The USDA has issued announced the first confirmed case of SARS-CoV-2 infection in dog in the US. The affected dog was a German Shepherd from New York state, and unsurprisingly its owner had COVID-19. Interestingly, this dog did have signs of respiratory disease,  a finding that hasn’t been reported in dogs to date. It tested positive for the virus by PCR, and also had antibodies against SARS-CoV-2. Another dog in the household was healthy, but also had antibodies, indicating it had been infected too.

This case is noteworthy for a couple of reasons:

  • The positive dog was sick, though that still doesn’t necessarily mean the illness was due to the infection with SARS-CoV-2. The dog could have had other underlying disease due to some other cause.  Hopefully more information will come to clarify that. However, if this dog was sick because of SARS-CoV-2 infection, it would run contrary to the evidence to date that indicates dogs can be infected but don’t (typically) get sick.
  • Both dogs in the household were infected, even though only one got sick and tested positive by PCR.  The assumption has been that human-to-dog transmission is uncommon, and that still might be the case, but finding transmission to multiple dogs in a household is interesting.

Overall, it doesn’t really change our main talking points, but it highlights the need for more study.

A few quick updates on some recent SARS-CoV-2-related stories.

North Carolina dog: Positive result not confirmed

This case, a pug in North Carolina that had an oral swab that supposedly tested positive for SARS-CoV-2 as part of a Duke University household surveillance study, was reported a few weeks ago.  It was strange that there was no confirmation of the test result since then. Now we know why.  It appears the original test result was actually “inconclusive” (i.e. not strong enough to be truly considered positive). Follow up PCR testing was negative. That in itself doesn’t mean the dog wasn’t infected, since it could have been a short term infection that wasn’t sampled during peak shedding. However, no antibodies were detected in the dog. That indicates the immune system didn’t recognize the presence of the virus. It’s not completely definitive, but supports this not being a true infection.  Perhaps transient contamination of the dog’s mouth with virus from its infected owners could have caused the original inconclusive test result.

Hydroxychloroquine/chloroquine study debate

This topic is a bit outside the animal health-related area, but is still interesting (and relates to some of my recent Twitter ranting about the state of scientific publication). The high profile Lancet paper that reported increased deaths associated with hydoxychloroquine use in COVID-19 patients, and led to WHO suspending that arm of its study, has been challenged because of numerous concerns about data and data availability. It doesn’t mean the results are necessarily wrong, but questions about the data mean that things need to be clarified, which the authors have apparently been reluctant to do so far. An open  letter to the journal outlines various problems with the report and has a large and reputable list of signatories.

Tiger SARS-CoV-2 whole genome sequencing

There’s not really anything notable here in the big picture, but anyone with an inclination towards whole genome sequencing data might be interested in the sequence results from the virus isolated from one of the Bronx Zoo tigers.

SARS-CoV-2 in a cat in Russia

Just one more report of a cat with SARS-CoV-2 infection, presumably from its infected owner. Not surprising.

I keep saying I’m going to stop talking about sporadic new SARS-CoV-2 infections in animals unless there’s something noteworthy. I’ll mention some recent cases in a dog and some cats in the Netherlands because I think there are some unique aspects that fit that bill.

Infected dog

This infected dog was euthanized on account of severe respiratory disease. So far, it has appeared that dogs don’t get sick if they are infected with SARS-CoV-2. Disease of any sort, let alone fatal disease, would therefore be noteworthy in a dog.  One report said “The American bulldog’s blood tested positive for SARS-CoV-2 antibodies, but the dog had tested negative for an active case of Covid-19.” I assume that means it was PCR negative, but that doesn’t mean it wasn’t infected. They added “It was thus unclear if the dog’s worsening condition was as a result of the infection, or due to other health issues.”  Hopefully more testing is being performed  to see if there were other problems that could have accounted for severe disease or whether SARS-CoV-2 might have been the cause.

Infected cats on a mink farm

During our national working group discussions of the outbreaks of SARS-CoV-2 on Dutch mink farms (now 5 affected farms), the question of whether there were other animals like barn cats on the properties was raised. The answer to that is apparently “yes.”

Three of 11 tested cats on the farms had antibodies against the virus, indicating they had been infected. That leads to questions about how they were exposed. Investigating that involves interviewing farm staff to see how much human contact they had, to get some idea whether contact with infected people or indirect contact with infected mink (e.g. droplets/aerosols from being in the affected barns, contact with potentially virus-contaminated manure) was the likely source.  This highlights the importance of preventing exposure of other animals and containing exposed/infected animals. We want to keep this virus confined to humans as much as possible, and not create opportunities for animals to pass it back to people or for animals to spread the virus to other domestic animals or wildlife.

Nothing too remarkable to report, but here are a few recent developments.

