By the ninth installment in this series we’ve moved away from our familiar domestic animals, but there are still a few species worth highlighting.

Bats aren’t actually one species though, they’re a diverse group of over 1400 unique species. Some eat insects, some eat fruit, some eat small critters like frogs, and some eat blood (yes, vampire bats do exist, but no, they don’t die if they’re exposed to garlic or sunlight). One thing they have in common is they are all flying mammals that live in large groups.

Bats are obviously a concern when it comes to SARS-CoV-2 because this virus (as well as its close relatives, the original SARS virus and the MERS virus) likely originated in bats. Bats can be little coronavirus factories, but remember that there are huge differences between bat species. We shouldn’t talk about “bats” as the source of SARS-CoV-2, because we’re really talking about one particular species, Chinese horseshoe bats (Rhinolophus sinicus), as the likely source.

Just because a virus can infect one species of bat, it doesn’t mean it can infect them all. That’s important because bats are incredibly widespread internationally, and often travel long distances (and obviously aren’t stopped by international borders). We don’t want SARS-CoV-2 to spread to other bat populations. The more we can keep this a human disease, the better, since it’s easier to control a pathogen in one species versus many (especially when some of them can fly).  That’s one reason field research involving bats has been curtailed or suspended in many areas during the pandemic. We don’t want people getting near bats, as more person-to-bat contact increases the risk of exposing the bats to, and potentially infecting them with, SARS-CoV-2.  The odds of such transmission are pretty low to start, given the small number of people who do that type of work and their limited direct contact with bats; however, it’s a small risk with potentially very big implications, so curtailing field research for now is logical.

We also don’t know the potential range of bat species that might be susceptible to SARS-CoV-2. Predictive studies based on ACE2 receptors suggest that most bat species are probably not susceptible. However, many still might be susceptible.  We have to be very careful with these types of studies, as they’re useful but far from definitive.  As you can see from the figure below from one ACE2 receptor study, it actually predicted horseshoe bats aren’t susceptible to SARS-CoV-2, despite the fact they are a leading candidate for being the initial source of the virus.Experimental studies are one way to sort this out, but they aren’t common because they’re expensive and difficult to do with bats (let alone when you toss a dangerous virus into the mix).

One experimental study from earlier this year looked at susceptibility of Egyptian fruit bats (Rousettus aegypticus) and found that 7/9 bats exposed to SARS-CoV-2 developed a transient infection. One of three bats that were placed in contact with those bats also became infected. That’s a bit concerning, since this species can be found in parts of Africa, Asia and around the Mediterranean.

Research involving other common bat species is lacking. So, prudence would dictate that we treat all bats as potentially susceptible until we know they are not. There are a number of other reasons to avoid direct contact with bats as well (rabies being a big one), but keeping bats away from people and people away from bat habitats is particularly wise now.

To finish off… yes, bats can carry lots of potentially harmful viruses. But, they also do a lot of good things ecologically, like eating tonnes of mosquitoes (which are important disease vectors too). Don’t blame this all on bats. We (people) are the ones who got it from the bats and then spread it all over the world.

Image: Horseshoe bat (source: http://www.bio.bris.ac.uk/research/bats/China%20bats/rhinolophussinicus.htm)

This one’s easy. Birds are not susceptible to SARS-CoV-2. Stop reading here if that’s all you want to know.  If you’d like a little more detail read on…

The SARS-CoV-2 virus originated in mammals (most likely in bats, which will be the topic of the next review) and has spread to other mammals (especially people, of course). Birds are, well, birds, so they’re not mammals. Some viruses like both birds and mammals, but most don’t.

Researches have looked at this, and experimental infection studies have not resulted in evidence that birds are to any degree susceptible to SARS-CoV-2. This includes a study that looked at chickens, one that investigated chickens and ducks, and one that looked at chickens, turkeys, ducks, quail and geese.  Those fit with the predicted poor susceptibility of chickens to SARS-CoV-2 based on their ACE2 receptor (the cellular structure the virus uses to attach to and invade cells – no attachment, no infection).

So, why bother investigating birds, since it wasn’t likely that they’d be susceptible to a mammalian coronavirus in the first place?

It was really important to check and verify that birds are low risk for a few reasons:

  • There are massive numbers of domestic birds all over the world. That means lots of potential for exposure to infected people. If this virus got into a large group of birds (like on a poultry farm) and they were susceptible, there’d likely be big risks for the birds, as well as for transmission back to farm workers and issues with contaminated manure (just like we’re seeing in mink).
  • Jumps to new species in large groups is a perfect recipe for unpredictable mutations (which has also been a concern in mink).
  • Perhaps the biggest reason for wanting to know is simply that birds live everywhere we do, and beyond. There’s lots of potential for direct and indirect exposure of domestic (and wild) birds to this virus from human sources, and additional potential for contact between domestic birds and wild birds, which can then rapidly spread pathogens over long distances (as with avian influenza viruses).  So, we needed to be confident that this virus couldn’t establish itself in any bird populations.

That’s why the work was done quickly at the start, and thankfully birds seem to be completely resistant to SARS-CoV-2.

(All that said, if you have COVID-19, don’t cough in your bird’s face. The non-scientific part of my brain still never wants to tempt fate.)

