Long-term multi-systemic complications after SARS-CoV-2 Omicron and Delta infection in children: a retrospective cohort study

Abstract

Objectives: Most studies on long-term sequelae of SARS-CoV-2 infection in children were conducted pre-Omicron and pre-dated vaccination rollout. We examined long-term risk of new-incident multi-systemic sequelae following SARS-CoV-2 Delta/Omicron infection in a multi-ethnic Asian paediatric population.

Methods: Retrospective cohort study of Singaporean children aged 1-17 years infected during Delta/Omicron BA.1/2 transmission, and contemporaneous test-negative groups. Cox regression was utilized to estimate risks of new-incident sequelae at 31-300 days post-infection.

Results: A total of 267,952 SARS-CoV-2-infected children were included, together with 273,517 test negatives. ≥95 % were infected during Omicron. During Delta, 23.6 % of infected cases were fully vaccinated; during Omicron, 60.4 % were fully vaccinated. ≥98% had mild infection not requiring hospitalization. Overall, there was a modestly increased risk of long-term respiratory sequelae (adjusted hazard ratio [aHR] = 1.09, 95 % CI: 1.01-1.18) and specifically bronchitis (aHR = 1.17, 95 % CI: 1.06-1.29) in the SARS-CoV-2-infected group vs. test negatives. During Delta, an increased risk of endocrine conditions (e.g. diabetes) was observed (aHR = 3.63, 95 % CI: 1.25-10.50); whereas during Omicron, an increased risk of bronchitis (aHR = 1.09, 95 % CI: 1.02-1.20) was observed in COVID-19 cases vs. test negatives. Elevated risk of bronchitis was observed among unvaccinated COVID-19 cases (aHR = 1.17, 95 % CI: 1.06-1.29) vs. test negatives, but not in individuals who had received ≥1 vaccine dose. Risks of chronic sequelae after COVID-19 hospitalization were comparable with those after historical influenza hospitalization; albeit reduced when compared with respiratory sequelae after historical hospitalizations for respiratory syncytial virus.

Discussion: Evidence of chronic sequelae in organ systems other than the respiratory system was limited in a paediatric cohort predominantly infected with mild SARS-CoV-2 Omicron infection. Risks of chronic sequelae in hospitalized COVID-19 cases did not substantially differ from historical influenza hospitalizations. Elevated risk of bronchitis was observed after SARS-CoV-2 infection in children vs. test negatives; an increased risk of respiratory sequelae was documented post respiratory syncytial virus hospitalization versus COVID-19, including children aged under 5 years.

Keywords: COVID-19; Children; Long COVID; Omicron; SARS-CoV-2; Vaccination.