One thing we’ve been watching for with SARS-CoV-2 in animals is whether we will see establishment of “animal” variants. Humans have done an effective job of infecting a wide variety of animal species with this primarily-human virus. Fortunately, thus far these infections usually die out rapidly in that animal or group of animals (mink being a notable exception). In that scenario, the broader implications of spillover into animals are limited, because there’s not enough long-term transmission for animals to become true reservoirs or for new variants to emerge.

White-tailed deer have been a particular concern lately because they are quite susceptible to infection with SARS-CoV-2, they can spread the virus effectively deer-to-deer, and they live in large enough groups that the virus could potentially be maintained in the deer population even without regular contact with infected people.

Until recently, surveillance of deer for exposure to and infection with SARS-CoV-2 (primarily in the US, but now in Canada as well) yielded a mix of good news and bad news. The good news was that the strains found in deer were the same as those found in people in the same area around the same time. That suggests that transmission was commonly occurring from people to deer, but without evidence of long-term circulation in deer population or mutation of the virus to adapt to deer.

However, there is now new evidence based on a pre-print study from a Canadian research group (Pickering et al. 2022) that the SARS-CoV-2 virus may have been circulating in some deer populations for longer that previously thought, leading to emergence of a divergent strain of the virus.

Here is the (not so) short summary of their findings:

  • Nasal swabs and retropharyngeal lymph nodes (glands located at the back of the throat) were collected from 300 hunter-collected deer in Ontario between November 1 and December 31, 2021.
  • Five (2.3%) nasal swabs and 16 (5.3%) lymph node samples were PCR positive for SARS-CoV-2, for an overall prevalence of 6% in the deer sampled. That’s a low percentage, which is good, and is consistent with some earlier Canadian deer surveillance, though some US studies have reported much higher rates of exposure and infection among deer in some states.
  • All positive deer were from southwestern Ontario.

The good news aspect of the low prevalence is offset by some bad news about the genetic makeup of the viruses that were found. Sequence analysis was only possible for a subset of positive samples. (There can be various reasons for that. Most often, it’s because there’s enough virus to yield a positive PCR result but not enough to be able to get good sequencing data). Using a couple of techniques, they ultimately managed to get full sequence data from 5 samples and partial genomes from 2.  The deer SARS-CoV-2 viruses belonged to the B1 lineage, which encompasses a wide group of common strains. However, the deer samples formed their own group that was very different from other reported sequences in B1 lineage, with the closest “relatives” being sequences from people collected in Michigan in November/December 2020 (where they had also seen spillover into the deer populations there). (See image below, or click here to enlarge image.)

  • We have to be a bit careful when looking at sequence databases because we can only compare “new” strains with sequences that have been deposited. That doesn’t mean these strains don’t exist anywhere else, it just means they haven’t been reported from anywhere else. Yet, given the scope of SARS-CoV-2 surveillance worldwide, it’s supportive of this being a divergent deer-associated lineage.
  • The fact that the most closely related strains of SARS-CoV-2 are from Michigan in 2020 raises a few interesting questions. Michigan is just across the border from Ontario, but it’s not a simply border for deer to cross because of the Great Lakes and associated rivers. There’s no direct land bridge, so it’s not just a matter of a deer wandering across a political border on a map.
  • It was also noted that the November/December 2020 sequences from human samples from Michigan were closely related to  sequences from mink samples from the same state collected in September/October 2020.

This brings up many other questions, such as:

  • Did a “human” strain of SARS-CoV-2 spread from people to deer in Ontario and then mutate, or did deer pick this up from other wildlife?
  • If SARS-CoV-2 is present in other wildlife, which species are of concern and how did they get it?
  • Could this strain be present in wildlife in Michigan and have moved to Ontario via a non-deer wildlife species?

The other question that obviously comes to mind is “Is this strain actually present in people, and this really just represents human-to-deer transmission of a strain we haven’t detected in people?”  That’s a reasonable question but a few things make it less likely.  A strain like this, that is quite divergent genetically, presumably mutated over time to get to where it is. If this had occurred in people, odds are reasonable that sequences from one or more of those intermediary strains would have been identified at some point, even though we don’t sequence the virus from every single human infection. That’s not the case here. That could just reflect variant development in an area where testing was limited, so we can’t dismiss the possibility completely. However, it supports the notion that this strain might have evolved in animals (deer or otherwise).

Potential deer-to-human transmission

Another noteworthy aspect of this report is information about a potential deer-to-human transmission event. One human sample from Ontario from December 2021 was found with most (80 of 90) of the same mutations and was consistent with this deer-group of viruses. It wasn’t possible to say where this strain fit into the timing of viral evolution, i.e. was it a step along the way of the progression to the deer lineage, or was it derived from a deer strain?  The human sample pre-dates the deer sampling, but we have to be careful interpreting timing of deer samples because collection occurs during a defined time of year: hunting season. So, while these strains were first found in deer in samples from November/December 2021, we have to assume that they were present earlier. There’s also a plausible epidemiological link between the infected person and deer, as there was known “close contact” with deer.  Note: that’s contact with deer, not the known-positive deer.  Further details of the “close contact” were not provided.

