Post-Ebola syndrome presents with multiple overlapping symptom clusters: evidence from an ongoing cohort study in Eastern Sierra Leone.

BACKGROUND Following the 2013-2016 West African Ebola outbreak, distinct, persistent health complaints were recognized in Ebola virus disease (EVD) survivors. Here we provide an in-depth characterization of post-Ebola syndrome over 2.5 years after resolution of disease. Additionally, we report sub-phenotypes of post-Ebola syndrome with overlapping symptom clusters in survivors from Eastern Sierra Leone. METHODS Participants in Eastern Sierra Leone were identified by the Sierra Leone Association of Ebola survivors. Survivors and their contacts were administered a questionnaire assessing self-reported symptoms and a physical exam. Comparisons between survivors and contacts were conducted using conditional logistic regression. Symptom groupings were identified using hierarchical clustering approaches. Simplified Presentation of Incredibly Complex Evaluations (SPICE), correlation analysis, logistic regression and principal component analysis (PCA) were performed to explore the relationships between symptom clusters. RESULTS 375 EVD survivors and 1040 contacts were enrolled into the study. At enrollment, EVD survivors reported significantly more symptoms than their contacts in all categories (p<.001). Symptom clusters representing distinct organ systems were identified. Correlation and logistic regression analysis identified relationships between symptom clusters, including stronger relationships between clusters including musculoskeletal symptoms (r=0.63, p<.001; and p<.001 for correlation and logistic regression, respectively). SPICE and PCA further highlighted sub-phenotypes with or without musculoskeletal symptoms. CONCLUSIONS This study presents an in-depth characterization of post-Ebola syndrome in Sierra Leonean survivors over 2.5 years after disease. The interrelationship between symptom clusters indicates that post-Ebola syndrome is a heterogeneous disease. The distinct musculoskeletal and non-musculoskeletal phenotypes identified likely require targeted therapies to optimize long-term treatment for EVD survivors.