I’ve been a laggard with blog posts lately.  It’s a bit crazy and it’s been easier to get things out quickly via Twitter (@weese_scott). However, one interesting topic I wanted to get back to is SARS-CoV-2 in deer. It’s caused a big stink in some areas and, like a lot of things involving this virus and animals, we don’t really know the big picture implications yet.  I wrote about SARS-CoV-2 in deer a few months ago, but some new data have come out recently that raise even more issues.

Story #1

Earlier this year, there was an experimental study that showed white tailed deer are susceptible to SARS-CoV-2 and, importantly, are able to spread it deer-to-deer.  At the time that put deer onto a fairly large and growing list of species that are susceptible this virus, but there are some specific concerns with a wildlife species like deer.  We really don’t want SARS-CoV-2 to become established in wildlife, as that creates the potential for a reservoir of infection for people and other species, and the potential for emergence of new mutants (variants of concern) that could cause issues if they spread back into people (spillback). One key thing that’s needed for an animal reservoir is a large enough group of susceptible individuals to allow continued circulation of the virus, and there are in fact large relatively mobile populations of deer across wide ranges in North America.

However, “susceptible” and “relevant” aren’t the same, and we didn’t know whether there was much chance deer were actually going to be exposed to SARS-CoV-2, and how likely infection in deer would be in the real world.  The answer surprised us (or at least me).

Story #2

SARS-CoV-2 in deer went from a theoretical risk to a real world issue when the USDA released a study reporting high rates of seropositivity (antibodies against the virus in blood) in deer in various parts of the US. Overall, 40% of tested deer from 4 US states had evidence of previous infection. A subset of samples was also tested with the standard virus neutralization test, with good agreement. That, and the lack of positive results in samples collected pre-pandemic (see figure to right) suggested the results were reliable.

Story #3

Some recent pre-print studies have taken this issue a step further.

Hale et al. (2021) reported detection of SARS-CoV-2 by PCR in 36% (129/360) of deer sampled in northeast Ohio between January and March 2021. Interestingly, at least three different lineages (strains) of virus were identified, meaning at least three different introductions into the deer population. As expected, they were lineages common in people in the same areas, and people were the most likely source of the introductions.

Kuchipudi et al. (2021) performed PCR testing on retropharyngeal lymph nodes (i.e. the lymph nodes at the back of the throat) from wild and captive deer in Iowa. SARS-CoV-2 RNA was identified in 33% of samples from April to December 2020, and a whopping 83% of samples from November 23, 2020 to January 10, 2021. Twelve different lineages were identified. None of 17 samples collected earlier (April-August 2020) were positive.

Does this mean people can get infected with SARS-CoV-2 from deer?

  • We don’t know.

Does this mean the SARS-CoV-2 virus is actively circulating in deer?

  • We don’t know.
  • High rates of seropositivity could mean that the virus gets into a deer population, spreads quickly, infects a lot of deer but then burns out and disappears. That would be good. However, it could also mean that the virus circulates through the population as it continues to find new susceptible deer at a slower pace. This is a big question that needs to be answered.

Does this mean the SARS-CoV-2 virus is likely in deer populations elsewhere?

  • We don’t know. (Sensing a pattern here?)
  • It seems likely and it’s being actively investigated.  So far it’s only been found in deer in the US.

Are “deer variants” of SARS-CoV-2 being created?

  • We don’t know. None have been found to date.
  • The likelihood of “deer variants” emerging really depends on the amount of virus circulation in the deer population. Mutations occur during virus replication. The more transmission, the more replication and the greater the risk of variants emerging.

What’s the risk to the general public from SARS-CoV-2 in deer?

  • Pretty low. (I could say “we don’t know” but I’ll mix it up.)
  • Few people have close contact with deer (although every time I say or write that, I get flooded with emailed pictures showing deer hanging out on front lawns, porches, lounging in the yard with dogs, etc. so it may be more common for some than most).
  • It’s direct contact or close range aerosol transmission that I’m worried about, and since deer are outdoors in well ventilated spaces, simply being in the same area as deer shouldn’t pose any risk.

What’s the risk to hunters from SARS-CoV-2 in deer?

  • That’s a big question. Hunters will have the closest direct contact with deer and have the potential for exposure to respiratory aerosols in wounded animals, as well as close contact with carcasses. We have no idea what the risks might be.
  • To be prudent, we should assume there is some risk from this kind of close contact associated with hunting in areas where this virus might be circulating in deer.

Should hunters do anything different?

  • It’s hard to say, but a little bit of practical prevention makes sense. It has been recommended that hunters wear a mask when handling deer carcasses . That’s reasonable.
  • However, since dead deer don’t breathe, we’re not worried about exhaled respiratory aerosols when people handle carcasses. We’re mostly concerned about splashes or direct contact with respiratory tissues or secretions (+/- feces). So, wearing a mask when dressing a carcass, for example, still makes sense, to protect from splashes and prevent hand-to-mouth contact (which occurs more often than most people realize) when a person’s hands may be contaminated.
  • Keep in mind that if we’re worried about splashes, eye protection also makes sense.
  • Being particularly careful around wounded deer, avoiding close contact and using a mask and eye protection if such an animal must be approached would also be reasonable.

