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Long-term multi-systemic complications after SARS-CoV-2 Omicron and Delta infection in children: a retrospective
Liang En Wee1, Jue Tao Lim2, Janice Yu Jin Tan3
1National Centre for Infectious Diseases, Singapore; Duke-NUS Graduate Medical School, National University of Singapore, Singapore; Department of Infectious Diseases, Singapore General Hospital, Singapore.
Insights
Long-term respiratory issues like bronchitis were slightly more common after SARS-CoV-2 (COVID-19) infection in children, particularly in unvaccinated individuals. Chronic sequelae risks were comparable to influenza hospitalizations.
Area of Science:
- Pediatric Infectious Diseases
- Respiratory Medicine
- Endocrinology
Background:
- Previous studies on long-term SARS-CoV-2 sequelae in children predated Omicron variants and widespread vaccination.
- Understanding post-COVID-19 conditions in diverse pediatric populations is crucial for public health strategies.
Purpose of the Study:
- To investigate the long-term risk of new-onset multi-systemic sequelae in children following SARS-CoV-2 infection during the Delta and Omicron (BA.1/2) waves.
- To compare risks between infected children and contemporaneous test-negative controls in a multi-ethnic Asian cohort.
Main Methods:
- Retrospective cohort study involving Singaporean children aged 1-17 years.
- Inclusion of SARS-CoV-2 infected cases and test-negative controls during Delta/Omicron BA.1/2 transmission periods.
- Utilized Cox regression to estimate risks of sequelae at 31-300 days post-infection.
Main Results:
- A modest increased risk of long-term respiratory sequelae, specifically bronchitis, was observed in infected children versus controls.
- During the Delta wave, an increased risk of endocrine conditions (e.g., diabetes) was noted; during Omicron, bronchitis risk was elevated.
- Bronchitis risk was higher in unvaccinated COVID-19 cases but not in vaccinated individuals.
Conclusions:
- Limited evidence of chronic sequelae in non-respiratory systems was found in a pediatric cohort with predominantly mild Omicron infections.
- Chronic sequelae risks in hospitalized COVID-19 cases were comparable to historical influenza hospitalizations.
- Respiratory sequelae risk post-respiratory syncytial virus hospitalization was higher than post-COVID-19 hospitalization, even in children under 5.
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.
