Hantavirus Disease in a Changing World: Reservoir Ecology, Endothelial Dysfunction, Clinical Management, and the 2026 M/V Hondius Andes Virus Outbreak

Hantaviruses are zoonotic, tri-segmented negative-sense RNA viruses maintained in diverse mammalian reservoirs. Human disease is caused predominantly by orthohantaviruses and manifests chiefly as hemorrhagic fever with renal syndrome (HFRS) in Eurasia or hantavirus pulmonary/cardiopulmonary syndrome (HPS/HCPS) in the Americas. Andes virus (ANDV) is epidemiologically distinctive because limited human-to-human transmission has been repeatedly documented. This update-oriented narrative review synthesizes evidence available through to 28 August 2026 and is organized around an integrative framework linking reservoir ecology and spillover, ANDV-specific person-to-person transmission, endothelial and immune dysfunction, clinical phenotype, critical-care management, and One Health preparedness. The recent 2026 M/V Hondius outbreak is used as a case study of how a primarily rodent-borne infection can generate international operational consequences in a mobile, closed setting. Recent HFRS surveillance from Asia and Europe is included to balance the ANDV-focused outbreak analysis. Severe disease is associated with endothelial barrier dysfunction, capillary leak, thrombocytopenia, myocardial or renal involvement, and dysregulated host responses rather than widespread endothelial necrosis. Current evidence supports early recognition and organ support; evidence for ribavirin, immune plasma, monoclonal antibodies, and host-directed vascular therapies differs substantially by syndrome and remains limited or investigational for HPS/HCPS. The M/V Hondius event ultimately involved 13 cases (12 confirmed and one probable) and three deaths, with no further secondary cases after completion of international follow-up.