Headline:  “Are Dogs Spreading SARS-CoV-2?  Study Finds Living With a Dog Increases Risk of Contracting COVID-19

NO, it did NOT!

Even though the paper said that, it’s not what they actually found.  Unfortunately, a lot of people are reading that headline, or worse, they’re reading “…yada yada… dogs spreading SARS-CoV-2… yada yada.

What did the study really find?

Let’s break down some important aspects of the paper on which this headline is based.  The study, entitled “The spread of SARS-CoV-2 in Spain: Hygiene habits, sociodemographic profile, mobility patterns and comorbidities“(Rodriguez-Barranco et al. Enviro Res 2021), reported that people who walked their pets were 78% more likely to have reported having had or maybe had COVID-19.

  • They didn’t investigate that any further, and it’s not clear what “walked their pets” entailed (e.g. walking a dog once outside the house vs walking a dog on a regular basis).
  • The question, strangely, asks about walking “pets” not “dogs.” It’s reasonable to assume that the pets were at least mostly dogs, but they didn’t actually specify that.
  • How the authors analyzed the data is also unclear. The answer options for the pet-walking question were yes / no / I don’t have a pet. However, for analysis, they combined pet owners who didn’t walk their pets and non-pet owners (further demonstrating that they did not look at the risk of living with a pet).
  • They said that 6.9% of people who walked their pet had been infected, vs 4.2% of those who did not take their pet for a walk, despite the fact that most of the latter group actually didn’t own a pet at all.

So what they really looked at was leaving the house with a pet (vs living with a pet), and that raises some serious questions about how clearly they thought about the results. The focus should be on the “going for a walk” component, since that’s what they actually studied. Unfortunately, they didn’t also ask if people went for walks without pets.

Some of the other study results also raise more questions than answers:

  • They reported that people who used home delivery for food were almost twice as likely to have had COVID-19. Does that mean they were getting infected by delivery people and would have been safer shopping? Presumably not.  My concern is that there was some reason that people were more likely to order food, and that was also a risk factor for COVID-19. For example, if they knew they had been exposed or were in some other high risk situation, that might lead people to avoid stores and also be at higher risk of being infected.
  • Another big issue is the fact that people with COVID-19 were presumably more likely to order delivery after being diagnosed. The survey doesn’t ask what they did BEFORE getting infected (if they had COVID-19), just what they did during Spain’s period of restrictions. So, finding increased risk from home delivery might actually be because people who were more likely to use home delivery were otherwise higher risk or already had COVID-19.

Another concern is who they surveyed. The study population is critical for any study like this. You need to understand the study population to understand the results and any potential bias. You can get really misleading information or not understand your results if you don’t understand the group of people that provided them and how they compare to the general population.

Why is the study population so important? Here’s an over-the-top example to illustrate:  Let’s say a study said “pet owners were significantly more likely to say their dog was an important part of the family compared to cat owners,” but the study only enrolled people through websites like www.ilovemydog.com and www.mycatisademonicpsychopath.org – you can see how we might end up with a biased understanding of the situation.

In the discussion of the Spanish study, the authors mention that most respondents were graduate or post-graduate students, which is a pretty specific group. We have to consider how well they represent the general population. The farther away they are from average, the less confidence we have in extrapolating results to anyone other than graduate and post-graduate students.  I’m not saying there’s a problem using this study population. What I’m saying is we just don’t have enough information to know what it means. That’s one of the (many) things I’d flag reviewing a paper like this.

Survey response rate (and response bias) is also an issue, but I deleted my detailed comments on that since this post is already getting quite long (and probably a bit dry).

The way the authors wrapped things up is a big issue for me.

In the discussion they say, “These results point to living with dogs as a strong risk factor for COVID-19 infection.” Their concluding statement was, “The results of this study demonstrate that living with dogs… have been the main routes of transmission of SARS-CoV-2 during the most restrictive period of confinement in Spain.”

Neither of those is true.

Pet ownership was not associated with increased risk of COVID-19. Their statistical analysis of pet ownership did not identify any risk. Walking a pet was a potential risk factor, not owning or living with a pet. There’s a long paragraph in the discussion talking about risk from dogs, despite the fact the paper didn’t actually look at that, and they did not find a risk from pet ownership.

So, what does this study tell us about pets and risk of COVID-19?

It’s hard to say… probably nothing.

This study raises some interesting questions but doesn’t provide many answers. It certainly doesn’t provide answers about risks associated with pets. A more rigourous peer review could have helped catch and address some of those issues.

The study does NOT show pet ownership was a risk factor for COVID-19.

  • If the pet walking risk factor is real, I suspect the critical factor is more “walking” than “pet.”

I’ll stick with the same messaging I’ve had for months about animals and COVID-19:

  • If you have or might have COVID-19, stay away from animals (human and non-human).
  • If your pets have been exposed to someone with COVID-19, keep them away from others (just like you would if you or your kids were exposed).
  • Relax.

I’m going to have to go back to the start soon and update previous reviews of COVID-19 in animals, but there are still a couple of more species worth mentioning first. Cattle are an obvious consideration because they are important food animals that are widely raised in countries around the world, and they are often housed in large groups. Some cattle, especially dairy cattle, have a lot of contact with people. More human contact means more risk of exposure to the SARS-CoV-2 virus, and more animals in a group means more risk of animal-to-animal spread (and possibly mutation of the virus, as has recently been seen in mink in Denmark).

