The latest zoonotic threats from SARS-CoV-2 and avian flu to other virulent pathogens: the work of Host-Pathogen Interactions Pillar 2

As co-leaders of CoVaRR-Net’s Host-Pathogen Interactions Pillar and in their own independent research, Drs. Angela Rasmussen and Jason Kindrachuk are focused on emerging zoonotic pathogens, including and beyond SARS-CoV-2, that have spread among animal species and have – or have good potential – to spread from animals to humans. If enough mutations occur, each one could – like SARS-CoV-2 did – cause significant human-to-human transmission. Aiming to avoid another pandemic, the researchers are doing surveillance and research in Canada and elsewhere in the world, studying how pathogens are evolving in animals and how infections in diverse animal species in Canada can influence human health.

SARS-CoV-2 started in animals, spread to humans, and has since been spreading back to animals such as tigers, lions, panthers and otters in zoos, mink on mink farms, gorillas, bears, hyenas, hippopotamuses, white-tailed deer, mule deer, marmosets, giant anteaters, and domesticated pets such as cats, dogs, hamsters, and ferrets.

The vicious circle has serious potential consequences. When the virus is rapidly transmitted within animal species, SARS-CoV-2 mutations are more likely to occur. When transmission goes from one species to another, the evolution of the virus is accelerated, bringing a possibility of many new mutations. “A real risk of the virus moving back into animals is that SARS-CoV-2 will become endemic in all these animal reservoirs. When the virus transmits either within an animal species or between species, it can evolve in unpredictable ways, and that could make the virus worse when it moves back into people,” explains Dr. Rasmussen, Research Scientist at the Vaccine and Infectious Diseases Organization (VIDO), University of Saskatchewan. “We need to worry about that.”

Dr. Rasmussen and Dr. Kindrachuk have tested susceptibility in more than 70 North American species and are now collaborating with Parks Canada and the Saskatoon Forestry Farm Park & Zoo to conduct surveillance and develop research tools from species that may include bison, bighorn sheep, foxes, deer, bears, and various small mammals. Dr. Rasmussen is using a similar approach to identify species that were sold at the Huanan Seafood Market in Wuhan, China, and that are susceptible to the ancestral strain of SARS-CoV-2 and may have been the intermediate hosts from which the virus jumped to start the pandemic in late 2019.  “Working with these wildlife samples in the lab will allow us to prioritize susceptible North American species for surveillance and better understand host-pathogen interactions,” she says, noting that SARS-CoV-2 has moved back into humans from infected farmed mink, domesticated cats, and white-tailed deer.

The first probable case of SARS-CoV-2 jumping from a white-tailed deer to a human in Canada was reported in 2022 by a research team that included Dr. Brad Pickering, a Pillar 2 Deputy and Research Scientist, head of Special Pathogens, National Centre for Foreign Animal Disease, Canadian Food Inspection Agency. A highly mutated version of SARS-CoV-2 was identified in samples of hunted deer and in a southwestern Ontario resident, who had been in close contact with deer. This highlights the potential for deer or other animal species to act as reservoirs for transmission of new and divergent variants back to humans.

CoVaRR-Net researchers also aim to understand the virus’s impact within each species and across different species. “By obtaining molecular profiling data from animal models and wildlife samples, we aim to assess the susceptibility of different species to SARS-CoV-2 infection and look at their response to predict the severity of infection. Using machine learning, we may be able to predict the kinds of variants that are likely to emerge in advance. This could help us to predict outcomes and assess risks posed by novel emerging variants to both humans and animals,” says Dr. Rasmussen. “There is also the potential to expand this innovative approach to other zoonotic viruses.”

Panzootic spread of bird flu elevates the risk for humans

Dr. Rasmussen co-authored a leading international scientific report published in May on how avian influenza – H5N1 – jumped from wild birds into dairy cattle, spread among cattle, and infected a Texas dairy farm worker.

“Our analysis showed early on that the first cattle outbreak in Texas originated from a single H5N1 reservoir and wasn’t detected or identified for several months. A reshuffling of genes within North American avian viruses happened shortly before the cattle outbreak, and these changes allowed the virus to more readily infect cows and other mammalian species,” explains Dr. Rasmussen. “The data also showed H5N1 transmission between cattle was extensive enough to spill back into wild birds, poultry, cats, raccoons, and other species.”

Zoonosis refers to an infection or disease that is transmitted from an animal to a human host and/or the other way around. SARS-CoV-2, Ebola, mpox (formerly monkeypox), and certain avian and swine flus are examples of zoonotic viruses. H5N1 has now infected more than 200 mammalian species, including many species not previously known to be susceptible to the virus. There have also been sporadic confirmed cases of H5N1 infecting people so far this year. Dr. Rasmussen is concerned that as the virus spreads more widely among cattle and crosses into more species, more agricultural workers will be exposed and infected with H5N1, and this viral strain is more likely to adapt in ways – such as the ability to grow in the respiratory tract – that could lead to a human outbreak.

If bird flu continues to spread and becomes endemic in cattle, Dr. Rasmussen says it will pose multiple risks to Canada in terms of the agricultural industry, food security, and human health. There have been no confirmed cases of avian flu in Canadian cattle yet. “Canada is such a big importer of U.S. cattle, bringing in over 300,000 cattle a year. We need to know if H5N1 is in cattle in Canada and what the possibilities are if it comes here.”