Does venison pose a risk?

  • Presumably not.
  • SARS-CoV-2 doesn’t survive long outside the body, and high levels of virus wouldn’t be expected in deer meat. Contamination of meat from feces or respiratory secretions is always possible, but good hygiene can reduce that. It’s not really different from how you’d prevent contamination with typical foodborne pathogens.  We should handle meat (from any animal) like is has various infectious agents in/on it, use good hygiene and cook it properly. Any SARS-CoV-2 contamination would be effectively controlled through those same measures.

How do we figure out how SARS-CoV-2 gets from people to deer?

  • That’s a huge challenge. Figuring out how it gets into deer will be very tough and I’m not sure we’ll have a good answer soon.
  • Is it from rare human-deer interactions that involve close contact but leave a live deer? (i.e. not hunting)
  • Is it from deer coming in contact with contaminated items like garbage from infected people?
    • Unlikely, since things like that aren’t thought to be a realistic source of human infection and deer aren’t classical dumpster divers.
  • Is it from deer coming in contact with human wastewater?
    • Probably not. We can use wastewater for surveillance but we typically only detect bits of viral RNA, not viable virus. We don’t have evidence that infectious virus is released in wastewater.
  • Could there be an intermediate animal host that carries the virus from humans to deer?
    • Cats would be a leading candidate, if they have contact with infected people in a household but are allowed outside and then have contact with deer. It seems like a stretch based on cat behaviour, but can’t be ruled out.

Where do we go from here?
We need more surveillance, especially from other regions. It’s critical to determine if the virus is actually undergoing sustained transmission in deer populations, and if so where. If it is circulating on an ongoing basis in deer, we’ll need surveillance to look for emergence of significant variants. Hunting history and deer contact history should be considered when investigating new cases of COVID-19 in people, especially when there’s no other clear source. If the virus is circulating in deer, we’d also want more wildlife surveillance of other potentially susceptible species, to see if it’s spreading into other populations that could also become reservoirs.

Closing notes (the usual)

  • The best way to keep this virus out of deer is to control it in people.
  • The best way for a hunter to reduce their risk of getting COVID-19 is vaccination.

Mink are not a species most people think about. When they do, they typically think of mink coats or fur farming protests. While the mink industry has been on the decline in most regions for many years, there is still a massive number of mink being farmed for fur internationally. Some of these farms are very large, which makes for lots of animals in close contact with each other, and in contact with their human caretakers, which leads to the risk of pathogens such as SARS-CoV-2 passing back and forth between them all.

Mink aren’t the only critters in the mustelid family that are a concern when it comes to SARS-CoV-2. Any species from the mustelid family probably has similar susceptibility to the virus.  The domestic pet relative of mink is the ferret. Ferrets are “niche” pets but they’re far from rare, and many ferrets have very close contact with their owners.

So, we have widely different issues in how we manage and interact with different mustelids, whether on a farm, in the home or in the wild. Regardless, the net result is situations where there’s a good chance for respiratory virus transmission.

What’s the story with mink and SARS2CoV-2?

There’s been a lot of attention paid to mink during the COVID-19 pandemic, even since the original review I posted last October.  I think it’s fair to say this caught us off guard. No one was talking about mink or risks to/from mink farms at the start of the outbreak, even among those of us who were thinking about risks from other species (lots of people tried to ignore animal risks altogether from what was clearly an animal-origin virus, but that’s a rant for another day).

While we may not have initially paid attention to mink, SARS-CoV-2 did. Mink are highly susceptible to this virus, and there have been widespread outbreaks on mink farms, first identified in the Netherlands but subsequently in multiple countries as well (including Canada and the US).

What happens when SARS-CoV-2 makes its way (from people) onto a mink farm varies, and there are still lots of knowledge gaps. Some affected farms have had few health issues, while others have reported widespread illness and deaths amongst mink, especially older or pregnant mink. The virus seems to have persisted on some farms, at least for a while, with little apparent disease, while on others it seemed to burn through the population and then disappear like a more classic respiratory outbreak. Why? We’re not sure. This virus clearly can cause disease in mink, but it doesn’t always. There may be a predilection for severe disease in mink of a certain age, or in pregnant mink (as with people), but there are still lots of things we don’t understand.

Can mink infect people with SARS-CoV-2?

