Andes virus is a New World orthohantavirus carried primarily by the long-tailed pygmy rice rat, and it is unusual among hantaviruses in its capacity for person-to-person transmission, a feature documented in household clusters in Chile and in so-called super-spreading events in Argentina. Infection produces hantavirus cardiopulmonary syndrome, a biphasic illness that begins with a prodrome of fever, myalgia and gastrointestinal symptoms before progressing abruptly to cardiopulmonary compromise. The hallmark pathophysiology is a dramatic increase in microvascular permeability driven by infection of endothelial cells, leading to non-cardiogenic pulmonary edema, hypoxemia and myocardial depression. Unlike many viral hemorrhagic fevers, the dominant clinical problem is the lung and heart rather than bleeding, and the window from first respiratory symptoms to critical illness can be a matter of hours.

The new study was motivated in part by renewed international attention to the disease after a reported case-outbreak of hantavirus cardiopulmonary syndrome on a cruise ship, an event that highlighted how rarely appreciated zoonoses can surface in unexpected settings and how gaps remain in global preparedness. The research team, led by Gabriela Meza-Fuentes and René López of Universidad del Desarrollo and Clínica Alemana in Santiago, used Chile’s Diagnosis-Related Groups database to identify patients admitted with the syndrome over a six-year window, a period spanning the pre-pandemic baseline, the COVID-19 pandemic itself and the post-pandemic recovery.

The cohort comprised 215 patients with laboratory-confirmed hantavirus cardiopulmonary syndrome, of whom 69.3 percent were male and 87 percent were adults. Respiratory support was required by 148 patients. Within this group, the escalation of organ support was striking: 14.2 percent received non-invasive ventilation, 36.5 percent were managed with invasive mechanical ventilation, and 49.3 percent ultimately needed extracorporeal membrane oxygenation. In other words, among patients who could not maintain oxygenation on their own, half progressed to the most invasive form of life support available, reflecting the fulminant nature of the cardiopulmonary phase and the limited ability of conventional ventilation to compensate for a lung flooded with protein-rich edema fluid.

Outcomes tracked this intensity of care. The median hospital length of stay was eight days, with an interquartile range of three to fifteen days, and overall in-hospital mortality was 20.5 percent. Case fatality rose steeply with the level of organ support, reaching 29.6 percent among patients on invasive mechanical ventilation and 32.9 percent among those supported with ECMO. These figures are consistent with the historical literature, in which venoarterial or venovenous extracorporeal support has been credited with rescuing a substantial fraction of patients who would otherwise have died of refractory hypoxemia and shock. Early reports from the late 1990s in North America, and subsequent Chilean and Argentine series, established ECMO as the single most effective rescue therapy for the syndrome, and the current cohort confirms that this dependence has not diminished in contemporary practice.

Perhaps the most consequential finding of the temporal analysis concerns the pandemic period. After adjusting for covariates, the COVID-19 pandemic years were independently associated with higher in-hospital mortality from hantavirus cardiopulmonary syndrome, with an adjusted odds ratio of 2.73 and a p-value of 0.045. This echoes observations from other settings in which critically ill patients without COVID-19 fared worse during pandemic surges, a phenomenon attributed to strained intensive care capacity, deferred admissions, exhausted staff and reduced availability of highly specialized resources such as ECMO referral. For a disease in which survival hinges on timely transfer to a center capable of extracorporeal support, pandemic-era system stress could plausibly have delayed the escalation of care precisely when patients were deteriorating fastest.

The pathophysiological substrate of the disease helps explain why it remains so refractory to treatment. Hantaviruses enter host cells through protocadherin-1 and related receptors, infecting pulmonary endothelium and, as recent biomarker work suggests, the alveolar epithelium as well. The resulting vascular leak is amplified by sensitization to vascular endothelial growth factor, while the myocardium fails in a manner resembling a viral cardiomyopathy. Because the injury is primarily immune-mediated and permeability-driven rather than cytopathic destruction, antiviral drugs and corticosteroids have both failed to show clear benefit in randomized trials, including a double-blind Chilean trial of high-dose methylprednisolone and a multicenter trial of human immune plasma. Supportive critical care, fluid-restricted hemodynamic management and extracorporeal rescue therefore remain the pillars of therapy, and mortality has changed little over two decades.

The authors note that their dataset, derived from a national administrative database, captures the real-world distribution of organ support across both public and private hospitals, rather than the referral-biased case series that have dominated the literature. This matters for planning: hantavirus cardiopulmonary syndrome is seasonal, tied to rodent population dynamics and human exposure in rural central and southern Chile, and clusters of severe cases can rapidly consume regional ECMO capacity. With person-to-person transmission documented and the virus endemic across a broad swathe of Patagonia on both sides of the Andes, the study provides a contemporary benchmark against which emerging interventions can be judged. Several candidate therapeutics, including monoclonal antibodies directed at the viral envelope, are in preclinical development, and any future trial will need outcome data of exactly this kind to size studies and define endpoints.

For clinicians, the message is sobering but practical. Hantavirus cardiopulmonary syndrome in the modern era still kills one in five hospitalized patients, and among those who need respiratory support, the majority will require invasive ventilation and nearly half will need extracorporeal life support. Early recognition of the cardiopulmonary phase, immediate referral to centers with ECMO capability and vigilant preservation of critical care capacity during health system crises are the interventions most likely to move these numbers. The finding that pandemic-era mortality nearly tripled serves as a warning that even a well-organized national response can be vulnerable when intensive care resources are diverted, and it underscores the preparedness gap that recent commentaries on rare zoonoses have emphasized for Andes virus and its relatives.

The study was supported by Chile’s National Agency for Research and Development, and its dataset is publicly available through the Chilean National Health Fund’s open data platform. As climate change, land-use change and human encroachment on rodent habitats continue to reshape the ecology of zoonotic spillover in South America, national cohorts of this kind will remain essential for tracking whether the critical care burden of Andes virus infection is shifting, and whether decades of experience with extracorporeal support are finally being translated into falling mortality.

Subject of Research: Critical care burden, organ support use and outcomes of Andes virus-associated hantavirus cardiopulmonary syndrome in Chile.

Article Title: Temporal trends in critical care burden and outcomes of Andes virus-associated hantavirus cardiopulmonary syndrome: a national Chilean cohort

Article References: Meza-Fuentes, G., Delgado, I., Vial, P. A., Godoy-Faúndez, A., Rivera, D., Bernal, Y., Graf, J., & López, R. (2026). Temporal trends in critical care burden and outcomes of Andes virus-associated hantavirus cardiopulmonary syndrome: a national Chilean cohort. Intensive Care Medicine. https://doi.org/10.1007/s00134-026-08599-9

Image Credits: AI Generated

DOI: 10.1007/s00134-026-08599-9

Keywords: Andes virus, hantavirus cardiopulmonary syndrome, critical care, ECMO, mechanical ventilation, in-hospital mortality, Chile, zoonosis, COVID-19 pandemic, intensive care, respiratory support, epidemiology