Clinical phenotypes of severe dengue and their temporal evolution during a Reunion Island epidemic: a retrospective cohort study

The clinical heterogeneity of severe dengue suggests the existence of distinct organ dysfunction patterns. This exploratory study aimed to describe these patterns at ICU admission in Reunion Island (2017–2022) and to analyze how they evolved over time throughout the epidemic. We performed a multiple correspondence analysis followed by ascending hierarchical clustering, using organ failure profiles at ICU admission in patients with confirmed severe dengue. We then evaluated the predictive performance of these phenotypes for adverse outcomes, compared their temporal distribution during the epidemic, and performed a survival analysis. Out of 137 included patients, we identified three phenotypes. Phenotype 1 (39.4%) showed a thrombocytopenia-predominant pattern without additional organ failure and the best prognosis (0% mortality); whether this represents a distinct phenotype or the less severe end of the spectrum remains uncertain. Phenotype 2 (23.4%) showed cardiorespiratory involvement without coagulopathy, with a mortality rate of 22%. Phenotype 3 (37.2%) was the most severe form, with multiple organ failure and the highest mortality rate (45%). Renal failure was not a discriminating factor. Phenotype 3 predicted ICU mortality with a sensitivity of 76.7% and specificity of 73.8%; internal exploratory estimates pending prospective validation. Phenotype distribution did not vary significantly across the epidemic period despite a serotype shift in 2020; individual serotype data were available for only 55 of 137 patients. Severe dengue exhibited clinically relevant phenotypic heterogeneity. If externally validated, early identification of these organ dysfunction patterns might eventually inform risk stratification, though prospective applicability remains to be demonstrated.