This gets us back to the “chicken vs egg” discussion.  Did this person get infected from deer, or were they a source of infection for deer?  Until December 2021, virtually all PCR-positive samples in Ontario were being sequenced, so it’s unlikely this strain was emerging in people in a lead up to a spillover into deer. There was less testing (and sequencing) in humans in late 2021 as the omicron surge overwhelmed testing capacity in Ontario.

Have there been more human cases of this strain?

  • That’s hard to say, since this was a very recent observation in deer and the risk of spillback into people was probably most likely during the recent hunting season. Omicron blasted through Ontario at the same time, and there were severe limitations in testing. At that point only a minority of people got tested, particularly of otherwise healthy people from the community (who would be at greatest likelihood of deer exposure). There’s currently no evidence of onward human-to-human spread, but we have to realize that surveillance decisions made by the province impact the ability to detect spread of new variants.

I won’t get much into the genomics themselves, since this post is pretty long and the story above is the key. More details about these new finding are in the paper. However, the quick version is that many of the mutations that were found in the strains from the deer are consistent with those found in animals such as bats, cats, hamsters, mink and, yes, other deer. When a virus jumps to a different host, we can see some more common genetic changes as it adapts to that new species.

Ultimately, to answer these and other questions, we need more samples from deer from different areas and over time, and more comparison with human-derived virus sequences. The current story is based on a small number of samples from a narrow window in time, but the story is pretty compelling and concerning.

If this is truly a deer strain of SARS-CoV-2, what does that mean?

That’s still hard to say. The big question is what happens over time.  Will this strain (or others) be maintained in deer? If so, will deer become a true reservoir, where they can then potentially infect people and other animals?

The “other animals” component is often neglected, but it’s important. If deer are a reservoir, they could spread it to other potential reservoir species, amplifying the problem. They could also spread it to other susceptible species that are not likely to become reservoirs based on numbers and population dynamics, but that have closer contact with people. For example, we’re not going to see a reservoir in domestic cats because there’s not much chance of sustained cat-to-cat spread in most situations. However, cats are highly susceptible and indoor-outdoor cats have abundant contact with wildlife (including deer) so they could plausibly be a bridge from wildlife reservoirs to people.

A closing piece of good news is that it looks like these deer variants are as effectively neutralized by vaccine antibodies as other lineages.

Much of the story here is quite speculative, but it’s why we’ve been talking about the need to study SARS-CoV-2 in animals from the start of the pandemic. Those pleas were largely ignored for a long time, so now we’re playing catch-up. I’d hoped we would be lucky and that our negligence in supporting study of animals wouldn’t come back to bite us in the butt. I’m not as convinced that’s going to be the case now. It’s hard to say if we could have done anything differently if we’d had support to investigate earlier, but it certainly wouldn’t have hurt.

The image below from the preprint article (Pickering et al. 2022) depicts an overview of the potential zoonotic scenarios underpinning the evolution of the SARS-CoV-2 strains in white tailed deer in Ontario, and the one associated human case (click here to enlarge).

Throughout the pandemic, countless decisions have had to be made, often with limited data. As more information becomes available, guidance and recommendation are updated. That sometimes upsets people, but it’s a good thing because it means we know more. If no recommendations had changed since early 2020, it would mean that we were really intuitive or lucky with our first recommendations (not likely), that we haven’t learned anything  in two years, or that we haven’t applied any of our new knowledge (the human factor, which is often the biggest barrier).

A common question I get is, “how long should an animal from a COVID-19-positive household be isolated when it is taken to an animal shelter?”  Answering that is a challenge, in part because we need to balance being proactive and practical. Longer isolation is better from a disease control standpoint, but it’s more expensive, more of a hassle, ties up often limited isolation space, and complicates care or adoption.

So, we try to find a sweet spot in the middle that minimizes risk as much as possible while not being completely disruptive, all based on pretty limited data.

  • We use data from experimental studies and natural infections in animals, information from human isolation guidelines, and then we essentially just pick what we hope is a reasonable number. Not completely scientific, but with scientific underpinning.  It’s the best we can do at this point with the information available.

Our initial guidance for isolation of exposed pets coming into animal shelters erred on the side of caution, and was therefore set at 14 days.

Over time, guidance for isolation of infected and exposed people has changed, and we ended up in a situation where isolation of pets was stricter/longer than in humans (despite humans likely being the most susceptible to SARS-CoV-2). There actually is some sense to that, because the implications of isolation played a big role in changing the guidance for humans, and recent changes have focused more on getting people back to work than high level confidence that they are no longer infectious. We can sometimes take a stricter approach with animals since there isn’t a societal need to spring a cat from isolation a few days earlier.