For most species, I say “we don’t know if they can infect people and it would be hard to figure out”, we know that SARS-CoV-2 can definitely be transmitted from mink back to people, because of the nature of spread and sampling that has been done on mink farms and the people who work on them. If mink and people on a farm all had positive tests, you couldn’t necessarily determine whether some of the people were infected by mink or whether the people all infected each other. However, viral sequencing and the timing of infections on some mink farms has provided more information than we can usually get. Tiny, mainly innocuous changes in the virus commonly occur during replication, and those changes create a kind of “signature” that can help us track the virus better. Using sequencing, you can track how the virus evolves on a farm, where the initial infections are a strain that’s present in people in the community (since that’s where the virus usually comes from), and then the strain changes a bit as it’s transmitted over and over between mink. If that slightly modified strain then pops up in people on the farm, it’s strongly suggestive that the virus was spread from mink back into people.

Are mink farms a reservoir for the SARS-CoV-2 virus?

That’s an important question and a big concern. “Reservoir” can be considered a few different ways. The main concern is whether the virus can spread on a farm for prolonged periods of time, creating an ongoing source of exposure to people (and possibly wildlife) on the farm, including new variants of the virus.

Can the virus spread from mink farms to the community?

  • Yes. That’s been shown. It’s rare in the grand scheme of human COVID-19, but it has happened.

Can the virus spread from farmed mink to wildlife or other animals?

  • When SARS-CoV-2 is present on a farm, there could be exposure of a range of wildlife that may come and go from the property through contact with mink feces (which fall through the animals’ cages and accumulate under them) or from aerosol exposure (e.g. virus in dust particles within the animal sheds). There’s also the potential for exposure of farm animals (farm dogs, barn cats). Transmission to farm dogs and cats has been identified.
  • Infected “feral” mink were found around an infected farm in the US; these were presumably mink that had escaped at some point from a nearby farm, but it shows another way the virus can make its way off the farm.  This has also been seen in Spain, where infected feral American mink were found (and at some distance from the closest mink farm…). Since American mink are not native to Europe, it’s safe to say those mink (or their ancestors) were escapees at some point. Where the virus could go from there is a good question. It might just burn out in the wildlife population (since wild mink are primarily solitary creatures), but if it’s able to continue to find susceptible hosts (e.g. wild mink, certain mouse species, white tailed deer), it’s possible mink farms could be a source of broader spread, bridging human SARS-CoV-2 with wildlife.

Can the SARS-CoV-2 virus be sustained on a mink farm long term?

  • A big factor that might influence the risk from mink farms is whether there is long term, sustained transmission of the virus within the farmed animal population. If the virus enters a farm, burns through the population quickly, and is eliminated (either naturally or through culling of infected animals), then there’s lots of transmission but over a very short period of time. If SARS-CoV-2 enters a farm and continues to spread over months (or even) years by continuing to find new susceptible mink in the population to infect (or re-infect), the risk probably increases substantially. We don’t know how much of a risk it is, but we know there’s some risk because the virus already seems to have maintained itself on certain farms for a long period of time (months). We still have limited information about the long term outcomes, because many infected farms were depopulated, and on those that weren’t long term testing wasn’t necessarily done (or reported).

Are mink a source of new variants of SARS-CoV-2?

In the first 3 parts of this review update that I posted last month, I dismissed the potential for dogs, cats and pigs to be significant sources of new SARS-CoV-2 variants because of reasons like poor susceptibility (pigs), minimal virus shedding (pigs, dogs) or lack of enough animals in close contact for sustained transmission within the animal population (dogs, cats).

Unfortunately, mink create the perfect storm for new variant emergence. They are a highly susceptible species that can effectively transmit the virus mink-to-mink and mink-to-human, and they are raised in large enough groups that there can be widespread and sustained transmission. Since variants emerge due to random mutations, and the likelihood of that is dependent on lots of virus replication, and more transmission leads to more replication, variant emergence is definitely a concern on large mink farms.

“Mink strains” of SARS-CoV-2 have been identified. Whether that’s because the virus adapted to be better able to infect mink or the changes were purely random (i.e. conferring no specific advantage to the new strain in terms of infecting more mink) isn’t clear. However, the new strains provide a way to help track virus transmission in some situations. In early outbreaks, there was concern about a mink variant that was identified in the Netherlands. There was also concern that mink strains with a common mutation (Y453F) that spread from mink farms into the general human population in Denmark might be less responsive to antibody-based treatments used in people  (these are important therapies for high-risk people with early infection). However, there was no evidence that these mink strains would compromise vaccine efficacy, and fortunately they didn’t end up being a significant problem as they weren’t any worse than “regular” strains in people in terms of disease. In fact, there’s some (albeit pretty weak) evidence that mink-derived variants might be less virulent in people. I think we have to assume both things could happen: mink could be the source of new variants of concern that pose more risk to people, as well as new variants that would pose less risk to people. We can’t really predict what will happen, or when.

Realistically, the biggest risk of variant emergence still lies in the human population, since we still have rampant human-to-human transmission of SARS-CoV-2 internationally. But mink are a potential source, and all it takes is one event with the right (or wrong) mutation to cause a problem. Further, as we (eventually) control this virus in the human population, animal reservoirs will become more important, as the relative risk from them will increase if true reservoirs are being created through infection of different wild and domestic animal populations.

