r/Virology

I do not wish to come across as alarmist. I have research experience with and publications on SARS-CoV-2 but have been working in autoimmunity since 2024. I hope we can avoid the same early improper assumptions made with COVID, but I fear public health guidance has already dropped the ball by telling mainstream media that the virus is not mutated and that it does not spread easily through air. Within the virology and epidemiology community, I have seen a surprising lack of disregard for certain facts.

The dogma since the release of the Swiss patient’s Andes virus sequence has been that the lack of reassortment is evidence that the virus does not have significant or consequential mutations. This is obviously false and anyone who has taken an infectious diseases or virology course should know this.

There are indeed mutations in the M segment, including in the regions coding the receptor-binding Gn and Gc proteins. It is not known if these mutations are consequential for human transmission, but it can’t be said that it’s impossible. Though it is rare that such a beneficial mutation would occur within an animal reservoir, it can happen. Keep in mind that SARS-CoV-2 gained its furin cleavage site before it started spreading in humans. But this is a very rare occurrence and I’m hoping it isn’t what happened here, though the spread on the ship gives me pause.

Lytras analysis does not show convincing evidence that genetic differences in the surface proteins would not confer improved human-to-human transmissibility. It is also not evidence of the contrary.

I wouldn’t write off the genetic distance between the Epuyén virus with the Swiss-resident virus. For example, SARS-CoV-2’s high transmissibility is attributed largely to the furin cleavage site, which was not present in more closely related coronaviruses, but was indeed present in some that were more distantly related.

The most genetically similar virus only spread to household members and healthcare professionals in direct contact with the index patient (Martinez-Valdebenito, 2014). However, the Andes virus from the Hondius appears to spread more easily. I understand that they were on a small cruise ship, but there was transmission thought to have occurred from brief “passings by”, which seems to align more closely with the manner of spread of the 2018-2019 outbreak in Epuyén, Argentina. It also seems that the incubation period is shorter than previously described.

Still, cruise ships are unique environments. There are so many factors including shared serving utensils, poor air circulation, close sleeping quarters, potential swinging, etc. That may not sufficiently explain (in my opinion) the differences in spread and incubation period.

Anxiously awaiting good news that those on the Hondius do not spread the virus as it spread on the ship, but I can’t help but hold my breath.

Please share your thoughts and pertinent new information as it becomes available.

This will be where we are aggregating specific articles and discussion regarding the cruise ship hantavirus outbreak.

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08 May: The sequence results are now in for one Swiss case. See here.

08 May: The flight attendant exposed to the 69 year old patient on a flight has tested negative for hantavirus.

CHI-Hu13724 in comparison to previously known Andes Virus Haplotypes:

• Is the first Andes Virus haplotype identified in 20 years
• Has increased silent spreading capabilities
• Is less lethal

Source: https://pubmed.ncbi.nlm.nih.gov/41070183/

Disclaimer: Which haplotype we are currently dealing with is not publicly known.

Given the possible new silent spreading capabilities of the virus, could it already be widespread in parts of South America?

My observation is the people who have died have been elderly.

Harvard Professor Joseph Allen, an expert in exposure assessment science, recently stated that official public messaging regarding hantavirus transmission—specifically the emphasis on "prolonged contact"—contradicts established scientific evidence.

Source: https://www.ms.now/news/hantavirus-outbreak-mv-hondius-cruise-ship-transmission-risk-public-health

Between Spring of 1951 and the armistice of July 1953, an unnamed disease infected UN soldiers among the ridge lines and rice paddies of central Korea. They’d begin presenting with sudden headaches, high fever, a spreading flush in the face and neck, and then days later having blood seep from the skin. The doctors in the Mobile Army Surgical Hospital (MASH) units had never seen anything like it, resorting to attempts of treatment using the likes of quinine and penicillin but nothing worked. Thankfully the disease wasn’t spreading from patient to patient. But that made the central question more unsettling: where was it coming from? The answer seemed to be the ground itself.

