Characterization of post-acute multi-organ sequelae following dengue infection

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

National dengue registries and healthcare-claim databases in Singapore were utilized to build a retrospective population-based adult cohort with laboratory-confirmed dengue infection (1 January 2017-30 June 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 hospitalization, and death up to 300 days post-dengue infection were systematically contrasted against population-based controls, using competing risk regression.

55 870 dengue-infected individuals and 3 072 309 uninfected controls were included; the majority had mild initial infection not requiring hospitalization. In the post-acute period, there was a 19.0% (adjusted hazard ratio [aHR] = 1.19 [1.13, 1.26]) increased risk of any post-acute sequelae, with a 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 vs. controls. There was also a 37.0% increase in the risk of autoimmune disorders (aHR = 1.37 [1.24, 1.52]), a 19% increase in the risk of endocrine disorders (aHR = 1.19 [1.12, 1.25]), a 42.0% increase in the risk of gastrointestinal sequelae (aHR = 1.42 [1.17, 1.72]), and 230.0% increase in the risk of renal sequelae (aHR = 2.30 [1.69, 3.12]). Post-acute risk of all-cause hospitalization (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 among dengue-infected cases increased over the 31-300 day follow-up period, vs. uninfected controls. Risks of post-acute sequelae were increased in hospitalized dengue patients, older age groups (61+ years), those with comorbidities and across DENV-2/DENV-3 predominant transmission.

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