How about ferrets? Are they as susceptible as mink to SARS-CoV-2?

Whether ferrets are “as susceptible” to the virus is hard to say, since they haven’t been directly compared. However, ferrets are clearly susceptible and are able to effectively transmit the virus to other ferrets. We’ve seen this in multiple experimental studies where ferrets were infected, got sick and were able to transmit the virus ferret-to-ferret.

I was a bit surprised that we didn’t see reports of naturally infected pet ferrets early in the pandemic. That was likely because of limited numbers of ferrets and limited testing. In our surveillance, we only got to test a handful of ferrets.  Despite the small number of reports, there have been documented infections in pet ferrets (e.g. Giner et al. 2021, Gortazar et al. 2021, Racnik et al. 2021) As with dogs and cats, infection in ferrets is likely under-diagnosed, and may actually be a common event that occurs under the radar in households where people have COVID-19. I assume the odds are 50:50 or greater than a ferret from a household with active COVID-19 in a person is, was or will become infected, if it has close and/or regular contact with infected people.

The health impact of SARS-CoV-2 infection on pet ferrets hasn’t been well described. Some get sick, but it’s mainly been mild disease, which fits with the findings of experimental studies as well. Some report infections with limited or no obvious signs of disease (e.g. Shi et al. 2020,  Schlottau et al. 2020Kim et al. 2020). However, more serious disease, sometimes requiring euthanasia, has been reported. That might be related to the dose of virus, as high doses were used in the experimental study where more serious disease was encountered. The overall health risk to pet ferrets is probably low, but we can’t rule out the potential for severe disease, particularly in older or pregnant ferrets, or ferrets with pre-existing health problems.

Can ferrets infect people with SARS-CoV-2?

We don’t know, but they probably could. Since ferrets are susceptible and can infect other ferrets, and we know that mink can infect people, it makes sense that ferrets could also infect people. However, the true risk to ferret owners needs to be considered.  Being able to infect a person is one thing. Actually being an important source of infection is another. To pose a risk, ferrets have to first be exposed to a person with SARS-CoV-2 infection. This would almost always be their owner. In that situation, the owner poses greater risk to other people in the household than the ferret does. The main risk to others is if the ferret leaves the household (e.g. if it needs to be taken to a veterinary clinic for an exam) during the period when the household members are infected.

What are the recommendations when it comes to mink, ferrets and SARS-CoV-2?

Anyone with COVID-19 should absolutely not go anywhere near a mink farm. Period.  That’s the big one. If we’re going to continue to farm mink for fur, there needs to be a strong focus on biosecurity and surveillance for this virus. Surveillance is an issue because of cost (i.e. who pays?) and the general lack of desire among many parties involved to really know what’s going on (especially if the mink don’t look sick).

In terms of ferrets, the same general approach that we recommend for dogs and cats applies:

  • If you have COVID-19, try to limit or avoid contact with your ferret.
  • If your ferret has been exposed to someone with COVID-19, keep it away from other people and animals.
  • If your ferret has been exposed to someone with COVID-19 and is sick, let your veterinarian know, to help determine whether it might be infected with SARS-CoV-2 (do that by phone, at least initially, rather than showing up to the veterinary clinic directly with your ferret).

Next up for a review update… horses.

I’ve meant to write more about SARS-CoV-2 in deer, and USDA’s recent announcement of infected deer made me get my butt in gear (warning: long post approaching).

What do we know about SARS-CoV-2 infection in deer?

We now have three different pieces of evidence:

There are two broader concerns with these findings regarding SARS-CoV-2 in white-tailed deer:

  1. Reservoir for human infection: More infected individuals (human or animal) means more potential exposures for people. If this virus is present in deer (or other wildlife) that creates more opportunities for exposure.
  2. Potential for virus mutation: This is the big concern, but linked to the reservoir concern too. As I’ve said since this pandemic started, we really want to keep this a human virus – we don’t want it to spread to other species. Yes, it’s likely present in the original reservoir host population (presumably bats), but if it gets into other species, especially those that live closer to and interact more with people, and/or  are present in larger numbers, the risk of a significant mutation occurring and spilling back into the human population increases.

Virus mutations are random events that happen all the time, but the more transmission there is, the opportunity the virus has to mutate. If there is sustained transmission in a wildlife population (or any population for that matter), it’s essentially guaranteed that new strains (variants) will develop over time. What that means in the bigger (human) picture could vary. Because they’re random, mutations can be good or bad for the virus, by making it either more or less transmissible, for example. What we’re concerned about is emergence of new variants that are more adept at infecting people and/or harder to prevent or treat, and those variants then finding their way from the animal population (in this case deer) back into people, and then spreading from person-to-person.

In the big picture, is SARS-CoV-2 in white-tailed deer a problem?

It’s hard to say. Currently, human-to-human transmission is still the problem. New mutations are going to develop in people because of widespread transmission internationally, and until we have good vaccine coverage everywhere (not just rich countries) we’ll have persistent and high risk of new variants emerging in people.

