What is Hantavirus? A cruise ship raised global attention.

-On 6 April 2026, an adult male on a cruise ship complained of fever, headache, and mild diarrhea. On 11 April, the patient suffered from respiratory distress and died on the same day. 

-An adult female who was a close contact of the previously mentioned patient complained of gastrointestinal symptoms on 24 April 2026 and deteriorated later and died on 26 April. 

-On 24 April 2026, an adult male suffered from a febrile illness, dyspnea (shortness of breath), and signs of pneumonia. He was hospitalized in an Intensive Care Unit (ICU), and his PCR confirmed hantavirus on 2 May 2026. 

-On 2 May 2026, an adult female, who presented with symptoms and signs of pneumonia since 28 April, died. 

-On 2 May 2026, it was reported to the World Health Organization (WHO) that a group of passengers on a cruise ship (147 individuals including 88 passengers and 59 crew members) suffered from severe respiratory illness. 

-On 4 May 2026, five suspected cases and two laboratory-confirmed cases of hantavirus were reported, including three deaths. 

-On 4 May 2026, hantavirus infection was confirmed by PCR. Contact tracing has been started. 

-The symptoms included gastrointestinal symptoms and fever and rapidly progressed to pneumonia, acute respiratory distress syndrome, and shock with an onset between 6 and 28 April 2026. 

-An international response with case isolation, medical evacuation, and laboratory investigations has been performed, and further investigations are ongoing.

Viral hemorrhagic fever is a multisystem syndrome characterized by severe damage to the vascular system by the viruses from six distinct families: Arenaviridae, Nairoviridae, Filoviridae, Hantaviridae, Flaviviridae, and Phenuiviridae. They are enveloped RNA viruses carried in nature by arthropod vectors or animals. Humans become infected by contact with infected hosts or their contaminated excreta like saliva, feces, or blood. Symptoms of this syndrome include fever and hemorrhage (bleeding). Outbreaks of viral hemorrhagic fever are not easily predictable, and the severity of the disease depends on virus species. 

Human hantavirus is a rare but severe zoonotic virus that may be fatal. It is a negative single-stranded tri-segmented RNA virus belonging to Bunyavirales, family Hantaviridae, and genus Orthohantavirus. It is acquired through contact with saliva, urine, or feces of infected rodents. Andes virus, which is a specific species of hantavirus, can cause human-to-human transmission. 

Hantaviruses cause two acute febrile diseases in humans: Hantavirus pulmonary syndrome (HPS) and hemorrhagic fever with renal syndrome (HFRS).

The diagnosis of hantavirus infection is enzyme-linked immunoassay (ELISA) detecting IgM or rising titers of IgG antibodies or reverse transcriptase polymerase chain reaction (RT-PCR) detecting viral RNA.

Until now, there has been no FDA-approved antiviral therapy or vaccine against hantavirus infections. 

Studies showed that hantavirus is mainly transmitted through rodents (contaminated saliva, feces, urine, and aerosols). Although being rare, it can be transmitted through the bite of affected animals. 

So humans can be infected through the following:

-Being scratched or bitten by an infected rodent.

-Eating hantavirus-contaminated food.

-Breathing hantavirus-contaminated air.

-Touching the nose or mouth after touching contaminated objects.

-Contact with an infected human. 

This is an enveloped virus that becomes inactivated after exposure to detergents, high temperature (60°C for 30 min), organic solvents, UV radiations, and hypochlorite solutions. They become attached to the cell surface receptors of the host by glycoproteins and affect multiple cells such as lymphocytes, epithelial cells, and dendritic cells. Studies showed that there are two types of integrins (transmembrane proteins of the host cell) that are β1-integrin, interacting with Gn of apathogenic hantaviruses, and β3-integrin, which interacts with glycoproteins of pathogenic hantaviruses, playing an important role in viral attachment and entry into the cell. 

Hantavirus under a microscope consists of three genomic RNA segments: S (encodes viral nucleocapsid protein (N-protein)), M (encodes glycoprotein precursor (GPC)), and L (encodes viral RNA-dependent RNA polymerase (RdRp)). The GPC precursor cleaves into Gn and Gc glycoproteins that are incorporated in the virus envelope. 

The blood vessel wall of humans is lined internally by endothelial cells, making the body's vascular system susceptible to viral infection. 

After entering the host:

-Viral uncoating occurs.

-Viral transcription is initiated by viral RdRp through a unique cap-snatching mechanism to generate 5' capped viral mRNAs.

-The viral replication is related to the multifunctional N-protein that is involved in initiating viral transcription, facilitating mRNA translation, and viral genome encapsidation. 