Dr. Kindrachuk, the Canada Research Chair in Pathogenesis of Emerging and Re-emerging Viruses, and Professor, University of Manitoba, has teamed up with Dr. Rasmussen and other Canadian researchers to test milk sold in grocery stores to detect any fragments of H5N1. “Canadian research groups can augment federal surveillance by the Canadian Food Inspection Agency to provide an effective early warning system to detect evidence of avian influenza virus introduction in Canadian cattle,” Dr. Kindrachuk suggests. “Although pasteurization of milk protects people against infectious viruses, there is a risk that as H5N1 moves through animals it could adapt in a way that affects food security. The virus also poses serious risks to the health of animals. Among cats who drank raw milk at U.S. dairy farms, for example, more than 50% that tested positive for H5N1 died from the infection.”

Other pathogens in animals that have – or have potential – to spread to humans worldwide

While the avian flu has been the most prominent zoonotic threat making headlines in North America lately, CoVaRR-Net Pillar 2 researchers are monitoring these other zoonotic pathogens that have evolved to become more virulent and pose increasingly dangerous threats to humans:

mpox

Dr. Kindrachuk co-led last year a joint Canadian-Democratic Republic of the Congo (DRC) research team that identified a deadlier, more transmissible mpox strain in DRC, called clade Ib. The 2022 mpox outbreak, which spread to many countries including Canada, involved clade IIb, a milder version that largely impacted men who have sex with men. Dr. Kindrachuk has been working with DRC public health researchers to investigate and help contain an outbreak that has resulted in more than 20,000 documented cases and nearly 1,000 deaths in the DRC since January 2023. The virus has become endemic in several other Central African countries and is also transmitted to people from contact with infected wildlife. “Clade 1 mpox virus spread to 23 of 26 provinces in the DRC since early 2023. This clade is associated with more severe disease than that seen during the global epidemic (clade IIb), and infections have now been associated with wildlife contacts as well as through intimate (sexual) contact that includes heterosexual and same-sex contact,” he explains. “Given the increasing incidence of mpox associated with sexual contact in DRC, there is a significant risk for further geographic spread, including to neighboring regions and beyond, which could fuel another more dangerous global mpox outbreak, unless the global community helps to support and expand the DRC’s efforts to contain it.”

Borealpox

Borealpox, previously known as Alaskapox, is another emerging zoonotic virus found in voles, shrews, and red squirrels that Dr. Rasmussen is watching. “Six of the seven cases reported since 2015 have been relatively mild, but in January an immunocompromised man from Alaska died from the virus. We need to better understand the risks to people from orthpoxviruses, such as borealpox and mpox, as they evolve,” she says, noting one possibility being investigated is that domestic cats and dogs who hunt small mammals could retain the borealpox virus on their claws and transmit it when they scratch people.

SFTSV

SFTSV (Severe Fever with Thrombocytopenia Syndrome Virus) is an emerging tick-borne virus that has spread widely in Asia including China, South Korea, Japan, Vietnam, Thailand, and Taiwan over the past 15 years. The virus can be transmitted to humans through bites mainly from SFTSV-carrying Asian long-horned ticks, causing severe fever and death in more than 20% of cases. Human-to-human transmission has also been reported. “With endemic infection in East Asia and the recent spread of the Asian long-horned tick to over 20 states in the U.S., there is a significant risk that SFSTV will come to North America and that deadly outbreaks could start happening here,” Dr. Rasmussen suggests.

Heartland virus

The Heartland virus is an infectious disease people get from being bitten by an infected Lone Star tick. Researchers believe these ticks get the virus after sucking blood from infected animals such as deer or raccoons. Heartland virus has been reported in at least 10 U.S. states – though not in Canada yet — and causes hospitalization for dehydration, pain and fever for most infected people, and in some cases death. “The Heartland virus is genetically closely related to SFTSV. I’m concerned that these two closely related viruses could mix and match their genomes into another new, dangerous virus that would potentially pose a global threat to people unless it is contained,” cautions Dr. Rasmussen.

Dr. Kindrachuk says approximately 60 to 70 per cent of all new emerging infectious diseases circulating in the world today are zoonotic diseases. “We’re still living in a world where we mostly monitor new viruses only after human cases show up. We need to look and find more information about where the viruses are hiding in animals before they move into humans. Improving surveillance of SARS-CoV-2, mpox, and phleboviruses such as SFTSV, circulating in animals globally and in Canada, will put us in a better position to prevent and respond to new variants of these viruses, or any another type of emerging virus, that could trigger major human outbreaks or the next pandemic,” he says.

Avian influenza viruses may be transmitted from infected birds to other animals and potentially humans both directly and indirectly. Infection of wild birds, poultry, and mammals can happen directly through exposure to saliva, mucus or feces from infected birds, or indirectly through an intermediate, such as another animal.

Avian influenza virus infections in people can happen after close, prolonged, and unprotected contact with infected birds or other animals. This can occur when a person breathes in virus droplets or touches something that has virus on it and then touches their mouth, eyes or nose.