Covid-19 Insights: Pet/Animal Transmission, Male Mortality, and More About Antibody Testing

A conversation with Heather Zwickey, PhD

By Natural Medicine Journal

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This episode was recorded on May 4, 2020.

On this episode immunologist and integrative health expert Heather Zwickey, PhD, tackles tough questions about antibody testing concerns, why more men die than women, and what the risk is regarding animal transmission. Zwickey is executive program chair and a professor at National University of Natural Medicine in Portland, OR.

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Approximate listening time: 16 minutes

About the Expert

Heather Zwickey, PhD, earned a PhD in Immunology and Microbiology from the University of Colorado Health Sciences Center with a focus on infectious disease. Zwickey went on to complete a postdoctoral fellowship and teach medical school at Yale University. At the National University of Natural Medicine in Portland, OR, Zwickey launched the Helfgott Research Institute and established the School of Graduate Studies, developing programs in research, nutrition, and global health, among others. She currently leads an NIH funded clinical research training program. She teaches at many universities and speaks at conferences worldwide. At Helfgott Research Institute, Zwickey applies her immunology expertise to natural medicine, with specific interest in the gut-brain axis in neuroinflammation. 

Transcript

Karolyn Gazella: We have some new insights about various aspects of Covid-19 that we’ll be sharing on this episode. Hello, I’m Karolyn Gazella, your host and the publisher of the Natural Medicine Journal, a peer-reviewed online publication for integrative healthcare professionals. My expert guests to help us tackle the tough questions as a member of the Natural Medicine Journal editorial board. Dr Heather Zwickey is an immunologist and respected integrative health expert. She is also executive program chair and a professor at National University of Natural Medicine in Portland, Oregon.

Dr Zwickey, I just want to let you know how much I appreciate your willingness to always take the time and join me to answer difficult questions about this constantly evolving topic. Thank you so much.

Heather Zwickey, PhD: Well thank you and thank you for making this information available to all the natural medicine practitioners out there.

Gazella: Yes, and today we have a lot to cover. I have questions about antibody testing concerns, why more men die of Covid-19 than women and what the risks are regarding animal transmission.

I want to begin with antibody testing. What are you seeing specifically in the integrative health community among practitioners who are testing patients?

Zwickey: We’re seeing a lot of things, but the first thing we’re seeing is that some of the tests are showing a very high positive rate, which likely isn’t real. What I mean is, 70% of people do not have coronavirus at this time and yet some tests are showing a 70% positive rate. We’re seeing other practitioners that are using tests that are showing that everyone is negative. As a result, we’re hearing physicians in hospitals suggesting that some people don’t make antibody and that’s likely not the case.

In places where the FDA approved tests are being used, we’re seeing that everyone makes antibody if they get the infection, regardless of the severity. And we’re seeing that people who have been exposed and are asymptomatic carriers also make antibody. So when we’re seeing a lot of negative tests, it’s highly likely that some of these tests are not working.

Gazella: Which is very troublesome, this could be an incredible tool, but if the test doesn’t work then where are we at?

Zwickey: Exactly. My first concern is that when we use these non-FDA-approved tests, the results don’t tell us anything because we’re seeing too many cases of false positives and false negatives. And if patients believe they have antibody, they may take greater risks than they would otherwise. And if patients have a false negative, that could be problematic with asymptomatic carriers because they could be shedding and not know that they’ve had an infection.

Gazella: So is the key then to look for an FDA approved test and only utilize an FDA approved antibody test?

Zwickey: Yeah, that the key, and if you’re looking for FDA approved antibody tests, the website that I have found that I think is most up to date is Johns Hopkins. You can search and Google, Johns Hopkins antibody, Covid-19 tests, and you’ll come up with their site that has a list of what the various tests are, what they measure and don’t measure, and then they have which tests are FDA approved for diagnostics, which are FDA approved for research only and which ones have applied for FDA approval but are not yet approved. And I will tell you, just this morning the FDA has rolled back some of the emergency approvals they had given because there’s so much problem, especially with false negatives, that there are many, many tests out there. There’s over 120 labs offering tests and many are giving false negatives.

Gazella: So what do we know about whether these antibodies are protective?

