in Spain, and was only available for urban areas (municipalities with >10,000 inhabitants and a population density >150 habitants/km2). This index has been linked to each individual's most recent residential address and categorized into five quintiles, the first being the least deprived (Q1).

Our outcomes of interest were COVID-19 infection and vaccination. COVID-19 infections were defined as a positive SARS-CoV-2 test result [antigen or polymerase chain reaction] or a clinical COVID-19 diagnosis without a record of a COVID-19 infection 6 weeks prior, with the test or diagnosis date as the date of infection (40). In each study period, we only considered the first COVID-19 infection per person. COVID-19 vaccination was defined as having received at least one dose of a COVID-19 vaccine. The date of vaccination was the date of the first dose administration.

We described participants’ characteristics at baseline and compared them to people with missing data on SDI using standardized mean differences (SMD). We calculated the cumulative incidence of COVID-19 infection by study period and age group, according to SDI quintile, by dividing the number of incident COVID-19 infections by the number of individuals at risk. Vaccination uptake was calculated at the end of the vaccination period by dividing the number of individuals vaccinated by the number of individuals eligible for vaccination. We also described the proportion of individuals who had undergone one or more tests registered in the public health system during follow-up, according to the deprivation quintile at the end of each study period.

To assess the association between SDI and COVID-19 infection, we performed crude Cox proportional-hazard regression models to estimate hazard ratios (HRs) with 95% confidence intervals (CI) of COVID-19 infection by SDI quintile relative to the least deprived quintile, Q1. To assess the association between SDI and COVID-19 vaccine uptake, we performed crude cause-specific hazard models to estimate the HR with 95% CIs of vaccination by SDI quintile relative to Q1 (41). All the analyses were stratified by age group and study period. We visually inspected log-log survival curves to check the proportional hazard assumptions for SDI (Supplementary Figure S1). We performed crude models based on our assumptions on the relationship between our exposure and our outcomes, which we represented with direct acyclic graphs (Supplementary Figures S2, S3). As a secondary analysis, we stratified our analyses by sex.

As a sensitivity analysis, we excluded individuals with any prior history of COVID-19 infection before the start of each study period, as it might have influenced the risks of infection as well as of being vaccinated.

We used R version 4.1 for data curation and analysis.

Before vaccination rollout, children and adolescents living in more deprived areas were more COVID-19 tested than those living in less deprived areas: 32.1% (Q1), vs. 37.6% (Q5) in children and 45.9% (Q1), vs. 48.6% (Q5) in adolescents (Supplementary Figure S4). Cumulative incidence of COVID-19 infection was 5.8% in children and 8.6% in adolescents. Infections were more frequent in more deprived areas in both age groups, showing a clear gradient of increased infection with deprivation: 4.6% (Q1), 5.4% (Q3) and 7% (Q5) in children, and 7.5% (Q1), 8.5% (Q3) and 10.1% (Q5) in adolescents (Figure 3 and Supplementary Table S2).

After vaccination rollout, testing was higher among those living in less deprived areas: 71.4% (Q1) vs. 59.5% (Q5) in children and 17.9% (Q1), vs. 14.2% (Q5) in adolescents (Supplementary Figure S4). Cumulative incidence of infection was 33.6% for children and 1.6% for adolescents. The pattern of increased COVID-19 infections with increased deprivation was still seen among adolescents (1.3% [Q1], 1.5% [Q3] and 2.1% [Q5]). However, we found the opposite pattern among children, with those in the least deprived quintile having a higher incidence proportion of infection (39.3% Q1, 34.7% Q3 and 26.5% Q5).

Vaccination uptake was 44.8% for children and 72.6% for adolescents. We also found a pattern of increased vaccination among those living in less deprived areas: 51.9% (Q1) vs. 38.3% (Q5) in children and 84.8% (Q1) vs. 75.7% (Q5) in adolescents.

Before the vaccination rollout, we observed a pattern of increased risks of COVID-19 infection with increased deprivation in both age groups (Figure 4 and Supplementary Table S3). For instance, among children, HR of infection relative to Q1 ranged from 1.12 (95% CI 1.06–1.18) in Q2 to 1.55 (1.47–1.63) in Q5 areas.

After vaccination rollout, COVID-19 infection risk was higher among adolescents living in more deprived areas, while in children, we observed an inverse pattern, with a lower risk of infection with more deprivation (Figure 4 and Supplementary Table S3). The HR of infection ranged from 1.16 (1.02–1.32) in Q2 to 1.65 (1.46–1.86) in Q5 areas for adolescents, and from 0.94 (0.92–0.95) in Q2 to 0.62 (0.61–0.64) in Q5 areas for children.

In both age groups, those living in more deprived areas had a lower risk of vaccination (Figure 4 and Supplementary Table S3). The HR ranged from 0.92 (0.91–0.94) in Q2 to 0.58 (0.57–0.59) in Q5 areas for children and from 1.02 (1.00–1.04) in Q2 to 0.79 (0.77–0.80) in Q5 areas for adolescents.

In our secondary analyses stratifying by sex, results were similar among both sexes. Results were also consistent after excluding individuals with a previous COVID-19 infection (Supplementary Table S3).