Fortunately, the SARS-CoV-2 virus doesn’t seem to like cattle. We probably can’t say they’re not susceptible at all, but based on what we currently know we can say they’re minimally susceptible at most. In terms of spread of SARS-CoV-2, the risk to cattle is minimal, and the risk to people from cattle is pretty much zero.

There was some interest in determining if cattle were susceptible at the start of the pandemic, because cattle are susceptible to bovine coronavirus, which is also a beta-coronavirus, just like SARS-CoV-2. However, cattle were predicted to be low-risk for infection based on the form of their ace2 receptor, the site the virus uses to attach to and subsequently infect cells.  Predictions from these receptor-based studies haven’t always been accurate, but they seem to be true in this case. One experimental study in cattle has been reported so far (Ulrich et al.), and it supports the notion that cattle are pretty resistant to infection with SARS-CoV-2.  The researchers found that viral RNA was transiently detected at low levels (likely not enough to be infectious) from nasal swabs of 2/6 inoculated cattle, and those two animals developed a very low level of antibodies as well. No cattle that were co-housed with the inoculated cattle became infected. In summary, there was some degree of infection that stimulated the immune system to respond in two animals, but it was a minimal response.

As usual, the two important questions are:

1) Can cattle get sick from SARS-CoV-2?

  • We have a single study of 6 cattle of one type and age, which is far from definitive, but it doesn’t indicate any health risk to cattle.

2) Can infected cattle shed the SARS-CoV-2 virus? (and therefore pose a risk to other animals, including humans)

  • Virus shedding in cattle doesn’t appear to be a concern. Even if the odd cow can be transiently and mildly infected, it’s very unlikely they would shed enough virus to pass it along to another animal or person.

So, let’s not ignore cattle completely, and let’s still try to keep infected people away from them, but we can probably relax when it comes to SARS-CoV-2 and this particluar species.

Denmark is one of the largest mink producing countries in the world, and mink on numerous farms have been infected with SARS-CoV-2 from farm workers with COVID-19. At last report, 216 farms were affected. That wasn’t too surprising since outbreaks on mink farms have been seen in several countries, with particularly widespread infection on farms in the Netherlands. The issue is a recent report by the Serum Statens Institute (SSI) and some government releases about emerging “mink strains” of SARS-CoV-2 and a large number of human infections with a “mink strain.”

Crap.  Mutated virus. That sounds bad.

Not necessarily. Viruses mutate all the time. It’s a random event. It’s more likely to occur when there are large numbers of infected individuals, simply because there are then more opportunities for random mutation. A mink farm with thousands of closely housed and highly susceptible mink is a great place for that. It’s also probably more likely when a virus moves between species, as some random mutations might make it easier for the virus to infect their new host species.

So, what’s going on with SARS-CoV-2 in mink in Denmark?

At this point, five different variant strains of the virus have been found in mink, which include variations in the spike protein the virus uses to attach to (and subsequently infect) cells. If such a mutation makes it easier for the virus to attach to cells of a given species, it becomes more infectious to that species. Conversely, if a mutation decreases the ability of the virus to attach to cells, it makes the virus less infectious. The spike protein is also an important vaccine target, raising some concerns about whether mutations could decrease the effectiveness of some vaccines that are being developed (a bit more on that below).

One particular variant has been found in human samples too, some from people that are connected to the mink farms, and some from people who aren’t.  The variant strain has been found in 214/5102 virus isolates from people, 94% of whom are in North Jutland, where most of the infected mink farms are. This variant accounted for 40% of the isolates in that area, which is pretty impressive (not in a good way).

A translation of the Danish SSI report about the emergence of these variants in mink and their spread to the human population says “SSI estimated that continued mink breeding would entail a significant risk of recurrence of a large spread of infection among mink and humans, as seen in Western Denmark in 2020. SSI estimated that this would pose a major risk to public health. Both know that the many infected mink farms can lead to a greater disease burden among humans, and know that a large virus reservoir in mink increases the risk of new virus mutations occurring again, which vaccines may not provide optimal protection against. Overall, the immunity gained through vaccination or past infection may also be at risk of being weakened or absent. The overall conclusion, which was also supported by the Danish Health and Medicines Authority, was therefore that continued mink breeding during an ongoing COVID-19 epidemic entails a significant risk to public health. Including the possibilities for optimally preventing COVID-19 with vaccines.”

Is this really a “mink strain” of SARS-CoV-2?

It’s hard to say. It’s a strain that has been found in mink. It might have mutated in them or it might have mutated in the person that infected them. Most likely, it did evolve in the mink, spread to people, and then those people spread it to other people.  Everyone’s talking about it like it’s one strain, but there are actually several strains linked to mink now. One is getting the most attention, though.

How did hundreds of people get infected with this strain? Are mink everywhere in Denmark?

No, mink aren’t everywhere, but people are. This is a situation where (I assume) most of the transmission is still human-to-human. It came from people, probably changed in the process of being transmitted between so many mink and then was likely transmitted back to a few people with close contact with the mink, and is now back to being transmitted widely between people.

So, why do we care?