Deer probably contribute little to the risk, at least at this point.  For a deer variant to be of concern, it has to find and infect a susceptible person, and human-deer contact is fairly limited in the grand scheme of things. It’s possible, but a susceptible person is still more likely to be infected by another person than by a deer at this point.

While SARS-CoV-2 remains a human pandemic, deer are likely a niche issue. As the virus eventually gets controlled in humans (we hope), then wildlife reservoirs become more important, if they can be a source of new variants.

What do we need to do?

We need more information, as usual. We need to know lots of things like:

  • How widespread is infection in deer?
  • What’s the likelihood that an infected deer would infect a person through routine contact (e.g. hunting, handling animals or carcasses)?
  • Are variants emerging in deer?
  • Are deer infecting other wildlife?
  • Will transmission in deer be sustained, or (better for us) does this represent repeated short term transmission after introduction from people, or a rapid burn through the population?

This is one of those “let’s pay attention and get more info, but not freak out” situations. Throughout this pandemic, I’ve tried to balance increasing awareness with avoiding excessive concern or paranoia, and that applies here.

What should deer hunters do?

  • Get vaccinated.
  • Hunt with vaccinated people.
  • Use standard COVID-19 precautions around people.

Should hunters do anything specific when handling deer?

I don’t think we have enough evidence at this point to make specific recommendations for hunters handling deer. Good general hygiene is obviously important, but whether hunters should take extra precautions (e.g. mask and eye protection) is completely unclear. As we learn more, it’s possible that guidance will change.

What about venison?

There should be essentially no food safety risk when it comes to consuming venison. This virus does not survive well outside the host, so even if the animal was infected, the risk from handling meat is presumably negligible. Good hygiene practices used when handling raw meat of any kind should cover any theoretical risk.  It’s always important to cook meat properly before consuming it as well, and the virus would not survive that process either.

My usual ending for these posts is a reminder that COVID-19 is ultimately a human issue. Animal infections are a result of human activities and human contacts. The best way to reduce the risk of this virus entering animal populations is to control it in people.

Human vaccination is probably the best protection for deer.

Game-changing research?

Something that will be walked back in the future?

Something in between?

A press release from the US Department of Agriculture (USDA) about a study looking at antibodies against SARS-CoV-2 in white-tailed deer (and an infosheet about the same study) released today makes me wonder which of these will apply. The results are potentially game-changing, but it’s so far outside of what I’d expect that we have to make sure the results are real first. Since information is currently limited to the press release and infosheet, with no specific information about the study methods or details of the results, it’s hard to draw firm conclusions.  Based on the information available though, it could be a remarkable story.

We know from experimental studies that white-tailed deer are susceptible to the SARS-CoV-2 virus. So the USDA’s Animal and Plant Health Inspection Service (APHIS) set out to analyze blood samples from free-ranging white-tailed deer for antibodies against SARS-CoV-2.  The method of testing isn’t stated, but the USDA has excellent labs.  Samples were collected from deer in four different states (Illinois, Michigan, New York, and Pennsylvania) as part of wildlife damage management activities.

According to the USDA press release, antibodies to SARS-CoV-2 were found in 33% of 481 samples collected from white-tailed dear from January 2020 through 2021. This would indicate that these animals had been exposed to the virus sometime in the past, but the testing doesn’t tell us if there was active infection in the deer populations or if the deer could have infected others. The antibody testing only gives us a historical indication of previous exposure to the virus (or, potentially, a virus that induces similar antibodies that cross-react with the test).

Only 1/241 samples collected from deer before the COVID-19 pandemic began were positive. That was presumably a false positive result (no test is perfect, so typically we’d be quite happy with less than 1% false positives).  Less than 1% positive before the pandemic and 33% positive during the pandemic after would support true infection having occurred in these deer populations.

The number raises concerns for me.  The press release states that “the finding that wild white-tailed deer have been exposed to SARS-CoV-2 is not unexpected given that white-tailed deer are susceptible to the virus, are abundant in the United States, often come into close contact with people, and that, more than 114 million Americans are estimated to have been infected with COVID-19, according to the U.S. Centers for Disease Control and Prevention (CDC).

  • All true, and good reasons to investigate exposure in deer populations. However, 33% is very high, given the limited direct contact between people and deer. Deer would have to be very susceptible and very effectively able to transmit the virus widely within the deer population for 33% to be infected.

It’s very interesting info, but more details are needed. It could be a game-changer, or a testing issue. That needs to be sorted out.  Regardless, it’s a good One Health study that’s needed to help understand the ecology of this virus and potential risks.

Let’s just call this an “odds and ends” post. I’ll outline some interesting highlights from some recent papers, including a couple just posted overnight.

