The outbreak first came to the attention of the World Health Organization on May 2, 2026, when passengers aboard the MV Hondius, which carried 147 crew members and passengers from 23 countries, presented with fever and gastrointestinal symptoms that rapidly progressed to pneumonia, shock, and acute respiratory distress syndrome. Laboratory confirmation of Andes virus infection by polymerase chain reaction followed between May 4 and May 6. By July 2, 2026, 13 cases had been identified on the vessel, 12 confirmed and one probable, and three patients had died, yielding a case fatality ratio of 23 percent. Epidemiologists hypothesize that an initial case acquired the infection from a rodent before boarding, with subsequent human-to-human transmission occurring during the prolonged, close contact that confined shipboard conditions inevitably produce.

Andes virus, formally Orthohantavirus andesense, occupies a unique position among hantaviruses. While hantaviruses are typically transmitted from rodents to humans through contact with urine, feces, or saliva, and humans are generally considered dead-end hosts, Andes virus is the only hantavirus documented to spread efficiently between people. First identified in Argentina in 1995, the virus has an incubation period ranging from 7 to 42 days, with a median of 18 days, and viral RNA has been detected in blood, respiratory secretions, urine, and semen. Transmission can occur through mucosal or respiratory exposure to infectious respiratory particles, although the virus is not classified as highly airborne. Case fatality ratios have reached 50 percent in some settings, and the virus has a documented history of super-spreading events, most dramatically during Argentina’s 2018 to 2019 outbreak, when transmission at a large social gathering linked to three super-spreaders produced the largest Andes virus outbreak recorded to date, with a case fatality ratio of approximately 32 percent.

Genomic sequencing of viruses isolated from the MV Hondius passengers detected no new lineages, and the circulating strain closely resembled Andes virus lineages previously identified in Argentina and Chile. The outbreak’s reproductive number was estimated at 0.7, considerably lower than the median reproductive numbers of 2.12 and 0.96 observed before and after infection control measures during the Argentine outbreak. Because the incubation period can extend to six weeks, disembarked passengers were asked to quarantine for 42 days, a duration that health authorities calculate provides a 96 percent probability of safe release. The episode has nonetheless highlighted the vulnerability of international transportation systems, where restricted spaces, overcrowding, inadequate ventilation, and limited access to intensive care can amplify transmission. Experts now recommend screening passengers boarding from hantavirus-endemic regions, controlling rodents on ships and in harbors, and establishing approved protocols for managing infectious diseases in international waters.

The pathogenesis of Andes virus infection centers on endothelial dysfunction. Hantaviruses target endothelial cells, producing enhanced microvascular permeability in the principal target organs: the lungs in hantavirus cardiopulmonary syndrome, which predominates in the Americas, and the kidneys in hemorrhagic fever with renal syndrome, which prevails in Europe and Asia. Immune-mediated mechanisms play a pivotal role. CD8-positive T cell activation has been documented during acute phases of both syndromes, immunoblasts circulate in patients experiencing shock or pulmonary edema, and fatal cases show high densities of cytokine-releasing cells in lung tissue. Elevated levels of tumor necrosis factor alpha can drive capillary leakage, pulmonary edema, and shock, while high interleukin 2 levels increase vascular permeability. Hantavirus cardiopulmonary syndrome unfolds in three phases: a prodromal phase of non-specific flu-like symptoms, a cardiopulmonary phase marked by pulmonary capillary leak and hemodynamic compromise that can culminate in cardiogenic shock, and a convalescent recovery phase.

Early diagnosis is critical because no specific antiviral agent exists. Reverse transcription polymerase chain reaction can detect viral RNA in whole blood during the asymptomatic and prodromal phases, and serological confirmation relies on IgM and IgG assays performed with chemiluminescence immunoassay technology. IgM antibodies appear at symptom onset, rise within a week, and clear after one to three months, whereas IgG antibodies emerge three to seven days after symptoms begin and persist for years, making them unsuitable for early diagnosis. Notably, some polymerase chain reaction-positive cases have been entirely asymptomatic, and viremia can precede symptoms. Differential diagnoses during the prodromal phase include influenza, COVID-19, viral and atypical pneumonias, yellow fever, dengue, leptospirosis, endocarditis with pulmonary edema, sepsis with acute respiratory distress syndrome, and arenavirus infections, underscoring the diagnostic challenge clinicians face.

