Ecological and Individual-Level Factors Associated With Hantavirus Cardiopulmonary Syndrome Notifications and in-Hospital Mortality Among Hospitalized Patients in Chile, 2005-2022.

INTRODUCTION: Hantavirus cardiopulmonary syndrome (HCPS) is a severe zoonotic disease caused by Orthohantavirus andesense (Andes virus, ANDV), with significant public health burden in Chile. Despite decades of surveillance, knowledge gaps remain regarding the ecological drivers of notification burden and the individual-level determinants of in-hospital mortality among hospitalized patients. This study aimed to address both dimensions simultaneously, providing a multilevel characterization of HCPS epidemiology in Chile from 2005 to 2022. METHODS: Two complementary analyses were conducted. First, an ecological study examined district-level HCPS notifications (2005-2022) using a negative binomial mixed-effects model, with predictors including male population rate, urbanization proportion, population density, season and burned area due to forest fires during the most recent summer season. Second, an individual-level analysis of hospitalized HCPS patients (2010-2020) used a logistic mixed-effects model to identify correlates of in-hospital mortality among hospitalized patients, including age, sex, indigenous group affiliation, hospitalization duration and number of surgical interventions. RESULTS: A total of 886 HCPS cases were notified across 187 districts, averaging 49.2 cases per year. Notifications were positively associated with higher male population rates and greater burned area due to forest fires, and negatively associated with urbanization and population density. Among 462 hospitalized patients, the in-hospital case-fatality ratio was 19.7%. Older age, female sex and indigenous group affiliation were significantly associated with higher in-hospital mortality risk among hospitalized patients. Shorter hospitalization duration and greater number of surgical interventions, as correlates of clinical severity and complexity, were also associated with in-hospital mortality among hospitalized patients. CONCLUSIONS: HCPS notification burden in Chile is shaped by environmental and demographic factors, with forest fire activity representing a novel and actionable ecological risk indicator. In-hospital mortality among hospitalized patients is disproportionately concentrated in older, female, and indigenous populations, highlighting the need for targeted surveillance, equitable healthcare access and integrated One Health strategies to reduce the burden of HCPS in Chile.