More on predicted susceptible hosts (pre-print (i.e. not peer reviewed) on BioRxiv)

This study looked at genomic data from 410 vertebrates, including 252 mammals, and the researchers ranked the different animal species in terms of their predicted susceptibility to SARS-COV-2.  This isn’t particularly new, as the first paper looking at the virus’ receptor (ACE2) in different animal species was published a couple of months ago, but this was a larger study that took a much broader approach.  Here are some noteworthy results:

  • The very high risk category included people (duh), gorillas, orangutans and various other non-human primates
  • The high risk category included a wide array of species, including critters such as the Chinese hamster, Narrow-ridged finless porpoise, white tailed deer, giant anteater, orca and reindeer.
  • Cats fell into the medium risk group, a bit surprising since we know from experimental and limited field evidence that cats are susceptible to infection.
  • Dogs were low risk, which fits with what we know from other work.
  • Ferrets were ranked very low risk, which is contrary to experimental studies done to date. The authors suggested that maybe the virus uses a different receptor in ferrets. That would be surprising though.  The result maybe just indicates how “predicted” and “real life” don’t always line up.

More experimental work on transmission in ferrets (another pre-print on BioRxiv)

This paper looked at transmission of SARS-CoV-2 between ferrets. They infected four ferrets, then 6 hours later added uninfected ferrets to the same cages, and to adjacent cages that were separated by steel grids, 10 cm apart.

Virus levels in respiratory secretions peaked 3 days after infection, and were detectable for 11 days in two ferrets, and for 15 days and 19 days respectively in two others (that’s pretty long).

All 4 ferrets added to the cages became infected, while 3 of the 4 ferrets in adjacent cages became infected.

This doesn’t add a lot of new information to previous ferret studies, but provides more evidence that ferrets are susceptible (despite the predictions from the study above) , that they can shed the virus for a relatively long time, and that they can infect other ferrets. Since they can infect other ferrets in adjacent cages, we have to assume there’s some risk that an infected ferret could transmit the virus to a person if they had close contact. This just re-inforces our standard messages about staying away from pets when you’re sick, and if COVID-19 is present in a household, pets should be kept inside and away from others.

Ivermectin as a potential treatment for SARS-CoV-2 infection (pre-print on MedRxiv)

There’s been some stir about the potential for the anti-parasitic medication ivermectin to treat COVID-19 in people, based on an in vitro study and some weak anecdotes. That hasn’t stopped people asking vets for more heartworm medication “for their dog” in the meantime.  The potential for ivermectin to be of any significant benefit in treating SARS-CoV-2 infection hasn’t seemed very strong, and this pharmacokinetic study supports that skepticism.

The overall message from this paper is that the levels of ivermectin that you can get in the body are “are orders of magnitude lower, as compared to the in vitro antiviral end-points, described in the study of Caly et al.” The 5 umol/L level of ivermectin that effectively eliminated almost all the virus in vitro is more than 50 times higher than what you get in the body even with a higher dose of ivermectin (i.e. 700 ug/kg) than what is normally used (i.e. 150-200 ug/kg).

So, although ivermectin can kill SARS-CoV-2, it takes a lot more than you would get with normal dosing. Trying to increase the dose to get levels that would kill the virus might be more likely to kill the patient from drug toxicity.  The authors’ well-said conclusion was “…the experimental design is based on clinically irrelevant drug levels with inhibitory concentrations whose targeting in a clinical trial seems doubtful at best.”

At some point, we’ll be able to look back on this pandemic. It will be interesting to see what long-term changes occur. Memory and motivation for change are often surprisingly limited, but I’m sure we’ll exit this with a least a few changes to how we live, work and play – and in some areas, how we eat.

There’s been a lingering question for a while about wildlife markets. The COVID-19 virus, like the SARS virus before it (and other emerging diseases), is believed to have made the jump to people via animal markets that included myriad wild and domestic animal species (and their products). The more contact we have with different animal species, especially wild animals that don’t usually have contact with people, and the more we enter their habitats, the greater the risk of exposure to novel pathogens. The majority of emerging diseases are zoonotic diseases (originating in animals).  It’s not a matter of whether there’s another disease lingering out there is wild animal populations, it’s a matter of when the next one will reach the human population and how much impact it will have.

China has come under a lot of pressure to ban wet markets, or extend the temporary ban that was put in place at the start of the outbreak. I’d like to see them closed for a variety of reasons, but we have to recognize the cultural, economic and food security issues that are present. A recent National Post article highlighted the importance of these disputed wet markets in China, including the following quote:

“Banning wet markets is not only going to be impossible, but will also be destructive for urban food security in China as they play such a pivotal role in ensuring urban residents’ access to affordable and healthy food,” said Dr. Zhenzhong Si, a research associate at the University of Waterloo who studies food security in China.

We also have to realize that banning something can just drive it underground, which can actually make things worse. My assumption was that we’d see more regulation of these markets, and that may be the plan in China.

A CNN article reports that China has issues a new draft list of animals that can be farmed for meat. Restricting farming to certain species doesn’t necessarily impact wet markets if live wild animals can still be caught and brought into these densely crowded (animal and human) spaces, so it will be interesting to see the impact of the new proposed rules if they are finalized.  This draft also includes a few major shifts for farming in China.