  • Anytime we see movement of a virus into another species, it’s a concern. Mink infecting people isn’t the real problem, since few people have any direct contact with mink. The issue is whether mink can complicate overall control of the disease in people. More species involved means more problems to address. Denmark was already culling affected and neighbouring farms, but as more mink farms get infected, that creates more opportunities for new strains to emerge.  So they’ve now made the difficult decision to cull all farmed mink in Denmark until the COVID-19 pandemic in people is under control.
  • Related to the above, the last thing we want is this virus in wildlife. Transmission to cats has been found on mink farms in the Netherlands, Fortunately, so far, we haven’t seen issues with SARS-CoV-2 infection in wildlife (but we didn’t see issues with mink either until we suddenly had a big issue with mink… if you catch my drift). Mink create a potential bridge to other species, and we don’t want that.

And the big one….

  • Is this mutation a problem for people? Early lab data suggest that this virus isn’t neutralized as well by antibodies from people infected with the more common strains found in the human population. That could impact the effectiveness of antibody-based treatments or vaccines, but it’s too early to say there’s a relevant issue. It’s certainly something that needs to be investigated as if it’s relevant. If it impacts vaccination, we start getting into a situation where we might need a vaccine that protects against multiple strains of SARS-CoV-2 (and none of the billions of dollars in vaccine development money has been spent looking at this new strain).

Some new outlets have talked about the chance for a “new pandemic.” Is that realistic?

No. Our current pandemic is doing just fine and isn’t going to be displaced. We are effectively transmitting the original virus between people, and we will probably effectively transmit this other strain too. It’s not likely to change the character of the pandemic (unless it impacts treatment or prevention). There’s no evidence that it causes more serious disease.

What does this mean in the big picture?

It’s too early to say. Whether this is an academic curiosity, a mutation that might lead to some interesting epidemiological data but has no additional health impact, or is a sign of a looming problem, is hard to say.

What do we do?

  • Relax.
  • Avoid kissing mink (most mink would eat your face if you tried, anyway).
  • Continue to pay attention to animals as potential sources of infection.
  • Most importantly: control human-to-human spread. The best way to prevent the spread of mink-strain COVID-19 is to prevent spread of COVID-19. Period.

In the big picture (jumping on my soapbox for a moment), this is why I’ve been saying these things since January. It’s why we criticized groups like CDC that said “there’s no evidence animals can be infected” before there was any effort to find out. We need to approach emerging diseases proactively, by looking for potential problems and taking steps to control them early, rather than waiting for definitive evidence of a problem.

Photo by Markus Winkler on Unsplash.

Perhaps this is one you didn’t see coming, but there have been lots of discussions about SARS-CoV-2 and marine mammals. You may think, “people don’t have much contact with marine mammals,” and of course you’d be correct, if you meant direct contact. However, human activity (and waste) can significantly influence marine mammal health.

What’s the risk of direct transmission of SARS-CoV-2 from humans to marine mammals?

This is a concern for a very small group of people, but human contact with marine mammals  does occur, with both captive animals and sometimes during field studies. Any direct contact poses some risk of transmitting pathogens (of many kinds) in either direction. We saw human-to-marine mammal transmission a few years ago during an MRSA outbreak in dolphins and walruses that we investigated.  If people can pass MRSA to marine mammals, we can presumably do the same with the SARS-CoV-2 virus. However, in the grand scheme of things, infection of captive marine mammals is of limited concern (at least beyond the individual animals in a collection).

How would wild marine mammals get exposed to the SARS-CoV-2 virus?

The main issue is exposure of marine mammals to the virus via sewage. The virus doesn’t like being outside of a warm body, but it will survive for a short period of time in sewage. Unfortunately we don’t know exactly how long it can survive in such waste water, or how different sewage treatment approaches influence survival of the virus.

We know that exposure to human sewage can result in transmission of pathogens to wild animals, so the concern isn’t unrealistic in areas where there is close proximity of marine mammals to human sewage effluent, especially if there are sewage infrastructure challenges that lead to release of poorly treated or untreated sewage.

Are any marine mammals actually susceptible to SARS-CoV-2?

We don’t know. As I’ve discussed before, we can look at their ace2 receptors (structures the virus uses to attach to and invade cells) for clues. We have to be cautious putting too much faith in predicted susceptibility based on ace2 receptors, and most of these studies have not included marine mammals anyway. However, a couple of studies ranked various marine mammals (including a variety of whales and porpoises) as having potentially “high” susceptibility (Damas et al., Luan et al.).

There is a pre-print available of a marine mammal-focused study modeling potential susceptibility to SARS-CoV-2. Th study predicted various whales, dolphins, seals and otters would be highly susceptible to the virus. Sea lions were lower risk, which would be a very good thing given how they congregate in large populations, often close to human populations. In contrast, the models predicted some species like beluga whales and bottlenose dolphins may be even more susceptible than people. High-risk species included a large number of species that are already vulnerable or endangered.

Overall, the risk to marine mammals is likely very low, especially in terms of creating a sustained problem.  This virus isn’t as hardy as most pathogens that we know can be spread via sewage. If infected, infected marine mammals would likely only spread the virus over short distances and short periods of time. A small pod of whales poses much less risk overall than a large population of sea lions, where there are enough individuals for sustained transmission in the group.

However, since some marine mammal populations are highly threatened, an outbreak localized to an individual pod or population could still have significant consequences.

