Objectives: Population-based cohort studies on long-term sequelae post-dengue are lacking, given dengue's disproportionate burden in tropical low-and-middle-income countries (LMICs) with limited access to diagnostic testing and follow-up. We estimated the 300-day post-acute risk of new-incident multi-systemic complications following dengue infection.

Methods: National dengue registries and healthcare-claims databases in Singapore were utilised to build a retrospective population-based adult cohort with laboratory-confirmed dengue infection (1 Jan 2017-30 Jun 2023) and a cohort of uninfected controls. Differences in baseline characteristics were adjusted using overlap weighting. Risks of new-incident complications across multiple organ systems, all-cause hospitalisation and death up to 300 days post-dengue infection were systematically contrasted against population-based-controls, using competing risk regression.

Results: 55,870 dengue-infected individuals and 3,072,309 uninfected controls were included; the majority had mild initial infection not requiring hospitalisation. In the post-acute period, there was 19.0% (aHR=1.19[1.13,1.26]) increased risk of any post-acute sequelae, with an 46.0% increase in risk of cardiovascular sequelae (aHR=1.46[1.01,2.10]) and 29.0% increase in risk of neuropsychiatric sequelae (aHR=1.29[1.14,1.45]) in dengue-infected individuals versus controls. There was also a 37.0% increase in risk of autoimmune disorders (aHR=1.37 [1.24,1.52]), a 19% increase in risk of endocrine disorders (aHR=1.19[1.12,1.25]), a 42.0% increase in risk of gastrointestinal sequelae (aHR=1.42[1.17,1.72]). and 230.0% increase in risk of renal sequelae (aHR=2.30[1.69,3.12]). Post-acute risk of all-cause hospitalisation (aHR= 1.22[1.20,1.25]) and death (aHR= 2.08[1.85,2.33]) were also elevated in dengue-infected cases. The cumulative number of post-acute outcomes amongs dengue-infected cases increased over the 31-300 day follow-up period, versus uninfected controls. Risks of post-acute sequelae were increased in hospitalised dengue patients, older age groups (61+ years), those with comorbidities and across DENV-2/DENV-3 predominant transmission.

Conclusions: Increased post-acute risk of multi-organ complications, all-cause hospitalisations and death was observed in dengue survivors, versus uninfected population-based-controls. Development of multidisciplinary care strategies to reduce chronic health loss post-dengue infection is crucial.

Keywords: Dengue; chronic; long term; post-acute sequelae.

Copyright © 2025 The Author(s). Published by Elsevier Ltd.. All rights reserved.

目标： 鉴于登革热在热带低收入和中等收入国家（LMICs）中的不成比例负担，以及这些地区诊断测试和随访的有限访问，长期后遗症的人群队列研究尚不充分。我们估计了急性期后300天内新的多系统并发症的风险。

方法： 利用新加坡国家登革热注册表和医疗索赔数据库建立了回顾性人群基础成年队列，该队列包括实验室确认的登革热感染病例（2017年1月1日至2023年6月30日）以及未感染对照组。通过重叠加权调整了基线特征差异。使用竞争风险回归方法，系统地将登革热感染后的多个器官系统的并发症、全因住院和死亡的风险与人群基础对照进行了对比。

结果： 研究包括55,870名登革热感染者和3,072,309名未感染者；大多数初始感染较轻，不需要住院治疗。在急性期后，相比对照组，登革热感染者有19.0%（aHR=1.19[1.13,1.26]）增加的任何急性后期并发症的风险，心血管系统并发症风险增加了46.0%（aHR=1.46[1.01,2.10]），神经精神并发症风险增加了29.0%（aHR=1.29[1.14,1.45]）。自身免疫疾病的风险也增加了37.0%（aHR=1.37 [1.24,1.52]），内分泌疾病的增加为19%，消化系统后遗症风险增加了42.0%（aHR=1.42[1.17,1.72]）以及肾功能障碍风险增加了230.0%（aHR=2.30[1.69,3.12]）。登革热感染病例在急性期后的全因住院风险（aHR= 1.22[1.20,1.25]）和死亡风险（aHR= 2.08[1.85,2.33]）也有所增加。随访的第31-300天期间，登革热感染者的急性后期结果累积数量比未感染者多。住院治疗患者、61岁及以上年龄组、伴有合并症的人群以及DENV-2/DENV-3主要传播区域中的急性后期并发症风险增加。

结论： 在登革热幸存者中观察到，相对于未感染的人口基础对照组，多器官并发症、全因住院和死亡的急性后期风险有所增加。制定减少登革热感染后慢性健康损失的多学科护理策略至关重要。

关键词： 登革热；慢性；长期；急性后期后遗症。