New World hantaviruses, such as Andes virus, cause respiratory illness, but they strike differently from common viruses that cause lung failure. Hantaviruses grow slowly and kill quickly, killing up to half of the people they infect. Yet, mysteriously, survivors suffer no lasting damage from the disease.
These are just some of the peculiarities that scientists have discovered and studied since these viruses were first recognized in the 1990s. What scientists have gleaned so far is how they monitor the more than 150 people currently in quarantine around the world. after the recent epidemic of Andean hantavirus on the cruise ship MV Hondius.
Already, three people have died in this epidemic and nine others are sick, some in critical condition. Research into how viruses behave in the body and how it defends itself could also lead to treatments against future epidemics.
Hantaviruses do things differently
Respiratory viruses such as influenza, RSV and coronavirus that causes COVID-19 infect and kill cells in the lungs, with immune system reactions worsening the damage. But even though New World hantaviruses cause a serious lung disease called hantavirus pulmonary syndrome, they do not attack lung cells.
Instead, the virus infects cells that line blood vessels throughout the body. The main target, explains clinical virologist Pablo Vial, is the tiny blood vessels called capillaries. Vial directs the hantavirus and zoonoses program at the German Clinic at the Universidad del Desarrollo in Santiago, Chile.
Infected cells can lose some functions, says Jonas Klingström, a virologist and immunologist at Linköping University in Sweden, “but they don’t die. They’re not killed.”
Another peculiarity is that the Andes virus, endemic in Chile and Argentina, and the Sin Numéro virus, present in the United States and parts of Canada and Mexico, contain only four proteins, while other respiratory viruses contain more than twice as many. Two of the four proteins help the virus enter cells, one replicates viral RNA and one forms the viral envelope. Old World hantaviruses, known mainly in Europe and Asia and which tend to damage the kidneys, contain an additional protein.
It’s a small toolbox, but hantaviruses make the most of it, evading the immune system while slowly replicating. “They are really sneaky,” says Klingström. “They can both inhibit antiviral responses, but they also avoid activating them.”
It can take up to 45 days for an infected person to develop symptoms. Most people infected with Andes virus will get sick enough to need oxygen, but 40% of them will recover without serious medical intervention, Vial says. The rest will suffer serious illness requiring intensive care.
The science behind a rapid decline
At some point during an infection, the tight junctions where proteins weld blood vessel cells to their neighbors loosen, causing blood vessels to leak. Blood plasma, the fluid part of the blood, can leak out while blood cells stay inside. Scientists don’t yet know what turns the tap on.
This is not viral replication, Vial says. Either way, it’s happening quickly, he said. Within hours, patients’ lungs fill with the escaping fluid, disrupting their breathing. Their hearts fail and their blood pressure drops, putting them into shock.
The long gap between infection and symptoms, along with the fact that Andes virus is the only hantavirus known to spread from person to person, explains why the crew and passengers of the MV Hondius and people exposed to a cruise passenger on subsequent airline flights are monitored for six weeks after their last possible exposure.
The rapidity between the onset of symptoms and the development of serious illness partly explains why the U.S. Centers for Disease Control and Prevention has called for the 18 Americans monitored in special quarantine facilities in Omaha, Neb., remain there at least until May 31, although some passengers have requested to quarantine at home.
Typically, 20 to 40 percent of people diagnosed with Andes virus infection die, Vial says. He’s helped treat many of the nearly 1,500 cases of Andean hantavirus diagnosed in Chile since 1995, and learned a few lessons along the way about how to treat shock and put people on ventilators without causing harm.
When a ventilator isn’t enough, doctors turn to extracorporeal membrane oxygenation, or ECMO. It is a heart-lung machine which pumps blood out of the body, oxygenates the blood and returns it to the body, giving rest to diseased lungs and heart. “I talk to patients at noon and at two in the afternoon, they’re already connected to mechanical ventilation, and at three o’clock they’re already on ECMO. So it’s a very, very rapid progression,” says Vial.