Is there a risk of SARS-CoV-2 transmission to people from marine mammals?

The risk posed by marine mammals to people is likely negligible. We’re pooping in their habitat more than they’re doing it in ours. Sure, an infected marine mammal would likely pose a risk from direct contact, but the odds of such contact are very low.  Outside of some very densly populated areas, I suspect the potential impact of marine mammal infections (should they occur at all) on human health is very low.

What are the recommendations with regard to marine mammals?

  • We need to learn more about sewage, as an indicator of infection of people in the community, but with that we should also aim to learn about the potential for viable virus escaping into nature and exposing wildlife (both terrestrial and marine). Detection of viral bits in sewage by PCR is one thing. Knowing how that correlates to infectious virus is key to assessing the risk of spillover into wildlife.
  • The risk of human-to-animal transmission can’t be ignored. Facilities with captive marine mammals should limit contact with them (just like they should be limiting human-to-human contact), and obviously there should be no contact with people who are infected or quarantined because they are high-risk.
  • Similar precautions apply to field research. This has been a tough topic for any field researcher, but the goal is to prevent problems, not react to them. So, we’re better off limiting direct contact with wild mammals (both terrestrial and marine) as much as possible. When contact is required, we need to maximize protective measures (e.g. masks), minimize contact time, minimize the number of people involved, and do everything possible to make sure infected or otherwise high-risk people don’t participate.

Image source: https://www.news-medical.net/news/20200817/SARS-CoV-2-poses-significant-threat-to-many-marine-mammal-species.aspx

What the story with SARS-CoV-2 in horses?

This one’s easy to answer: we have no clue.

There’s been almost no investigation or research regarding this virus in horses. Horses often get left out in situations like this because they’re livestock, but not (typically) food animals, and investigation of livestock tends to focus on food animal species. Horses are often more akin to companion animals, but a smaller number of people own or have contact with horses compared to household pets. Experimental studies aren’t commonly undertaken because trials in horses are generally very expensive due to their size and upkeep.

So, what do we actually know about SARS-CoV-2 and horses?

Not much.  As I’ve mentioned in several other posts, there are studies that have looked at the composition of the ace2 receptor in different animal species. Ace2 is the part of the SARS-CoV-2 virus that it uses to attach to (and ultimately invade) the body’s cells. If the virus can’t attach to cells, it can’t infect them. The structure of this receptor varies between species, and that accounts (in part) for differences in species susceptibility. Not all studies have included horse, but one ace2 receptor study suggested that horses might be susceptible to SARS-CoV-2 – possibly even more susceptible than a few species we already know are quite susceptible, such as cats and ferrets. Another study based on ace2 receptor analysis ranked the likely susceptibility of horses to SARS-CoV-2 to be equivalent to cats (specifically domestic cats and lions, both of which we know can be infected) and camels (which we also know nothing about, beyond their being a host for another zoonotic coronavirus, Middle Eastern Respiratory Syndrome Coronavirus (MERS-CoV)).

We have to take such predictive studies with a (big) grain of salt, because the real world situation hasn’t always mirrored what was predicted.  Those studies basically tell us we should pay more attention to horses and see if there’s a problem, not that a problem is necessarily likely.

Have any horses been tested for SARS-CoV-2?

Maybe.  I haven’t tested any, and I haven’t heard of anyone who has, but it’s possible someone’s looked but not found the virus, or antibodies against it, in horses. If there was a positive, I assume it would have been reported somehow somewhere. I suspect few, if any, horses have been tested.

What should be done with horses?

Some surveillance would be good. Testing horses that have been exposed to infected people would be interesting, and tell us more about interspecies spread of the virus. There have been outbreaks of COVID-19 in grooms in racing stables, a human population that’s probably very high risk for infection, and for working while sick. They usually have close and frequent contact with horses, so testing horses from stables with outbreaks in the grooms or other staff would be a good start.

However, as for all animal species, the most important thing to do is stay away from them if you have COVID-19 or if you’ve had high-risk exposure to someone with COVID-19. It’s better to prevent a problem than have to figure out how to deal with it after it happens. If we reduce the number of infected people who have contact with horses, we reduce any potential problems.

Image source: https://dailymemphian.com/article/15734/germantown-horse-mask-ordinance

I’ve spent a lot more talking about mink in the past few months than I ever thought I would. In regard to SARS-CoV-2 (the virus that causes COVID-19 in people), mink and ferrets (their close relatives) are a fascinating story, but I’ll try to be brief about it. Mink have become important because of the widespread outbreaks of SARS-CoV-2 on mink farms in some countries, and ferrets are important because they’re household pets and appear to be equally susceptible to the virus.  What we know about these two species within the mustelid family is quite different. We have good experimental data for ferrets and very little field data. For mink, it’s the opposite.

What’s the story with mink and SARS-CoV-2?

I think it’s fair to say this caught us off guard. At the start of the COVID-19 pandemic, no one was talking about risks to/from mink farms. Yet, mink are highly susceptible to the SARS-CoV-2 virus. There have been widespread outbreaks on mink farms in some countries, first in the Netherlands but now in several countries in Europe, as well as in the US. In the vast majority of cases, it is suspected that the mink were initially infected by a person, and then the virus spread further from animal-to-animal.  Some affected farms have had few health issues while others have reported considerable illness and increased mortality in their animals, which has led to widespread culling of mink in some countries to try to contain the spread of the virus.