Zwickey: Well, this is another great question. From past Coronavirus infections, we have some clues about what may happen here, but we don’t know for sure anything. From past infections, we know that people who are infected with Coronaviruses tend to seroconvert, they do make antibodies. And that’s true for the common cold and for MERS and for SARS. For the common cold, the antibodies don’t mean that you can’t get a second cold in the same season, so they’re not protective.

Now, could it be a viral variant causing a second cold? It could, but it could also just mean that the antibodies aren’t protective. We know that for MERS, people developed antibodies, but nine months later those antibodies were gone. However, let’s remember that it’s a T cell response that’s protective for viruses, and that proved true for MERS as well, that T cells were present nine months later and they were protective, but the antibodies were gone. It’s just that antibodies are what we use to measure the immune response because in order to get T cells, we’d have to do lymph node biopsies and nobody wants to do that.

Gazella: Right. The jury is still out then, whether or not the antibodies are protective when it comes to Covid-19. Is that correct?

Zwickey: The jury is still out. They may be protective and they may not be protective. We just don’t know.

Gazella: And do we know anything about length of protection? I guess if we don’t know if they’re protective, we certainly don’t know the length of protection that that you have.

Zwickey: We don’t. Our best evidence is from MERS where it looked like antibodies were around for 6 months, but by 9 months they were gone. That’s our best evidence at this point.

Gazella: It would be great to just nail some of these missing links down because this antibody testing could be such a significant factor in all of this, isn’t that correct?

Zwickey: It’d be crazy if we finally have good tests in 9 months and by then, everybody’s antibodies are gone.

Gazella: Yeah. So let’s move on to male mortality. Reports are showing that significantly more men die of Covid-19 than women. Do we have any idea as to why that may be?

Zwickey: We have theories, of course, we don’t know for sure why this is true just like we don’t have answers to most of the things. However, there’s a few different reasons why men and women could respond differently. First, we always think about hormones, and remember that hormones have an impact on the immune response. Hormones act as rheostat, like they can turn the response up or down. The type of response that we want to a virus is a TH1 response, and we know estrogen can drive that response. Testosterone actually slows down a TH1 response. This is one of the things that makes women more susceptible to autoimmunity than men. Their estrogen can drive that TH1 response.

Another thing that differs between men and women is their expression of TLRs. And remember that TLRs are the receptors that recognize different patterns expressed by pathogens, so some TLRs recognize bacteria and some TLRs recognize virus and some TLRs recognize fungus. Well, women express more TLR 3, 7 and 9, which are the receptors that recognize viruses. Men express more TLR 2 and 4, which is better for bacterial infections. Since this is a viral infection, women express more of the receptors, so they’re going to be better equipped to handle this particular infection.

Men and women also differ in their expression of melatonin, which is anti-inflammatory. And you’ll recall, I think 4 episodes ago, we talked about melatonin. Because melatonin is known to regulate that NLRP 3 inflammasome, and since women are making more melatonin, they can regulate the inflammasome better than men can. And if misregulation of the inflammasome is what’s causing death, women are going to be at an advantage here.

And then finally the diet differs between men and women. And that impacts the microbiome in that women tend to eat less, not all women, but some, tend to eat less. And we know that if you’re eating less, if you’re doing caloric restriction, again we get an anti-inflammatory response.

Gazella: Well, I’ll tell you those theories all make a lot of sense, so I’m glad that you were able to take us through that. Now, let’s talk about animals. For all of us animal lovers, let’s talk specifically about pets first. What do we know about dogs and cats? Can these pets get the virus from humans or can they spread it to humans and can it be spread from pet to pet? How much do we know about pets?

Zwickey: All right, so initially we didn’t think that pets could get SARS CoV-2. Let’s talk about the fact that now we’re changing that thought. Remember that the way that the virus gets into cells is through the ACE-2 receptors. So there was a paper out of China a couple of weeks ago now that suggests that dogs, cats, pangolins, and the Chinese hamster can get SARS-COV-2 based on the sequence of their ACE-2 receptors. There’s another paper that also says that ferrets can get SARS-COV-2. So for those of you who have ferrets as pets, they are capable of getting SARS COVIS-2.

Now, they’re able to get it at different levels based on how similar the ACE-2 receptor is to human ACE-2 receptor. So cats as an example, have about 85% homology in their ACE-2 receptor, and dogs have about 80% homology, which means that cats get infected better than dogs do, but both can actually be infected.