In many areas, it’s now recommended that people isolate for 5 days after onset of symptoms or a positive test (whichever is first). Those changes are a bit weak since we know a lot of people will still be infectious as of day 5, but the decision was driven a lot by economic concerns, and it’s clear the risk of transmission drops fairly soon after symptom onset. Part of this allowance also depended on strict adherence to some basic practices like masking (which obviously can’t be applied to animals in shelters) and testing (which we don’t routinely do in animals, and we don’t have validated rapid tests for animals either).

So, while 14 days of isolation for an exposed animal seems like overkill at this point, reducing it to 5 days is probably too far a leap in the other direction.  So shall we split the difference?

  • That’s pretty much it, to be honest. I’ve been recommending 7-10 days isolation for COVID-19-exposed pets coming into shelters. Ideally it’s 10 days, especially for cats since they are probably much higher risk than dogs.

That said, I get asked about different scenarios pretty much daily, and I say if there’s a compelling reason to shorten the isolation period, I’m fine dropping it to 7 days, particularly for dogs. It reduces confidence in protection a little bit, but sometimes those 3 days can have a significant impact on logistics or animal welfare, so it’s a cost-benefit decision based on many factors.

Understanding the epidemiology of the pandemic in a given area also is important in these decisions. If there’s rampant community transmission of SARS-CoV-2, and especially if there’s poor masking in the shelter and limited restriction of visitors, the added protection from a few more days of isolation is probably limited given the much greater human-to-human transmission risk.  If a shelter is still predominantly curbside or allowing only limited numbers of visitors by appointment, the relative risk from the animal is presumably higher (since there’s less human-to-human transmission risk), so being a bit stricter about the isolation period makes sense.

Take home message:

  • I think isolation of exposed pets in a shelter (or a clinic) for 7-10 days makes sense. The shorter window is more reasonable for dogs and in situations where there are significant isolation limitations or other needs to open up isolation space.
  • Five days of isolation for pets, as for humans, is a bit dodgy, since we don’t have the data to support it.  While we don’t have a good handle on the risks, a few extra days provides some added security.

As per yesterday’s post, another rabid imported dog was identified in Ontario, again from Iran. What’s particularly surprising about this case is the very long incubation period. The dog didn’t develop signs of rabies until over 6 months after importation, and it was confirmed that it was infected with canine-variant rabies (consistent with strains circulating in Iran) so it was infected before it came to Canada.  Even it this dog was exposed to rabies virus the day it left Iran, that’s a really long incubation period, and it highlights some of the challenges in controlling import-associated rabies.

It’s also led to more questions about how we can prevent rabies from being imported when we import dogs.

The answer is: We can’t.  There’s no way to completely prevent importation of dogs that are infected with rabies (unless we stop importation of dogs altogether).

What about vaccination requirements?

  • The main role of rabies vaccination requirements for imported dogs is to make sure dogs are protected from exposure to rabies here in Canada (where rabies is endemic in our wildlife).  Vaccination prior to importation is good, for sure, but it doesn’t mean the dog has zero chance of carrying rabies upon arrival.

Why doesn’t rabies vaccination ensure that a dog isn’t rabid?

  • Rabies can have long incubation period (as demonstrated by the latest imported case). If a vaccine is given to a dog that was already infected some time ago, odds are it’s still going to get rabies, but it may not happen until after it’s imported.  (Pets that are exposed to rabies, whether previously vaccinated or not, should be given an additional dose of rabies vaccine as soon as possible as their best chance for preventing clinical disease.  This is the same principal used in exposed people, who need to start post-exposure prophylaxis as soon as possible (ideally within a few days) after an exposure to prevent infection.)
  • We can require dogs be to vaccinated a month before they arrive here (this is currently a requirement for puppies less than 8 months of age imported for adoption or resale), but this strategy is still designed to make sure the dogs are protected from rabies exposure upon arrival, not before.

What about testing dogs for rabies on arrival?

  • The testing for rabies that’s used in Canada (which is the internationally accepted standard) involves testing brain tissue directly. That requires a dead dog, so it’s obviously not a viable import screening test.
  • Even when testing is done, it just tells us whether rabies virus has made it to the brain. It takes time for rabies virus to make it from the site of exposure (which can be anywhere on the body) to the brain. Infection of the brain is pretty late in the process, so dogs that arrive carrying the virus wouldn’t have any evidence of rabies virus in the brain until later, just before (about 10 days) they get sick.

What about testing dogs for rabies antibodies (titre testing)?

  • An antibody titre tells us that the body has responded to the virus or the vaccine. It doesn’t tell us whether the dog is infected or not.
  • A negative antibody titre would suggest that the dog wasn’t actually vaccinated for rabies (or the vaccine wasn’t any good, or the dog didn’t respond well to the vaccine) and that would mean it’s at higher risk of getting rabies if it’s exposed. It doesn’t tell us whether the dog is already infected or not.

What about quarantining imported dogs?