Eventually, the condition became known as Korean hemorrhagic fever, one of the illnesses now grouped under hemorrhagic fever with renal syndrome, or HFRS. Some 3000 UN soldiers were infected during the war with an estimated 150-300 having died of it. Exactly what killed them would remain a mystery for over 25 years until the isolation of the Hantaan virus (named after the river in Korea) in 1978. The first hantavirus outbreak recorded by western doctors is a story of a disease that hid in plain sight. The mouse carrying it likely seen thousands of times by soldiers as they stepped by them or kicked them aside without a second thought.

A Pre-Korean War Timeline

Obviously, the disease had a history before western doctors first encountered it. Since hantaviruses can be found in both New- and Old-World mammal species like mice, shrews, and bats, it is thought the viral family itself traces back millions of years. It’s also thought that Chinese medical literature from the year 960 contains descriptions consistent with hantavirus disease. It’s also been suggested as a possible cause for trench nephritis, a type of renal disorder encountered by soldiers during the American Civil War and during World War I. HFRS was observed in hospital in the Vladivostok region in WWI. There was also epidemic disease consistent with HFRS seen in both Russian and Japanese troops along the Manchurian-Soviet border; the linked citation also lists the incredible amount of names hemorrhagic fevers had attained by publication in 1963. It’s a hell of a list to say the least. They describe hemorrhagic fevers in “the northern belt, extending from the Soviet Far East and Korea, across Manchuria and Mongolia to the Urals, the Upper Volga, and Murrnansk Oblast; and on to the Scandinavian countries, Czechoslovakia, Hungary, and Bulgaria”. It’s fair to say hanta-derived hemorrhagic fevers were uncommon but far from an extreme rarity in Europe and Asia. Japanese Army doctors in WWII Manchuria would describe an epidemic of hemorrhagic fever among their troops with 10,000 said to have been affected and with a death rate up to 30%. Before 1951, Korea hadn’t been a hotbed of cases, with only a few cases described in the extreme northeastern corner of Korea by the Siberian/Manchurian borders with no recognized presence in central Korea.

Hantavirus in the Korean War

The Korean war officially got its start on June 25^(th), 1950, when the North invaded the South. From the summer of 1950 to Spring of 1951, the war would be a highly mobile one, with front lines moving dramatically up and down the peninsula. Until then, there hadn’t been any reports of hemorrhagic fevers in the American forces. By June of 1951 the frontline had stabilized near the 38^(th) parallel, with UN forces constructing bunkers, trenches, and fortifying positions across the central front in what became known as the “Iron Triangle” region (Cheorwon-Kimhwa-Pyonggang). The Yunchon and Cheorwon area seems to have been the center of where the first cases of hemorrhagic fever start popping up, soon spreading to Gimhwa and Pyonggang. It’s been proposed that HFRS may have been accidentally introduced through the Chinese army during the Korean War. A Time magazine article from the time reports at least 25 deaths with hundreds sick since June. In November of the same year, the Associated Press would report on the outbreak:

“A strange illness for which no sure cure has been found has broken out among United Nations forces in Korea, Gen. Ridgway’s headquarters said today. Brig. Gen. William E. Shambora, surgeon of the Far East Command, said the mysterious malady strikes suddenly and is characterized by fever and a headache... Sulfa and antibiotics have failed to stem the disease... The malady is strikingly similar to that reported by the Japanese among their Manchurian troops in 1939.”