Most patients who die do so either during their hospital admission or within 24 hours of their admission, Vial and his colleagues found when they examined 100 hantavirus cases treated at eight hospitals in Chile over about eight years. According to unpublished data, among these cases there were 21 deaths.
Although administering intravenous fluids is the standard treatment for shock, Vial does not advise it for patients with leaking blood vessels. This fluid ends up in the lungs, making the situation worse, he says.
Almost as suddenly as the leaks occur, the faucets run dry and patients can recover. “It takes 48 to 72 hours for this biological effect to reverse and become completely normal,” Vial explains. This is unheard of among respiratory diseases. Often people spend weeks in intensive care units for severe flu or COVID-19 and end up with injuries, scarred lungs who may never fully recover.
Antibodies developed during infection may have something to do with controlling the virus, but the immune system does not eliminate infected cells. How hantaviruses protect host cells remains a mystery.
Treatments for hantavirus are lacking
Doctors can provide supportive care for symptoms, but they cannot stop the virus. There is currently no specific treatment or vaccine against hantaviruses.
Vial and his colleagues tried several ways to keep hantavirus patients out of the intensive care unit. An antiviral drug that stops the growth of hantaviruses in laboratory dishes did not work in patients developing severe symptoms. Steroid treatment with methylprednisolone, which can help reduce damage from other respiratory diseaseslike COVID-19, also did not work. Give to people plasma from cured patients of a hantavirus infection is useful when people are just developing symptoms, Vial says. Antibodies in the blood of recovered people can prevent the virus from entering blood vessel cells.
Antibodies that persist for decades in people recovered from infection with Puumala virus, an Old World hantavirus, could also fight Andes virus, says Mattias Forsell, an immunologist at Umeå University in Sweden. The Puumala virus is carried by bank voles and caused, on average, around 3,100 cases per year in Europe from 2010 to 2020, notably in Finland, Sweden and Germany.
Forsell and his colleagues tracked the levels of hantavirus antibodies in the blood of about 150,000 study participants. Northern Sweden Health and Disease Study. In areas where Puumala virus is endemic, about 11 to 12 percent of participants have antibodies against the virus. These antibodies persist for at least 22 years, the team found. “These infections can actually confer lifelong immunity,” says Forsell. In unpublished studies, Forsell’s team found that some of these antibodies can latch onto other hantaviruses, including the Andes virus, and could thus form the basis of future treatments.
Discovering the cause of the leak and how it becomes blocked could also lead to new treatments. Klingström and other researchers found elevated levels of certain immune system proteins called cytokines in people with severe hantavirus illness. Among the cytokines believed to open connections between blood vessels are the proteins interleukin-6 (IL-6) and bradykinin.
Although IL-6 is usually produced by immune cells and sometimes by liver cells, blood vessel cells infected with hantaviruses also produce IL-6, Klingström and colleagues found. In the case of Andes virus, an increase in IL-6 levels in the blood has been associated with more serious diseaseKlingström and colleagues reported in 2019 in the Journal of Infectious Diseases.
IL-6 is a messenger molecule that signals immune cells to fight viruses, but it can also trigger damaging inflammation. Which route used by IL-6 to transmit its message determines whether capillaries will leak, Klingström and colleagues reported in 2025 in PLOS Pathogens. Some drugs already in clinical trials can block a harmful route of administration, which could stop capillary leaks, he says.
Vial and his colleagues also experimented with a drug called icatibant that blocks bradykinin. The drug is already approved to treat a rare genetic disorder called hereditary angioedemain which people develop spontaneous swelling of the face, hands and other parts of the body, and this helped a woman with severe Puumala virus infection recover quickly. But large clinical trials are needed to determine whether the medication is an effective treatment.
Ultimately, combinations of medications can prevent people from drowning in their own fluids, Klingström says. New treatments can’t come soon enough for those affected by the cruise ship outbreak, but he hopes attention to the outbreak will spur research that could benefit the more than 10,000 people infected with hantaviruses worldwide each year. “It should be possible to design treatments that could reverse this situation quite quickly,” he says, “and hopefully save patients from this potentially fatal disease quite quickly.”