  • Well, that would work but it’s impractical. The internationally accepted incubation period for rabies in dogs is 6 months, so that’s how long the dogs would need to be quarantined.  That’s expensive, logistically challenging and not good for dog welfare.
  • However, even a 6-month quarantine won’t catch every case.  The most recent rabid dog from Iran showed that.  It was imported in June and didn’t show signs of rabies until January, meaning it would have had to have been quarantined for over 6 months to detect this infection.

So, what do we do?

That’s a tough question. If we import dogs from rabies endemic areas, we have risk.

The risk presumably goes up when:

  • We know less about the dogs pre-import: Some imported dogs have more information about them than others. Dogs that were surrendered or from a facility where the health status is reasonably well know are lower risk. Dogs that have had rabies vaccination well in advance of importation are lower risk too, as that would help protect them from exposures pre-departure, but that’s uncommon. Not many dogs that make it into international import pathways are higher health status dogs with regular prior rabies vaccination (though there are some, like personal pets of individuals who have immigrated to Canada or returned from assignments overseas and could not bring their pets with them initially).
  • Dogs are imported sooner after being caught/collected: Similar to knowing more of the dog’s history, the longer an animal is at a managed facility, the greater the chance of detecting problems like rabies before the dog is shipped to another country. We’d need months of quarantine pre-departure to have much assurance, but more time means lower risk, to some degree.
  • There’s questionable vaccination status (false paperwork) or vaccine quality: Yes, va accination requirement isn’t anywhere close to perfect in terms of an imported rabies prevention tool, but it’s still useful and better than nothing (especially if there’s a required waiting period between vaccination and importation).
  • Dogs are imported shortly after they are able to be vaccinated: The latest imported rabid dog was about 3 months old when it was imported, so it would only have been able to be vaccinated right before it left (12 weeks being the typical minimum age).

Ultimately, the main way to reduce the risk is to reduce the number of dogs that are imported from high risk areas. The US has banned importation from over 100 countries considered high-risk for canine rabies, and that’s resulted in some of those dogs being diverted to Canada.

I’m not saying we should ban importation of dogs. There are good and bad points about canine importation.  However, we need to do it better.

  • Importers need to be more diligent and transparent.
  • Unscrupulous, unethical and just plain crappy importer groups need to be addressed.
  • Importers need to ensure that adopters understand the risks (and that the risks can never be completely eliminated).
  • Adopters need to be aware of the issues, be willing to accept the risks, and make sure potential problems are investigated so we don’t miss rabies or something else serious.
  • Ultimately, tighter regulations will help with many aspects of importation, but more for a range of other health and welfare issues than rabies, unless Canada takes similar steps as the US and bans importation from higher risk areas.

Still, if we’re going to continue to import dogs from other countries (or even move dogs from high-risk regions of Canada, like the far north), we’ll have to accept some degree of risk and make sure we have measures in place to contain those risk, as much as is possible.

For the second time in 7 months, rabies has been identified in a dog in Ontario that was imported from Iran through a rescue organization.  The first case was detected in July 2021 in an adult dog that started to develop signs of rabies within 10 days of arrival in Canada, and was euthanized 2 days later.  The second case was detected in January 2022 in a dog that was imported at the age of approximately 3 months in June 2021.  That dog developed neurological signs that progressed rapidly over six days despite medical treatment, at which point the dog was euthanized.  These cases each led to extensive investigations involving multiple public health units.  Toronto Public Health had to issue a press release in order to locate one person who had contact with the second dog.  A total of 51 individuals received rabies post-exposure prophylaxis (PEP) as a result of contact with the two dogs.  Both dogs had been vaccinated for rabies in Iran prior to importation with a vaccine that is not licensed in Canada.  In both cases, the rabies virus involved was confirmed to be a canine variant known to circulate in Iran.

  • The people at risk for exposure to rabies in these cases (who received PEP) would have had to have contact with saliva from one of the dogs during the risk period for virus shedding, which is up to 10 days prior to when the animal first shows clinical signs of rabies.  Exposure to saliva through bites is the highest risk for transmission, but most of the people in these cases were deemed to have high-risk non-bite exposure, meaning there was a risk they either got saliva from the dog in their eyes, nose or mouth, or saliva came in contact with a wound (broken skin) they already had.
  • Many of the exposed individuals were veterinary clinic staff who looked after the dogs.  This emphasizes the importance of taking basic precautions like wearing gloves and using face protection when handling animals with neurological signs that could have rabies (especially, but not only, when they have a history of being imported from a high-risk country).
  • Exposed individuals do not need to cover the cost of PEP themselves, but it is very expensive – approximately $2000 (or more) per adult.  Multiply that by 51… you can do the math.  Add to that the hours and hours spent by public health staff and other agencies tracing contacts and investigating these cases.  On top of the risks to human and animal health, these two imported dogs were extremely costly – but not to the people who imported them.

