Incidence, risk and severity of SARS-CoV-2 reinfections in children and adolescents: a population-level study between March 2020 and July 2022

Abstract IMPORTANCE During the COVID-19 pandemic children and adolescents were massively infected worldwide. In 2022 reinfections became increasingly common and they may continue to be a main feature of the endemic phase of SARS-CoV-2. It is important to understand the epidemiology and clinical impact of reinfections. OBJECTIVE To assess the incidence, risk, and severity of SARS-CoV-2 reinfection in children and adolescents. DESIGN, SETTING, AND PARTICIPANTS A population-level observational study was performed using surveillance data from the Autonomous Province of Vojvodina, Serbia between March 6, 2020 and April 30, 2022 with follow-up until July 31, 2022. The population-based sample consisted of 32 524 residents of Vojvodina <18 years of age with laboratory confirmed SARS-CoV-2 infection. EXPOSURES The surveillance database of the Institute for Public Health of Vojvodina was harnessed for epidemiological data of laboratory-confirmed SARS-CoV-2 infections. MAIN OUTCOMES AND MEASURES Incidence rates of documented SARS-CoV-2 reinfection per 1000 person-months. Estimated risk of documented reinfection ≥90 days after laboratory confirmation of primary infection. Reinfection severity and associated hospitalizations and deaths. RESULTS A total of 964 children (3.0%) experienced documented reinfection. The incidence rate of SARS-CoV-2 documented reinfections was 3.2 (CI 3.0-3.4) cases per 1000 person-months and was highest in adolescents aged 12-17 years (3.4; CI 3.2-3.7). Most reinfections (905, 93.9%) were recorded in 2022. The reinfection risk was 1.3% at six months, 1.9% at nine months, 4.0% at 12 months, 6.7% at 15 months, 7.2% at 18 months and 7.9% after 21 months. Pediatric COVID-19 cases were generally mild. The proportion of severe clinical forms decreased from 14 (1.4%) in initial episodes to 3 (0.3%) in reinfections. Reinfected children were 4.7 times more likely to suffer from severe disease during initial infection compared to reinfection (McNemar OR=4.7; 95%CI 1.3-16.2, p =0.015). Pediatric reinfections rarely led to hospitalization (0.5% vs . 1.3% during primary infections) and none resulted in death. CONCLUSION AND RELEVANCE Reinfections are becoming more frequent as the pandemic progresses, yet the risk remains substantially lower for children and adolescents compared to adults. Pediatric infections rarely had clinical consequences and reinfections were even milder than primary infections. Key Points Question What is the incidence, risk and severity of SARS-CoV-2 reinfection in children and adolescents? Findings This observational population-level study showed that the risk of pediatric reinfection remained less than 8% two years into the pandemic with an incidence rate of 3.2 (CI 3.0-3.4) cases per 1000 person-months. Pediatric COVID-19 cases were generally mild and reinfected children were 4.7 times more likely to suffer from severe disease during the initial infection compared to reinfection. Meaning These findings suggest that documented reinfection risk remains substantially lower in the pediatric versus the adult population, with an even more favorable profile compared to primary infections.