Wee Liang En, Lim Jue Tao, Tan Janice Yu Jin, Li Jiahui, Chiew Calvin, Yung Chee-Fu, Chong Chia Yin, Lye David Chien, Tan Kelvin Bryan
National Centre for Infectious Diseases, Singapore; Duke-NUS Graduate Medical School, National University of Singapore, Singapore; Department of Infectious Diseases, Singapore General Hospital, Singapore.
National Centre for Infectious Diseases, Singapore; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.
Clin Microbiol Infect. 2025 Apr;31(4):616-624. doi: 10.1016/j.cmi.2024.12.017. Epub 2024 Dec 26.
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.
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.
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.
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.
大多数关于儿童感染新型冠状病毒2（SARS-CoV-2）长期后遗症的研究是在奥密克戎毒株出现之前以及疫苗接种推广之前进行的。我们在一个多民族亚洲儿童群体中，研究了感染SARS-CoV-2德尔塔毒株/奥密克戎毒株后新出现的多系统后遗症的长期风险。
对在德尔塔毒株/奥密克戎毒株BA.1/2传播期间感染的1至17岁新加坡儿童以及同期检测呈阴性的群体进行回顾性队列研究。采用Cox回归来估计感染后31至300天新出现后遗症的风险。
共纳入267,952例感染SARS-CoV-2的儿童以及273,517例检测呈阴性者。≥95%的儿童是在奥密克戎毒株流行期间感染的。在德尔塔毒株流行期间，23.6%的感染病例已完全接种疫苗；在奥密克戎毒株流行期间，60.4%的感染病例已完全接种疫苗。≥98%的感染病例症状轻微，无需住院治疗。总体而言，与检测呈阴性的群体相比，SARS-CoV-2感染组出现长期呼吸道后遗症（调整后风险比[aHR]=1.09，95%置信区间[CI]：1.01-1.18）以及特别是支气管炎（aHR=1.17，95%CI：1.06-1.29）的风险适度增加。在德尔塔毒株流行期间，观察到内分泌疾病（如糖尿病）的风险增加（aHR=3.63，95%CI：1.25-10.50）；而在奥密克戎毒株流行期间，与检测呈阴性的群体相比，新冠病毒感染病例中支气管炎的风险增加（aHR=1.09，95%CI：1.02-1.20）。在未接种疫苗的新冠病毒感染病例中，与检测呈阴性的群体相比，支气管炎风险升高（aHR=1.17，95%CI：1.06-1.29），但在接种过≥1剂疫苗的个体中未观察到这种情况。新冠病毒感染住院后的慢性后遗症风险与历史上流感住院后的风险相当；尽管与呼吸道合胞病毒历史住院后的呼吸道后遗症相比有所降低。
在主要感染轻度SARS-CoV-2奥密克戎毒株的儿童队列中，呼吸系统以外器官系统的慢性后遗症证据有限。新冠病毒感染住院病例的慢性后遗症风险与历史上流感住院病例相比没有实质性差异。与检测呈阴性的群体相比，儿童感染SARS-CoV-2后支气管炎风险升高；与新冠病毒感染相比，呼吸道合胞病毒住院后记录到呼吸道后遗症风险增加，包括5岁以下儿童。