There are a few additional concerns with these outbreaks beyond the health of the animals themselves. One is zoonotic transmission back to people, as apparent mink-to-human transmission has been reported in one Dutch study. Infection of feral cats on mink farms has also been identified, which raises concern about the cats (or escaped mink) potentially infecting wildlife in the surrounding area.  Work on this issue is ongoing.

So, mink can be infected, the virus is effectively spread between mink, mink can potentially infect people in contact them, and mink may be a source of exposure for other animals. All of those are concerning.

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

Whether ferrets are “as susceptible” as mink is hard to say; however, they are clearly susceptible to infection, can get sick, and can shed enough virus to infect other ferrets, as has been demonstrated in multiple experimental studies. Notably, ferrets can be infected with fairly low doses of SARS-CoV-2.

One thing that raised some concern and confusion was a report that ferrets could spread the virus “via the air.” While the study showed that ferrets were able to transmit the virus to other ferrets in cages 10 cm away, the results weren’r actually indicative of true airborne spread (a bit of a loaded term). Rather, it was likely droplet spread over a short distance. A more recent study raised a bit more concern, as it  reported transmission of the virus between ferrets over more than 1 metre. In this study, airflow was high and was directed from the infected to uninfected ferrets, so while the virus traveled at least 1 metre under those conditions, we have to be careful when assessing what that means. I think it supports the fact that this virus can move in the air for short distances, but a lot of factors influence how far it goes and the risks associated with aerosol transmission. We’re learning more and more than ventilation and environmental conditions are important for human-to-human transmission as well.

How sick can ferrets get from SARS-CoV-2?

At the start, I was expecting ferrets to be susceptible to severe disease because ferrets can also get quite sick, and sometimes die, after infection with the original SARS virus. The SARS-CoV-2 doesn’t seem quite as hard on them, but experimental data are variable. Some studies have reported infections with limited or no obvious signs of disease (Shi et al.Schlottau et al., Kim et al.)  However, at least one study reported more serious disease from SARS-CoV-2 in ferrets, sometimes requiring euthanasia. The difference in results might be related to the dose of virus, with higher doses used in the experimental study where more serious disease was observed.

If ferrets are susceptible to SARS-CoV-2, why aren’t there reports of infected pet ferrets?

Good question. That probably relates to limited testing. In our Canadian SARS-CoV-2 surveillance study, we’ve only been able to test one ferret. I haven’t seen much other surveillance data in this species. There’s one pre-print study looking at human-to-ferret transmission in a household where there were two infected people and 29 ferrets, but they didn’t find any evidence of transmission to ferrets. However, it’s hard to conclude much from a study of one household. Testing of the ferrets started 16 days after the onset of the first person’s illness and 13 days after the onset of the second person’s illness. It’s a challenge getting samples from the animals early in the disease of the people, so we probably under-estimate transmission with studies like this (ours included). The same study looked for antibodies in the ferrets too, but it was antibodies from oral swabs that were submitted for virus testing, and I’m not sure anyone knows how sensitive that technique is. So, there was no evidence of human-to-ferret transmission, but it was only one household and the testing had some significant limitations. Study of more ferrets in more households is needed. The lack of reports of infected ferrets may also be a function of there being fewer pet ferrets compared to dogs/cats, and correspondingly less testing for that reason as well.  Ferrets seem to be more susceptible than dogs and cats in experimental studies.

Can ferrets infect people with SARS-CoV-2?

We don’t know.  Given their susceptibility to the virus, the experimental study data and evidence of potential transmission of SARS-CoV-2 from mink to people, I think we have to assume that an infected ferret might pose some degree of risk to people as well. However, if a ferret is infected, it almost certainly got it from a human household contact, and that person poses much more risk to others in the household than the ferret does. The main risk is if the ferret leaves the household (e.g. to see a veterinarian) during the period when people in the household are infected, as it may take the virus along for the ride and could then potentially spread it to others.

What should be done with mink and ferrets?

  • Anyone with COVID-19 should absolutely not go near a mink farm (or anyone who works on a mink farm). That’s the big one.

The same general approach that we recommend for dogs and cats applies to ferrets:

  • 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 or animals.
  • If your ferret has been exposed to someone with COVID-19 and is sick, let your vet know.  Discuss what to do over the phone, at least initially, rather than showing up to the veterinary clinic with your ferret.

Next up for animal reviews: Horses

Image source: https://www.cbc.ca/news/canada/newfoundland-labrador/covid-outbreaks-mink-farms-canadian-breeders-prepare-1.5769815

Moving on from cats and dogs, let’s talk about one of our major livestock species, pigs.

Are pigs susceptible to the SARS-CoV-2 virus?

  • Kind of, but not really. There are conflicting experimental data that show no or very little susceptibility to the virus.

Why did we talk a lot about pigs and SARS-CoV-2 initially?