-The multifunctional N protein plays diverse roles in the virus replication cycle. It is involved in viral transcription initiation in conjunction with viral RdRp, facilitates mRNA translation, and encapsidates the viral genome (33–36). 

Hantavirus is considered an emerging global threat with an annual rate of more than 200,000 cases worldwide. An HFRS outbreak occurred during the Korean War (1950–1953), with more than 3,000 US troops affected, and another outbreak occurred in the southwestern regions of the US in 1993, and it was mainly an HPS outbreak. Recently, the 2026 outbreak was detected in a cruise ship that raised the international attention. 

The fatality rate of hantavirus infection is high due to hemorrhagic fever renal syndrome (HFRS) and nephropathia epidemica (NE) in Europe, hemorrhagic fever renal syndrome (HFRS) in Asia, and hantavirus cardiopulmonary syndrome (HCPS) in North and South Americas. Case fatality of 1–15% for HFRS, 0.1–1% for NE, and up to 40–60% for HCPS.

About 90% of all documented cases were from China, with a high frequency of HFRS. From 2006 to 2012, about 77,558 cases and 866 fatalities were reported with a case fatality rate of 1.13%, according to the Chinese Center for Disease Control and Prevention (China CDC). Cases of HFRS were reported mainly in the autumn-winter and spring seasons. By 18 December 2021, about 8,502 cases with 54 (0.63%) deaths were reported compared to 7,793 cases and 46 deaths in 2020. About 3,145 cases of HFRS were reported in Asian Russia with a 1.7% morbidity rate from 1978 to 1995. 

Thousands of HFRS and NE cases are reported annually in Europe. In 2012, over 2,800 cases of HFRS were reported in Germany. 

About 143 cases of HCPS were reported in Canada in 2020. About 100 and 200 cases of HCPS are reported annually in Argentina, mainly in the summer and spring seasons. In 2017, Brazil reported 2032 HCPCS cases. 

In 2023, 1885 hantavirus infection cases were reported in Europe. In 2025, 8 countries in the region of the Americas reported 229 cases and 59 deaths with a case fatality rate of 25.7%. 

The clinical presentation varies depending on the geographic distribution of the viral strains; for example, in Asia, Hantavirus (HNTV) and Seoul virus (SEOV) affect the human kidney and cause hemorrhagic fever with renal syndrome (HFRS). While in North America, Andes virus (ANDV) and Sin Nombre virus (SNV) mainly affect the lungs, leading to Hantavirus cardiopulmonary syndrome (HCPS) or Hantavirus pulmonary syndrome (HPS) with a high mortality rate. In Europe, Puumala virus (PUUV) and Dobrava-Belgarde virus (DOBV) cause a mild form of HFRS.

Puumala virus (PUUV), Seoul virus (SEOV), Dobrava Belgrade virus (DOBV), and hantaan virus (HTNV) are known as the old world hantaviruses, while Sin Nombre virus (SNV) and Andes virus (ANDV) are known as new world hantaviruses. The mortality rate of HFRS is about 15% and up to 50% for HCPS. 

Symptoms of HPS occur mainly 2-4 weeks following the initial exposure to the virus but may appear 1-8 weeks after the exposure. The symptoms include fever, headache, dizziness, chills, and gastrointestinal problems (including nausea, vomiting, diarrhea, and abdominal pain) followed by hypotension and sudden respiratory distress. 

In HFRS and NE, kidneys are the main organ affected. Clinical presentation includes fever, myalgia, acute renal failure, ocular and central nervous systems, and thrombocytopenia (low platelet count). The clinical presentation occurs over five phases: febrile, hypotensive, oliguric, polyuric, and convalescent. Complications of HFRS and NE include bleeding, pituitary hemorrhage, pulmonary edema, severe encephalomyelitis, glomerulonephritis, disseminated intravascular congestion, respiratory distress syndrome, shock, and multiorgan failure. 

In HCPS, lungs are the main organ affected. Three phases occur: prodromal, cardiopulmonary, and convalescent phases. In the prodromal phase, symptoms include fever, malaise, headache, and gastrointestinal distress, and the phase lasts 1-5 days. Symptoms of the cardiopulmonary phase include cough, dyspnea and hypoxia, and pulmonary edema. In the convalescent phase, all symptoms are relieved except dyspnea, which may last up to 1-2 years. 

Diagnosis is based on symptoms of the viral infection, some lab tests, and PCR. 

-History: 

History of travel to places of infected rodents or contact with rodents or their excretions. The symptoms of hantavirus infection are nonspecific and resemble flu-like illness and many other viral infections.

-Laboratory tests:

A Complete Blood Count (CBC) and peripheral smear can be used. 