The second case was actually very unusual, not in its presentation, but in that the incubation period for the virus was very long.  We know based on genetic sequencing of the virus that the dog had to have been exposed before it left Iran in June (i.e. it was not infected with rabies after arrival in Canada), but it didn’t develop signs of rabies until mid-January, which is over 6 months.  Almost all dogs infected with rabies develop signs within 6 months (most in less than that), which is why this is the accepted international standard for quarantine of an exposed dog when required – but there is a very tiny number of documented cases with an incubation period longer than this.  We can add this one to that very short list.

Keep in mind that on July 15, 2021, the US Centers for Disease Control implemented a ban on importation of dogs from over 100 countries considered high-risk for canine rabies, including Iran.  Although the dogs in these two cases were both imported before the US ban went into effect, there is now potential for more dogs from these countries to be redirected through Canada, which may increase the risk of dogs carrying rabies entering Ontario and other provinces – like the 158 dogs and 146 cats that were recently imported from Afghanistan through Vancouver BC.

Veterinarians who examine a dog, cat, or ferret recently imported into Canada should make sure they get a copy of the animal’s previous vaccination record and/or health certificate and examine it carefully to ensure the animal is currently vaccinated against rabies if it is over 3 months of age.  If there is any question regarding the validity of the animal’s documentation or the reliability of any previous vaccinations (in terms of product used, route of administration, age at administration or any other concerns), then the animal should be revaccinated for rabies as soon as possible, and a new vaccination certificate issued by the attending veterinarian. Under the Health Protection and Promotion Act (Reg. 567), previous vaccination using products that are not licenced for use in Canada is considered invalid in Ontario.

*Remember*: Vaccination prior to importation is intended to help protect dogs from rabies exposure AFTER arrival in Canada. It does NOT reliably prevent rabies in a dog that was exposed to the virus prior to vaccination and import.  The typical incubation period for rabies in a dog can be up to 6 months, so any dog from a high-risk country (unless it has been effectively quarantined from other dogs for at least 6 months) must be considered at risk for developing rabies for at least that long, even if it’s vaccinated.

There will surely be much more discussion about rabies and canine importation issues in the weeks and months to come.  There are many long-standing issues with this practice, propagated by both well-intentioned but uninformed individuals and groups, as well as unscrupulous parties looking for a quick profit.  It will take coordination and collaboration by many to help solve the problems, including educating prospective dog owners who ultimately create the market for imported dogs.

As SARS-CoV-2 continues to rip through the human population, we’re getting more information about downstream impacts, including transmission to animals. One of my talking points since the start of the pandemic has been that we want to keep this virus in the human population. If we spread it to animals, it will be much harder to control in the longterm. That sentiment hasn’t changed.

While control of the pandemic at this stage is pretty much still solely dependent on addressing human-to-human transmission, as things slowly get more controlled in people, other sources of infection and other sources of variants become more relevant.  The potential for animals to be sources of variants is a realistic concern. It’s a potential (but unlikely) explanation for how Omicron emerged.  If the virus spreads widely and continuously in animals, it creates a situation amenable to new variant development, as I’ve previously explained. We’ve seen variants emerge in mink and spread into people, and widespread infection in deer adds another potential source, though we’ve yet to identify new variants in deer or deer-to-human transmission.

A report about a wastewater study from New York (Smyth et al. Nature Communications 2022) adds another twist to the story. Wastewater was collected from treatment plants in New York City, from January to June 2021. Researchers sequenced parts of the SARS-CoV-2 genome found in the water samples to look for mutations. They couldn’t look at specific strains since samples like wastewater are a complex soup of RNA pieces from lots of different strains, but they targeted the spike protein region, which we know is important for virulence (and it’s the region of the viral genome in which we see significant mutations in variants of concern).

Not surprisingly, a range of mutations were detected over the study period. That’s expected, since we’ve gone through serial waves of variants, and we know that a range of mutations are present in different strains of SARS-CoV-2. The trends in strain variation in wastewater over time largely mimicked those in people, since what’s circulating in people should be roughly the same as what’s in their waste.

But… there were some other sequences present in samples from 3 of the 14 wastewater treatment plants that were not consistent with what’s commonly found in people, and which did not correspond to any lineages in GISAID (an international genetic sequence depository).  These “cryptic lineages” also seemed to change a bit over time, acquiring other mutations. There were also differences in viral lineages that were found only at specific wastewater treatment plants, suggesting that the source of the virus was geographically constrained in these cases.

What does these study results suggest?

The study suggests that there is an unknown source of SARS-CoV-2 that’s not captured by routine clinical testing of people. That could be from virus circulating in people who aren’t getting sick and therefore aren’t being tested for surveillance purposes, or in people who are getting sick but are not tested for any reason. In either of these scenarios, there would have to be ongoing transmission between people to keep the specific viral strain in circulation in a relatively small area, and allow it to continue to evolve.  Longterm care facilities are a possible source, with a high risk and relatively immobile population (although it’s presumably also one where testing is still pretty common, so that doesn’t fit with the “unknown” component).

