Andes virus and the aging host: lessons from the 2026 outbreak and a framework for age-related disease severity.

Andes virus (ANDV) is the most virulent New World orthohantavirus, responsible for hantavirus cardiopulmonary syndrome (HCPS)-a severe and frequently fatal disease characterized by non-cardiogenic pulmonary edema, vascular collapse, and dysregulated immune activation. The April 2026 outbreak of ANDV aboard the cruise ship MV Hondius, in which several older adults were among those most severely affected, has renewed attention to host age as a potential determinant of disease severity. Although HCPS is predominantly reported in younger and middle-aged adults, this epidemiological pattern likely reflects occupational exposure bias and case ascertainment limitations rather than intrinsic age-related protection. Biological aging profoundly remodels vascular homeostasis through endothelial senescence, reduced nitric oxide bioavailability, chronic low-grade inflammation (inflammaging), immunosenescence, mitochondrial dysfunction, and a prothrombotic state-mechanisms that converge directly on the pathogenic pathways exploited by ANDV. Aging may regulate key ANDV entry receptors, including β3 integrins and possibly protocadherin-1, on pulmonary endothelial cells, while impaired type I interferon responses and T-cell dysfunction may facilitate viral dissemination and amplify immunopathology. Together, these hallmarks of vascular aging may constitute a biological "preconditioning" state that lowers the threshold for ANDV-induced vascular collapse, yielding an "acute-on-chronic endothelial dysfunction" syndrome in elderly patients. This mini-review integrates current knowledge of ANDV biology, person-to-person transmission dynamics, and the mechanisms of vascular aging and immunosenescence, proposing a testable framework for future investigations. Specific research priorities are identified-including age-stratified epidemiological analyses, comparative transcriptomic studies in young versus aged endothelium, and biomarker discovery-that would establish whether biological aging genuinely amplifies susceptibility to severe ANDV infection.