The list of animals that can be farmed obviously includes the typical food animal species (e.g. pigs, cows, chickens, sheep), and has a few others that are not too surprising (e.g. deer, ostriches). It allows farming of raccoons and mink for fur, but not meat.  Particularly noteworthy is that dogs are NOT included on the list. I don’t have an English translation yet, but the CNN article includes this quote from an “accompanying explanation” of the draft list:

“With the progress of human civilization and the public’s concern and preference for animal protection, dogs have evolved from traditional livestock to companion animals… …They are generally no longer regarded as livestock in the rest of the world. It is not advisable to list them under livestock or poultry in China.”

That’s quite a shift.

The potential impact depends on the draft actually being finalized and enforced, while preventing the dog meat trade from going  underground, but it’s encouraging. The impact also depends on this policy actually controlling the wild animal trade, and not just closing down large markets where people get food. Wild animal trade also includes catching animals for use in traditional medicine, entertainment or fur/fashion trade.  Any time we encounter something in the wild and bring it back to a village, town, city or market, we create a new contact point between people and wildlife, and each one is a risk.

We can’t expect an overnight change, and there will probably lots of loopholes, but this may be a step in the right direction.

Concerns about the animal aspects of the COVID-19 pandemic continue to come in waves. Most of the time they are ignored or dismissed, but there are also periodic flurries of attention and (often over-) reaction.  Lately, questions about vaccination of animals against SARS-CoV-2 follow have been on the rise.

Should domestic and wild animals be vaccinated against SARS-CoV-2?

  • Yes, no and maybe… but mainly no.  To properly assess this question, we need to step back and think about what vaccines can potentially do.

There are 4 main areas I think about when considering whether vaccination may be useful in any given species:

  • Prevention of disease:
    • This is really “prevention of severe disease.” If a species doesn’t get very sick and just has mild, transient illness, there’s little value in vaccinating from an animal health standpoint.
  • Prevention of transmission of the disease to people:
    • Transmission of SARS-CoV-2 from animals to humans has been documented or suspected in very few species. Most transmission is human-to-animal, and animals are most often dead end hosts (e.g. if my cat gets infected, he got it from someone in my household and is unlikely to spread the virus to any other humans).
  • Prevention of transmission to other animals:
    • Can the animal spread SARS-CoV-2 to other animals of the same species? Or be a bridge, spreading the virus to other domestic animals or wildlife?
  • Prevention of establishment of an animal reservoir where new variants could emerge:
    • This is the big concern with certain animal species (e.g. deer, mink) that are both highly susceptible and have a large population with frequent, close contact between animals, which allows for for potential long term, continued transmission of SARS-CoV-2.

Not many species check many (or any) of those boxes when it comes to vaccination against SARS-CoV-2.

The other thing to consider is what vaccines for animals may or may not actually be able to do. We have very little information about the very limited vaccines for animals that are currently out there. These vaccines are based on older technology than our human mRNA vaccines, and the older tech hasn’t been known to be able to produce highly effective coronavirus vaccines in the past. Vaccine science is improving, and I’m not trying to bash the animal vaccines or the companies (I’m grateful they’re working on them),  but I’m trying to be realistic.

Vaccines can have a range of effects, depending on their efficacy:

  • Reduction of severe disease
  • Reduction of disease
  • Reduction of infection (with or without disease)
  • Prevention of infection (sterilizing immunity)

We don’t know how effective animal vaccines are in different species.  Based on what we know about the more technologically advanced human vaccines, reduction of severe disease is likely a much more realistic target than reduction or prevention of infection (which would reduce the risk of transmission).

Another issue is the level of vaccine coverage that would be needed in a given species. For example, if we want to use vaccination as a tool to reduce establishment of the virus in wildlife, we need a vaccine that significantly reduces infection and transmission AND we need to vaccinate a large percentage of the population AND keep vaccinating animals over time, since population turnover is high in many wildlife species.

We also don’t know how long immunity persists in different species, or how it might hold up against different variants of SARS-CoV-2 (which we wonder about it humans as well…).

Once we start thinking about all these factors, I think it shows that the utility of vaccination in animals currently is going to be limited to a few niche situations.

Dogs / cats

  • Dogs and cats commonly get infected, but rarely get seriously ill. They are rarely going to be the source of infection for people (they are usually infected by their owners).
  • Dogs and cats don’t live in large groups where virus transmission can be sustained long term, such that it could create a reservoir and become a source of virus variants.
  • Indoor-outdoor cats are more of a risk as a bridge between infected households and other people or animals, but the odds of them playing a significant role in transmission are fairly low AND any effect on this would require a vaccine that prevents infection and virus shedding (unlikely).  The far easier and more effective solution is to keep cats from infected households indoors until the risk period for transmission has passed.
  • I’m glad we have vaccines ready in case something changes and we get a strain that causes more serious disease in dogs or cats, but I can’t see a use for vaccination in these species now.