The other potential explanation (and one that fits better in some ways) is movement of SARS-CoV-2 into an animal reservoir that lives in the urban environment, is susceptible to the virus, and is present in large enough numbers to both sustain transmission and to produce enough virus that it’s detectable in wastewater.

What’s the leading candidate for a potential animal source in this situation?

Rats. There are lots of them in New York, and rats have been shown to be susceptible to some SARS-CoV-2 strains.

Adding more to the potential rat story is the nature of some of the genetic mutations in the spike protein, as some of the mutations that were detected have been previously associated with increased infectivity of the virus in rodents.

Another interesting finding was as the concentrations of overall SARS-CoV-2 genetic material decreased over time (consistent with the decrease in human infections), the concentration of these cryptic strains did not show the same trend, providing more reason to think these lineages may not be directly associated with humans.

Is this proof of an animal reservoir in NYC?

  • No. There’s no smoking gun here, but these are very interesting data that provide yet more support for the need to consider transmission of SARS-CoV-2 from people to animals, and the potential for mutation and spill-back into humans. More study of rats is indicated, but we also need to know more about other urban (and non-urban) wildlife, as there could be alternative or additional sources.

No reason to panic, but another reason to investigate.

In 2021, the Ontario Ministry of Northern Development, Mines, Natural Resources and Forestry (NDMNRF) contacted the University of Guelph’s Centre for Public Health and Zoonoses (CPHAZ) about concerns pertaining to the use of the antiviral drug acyclovir in raccoons, specifically for “treatment” of distemper. While only used by a distinct minority of raccoon rehabilitators (maybe only 1 group), there were concerns about the potential impacts of this practice.

CPHAZ provided a summary report of the issues and various considerations, which can be found using the following link: Use of acyclovir in raccoons for the treatment of canine distemper virus infection

Short version: there are no plausible reasons to use the drug in raccoons, and a variety of potential concerns.  Check out the full report for more details.

Conflict of interest statement: None.

Funding: No funding or other support was provided for writing this report.

It’s been a pretty chaotic week in the zoonotic SARS-CoV-2 world, with a lot of attention being paid to hamsters in Hong Kong and deer in Canada.

However, one issue that’s gotten less attention is the need to keep up with this virus as it changes, through serial waves and new variants, and to remember the limitations of our knowledge. I do a lot of talks and interviews about SARS-CoV-2 and often get into discussions of which species are susceptible and which ones aren’t, but there are always some important disclaimers I try to include. One big one is “but, what we know about SARS-CoV-2 in animals almost all pre-dates Omicron. Most of it pre-dates Delta, and even Alpha.”

Why is that important?

If we look at what we know about SARS-CoV-2 in some species, it’s based on experimental models, where animals were deliberately infected using the virus strain that was available at the time. Through those studies, we’ve concluded that species such as cattle and pigs are poorly susceptible, and SARS-CoV-2 exposure of such livestock is unlikely to be of relevance for either human or animal health (though people should still avoid contact even with these animals if they’re sick). Most of those studies were done with the original (pre-variant) SARS-CoV-2 strain. They were really important studies, but the virus strains that were used aren’t relevant anymore. The concern is that it can lead us to say “We’re good here – we don’t need to worry about that species, so we won’t do any more surveillance or future studies”.

Does that matter?

Maybe. The major SARS-CoV-2 variants like Delta and Omicron behave very differently in people from the original strain, and in most cases we don’t know if the same is true in animals or not.  It’s a risky approach to assume they won’t behave differently in animals as well.

Can new variants behave differently in animals?

Yes, and susceptibility to variants can be affected both ways. Earlier in the pandemic, it was shown that a species of mice that wasn’t susceptible to the original SARS-CoV-2 strain was susceptible to the Beta and Gamma variants.  They then showed that the same didn’t apply to Delta.

More recently, reduced susceptibility to Omicron was reported in mice and hamsters. A study from a few days ago reported that Omicron doesn’t readily infect Syrian hamsters, a species that is susceptible to other strains.

These studies show the need to investigate the impact of each variant on each species.

None of this is meant to say that the sky is falling and we’re going to see a massive change in species susceptibility or emergence of new animal issues with SARS-CoV-2. However, it means that we can’t be over-confident based on what’s been seen in the past.  We have to remember the limitations of our knowledge and make sure that we try to keep up with changes in this virus rather than rely on outdated information.

We need to keep working to identify (and ideally head off) issues, rather than using the typical reactionary approach, where we wait until there’s clear evidence of a problem before we act. The need for more work includes a range of studies (field and experimental) and species (including some species that haven’t been investigated since those very early studies). It also requires motivation and financial support, which has been lacking in most areas.  The amount of funding I’ve had for SARS-CoV-2 surveillance is basically the equivalent to a few remdesivir treatment courses. We’ve gotten good stuff done, but it’s on a shoestring budget and with little coordinating assistance, unlike some other jurisdictions where public health has integrated animal surveillance studies into their COVID-19 response plans, which is really the way to go.