Dogs

Details about the first two SARS-CoV-2-positive dogs in Hong Kong have been published in Nature. We’ve previously heard most of the information before, but here’s a quick summary:

  • Two out of 15 dogs were identified as positive for SARS-CoV-2, after being in contact with COVID-19-infected owners.
  • The first dog was a 17-year-old Pomeranian. SARS-CoV-2 was isolated from nasal and oral swabs shortly after it arrived in quarantine, and it had positive nasal swab results multiple times over 13 days. It also produced antibodies against the virus (seroconverted). The repeated isolation of the virus and seroconversion are convincing evidence that the dog was infected. However, it did not have any apparent signs of illness from SARS-CoV-2. It died shortly after its quarantine ended but that was attributed to its old age and other issues, not the virus (see figure below for timeline info).
  • The 2nd dog was a 2.5-year-old German Shepherd, one of two dogs in the household of another COVID-19-infected person. The virus was detected from sets of oral and nasal swabs collected on arrival and the next day, but further samples were negative shortly thereafter. Rectal swabs were also collected at the second sampling time and were positive. This dog also seroconverted and remained healthy.
  • Unsurprisingly, when they looked at the genetic sequence of viruses from the dogs and their respective owners, viral sequences from the dogs were identical to those from their owners (and sequences from the two households were different). This supports the assumption that the dogs were infected by their owners.

Cats

Another couple of infected cats have been identified, one from Germany and one from France.

The German cat’s owner was in a retirement home with an ongoing outbreak, and had died of COVID-19. The cat was infected, while two other cats at the facility were negative. The cat was healthy, as seems to be fairly common with infected cats.

The other cat was the 2nd reported positive cat from France. This cat had respiratory disease that was non-responsive to antibiotics and anti-inflammatories, and it’s quite possible those signs were the result of COVID-19, but we can’t rule out other underlying causes based on the available information.

Mink

There are now four mink farms in the Netherlands with confirmed outbreaks of SARS-CoV-2 in the animals. There’s still limited public information about the number of infected mink or information about transmission patterns on these farms. With thousands of animals on each premisis, there is certainly concern about the potential for widespread transmission, as well as ancillary issues such as what to do with all of the potentially contaminated manure. There’s not much mention of illness in the mink, but it’s apparent that at least some have developed respiratory disease, including fatal infections, with pregnant mink seemingly predisposed to illness.

A few quick updates and comments.

Are pugs a high risk breed for SARS-CoV-2?

This question has come up a few times since the report of an infected pug in North Carolina. It has been suggested by some people in news articles that pugs are higher risk for getting infected. Like other brachycephalic (squishy faced) breeds, some pugs are at increased risk of respiratory disease in general. They are also at increased risk of complications if they get a respiratory infection of any kind. But they should otherwise not be at increased risk of getting infected with this particular virus compared to any other similarly exposed dog.

So, pug owners should relax (some have apparently already asked about getting rid of their dogs). If you own a pug, it is probably at increased risk of complications if it gets infected with SARS-CoV-2 (or any other respiratory virus), but it should not be at increased risk of getting infected in the first place, and the odds of any dog getting infected are very low.

Update on two positive cats in New York

Antibodies to SARS-CoV2 were detected in the blood of both cats from New York that tested positive by PCR in late April . This is not unexpected, but it is one more indication that they were truly infected.

Infected cat in France

In a study of cats owned by people with COVID-19 in France, one cat was identified as positive by PCR.  There’s no mention of how many cats were tested (yet). The positive cat had mild respiratory and gastrointestinal disease, and only its rectal swab (not the throat swab) was positive.

This result isn’t surprising either, as it’s likely that a reasonably large number of human-cat infections have occurred. As has been typical so far, the cat had mild disease. I’ve had some anecdotal reports that suggest some cats can get more serious disease but we need to properly investigate those. This report is just one more piece of evidence indicating that human-animal transmission of this virus is occurring. Human and animal health implications of this are probably limited but it’s an area we need to keep studying.

How to practice veterinary medicine in a COVID-19 world is causing a lot of angst. Questions about dental procedures often top the list. Rightly so, since those are perhaps the highest risk type of procedure for SARS-CoV-2 exposure from animals. Dentistry involves close contact with the face and respiratory secretions, and the potential generation of aerosols.

Routine procedures of all kinds have largely been postponed in most areas because of the need to restrict in-clinic care to urgent cases due to potential COVID-19 risks. As we learn more about the likelihood of human-to-pet transmission (our surveillance study is moving along nicely now) and the dynamics of transmission in people, it will get easier to make informed decisions about how to control the risks. Ultimately, patient-side testing might be a useful approach, but it’s hard to say whether that’s going to be needed or even an option, and that doesn’t help us right now.

In times of uncertainly, I’d always rather be over-prepared, within reason. That means erring on the side of protection, rather than being a case report. We have very little data to work with, so we have to base our recommendations on common sense and reasonable guesses. As with pretty much all of our other advice, things may change.  But, since I get asked about this so often, here are my thoughts and considerations around SARS-CoV-2 and veterinary dental procedures. (Remember I’m an internist, not a dentist! Dental colleagues should feel free to chime in and correct my blatant non-dentist errors and provide their thoughts.)