-Serological tests:

Enzyme-Linked Immunosorbent Assay (ELISA) and the strip immunoblot are used for the detection of IgG and IgM anti-hantaviral antibodies in the blood of patients. IgM appears early, while IgG appears later in the course of infection. The structural proteins forming the hantavirus (N protein, glycoproteins Gn and Gc) can trigger an IgM response early and are used to detect acute infection. The indirect immunofluorescence assay is more specific but may not be available or laborious. The most specific tests are neutralization tests, but they are expensive. Immunochromatographic tests are cheaper but less specific. 

Isolation in cell cultures requires specially trained personnel and BSL-3 conditions (Biosafety Level 3 (BSL-3) conditions are strict protocols used in clinical or research facilities when working with indigenous or exotic agents that may cause serious or potentially fatal disease through inhalation). 

-Molecular methods:

Real-time RT-PCR is a sensitive and fast technique that detects the viral RNA in the blood or tissues. It is useful during the viremic phase of the hantavirus infection. 

The microarray technique is another sensitive and fast technique that can detect thousands of viruses simultaneously, but it is costly and complex. 

Next-Generation Sequencing (NGS) is also expensive and requires complex tools. The viral genome can be detected before the appearance of the IgM anti-hantaviral antibody through reverse transcription of the viral genome from the patient samples and amplification of the required viral sequence through PCR. 

The criteria used to report hantavirus-positive cases are:

-The presence of clinical symptoms.

-Acute laboratory diagnostic results:

• IgM positive

• IgG positive with rising titers

• PCR positive or immunohistochemistry positive

Once HPS is suspected, immediate care should be provided to the patients, preferably in the intensive care unit (ICU), even before the diagnosis is confirmed, as the infection may progress rapidly, leading to respiratory failure and death. The cardiopulmonary dysfunction is mainly due to the circulating inflammatory mediators.

Management includes: 

-Careful monitoring of cardiac and respiratory functions 

-Supplemental oxygen 

-Fluid therapy 

-Broad-spectrum antibiotic therapy: Especially if additional bacterial infection is suspected, empiric broad-spectrum antibiotics are started. 

-Ribavirin has been efficient against hantavirus hemorrhagic fever with renal syndrome; however, there is no specific antiviral treatment for HCPS until now. 

-Antipyretics (to reduce fever) and analgesics (pain relievers) 

-Analgesics 

-Intubation and ventilation if needed. When patients experience hypoxia (body tissues do not receive adequate oxygen to maintain normal function) and progressive pulmonary edema, they usually require mechanical ventilation. 

-Extracorporeal membrane oxygenation (ECMO) has about an 80% survival rate once the earliest signs of decompensation are detected (the heart cannot pump enough blood to meet the body's needs, and the compensatory mechanisms of the body fail). 

-Isolation of detected cases and close contacts. 

Fatal infection is associated with severe myocardial depression, sinus bradycardia (the heart beats slower than normal, typically under 60 beats per minute (bpm) in adults) with subsequent electromechanical dissociation, ventricular tachycardia, or fibrillation (severe heart arrhythmias originating in the lower heart chambers (ventricles) that can cause cardiac arrest and death).

*Poor prognostic factors of HPS include:

- Cardiac index of less than 2.2 L/min/m² or

- Plasma lactate of greater than 4.0 mmol/L 

Most deaths of HPS occur within 24-48 hours of the cardiopulmonary dysfunction.

-Avoid contact with rodents or their excretions like saliva, urine, or droppings. 

-Use wet cleaning methods, not dry sweeping, and ensure proper ventilation. 

-Specific measures should be applied to pregnant women, children under 5 years old, the elderly, or any immunosuppressed individual, as they have a high risk of infection due to weak immunity. 

-Care for pet rats may prevent the transmission of hantavirus.

-Standard precautions should be applied, including hand hygiene, safe handling of blood or body fluids of any patient, and environmental cleaning. 

-Individuals living in endemic areas like rural areas or camping should take precautions to decrease the risk of exposure to infection. 

-Ensure safe food storage.

(1) Afzal S, Ali L, Batool A, Afzal M, Kanwal N, Hassan M, Safdar M, Ahmad A, Yang J. Hantavirus: an overview and advancements in therapeutic approaches for infection. 

(2) Mir S. Hantavirus-Induced Kidney Disease. Front Med (Lausanne). 2022 Jan 8.

(3) Hantavirus. Centers for Disease Control and Prevention (CDC). 

(4) Hantavirus cluster linked to cruise ship travel, multi-country. World Health Organization (WHO).

(5) Hantavirus. World Health Organization (WHO).