By April of 1952 there was an established Hemorrhagic Fever Center near the heavy concentration by the 38^(th) parallel with all suspected cases being evacuated by helicopter. The 8228^(th) MASH unit in Seoul is designated specifically as a medical center for hemorrhagic fever and cold-related injury, receiving over 2000 admissions that year alone, the vast majority of which were from the Army. There patients would undergo strict management of fluids, nursing care in critical phases, special positioning to prevent hypotension, electrolyte monitoring, and later dialysis. The virologist and civilian researcher for the army Dr. Joseph Smadel led a team to Korea to study the outbreak, finding 46 deaths among the 848 diagnosed cases (a case fatality rate of 5.6). The same year would mark the start of the 7^(th) Infantry Division’s formal control program involving the dipping of clothing in miticide, spraying the quarters with lindane, and rodent control. These would be crucial during the seasonal peak periods of May-July and October-December. This is also around the same time that the 11^(th) Evacuation Hospital in Wonju would become notable for their use of “artificial kidney” or dialysis machines, which was one of the earliest uses of dialysis in wartime for combat medicine.

The scientific investigation into its HFRS’s cause would continue through the war, with the Armed Forces Epidemiological Board’s Commission on Hemorrhagic Fever being tasked with investigating the disease. They saved 600 sera samples taken from 245 patients for future analysis. The 1954 medical report by Dr. Sidney Katz formally characterized the disease as “Hemorrhagic Fever of the Far Eastern Type” using what was known from the Russian and Japanese literature of the time to reconcile what he had seen in the Korean War data from UN troops. Katz’s report listed more than 25 diseases that could mimic early KHF, including malaria, scrub typhus, leptospirosis, and other hemorrhagic fevers. Scrub typhus is of particular note because it is actually present in Korea. The suspected vector of transmission changed over time, with early opinions leaning toward chigger mites which carried scrub typhus (thus the miticide dipping of clothes) or airborne transmission from rodent droppings, but they couldn’t isolate an agent of spread. Endemic cases among U.S. would continue to be documented through 1972 by South Korean physician, virologist, and epidemiologist Ho Wang Lee, with over 2800 total cases being observed from 1951 to 1972.

Lee’s team started capturing rodents during the ceasefire line in the 70s, even contracting the disease himself and being arrested by the South Korean military on suspicion of being a spy. In 1976, In 1976, they used sera from Korean hemorrhagic fever patients to show the same antigen is found in the lungs and kidneys of the striped field mouse (Apodemus agrarius). In 1978 the virus would be formally isolated from a sample mouse taken near the Hantan River, naming it the Hantaan virus with the genus subsequently being named after the first isolated sample.

The taxa would be greatly expanded across the next couple of decades, first with Seoul virus (carried by the Norway rat Rattus norvegicus) found to be distributed worldwide. A strain of the Hantaan virus was grown in a cell culture and found via electron microscopy to belong to the Bunyaviridae family, however with a lack of arthropod vector it is unique in that specific family of viruses. Sin Nombre virus would be identified in 1993 as a cause of a severe pulmonary syndrome in the Four Corners region of the American Southwest. The Andes virus, cause of the current outbreak aboard the MV Hondius vessel, was isolated in 1995 and was the first to be found to spread from person-to-person.

Ecology and Transmission: How Warfare Changed Both

As mentioned, the reservoir for the Hantaan virus in Korea and China is the striped field mouse. It also happens to be the most common small mammal in all of Korea, representing over 90% of the captured small mammals at training sites near the DMZ. They’re found throughout rural areas due to the agricultural fields and nearby forests/hilly regions (exactly that of the central Korean front during the war. The fatter, male mice hold significantly higher antibody prevalence than the smaller females. The transmission route is primarily via the inhalation of aerosolized rodent excrement like dried urine, feces, or nesting material which easily make their way into the air during types of cleaning like sweeping. Unlike the New World Andes virus, the variants found in Korea have no person-to-person transmission, a trait that complicated reasoning by early epidemiologists about why the disease wasn’t “catching.”