Clinically, initial symptoms of hantavirus cardiopulmonary syndrome typically emerge one to eight weeks after exposure and include chills, fever, gastrointestinal upset, nausea, vomiting, diarrhea, headache, dizziness, and myalgia, before sudden progression to respiratory distress, hypotension, and shock. A recent systematic review and meta-analysis identified prognostic factors for severe outcomes, including female sex, age over 18, rural residence, pulmonary infiltrates on chest radiographs, underlying disease with elevated serum creatinine and hematocrit, and signs of bleeding. For patients with severe disease, extracorporeal membrane oxygenation can be life-saving; in experienced centers in the United States, Argentina, and Chile, ECMO-supported survival has ranged from approximately 60 to 75 percent. Timely administration of antipyretics, vasopressors, fluid therapy, mechanical ventilation, and renal replacement therapy, tailored to infection severity and organ involvement, remains the foundation of care.

On the pharmacological front, favipiravir is the most studied antiviral under consideration for Andes virus, though most safety and efficacy data derive from its use against other viral infections. A recently published case report described a 69-year-old man, diagnosed through screening after repatriation from the cruise ship, who received a combination of oral favipiravir, subcutaneous icatibant, intravenous then oral ribavirin, and oral baricitinib over a proposed 10-day course. The patient developed hypoxemia, hyponatremia, thrombocytopenia, and bilateral interstitial infiltrates roughly 24 hours after diagnosis, but recovered clinically, radiologically, and laboratory-wise from day two without progressing to shock or requiring vasopressors or invasive ventilation. Ribavirin and favipiravir were discontinued on days five and nine, respectively, after recurrent diarrhea and hyponatremia. The authors caution that a single favorable outcome cannot establish efficacy, and larger studies are required. Icatibant, a selective bradykinin B2 receptor antagonist, is hypothesized to alleviate bradykinin-driven vascular leakage, while the interleukin 6 receptor antagonist tocilizumab showed striking signals in a MEURI case series: five of five untreated ICU patients with Andes virus cardiopulmonary syndrome died, compared with four of five survivors among those receiving a single 8 mg/kg intravenous dose within 24 hours of admission. By contrast, a double-blind randomized trial in Chile found that high-dose intravenous methylprednisolone provided no significant clinical benefit in hantavirus cardiopulmonary syndrome, and monoclonal antibodies, molnupiravir, and baloxavir remain at earlier stages of investigation.

Vaccine development remains an empty pipeline in Western nations, with no approved hantavirus vaccine in the United States or Europe, although the inactivated Hantavax vaccine is used in Korea and China. A DNA vaccine targeting the Andes virus glycoprotein has completed Phase I testing: in a randomized controlled trial of 48 healthy adults, needle-free administration of 2 mg or 4 mg doses in three- or four-dose schedules was generally well tolerated, induced neutralizing antibodies, and achieved seropositivity rates of 67 to 90 percent by day 337, with only mild to moderate adverse events. Viral vector vaccines based on vesicular stomatitis virus and mRNA vaccines using both uridine and N1-methylpseudouridine platforms are in preclinical development, and recombinant human monoclonal antibodies JL16 and MIB22 have provided high levels of post-exposure protection in animal models by neutralizing viral glycoproteins. The review’s authors conclude that while the public health risk from the current outbreak remains low, the MV Hondius episode demonstrates that Andes virus could become a broader global concern, and they urge accelerated development of specific antivirals and vaccines, particularly mRNA platforms, alongside sustained vigilance in isolation, physical distancing, rodent control, and global cooperation to manage unpredictable outbreaks in the years ahead.

Subject of Research: Epidemiology, pathogenesis, and pharmacological management of the 2026 Andes virus outbreak linked to a cruise ship

Article Title: Incidence, pathogenesis, clinical manifestations, and pharmacological management of the 2026 Andes virus outbreak

Article References: Ghasemiyeh, P., & Mohammadi-Samani, S. (2026). Incidence, pathogenesis, clinical manifestations, and pharmacological management of the 2026 Andes virus outbreak. Virology Journal, 23(1), Article 208. https://doi.org/10.1186/s12985-026-03298-9

Image Credits: AI Generated

DOI: 10.1186/s12985-026-03298-9

Keywords: Andes virus, hantavirus, hantavirus cardiopulmonary syndrome, MV Hondius, cruise ship outbreak, human-to-human transmission, favipiravir, tocilizumab, ECMO, DNA vaccine, mRNA vaccine, public health

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