We’re still at a time when SARS-CoV-2 is screaming through the human population, but that stage will end. Eventually we’ll reach a point where the biggest pool of potentially susceptible individuals is animals, and the relevance of animal reservoirs and animal populations as sources of variants will increase. We’re better off figuring out the issues now (as much as we can) rather than continuing to try to play catch-up later.

I doubt it will involve tunnelling under the wall and fake travel documents, but the 2022 Great Hamster Escape is apparently underway in Hong Kong. It’s not surprising, following the recent heavy-handed over-reaction to finding SARS-CoV-2 in a small number of hamsters, and the attempted blame-shifting (COVID-19? No, we don’t have any of that spreading in people here… just imported on packages from Canada and in those fuzzy biohazardous rodents).

The Guardian recently posted an article about the hamsterexodus from Hong Kong, which stated “Local media was awash with footage and images of crying children saying goodbye to their hamsters, and interviews with people working to save them. Many spoke anonymously, their voices and faces disguised out of fear of retribution amid Hong Kong’s worsening security crackdown.” 

  • I know there’s a lot of crazy in this pandemic, but this has to be one of the more bizarre scenarios.

Let’s consider the actual risk of SARS-CoV-2 transmission from hamsters:

  • The risk is presumably near zero. Hamsters can be infected by people. That’s why they’ve been found carrying “human” strains. We (people) are doing a great job of spreading this virus to a variety animal species; some  get sick, some get subclinical infections, and some don’t get infected at all.
  • There’s plausible risk of transmission back to people from some animal species. Hamsters can spread the virus hamster-to-hamster, so it’s not impossible they could spread it hamster-to-human.  However, we need to consider the odds of getting SARS-CoV-2 from a hamster vs a human (exceptionally low), and whether we can use safe, practical control measures for hamsters (pretty easy considering their size and that they’re usually kept well contained anyway).

Killing hamsters that have been in households for weeks is particularly dumb. Even in the very unlikely scenario that the hamster was infected, hamsters only shed the virus for a short period of time (a few days), so there would be no risk now.

Identification of SARS-CoV-2 in hamsters in Hong Kong is an indication that there is more spread in people than is understood (or acknowledged). Culling hamsters is either a misinformed response or an attempt to deflect blame for burgeoning local human transmission (or both).

As someone who works in zoonotic diseases and One Health, I deal with the ever-present issue of trying to raise awareness while preventing people from over-reacting, panicking or doing something stupid. It can be tough, since we want people to realize that animal-to-human transmission of infections is an important issue, but don’t want them huddling in their bathrooms afraid that their pet is going to somehow kill them.

We’ve had repeated examples of both sides of this when it comes to SARS-CoV-2 in animals, while trying to get agencies to pay attention to potential zoonotic transmission risks and also trying to prevent them for over-reacting. There’s a sweet spot in between, but it often gets missed.

Today’s report of Hong Kong’s plan to kill thousands of small mammals is an example of a huge miss.  Hong Kong did a great job regarding animal aspects of SARS-CoV-2 at the start of the pandemic by proactively quarantining and testing pets of people with COVID-19, and that helped us understand a lot about the disease in dogs and cats. Their proactive approach decreased over time, logically based on evolving information, so this extreme reaction now is a bit surprising.

What triggered this response?  Infection of a person – the origin of most SARS-CoV-2 infections in animals.

Here’s how the story goes.  A pet shop worker was identified with COVID-19 caused by the delta variant. Another person with COVID-19 reported visiting the store around the same time, and her daughter had handled a hamster. In response to that, officials tested hundreds of animals at the workplace.

That’s fine.  Actually, that’s great, since it can provide us with more information about human-to-pet transmission risks.

  • 11 infected hamsters were identified
  • Other species all tested negative

However, the subsequent response to the test results was the problem.

  • ~2000 small mammals across 34 different pet stores and housing facilities will be euthanized.
  • Anyone who purchased a hamster after December 22 will be required to surrender the pet to authorities for euthanasia. (A “hamster hotline” has even been set up for this.)

Does this response make sense?

No. It’s good to pay attention to and evaluate risks, but too often “kill the animal” is the “easy” response to something that just needs some thought and effort.

What could feasibly be done instead?

Small mammals are very easy to isolate safely. If there’s concern, they could quarantine the animal facilities or stores, do some more testing and handle things with basic infection control measures. The risk wouldn’t be zero (there’s rarely a scenario with zero risk when it comes to infectious diseases) but the risk would be exceptionally low, animals wouldn’t be unnecessarily killed, and we’d get more important information about this virus in animal populations.

