Hantavirus: A Comprehensive Narrative Review of Virology, Epidemiology, Pathogenesis, Clinical Manifestations,...

Hantaviruses are a genus of negative-sense, single-stranded, tri-segmented RNA viruses that are distributed worldwide. They cause two severe zoonotic diseases in humans: haemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS), also known as hantavirus cardiopulmonary syndrome (HCPS). Hantaviruses are primarily spread by inhaling aerosolised excreta from infected rodent reservoirs. Over 50 rodent species on six continents have been found to carry hantaviruses, with only one reported case of human-to-human transmission, involving the Andes virus (ANDV) in South America. HFRS is estimated to cause 100,000-150,000 cases worldwide annually, mainly in Asia and Europe. HPS/HCPS is far less common, with case fatality rates of 25%-40%, predominantly in the Americas. The pathogenesis of hantaviral disease is characterised by viral infection of endothelial cells, dysregulation of vascular permeability, and dysregulated innate and adaptive immune responses, leading to cytokine storm physiology. Diagnosis relies on enzyme-linked immunosorbent assay (ELISA)-based serology and reverse transcription polymerase chain reaction (RT-PCR). Strain characterisation and outbreak investigations are increasingly being performed using next-generation sequencing. No hantavirus species has a licenced vaccine outside of HTNV and SEOV, for which inactivated rodent-brain-derived vaccines remain in limited regional use in Korea and China. Regulatory-agency-approved antiviral therapy is similarly lacking worldwide, and management remains largely supportive. Ribavirin has shown benefit in reducing mortality and renal morbidity in HFRS when initiated early, but has not demonstrated efficacy in HPS/HCPS in controlled trials. Recent advancements include the development of monoclonal antibodies, candidate mRNA and subunit vaccines, and an improved understanding of the mechanisms of immune evasion. This review synthesises the latest information on hantavirus biology, clinical medicine and public health. This highlights the critical gaps that must be addressed to counter the growing threat posed by this pathogen in an era of climate change and global ecological transformation.