At the start of the pandemic, we were worried about the potential for this virus to infect pigs because of their ace2 receptor, which is used by SARS-CoV-2 to invade pigs’ cells. If the virus can’t enter an animal’s cells, it can’t infect them. Different animals have slightly different ace2 receptors on their cells. The pig ace2 receptor is quite similar to the one people have,  suggesting there could be similar susceptibility to SARS-CoV-2. Looking at ace2 receptors has been interesting, but we’ve also seen the limitations of this method, with some purportedly low-risk species being susceptible and some purportedly high-risk species being resistant. Ace2 is only a part of the picture, so while it’s worth considering, it really doesn’t answer the question of whether there’s a concern with pigs.

Trying to grow the virus in a laboratory in cell lines from a particular animal species can provide some additional information on potential susceptibility. In one study, SARS-CoV-2 was grown in 2 of 3 pig cell types, but did not damage the cells. In another study, the virus was grown in pig cell lines and caused some cell damage.  These all raised concerns about the virus’ ability to infect pigs, but there are limitations to what in vitro studies can tell us. To get the real story, we need to look at real pigs.

So, forget about pig cells – are actual pigs susceptible to SARS-CoV-2?

In three separate studies (Shi et al.,  Schlottau et al., Meekins et al.), pigs were experimentally inoculated with SARS-CoV-2 and mixed with naive pigs. Nothing remarkable happened. None of the pigs got sick and all samples collected were negative for the virus. Antibodies against the virus weren’t found in any animal. All of these results indicated that the pigs were not infected, and there was a collective sigh of relief as it appeared that concerns about pigs were unnecessary.

In another study, pigs were exposed to the virus via the nose, trachea and injection. All the pigs stayed healthy and the virus wasn’t detected in any samples, but antibodies against the virus were found after pigs were injected with the virus. Exposure by injection doesn’t tell us much about natural infection, and the other results are consistent with no natural susceptibility.

However, leave it to Canadians to be disruptive – an experimental study conducted by the CFIA found slightly different results in pigs.  It didn’t raise major concerns, but it suggested things are not not quite as clearcut. In that study, 16 pigs were exposed to a higher dose of the virus than in previous studies.  Once again, nothing remarkable happened. Some developed mild discharge from the eyes for a few days. One had a slight cough and was mildly depressed for a few days. However, low levels of virus were detected from respiratory samples by PCR from two of the sixteen pigs, although live virus could not be isolated. The virus was also isolated from a lymph node of one pig, and antibodies were detected in the blood of two pigs, supporting some level of true infection. Two pigs were added to the exposed pigs 10 days after inoculation, and they did not get infected. Overall, 5 of the 16 pigs (~30%) had some evidence of mild infection. So, this study showed some degree of susceptibility, but with infrequent mild disease and no evidence that pigs are infected to the degree that they would be able to pass on the virus to other animals or people.

Have any pigs outside of the lab been infected with SARS-CoV-2?

There are no reports of infected pigs to date, but I’m also not aware of any testing of pigs on farms. Field data are always useful because experimental studies don’t tell the full story of what happens in the “real world.” Some data about pigs exposed to infected farmers would be useful to have, to round out the story, but it would probably be low yield research since it’s quite unlikely anything would be found.

What should be done with pigs?

The same general recommendations apply as for other animal species. While the risks are low, we can’t say they are zero. If we keep infected people away from animals, we don’t need to worry about human-to-animal transmission, and any subsequent animal health or animal-to-human transmission issues. While the odds of someone infecting a pig are very low, it’s best to avoid exposing pigs to infected people whenever possible. That may not be an option on small farms run by one person or a family, but the more we can keep infected people away from animals, the better.  In short, better to be safe than sorry.

Next up for animal reviews: probably mustelids (mink and ferrets).

Image source: https://theconversation.com/could-chinas-strategic-pork-reserve-be-a-model-for-the-us-139949

Round two of my COVID-19 in animals summaries: Dogs

Are dogs susceptible to the SARS-CoV-2 virus?

Yes, but not very… maybe.  It depends what you mean by “susceptible.”

Nice and clear, eh?

There’s a difference between being infected and getting sick. Dogs can be infected by the SARS-CoV-2 virus (which is the virus that causes COVID-19 in people), but they don’t seem to be as susceptible as cats, and it’s debatable whether dogs get sick (more on that below).

Infection in dogs has been shown in a few different experimental studies, and through identification of infected pet dogs that were exposed to people with COVID-19.  In one small study, SARS-CoV-2 was detected by PCR in experimentally infected dogs, but the researchers could not isolate any “live” virus from the animals, suggesting the virus was present at a low level and the dogs were probably not infectious. The dogs remained healthy, but some developed antibodies against SARS-CoV-2, supporting the idea that they were truly infected and their immune systems responded accordingly. They did not pass to virus to other dogs with which they were co-housed. In the end, some or all of the exposed dogs got infected, but none got sick and they didn’t infect any other dogs.

Another experimental study yielded similar results, in that dogs were infected and mounted an antibody response, but didn’t get sick and were probably not infectious.

How often do dogs get infected with SARS-CoV-2?

We don’t know. Surveillance has been limited, so the scope of human-to-dog transmission isn’t clear. In Hong Kong, early in the pandemic, they quarantined pets of COVID-19 patients who could not care for them (e.g. owner lived alone and had to be hospitalized), and the pets were all tested at the quarantine facility. Hong Kong authorities identified SARS-CoV-2 in nasal, oral and/or rectal swabs from  2/15 dogs that were quarantined following exposure to their infected owners. Neither of the positive dogs had signs of infection, both developed antibodies to the virus, and gene sequencing of showed that the virus from the dogs was the same as that of their respective owners. Of particular note was they were able to isolate live virus from one of the dogs, which suggests the dog could have been infectious to others, at least briefly.