Hamsters, like other susceptible species, don’t shed the SARS-CoV-2 virus for long when they’re infected. So, short term isolation would allow the virus to be naturally eliminated in an individual hamster or group. Yes, it takes some time, effort and possibly money, but those would be pretty limited, and it would also spare animal owners having to give up their pets.  The risk, costs and time required to track down and euthanize all the animals might be greater than would be required to isolate them.

Five human deaths due to rabies were reported in the US in 2021, the highest annual case count in the last decade. Obviously, that’s still a very small number overall and pales in comparison to other infectious diseases in the US, and to rabies deaths in other parts of the world like Asia and Africa which are estimated to number in the tens of thousands every year. However, it’s still noteworthy as rabies is an almost invariably fatal infection that’s almost completely preventable in a country with resources like the US. Rabies vaccination is incredibly effective, as is rabies post-exposure prophylaxis (the series of antibody and vaccine injections someone should get after potential exposure) – when it’s given in a timely manner.

Knowing why these rabies deaths occurred is important for figuring out how to prevent more cases in the future.

Four cases involved exposure to bats. While canine rabies (the rabies strain that is adapted to and circulates in dog populations in some regions of the world) has been eliminated in the US and Canada, wildlife rabies remains a challenge. That’s particularly true with bats. While there are effective measures to help control rabies in terrestrial wildlife like raccoons (e.g. oral rabies vaccine baits such as ONRAB, which is produced here in Ontario), there are currently no effective means for controlling rabies in bats, even though the virus is endemic at a low level in virtually all bat populations in North America.  So there’s currently not much we can do about bat rabies except recognize the risk and try to prevent exposure (or respond when someone is exposed). That’s often the issue.

Three of the rabies deaths in the US in 2021 occurred over a 6-week period in the fall.  All three victims knew they had contact with a bat, but two of them released the bat (so there was no chance to test the animal for rabies), and they didn’t seek care for possible exposure. That typically happens when people don’t understand the issues with rabies and/or they don’t realize they were exposed. Bat bites can be very tiny and hard to detect (even when someone consciously comes in contact with a bat) but can still transmit rabies virus. One other person submitted the bat with which he had contact, but then declined post-exposure prophylaxis (even after the bat tested positive) because of a fear of vaccines (which begs the question as to why the bat was submitted for testing anyway…).

  • These cases highlight ongoing knowledge gaps among the general public. Too many people don’t understand that bats are a source of rabies, that transmission can occur with even minor contact, that testing is available (and free), and that post-exposure treatment is available, safe and effective. Even when someone can’t submit the bat for testing, if they report significant exposure to a bat (e.g. direct contact) , they can recieve post-exposure prophylaxis as a precaution. So, all three of these deaths were avoidable.

An additional bat rabies death in Minnesota unfortunately shows why we have to say “almost” all cases are completely preventable. I haven’t found a primary report about this case, but various media articles indicate the victim was bitten by a bat, got post-exposure prophylaxis, but apparently had an unrecognized immune disease that hampered response to treatment, and therefor went on to develop rabies regardless and ultimately died.

The fifth case was a person who was infected with rabies by a dog.  While canine rabies strains have been eliminated from the US, it’s important to remember that dogs can still get infected with wildlife strains, and canine rabies is also widespread in many other parts of the world. An infected dog can pass any of these strains on to a person.  The victim in this case was bitten by a dog in the Philippines and developed rabies after returning to the US. Travellers too often don’t think about rabies, but massive numbers of individuals travel to rabies-endemic areas each year. Rabies vaccination is indicated in people who are likely to have  exposure to dogs during travel. However, the bigger issue is awareness in people who have unplanned encounters with dogs. People often don’t realize the risk of rabies exposure from contact with dogs in these countries, and don’t know what to do if they are bitten while traveling. Even if they don’t get treatment during their trip, most of the time they could get it once they return home, and it can still be effective as long as it’s given before the virus reaches the central nervous system (brain), which is when most signs of rabies start to appear. We want people to get treated promptly, but it can wait a short time if necessary (unless there’s exposure to the virus via the eyes… it’s a very short distance between the eyes and the brain). Yet, too often, bites don’t get reported and therefore treatment can’t be offered.

The common theme here is the need for public education. There’s limited penetration of rabies awareness education for the general public in North America. Travelers too often don’t get travel medicine consultations (and the quality of those, when it comes to zoonotic diseases, can be variable). A little knowledge can go a long way towards preventing rabies. The key is recognizing situations where exposure is possible, especially bat bites and bites from other wildlife rabies reservoir species (e.g. raccoons, skunks, foxes), and dog bites in areas where canine rabies is endemic. Bites from dogs in areas where canine rabies doesn’t exist are lower risk, but we still pay close attention to dog/cat bites because of the potential the dog/cat was exposed to rabies from wildlife. While that’s rare it still happens, and it’s why we need good rabies vaccine coverage in domestic dogs and cats, so that they don’t get rabies and then in turn transmit rabies to people.

Image: Anterior view of the face of a Myotis lucifugus, or little brown bat (source: CDC Public Health Image Library)