An aspect of the war itself that seems to have been crucial to an outbreak like was seen is the fact that in summer of 1951 the Korean War shifted from a mobile phase into static trench warfare. Digging into the hillsides to construct bunkers and trenches meant disturbing the soil, creating new rodent habitat, and would’ve produced the aerosolized dust that transmits the viral particles. Veterans recalled rats “nearly as big as cats” having been their “daily companions” through this period of the war. They were so prominent in the fortified positions because of the deforestation that was occurring as a result of bombing and deliberate land clearing which concentrated the mice in the remaining habitats near the bunkers and agricultural areas.

It’s hard to directly quantify the impact relative to other diseases, but in 1953 disease as a whole accounted for over 40% of the hospital admissions among Korean War combatants with hemorrhagic fever being but one component of that broader infectious disease burden that included malaria, dysentery, scrub typhus, and various respiratory illnesses. The course of illness was about five-to-six weeks due to the lengthy recovery which could involve gaining back as much as 50 pounds lost during the illness. Hemorrhagic fever during the Korean War was a nightmare no soldier was prepared for. Command was somewhat lucky it only took as many lives as it did, because a more virulent strain may not have been as kind on the numbers and even less kind on morale.

Biological Warfare?

Public health and germ warfare during the Korean War, author unknown, ca. 1952 https://www.nlm.nih.gov/hmd/topics/chinese-posters/poster-politics_101559945-sm.html

I’ll end with a bit on something that came out of the confusion that goes hand-in-hand with the fog of war. I’m admittedly going to rely heavily on the wiki here as I haven’t read the multiple books on the topic yet. The Chinese and North Korean governments both claimed that in 1951 and 1952 the United States was using biological weapons, citing the hemorrhagic fever and other diseases taking hold in their troops. The Soviet Union even took these claims to the UN. There was a bit of a history to this, as in 1949 the Soviets had put out propaganda claiming the US was testing biological weapons on the Alaskan Inuit populations, with the Chinese even claiming the US was working with Shiro Ishii, a Japanese WWII General who focused on biological warfare in China. North Korea claimed the US was spreading smallpox as a form of biological warfare in North Korea. Mass demonstrations would take place in the USSR and its Eastern Bloc countries

The central evidence during the Korean War was the confession of one Colonel Franke Schwable. The captured Marine pilot stated in February of 1953 that B-29s had flown biological warfare missions based out of Okinawa starting in November of 1951. He was one of a few POWs who made similar statements. The U.S. would declare the statements made as a result of torture and upon release they did take back those claims (although under threat of a treason charge). These claims had an air of credibility to them as the US had concealed some of the atrocities committed by the Japanese Unit 731 led by the aforementioned General Ishii, who was exempted from war crimes and placed on the American payroll in exchange for data (Operation Paperclip wasn’t the only time we used the worst of the worst to work on our behalf). While there wasn’t any confirmatory evidence about Ishii working on Korean War operations on behalf of the US, the years of lying about the Unit 731 arrangement made it hard to deny.

The strongest bit of counter-evidence comes from Soviet and Chinese documents that were released in 1998 by Kathryn Weathersby and Milton Leitenberg who work on the Cold War International History Project. They included hand copied records from the Russian Presidential Archive with a statement from their secret police (NKVD) chief stating “”False plague regions were created, burials … were organized, measures were taken to receive the plague and cholera bacillus. The advisor of the MVD DPRK proposed to infect with the cholera and plague bacilli persons sentenced to execution.” North Korea had literally gotten plague cultures from China and infected a couple of prisoners, then using those tissue samples to claim to the international investigators that the US was engaging in biological warfare. The same documents note the disinformation campaign started to wind down after the death of Stalin in March of 1953. I don’t know enough to judge the claims on their merits, and the U.S. record on Unit 731 makes blanket innocence hard to take on trust. But the available Soviet and Chinese archival evidence strongly suggests that at least part of the Korean War biological warfare campaign was deliberately fabricated. That said, the evidence for and against these specific claims are wrapped up in multiple books, so I don’t quite have the full grasp on the claims. If enough people want a piece on that or US bio-warfare in general, I’d be happy to research further!