Additional data has been limited, in large part because it’s a logistical challenge to sample dogs in households with infected people during their isolation period. One small study in Spain didn’t detect SARS-CoV-2 in any of the 12 exposed dogs tested.  An investigation of pets from a cluster of infected and exposed veterinary students in France also failed to identify the virus in 12 other dogs, although it wasn’t clear how many of the dogs were actually exposed to an infected person.  A study from Italy reported no detection of the virus in 64 dogs from households with previous human COVID-19 infections, including 3 dogs that had respiratory disease.

Our Canadian study didn’t initially find the SARS-CoV-2 virus in any of 18 dogs (more to come on the expanded version).

There are still numerous reports of individual infected dogs from different countries. In the US, approximately 23 dogs have tested positive for the virus so far. That’s not a lot in the context of the dog population, but remember that not many dogs have been tested. Furthermore, testing has focused on looking for the virus by PCR. That will underestimate infections, because based on what we’ve seen so far there’s only a short window of time when you can get a positive PCR result from an infected dog. Dogs seem to only shed the virus for a few days after infection, so sampling dogs in infected households (after the people are no longer infectious and it’s safe to do so) runs the risk of a lot of false negatives simply based on the timing of sampling.

Studies looking at antibodies in dogs (and other animals) will be more informative, if the tests are accurate.  Antibodies are an indicator of past infection, and they tend to hang around significantly longer than the virus itself.  So unlike PCR-based surveillance, we don’t have to get into the household right away during the time of human illness – we can test dogs later to see if they were infected.

Not a lot has been reported yet on antibody testing (also called serology) in dogs. A study in Italy found antibodies to SARS-CoV-2 in 3.4% of dogs; 6/47 (14%) dogs from known-positive households, 1/7 (14%) dogs from households of suspected cases, and 2/133 (1.5%) dogs from other households. Whether the 1.5% prevalence in other dogs is from dogs that were infected by owners that were never diagnosed, or it represents the false positive rate of the test isn’t clear. A French study found antibodies in 2/13 (15%) exposed dogs and 0/22 dogs from households with no known cases of COVID-19.  Those results are similar to our preliminary 20% (2/10) prevalence in dogs from positive households in Canada so far. Obviously, we need to test a lot more dogs to get better estimates, and the study is ongoing.

Do dogs get sick from SARS-CoV-2?

That’s still unclear. I’d say that evidence is still far from convincing. There are a few poorly documented reports of sick dogs, but the question largely unanswered in those cases is “were they sick from infection with SARS-CoV-2, or were they sick with something else and coindicdentally happened to have been infected by this virus at the same time?” My guess is that disease is rare in dogs, but not impossible, especially in animals that may have other comorbidities that make them more prone to severe disease from many other pathogens as well.

Can dogs infect other animals or people with SARS-CoV-2?

Probably not, but that’s unclear too. Dogs are likely much lower risk that cats in terms of transmission. The fact that live virus was isolated from a dog at one point raises concern, because if there was live virus in the dog’s nose, you have to assume there was some risk of exposure to in-contact individuals. Whether the dog was shedding enough virus to actually infect someone is completely unknown. Lack of transmission in experimental studies isn’t a guarantee (because of the artificial environment and very small animal numbers) but provides more support of limited risk.

Overall, I’d say the risk of transmission of SARS-CoV-2 from dogs is very low. I don’t think we can say it’s zero, but I think it’s unlikely that a dog would pose a realistic risk.  That said, why chance it? If a dog is infected or at risk of being infected (i.e. living in a household with an infected person), it should be kept away from other people and pets. Dogs interact nose-to-nose and nose-to-bum a lot, and we have a lot of contact with their faces. We’ve seen transmission of other respiratory viruses between neighbouring dogs through fence-line contact, so keeping exposed dogs under control and away from others is reasonable and practical.

Could dogs be an important reservoir of SARS-CoV-2 once it’s controlled in people?

No. Dogs are not susceptible enough to the virus. For dogs to be a reservoir, they’d have to be able to keep spreading it dog-to-dog. That’s not going to happen because of the low susceptibility and short shedding time. You’d need a very large number of dogs in regular close contact to even begin to get a risk.

Could dogs be a bridge to transmit SARS-CoV-2 to wildlife?

Probably not, or at least they’re much less likely to be a bridge than cats. Their low susceptibility, short period of infection, limited (if any) infectivity and limited direct contact with wildlife mean the odds of them being infected by their owners and then infecting wildlife are pretty negligible.

So, we shouldn’t worry about COVID in dogs?

Worry, no. But, we should pay attention.

What should be done with dogs?

Do the same things recommended for cats:

  • If you are infected, try to stay away from animals – all animals, human and otherwise.
  • If your dog has been exposed, keep it inside and away from others.

Ultimately, dogs are part of the family – so if your family is being isolated, the cat needs to be a part of that.

and

Relax. This is almost exclusively a human virus. With a modicum of common sense, the risk posed from pets approaches zero.