Mink

  • Mink check a few of the boxes for vaccination, as a species that is susceptible, gets sick, is housed in large populations (i.e. farmed mink), that has generated new variants in the past, and can spread the virus to people  and other species.
  • Vaccination of all mink on a farm is also possible.
  • Vaccination is probably a more effective tool for mink health than public health, given the questions above about whether vaccines actually reduce or prevent infection, and therefore transmission. If vaccination just reduces disease but still allows for transmission between and from mink, then it might not be useful or might even be counterproductive for public health purposes.

Zoo animals

  • Here’s where there’s the most potential for benefits from vaccination against SARS-CoV-2 in animals. Some zoo species are highly susceptible and can die from infection with this virus. These animals can be valuable emotionally and economically, and from a conservation standpoint. So, more zoos are vaccinating their non-human primates (e.g. apes) and big cats. Some are also vaccinating their mustelids (i.e. species related to mink; some, like the black footed ferret, are highly endangered) and cervids (i.e. species related to deer, since we know white-tailed deer are quite susceptible and can spread the virus).

Wild deer (specifically white-tailed deer)

  • Deer check a few of the boxes for vaccination, as they are highly susceptible and may be able to maintain circulation of the virus in area where they have a high population density, potentially leading to new “deer” variants.
  • However, we would need a vaccine that significantly reduces infection and therefore the risk transmission (and I’m not very confident we have that).  Deer don’t appear to get significantly ill themselves (thus far), so vaccination isn’t directly helpful to the deer.
  • To be useful, it would also require vaccination of a LOT of animals. For example, if we need to vaccinate 80% of the wild deer population… well, good luck finding a way to do that.
  • Furthermore, lots of new deer are born every year so vaccination campaigns would have to be continued until SARS-CoV-2 is out of circulation in deer and people.  That doesn’t seem very practical to me. Rabies vaccination of some wildlife species is used in some areas (including Ontario) and it’s highly effective. However, it uses a highly effective vaccine that can be delivered through baits that can eventually cover a pretty high percentage of the target population, and it does have to be repeated at least annually until the virus is eradicated from an area.  It also takes a lot of effort and coordination.  It would be very tough to do the same for SARS-CoV-2 vaccination in deer.

We’re not going to vaccinate our way out of animal issues with this virus. We need to control SARS-CoV-2 in humans to have any hope of controlling SARS-CoV-2 in animals. Vaccine research is important so that we have vaccines available should opportunities for their use be identified, and continued vaccine development may get us to the point where we have a highly effective vaccine that stops transmission. However, without that, the potential impact of vaccination of most animals is limited.

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.

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.

At the start of the COVID-19 pandemic, many major agencies took a head-in-the-sand approach to concerns about the potential for SARS-CoV-2 to infect different animal species. Fortunately,  over the last year a considerable amount of work has been done to help figure out the range of species that are susceptible to this virus, and shed some light on how animal populations might ultimately impact control of the virus, based on the potential for for infecting wildlife in particular (which comes with the risk of creating  wildlife reservoirs, and potential sources of new virus mutants). We now know of a few wildlife species that are susceptible (and can transmit) SARS-CoV-2, but there are so many wildlife species that our knowledge still just scratches the surface.

A recent study in pre-print posted on bioRxiv (Bosco-Lauth et al. 2020) looked at SARS-CoV-2 susceptibility in deer mice, bushy-tailed wood rats, striped skunks, cottontail rabbits, fox squirrels, Wyoming ground squirrels, black-tailed prairie dogs, house mice and raccoons. They did this by catching wild animals and experimentally exposing them to the virus, and then monitoring them in captivity. The study was pretty small (2-9 animals per species) but provides some useful information.

  • Deer mice, bushy-tailed woodrats, and striped skunks were susceptible to infection and shed the virus after infection, but they didn’t get sick (i.e. all infections were subclinical).
  • Cottontail rabbits, fox squirrels, Wyoming ground squirrels, black-tailed prairie dogs, house mice, and raccoons were not susceptible to infection.

That’s a bit of a mixed bag of results. The more wildlife species that are susceptible, the greater the potential problems.  We’re also more concerned about species that may have more contact with people (e.g. urban wildlife), those that live in large groups (where an infected individual can spread the virus to lots of others, potentially leading to sustained transmission in the population and creation of a reservoir), and those that can travel long distances (and could thereby carry the virus to new areas).

One highlight of this study for me is that raccoons were not susceptible, because they’re a very common, social wildlife species that lives in large urban centres where COVID-19 is (at the moment typically) rampant in people. Raccoons are one of the species I’ve been most concerned about in terms of a jump to wildlife.

The authors sum things up nicely “… we will undoubtedly continue to discover more susceptible species as the search for zoonotic reservoirs continues. COVID-19 is just the latest in a series of examples of how the human-wildlife interface continues to drive the emergence of infectious disease.”