Now, based on SARS, we didn’t predict that 80 or 85% was actually enough homology to warrant an infection. However, now we’ve discovered that it is and it appears that pets can get those infections from humans, whether it can then be spread back to humans has not been reported, but I’m going to go out on a limb and assume that it can, simply because if we’re having that close relationship with our pet, the spit can go both ways.

And then I was chatting with a virologist friend on Friday and he pointed out that this is an RNA virus, which is highly mutable. And his concern was that when the virus jumps hosts, when it goes from humans to cats, it’s going to encourage mutation. And so whether or not we’re getting pet-to-pet spread now, the likelihood is that once it’s jumped hosts once, that it will jump hosts again. And so we likely will get pet-to-pet mutation and we may get other animal mutation that happens then.

Gazella: Yeah. And I want to talk about other animals in a minute. So what should practitioners tell their patients with pets when it comes to keeping the patient and their pet safe?

Zwickey: Well, so first, remember that we think respiratory droplets are the most significant way this virus is spread. So since your pet is probably below you on the ground, they can breathe your respiratory droplets as they fall, and if they lick you and lick the furniture et cetera, then all of those droplets are potential sources of viral shedding.

And then if the pet gets a GI infection, which is just as possible as it is in a human, it could be spread through stool. So be vigilant with the hygiene. That’s what’s most important. And hygiene for both you and your pet.

Gazella: And then if somebody tests positive, they should also isolate from the pet, correct?

Zwickey: That’s right. Yep.

Gazella: Okay, cool. Let’s talk about animals in the food supply, even mice and rats. So how much do we know about transmission among pigs, chickens, and rodents?

Zwickey: So the same paper that predicted cats and dogs and hamsters, said there was not likely transmission into mice and rats. However, there’s a single amino acid that currently prevents binding of the SARS-COV-2, to the mouse and rat ACE-2 receptor. So if a mutation happens, this could change.

Pigs, however, can get infected. Pigs’ ACE-2 receptor is actually more similar to humans than cat ACE-2 receptors. And so we know that pigs can get infected as can ferrets, orangutans, and monkeys, in addition to our cats and dogs. Probably not chickens. However, we should worry about infections in pigs. And now that we’re seeing some of the pork processing plants shutting down, that might actually lead to a little concern.

Gazella: I was thinking about that. I know that it’s not transmitted through food-

Zwickey: No, it’s not.

Gazella: But if the animal that has it, that is then slaughtered and goes into the food supply, is that-

Zwickey: No, we worry more about the workers.

Gazella: Okay, I see. And as you said, we’re seeing such a high prevalence in these facilities, that would definitely be cause for concern.

Now, Dr Zwickey, some states have loosened their social distancing rules and are opening up certain businesses. Now, as an immunologist, what is your advice to practitioners as to how they may want to advise their patients in those states? For example, do you still encourage strict social distancing when possible?

Zwickey: Yes, so I think practitioners have a challenge on their hands. Of course, physical distancing, hand-washing, and all of our other protective measures are super important, but you might even consider doing things like temperature checks for your patients or ask them to check their own temperature before they come in. Because remember, if you see a patient who likely has Covid-19, whether they are symptomatic or asymptomatic and you’re exposed, then you may need to self-isolate for a few hours, a few hours being 72 hours. Make sure that you don’t pick it up. And then you’re also going to want to disinfect your office to ensure you don’t spread to others. So having some sort of temperature check before a patient comes in, so that you have some way to limit the amount of shedding that can happen in your office, is going to be what’s important.

Gazella: Yeah, great advice, and I know that we’re probably going to be talking again soon, but is there anything else that you’d like to add or anything that we missed that you wanted to add today?

Zwickey: No, I think the only thing that I would emphasize is that currently, the majority of the antibody tests that are out there don’t work. And so don’t waste your money, don’t waste your patient’s money, and don’t waste your time. Wait until you can get an accurate antibody test and use those.

Gazella: Great advice. So once again, Dr Zwickey, thanks for helping us get some clarity on these important issues during this very difficult time.

I want to remind our listeners, if this is the first time you’re listening to the Natural Medicine Journal podcast, you can find past episodes at naturalmedicinejournal.com.

Thanks for listening and thanks for all you do to help keep your patients safe and healthy. Take good care everyone.

About the Author

Natural Medicine Journal is an electronic peer-reviewed journal and open access website dedicated to the field of integrative medicine.