Comprehensive Assessment of Paediatric SARS-CoV-2 Infection: A Danish Population-based Cohort Study

Background: Conflicting evidence exists regarding the risk of adverse events to SARS-CoV-2 infection in children.

Objectives: To assess the risk of acute and post-acute adverse events following SARS-CoV-2 infection in children and adolescents in Denmark, and to evaluate real-world effectiveness of the BNT162b2 mRNA vaccine (Pfizer-BioNTech) among adolescents.

Methods: A nationwide cohort study utilising Danish health care registries. All Danish children and adolescents < 18 years of age who were either PCR-tested for SARS-CoV-2 until 31 October 2021 or vaccinated with the BNT162b2 mRNA vaccine until 02 October 2021 were eligible for inclusion. In evaluation of acute and post-acute outcomes following SARS-CoV-2 infection, we assessed the risk of hospitalisation, intensive care unit (ICU) admission, serious complications including multisystem inflammatory syndrome in children (MIS-C), myocarditis and neuroimmune disorders, as well as the risk of initiating drug therapy and health service utilisation up to six months after testing. Comparing vaccine recipients to unvaccinated peers, we evaluated the vaccine effectiveness towards SARS-CoV-2 infection as one minus the risk ratio at 20 days after the first dose and 60 days after the second dose.

Results: Among 961,977 children PCR-tested for SARS-CoV-2 in Denmark, 74,611 (7.8%) tested positive. Among these, 0.49% (95% CI, 0.44 to 0.54) were hospitalised for 12 hours or more and 0.01% (0.01 to 0.03) received ICU treatment within 30 days of testing. The risk of MIS-C within two months of SARS-CoV-2 infection was 0.05% (0.03 to 0.06), whereas there were no cases of myocarditis outside of MIS-C, encephalitis and < 5 cases of Guillain-Barré syndrome. In the post-acute phase from 1 to 6 months after infection, SARS-CoV-2 positive children had a 1.08 times (95% CI, 1.06 to 1.10) increased rate of general practitioner vistis compared to a reference cohort sampled among all children tested for SARS-CoV-2. Among 229,799 adolescents immunised with BNT162b2, the estimated vaccine effectiveness against documented SARS-CoV-2 infection was 62% (59 to 65) 20 days after the first dose and 93% (92 to 94) 60 days after the second dose.

Conclusions: The absolute risks of adverse events after SARS-CoV-2 infection were generally low in Danish children, although MIS-C occurred in 0.05% of children with PCR-documented SARS-CoV-2 infection. In adjusted analyses, SARS-CoV-2 positive children had slightly increased rates of general practitioner visits which could indicate persisting symptoms to SARS-CoV-2 infection. The BNT162b2 mRNA vaccine was effective in preventing SARS-CoV-2 infection with the delta variant in adolescents.