Is the patient at high risk for SARS-CoV-2 exposure?

Querying the pet’s likely exposure risk is a good first step. The potential presence of asymptomatic (human) infections in household contacts means that a lack of known exposure it not 100% protective, but if the pet does come from a household where COVID-19 is present, we know there’s some degree of increased risk. My concerns are also greater with cats vs dogs, since cats are likely at greater risk of infection, and infected cats maybe would have more virus present in respiratory secretions compared to infected dogs.

How long should a patient be considered high risk?

This is yet another area where we have very limited information. However, based on what we do know, it’s reasonable to estimate that the risk of a pet shedding the virus would be very low by 14 days after its last potential exposure. That means 14 days after the last infected person in the household is deemed non-infectious (often 10-14 days after the start of their illness) .

Does the patient have signs suggestive of SARS-CoV-2 infection?

Any acute unexplained onset of respiratory or GI disease in an exposed animal needs to be considered high risk. Lots of things can cause these problems but if there’s plausible exposure, we need to be wary of SARS-CoV-2. That would mean the risk to veterinary personnel would be even higher, and the threshold of urgency for doing any procedure would have to be quite high.

Can the patient be managed by telemedicine and medication?

No, we can’t extract a tooth over the phone. However, some patients might be manageable in the short term (a couple weeks) with analgesics and/or antibiotics (that’s the recommended approach in human dentistry in some regions). We don’t want to throw those drugs around unnecessarily (the demise of antimicrobial stewardship is a concern in human medicine with the focus on COVID-19), but there may be some cases in which we can delay the definitive treatment long enough that the patient is no longer a high risk to staff.

The patient is high risk and the procedure has to be done. How can we reduce the risk?

The first question is probably “should I handle the case?” If a clinic or clinician are not adequately equipped with PPE and are not comfortable handling the case, referral to a colleague or specialist who is is reasonable.

If the case will proceed, here are some considerations for reducing the risk of SARS-CoV-2 exposure:

  • Minimize aerosol generating procedures. This might involve use of older techniques and manual instruments over instruments (e.g. burrs) that will aerosolize respiratory secretions. Think about every step, whether it’s needed and how it can be done the most efficiently.
  • Consider staging the procedure. If the urgent aspect of the patient’s problem can be managed quicker and/or with less use of aerosol-generating techniques, consider taking care of that part to control pain and limit disease, with a plan to finish the job later. Yes, that requires another anesthesia and more cost, but if the best way to fix things involves lots of aerosol generation and that can be delayed, it may reduce the risks.
  • Wear proper PPE. For an animal from a high-risk household, that means a gown, gloves, N95 respirator and eye protection. A surgical mask plus a face shield is probably an acceptable alternative to the respirator and eye protection, unless the animal has signs consistent with SARS-CoV-2 infection. However, the lower the level of PPE available, the more I’d want to limit the procedure and reduce aerosolization.
  • Consider where the procedure will be performed. It’s ideally done in a closed area where aerosols are confined, and where potentially contaminated surfaces are easy to identify and disinfect. Movement into and out of the room should be minimized to limit airflow disruption. The area should be as free of other items as possible, so that there are fewer potentially contaminated surfaces to address when the procedure is done.
  • Limit people in the area to essential personnel only. Make sure no other patients are in the aerosolization zone.

Hopefully we’ll learn more about the risks and the best ways to control them, and hopefully the risks are actually exceptionally low. We need to balance practicality, patient care and occupational health, and we’re trying to do that largely blindfolded at this time. A little common sense and basic infection control knowledge can go a long way, though.

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.

More information is available from the OIE (World Organization for Animal Health) about the second dog in Hong Kong that was identified as positive for SARS-CoV-2, the virus that causes COVID-19, back on March 19th.

The dog in question, a two-year-old German Shepherd, and another dog from the same household were quarantined on March 18 when the infected owner had to be hospitalized.  Both dogs were tested repeatedly by the Hong Kong authorities.  The other dog was negative on all tests, but the one dog had positive test results on March 18, 19 and 20. It also later developed antibodies against the virus in its blood (as did the first dog from Hong Kong that tested positive).   In this case, live virus was isolated from the dog, which provides solid confirmation that it was infected (though it’s not clear from which samples the virus was isolated).

The dog remained healthy and had negative test results after those first three positive tests. That’s consistent with the current thought that dogs have relatively low susceptibility to the virus and don’t shed it for long if they happen to become infected; however, we don’t know when the dog started shedding. We know it shed for at least 3 days once it arrived in quarantine, but we don’t know if it may have started shedding earlier than this.

Here is an updated version of the decision tree for screening of owners / patients coming to veterinary clinics, which I originally posted a few weeks ago, to help with identifying higher risk situations. We also have a Russian translation courtesy of Dr. Varvara Solovyeva.

You can use the links below to download the pdfs: