COVID-19: Is Our Past Our Future? with Michael G. Schmidt, PhD

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[00:00:04] Loretta Lynch-Reichert: Happy New Year, everyone from the Medical University of South Carolina Science Never Sleeps podcast team. I am your host, Loretta Lynch-Reichert. In February of 2020, my guest at our in-person Science Cafe series included Dr. Robert Ball, infectious disease clinician, and Dr. Michael Schmidt, professor and scientist in the department of microbiology and immunology here at MUSC. That was almost one year ago. It is 2021 and we are still in the midst of managing the COVID-19 pandemic and so we thought it would be helpful to get a perspective on where we have been, where we are now, and where we hope to be. Today, Dr. Schmidt returns via our Science Never Sleeps podcast to address those questions and offer insight into the virus variants we are now hearing about. Welcome, Dr. Schmidt.

[00:00:56] Michael Schmidt, PhD: Well thank you, Loretta, and Happy New Year to you as well and to all the listeners.

[00:01:01] Lynch-Reichert: Thank you so much.

[00:01:02] Schmidt: It’s going to be hard to top 2020. While mother nature dealt the human race a bad hand, both the scientific and medical community responded in a way that we should all get a great sense of relief from. Namely in the span of...

[00:01:21] Lynch-Reichert: Yeah, I totally agree.

[00:01:21] Schmidt: In the span of less than 11 months, we learned quickly how to identify a new virus, first from our friends in the clinic – the medical community did great work telling us what to look for, helping the public identify their loved ones who may be ill so they can get the help that they needed. And we all now know the symptoms associated with COVID-19. They sound very familiar, and they almost read like the flu but what we now know is that this is not like any flu that the human race has ever seen.

[00:02:07] Lynch-Reichert: Indeed. Let’s go back to February 2020 when both you and Dr. Ball spoke for our Science Cafe audience about what was not yet called a pandemic, but a virus that appeared to be spreading to America from overseas. From the scientific perspective, what were you and colleagues looking at to determine what this virus was?

[00:02:27] Schmidt: Well, by that point, in February, we knew what it was. Our Chinese colleagues had done a tremendous amount of work in the space of one month. They had already sequenced the virus and published that sequence, and we now know in hindsight that that sequence published in January of 2020, the scientific community got very busy very fast. They began to design PCR primer sets to help our diagnostic colleagues develop a test. Many of us have actually taken that test where the swab goes up our nose and many of us feel like we’re getting a brain biopsy and... but more importantly, the scientific community began to look at that sequence of RNA – the virus makes a thirty thousand molecular weight piece of messenger RNA that has the instructions set to make us sick. The science teams across the globe got busy and began to look for candidates that they could put into a vaccine and we now know in hindsight that one of the sequences they identified – the famous spike protein – that protein went into some of the very early vaccine constructs, namely the messenger RNA constructs, that are now two of the emergency use vaccines that we have available in the United States. So as early as January, the science teams were looking at the data coming out of China, where the virus emerged, and they began to design a new vaccine that the human race had never before used in people, and they got it to work. And that’s effectively what has placed all of us at the beginning of the tunnel that is going to end our pandemic.

[00:04:54] Lynch-Reichert: And that is... I think folks really need to understand something here because what that means is you were all probably already monitoring the chatter from a scientific point of view and I think it sounds like a great collaboration across the globe where folks were saying ‘okay, this is something we really need to pay attention to and really need to put our energies into’ and the fact that you weren’t quite sure what you were dealing with says a lot about the research team not backing down, they wanted to figure this out and they knew it could disrupt human life. And I really applaud you all for that.

It is very interesting to me that it was kind of understood or known something in January that we in America weren’t even talking about it much until after our February 11th Science Cafe, the news media started pushing it out. So I think what it also suggests to me is that you’re all very cautious – you want to make sure you know what you’re dealing with before you share that information to a larger audience, is that fair to say?

[00:06:03] Schmidt: Oh absolutely, Loretta. We’re sort of the first subscribers to the Hippocratic oath of doing no harm and what we don’t want to happen is we don’t want to panic the general public, and so consequently we’re often very cautious and reserved in our statements, but at the same time, we were listening to our healthcare collaborators, those heroes that are working in the clinic that were treating those early patients and early one we unfortunately saw a large number of the first COVID-19 patients dying, dying very quickly and we had to invent a new form of medicine.

And so here again is where this collaborative nature of basic science and translational science and clinical science got together. You know, we all... it was the ultimate mashup that started very early in March. Last year I had the privilege of being the chair of the advisory board of microbial sciences for the American Society for Microbiology and one of my acts as chair of that advisory board to the ASM was to convene a global summit on how the science community could help our clinical colleagues. And so I assembled a team of international experts and had them all get together and say ‘okay, how can I in my little lab contribute to the effort in fighting this emerging disease that we now know has had global consequence?’ and that summit, we had experts from across the globe and one of the experts that we were fortunate enough to get to speak was Forrey and Kramer. Some of our listeners may be familiar with Dr. Kramer, he was one of the very early developers of the antigen that has gone into many of the rapid antigen tests, and he was also involved in developing antibody tests.

So he was really at the forefront and again, he really shared everything that he and his team were developing at Mt. Sinai – made it freely available to anyone and everyone who asked – and here at MUSC our teams asked for it, received it, and quickly put it to work insofar as MUSC developed its own antibody test to effectively bridge the gap between the time the commercial diagnostic companies could get things up and running. So again, we weren’t just sitting around on our hands, we kicked the tires and lit the fires and got to work very quickly addressing this problem because our clinicians were telling us this is not like any virus they have ever seen before, and we had better pay attention.

[00:09:40] Lynch-Reichert: I love that you guys didn’t... I love the fact that you all – you probably as a microbiologist live for this, this kind of trying to understand what is going on and how you could fix it and especially when your clinicians, who are just down the hall here at MUSC are telling you ‘listen this is not something we know how to fix right now’ and again, I think that speaks well to what the nature of researchers, what they do and what type of people they are. For them this is a challenge they were not going to back down from.

[00:10:18] Schmidt: Kudos should be thrown out to everyone on that team, but especially Shatish Nadig. He did a fantastic job shepherding standing up the antibody test here at MUSC and he has since handed it off to the clinical diagnostic team here at MUSC, but it was a team effort and again that’s one of the things that... you know, no one was worried about who was in charge of what we just said okay folks we need to solve this problem and protect ourselves against mother nature’s wrath that came in the form of this new, little seemingly coronavirus, which many of us who are microbiologists and virologists appreciate is one of the viruses that causes the common cold. And if you asked us five years ago ‘are you afraid of coronaviruses?’ aside from SARS the original which was a flash in the pan and only caused about 8,000 illnesses, this particular virus by the end of 2020 had infected over 90 million people on the face of the earth, killing almost 2 million of them...

[00:11:43] Lynch-Reichert: That’s incredible.

[00:11:44] Schmidt: ...and here in the United States, we have infected over 22 million of our citizens and unfortunately lost over 375,000. Folks who were alive last year at this time.

[00:12:00] Lynch-Reichert: Right. It’s a horrible situation. Let me ask you this – as the research community and clinical community were collaborating, working together, I know many folks were bewildered that information kept being revised on how to manage the virus and began to question what they were hearing. Would you explain why it took some time to understand the virus and to be able to communicate with concrete guidelines about what you factually knew?

[00:12:31] Schmidt: Oh that’s easy. We didn’t know anything. This was a brand-new virus. I mean I challenge you. You can do this experiment at home – open a brand-new computer, get into a brand-new car and try to figure out all the features without reading the manual. We not only didn’t have the manual for this coronavirus, we didn’t even know that there was a manual. I mean, we literally had to take this virus apart and there have been so many papers published in this last year on coronavirus. It’s a challenge just to keep up with reading just the titles and the abstracts of the manuscripts coming out. Now one of the great things about science is we know what we don’t know and that we’re very happy to change our thinking when the data are arguing that we need to adjust what we are thinking about. And this was certainly the case with the SARS-CoV-2 virus.

We didn’t know very much about the virus. We were basing it on past experiences, and we were learning from the unfortunate individuals who effectively succumbed to the virus. And every clinical observation was being integrated into our thinking, which is why we have such an elaborate checklist many of us go through each morning before we put our pants on to go to work because, you know, one of the things is you don’t go to work if you’re sick. And so the checklist that was developed that each and every one of us in the healthcare field do each day is first we take our temperature, we ask the question ‘is it above 100.4 Fahrenheit or 38 degrees Centigrade’ and are we having fever chills cough shortness of breath... you guys know the list, we all know the list. One of the big things was how many people lost their sense of taste or smell.

I heard a funny story from Tom Hanks on one of the year end news reports, he said that he never lost his taste – Tom Hanks of course the actor succumbed to SARS-CoV-2 in Australia very early on and he was sort of the poster child of a celebrity who caught the disease. His poor wife caught the disease and they were sheltering in place in Australia and he said their cook was making them all this delicious food and he was just eating it up and his wife said to him ‘we have to fire the cook, everything she cooks tastes like sand’ and of course, she had lost her taste and smell. So everything did indeed taste like sand.

And we now know why you lose your sense of taste, why you lose your sense of smell and it’s simply because of what collateral damage the virus is doing in our upper respiratory cavity where our smell receptors are and how it’s damaging it. I know that I’m not a neuroscientist, so I’m not going to explain that. I’ll leave you to another science never sleeps with a neuroscientist, asking them why do we lose our sense of taste and smell with respect to COVID, but you know, we were learning as quickly as we could. We were developing the diagnostic test and one of the things that we learned is that people are infectious or contagious before they display symptoms and candidly this is how the virus got a foothold in America.

People were out, about doing their daily work and remember in the early days of the epidemic we weren’t wearing masks and in fact, we were trying to save or conserve masks for the healthcare workers and that was probably our first mistake. We should’ve went to masks straight away. Our friends in Taiwan went to masks immediately and the number of viral cases in Taiwan is not only less than the United States, it’s less than the total number of cases for South Carolina. So the Taiwanese always... they had a mask culture already. Taiwan as you know was a very densely populated country and they had a culture where mask wearing wasn’t any big deal. So very quickly during the early days of the outbreak in China, Taiwan being just literally across a body of water from the mainland, immediately went to mask wearing and they of course didn’t see the rapid spread that we unfortunately have witnessed here in the United States and that’s one of my big take home messages is, you know, mask wearing works.

And I'll put it into perspective that we can all think about. Now remember, you’re contagious before you know you’re infected. So here’s some of the kinetic details – now, the first thing that you have to know is that it takes between 250 and 1,000 infectious particles to effectively make you sick. So rule of thumb, just use 1,000 because it’s easier to do math that way. So 1,000 particles. When you’re sitting, just breathing normally, you will shed 20 viral particles per minute. So if I’m sitting in the same room with you and Jonathan, and we’re just sitting there not saying anything to each other, in order for you to get an infectious dose from me, if I was infected, you would have to be in the room with me for 50 minutes. However, if I open my mouth and begin to talk, that number goes up to 200 viral particles per minute. Now if we’re just having a conversation for 5 minutes, that’s your infectious dose. You and Jonathan are now infected. However, if I cough or sneeze or use my outside voice or even sing, I can dump a million to 200 million viral particles into the air and as you go to sneezing and coughing and singing, that energy from our lungs and vocal cords makes the liquid that is transporting the virus much smaller and that’s of course one of the early lessons we learned from that church choir in the Washington state area where many of the congregation got infected just from choir practice.

[00:20:25] Lynch-Reichert: Our December Science Never Sleeps podcast was with Dr. Lucinda Halstead, she’s in the department of otolaryngology and indeed, she discussed her colleagues across the globe have done a lot of experimentation and study on how the virus is transmitted using choral and use of wind instruments and how far it transmits. And then they came up with just like the researchers here in America, they came up with some very innovative ways to mitigate the transmission while still allowing for performance, as you’re explaining to us it’s the aspiration if you will during singing and playing a wind instrument that really made it a deadly disease for those performers and they have come up with some mitigating devices and ways to manage that. What type of masks should we be wearing to really get the full effect of the safety precautions that a mask can offer?

[00:21:29] Schmidt: Well, the first thing that you need to appreciate is that viruses are small so it’s really very challenging to wear a mask that will not make it a struggle to breathe that can exclude viral particles of 100 nanometers. I mean that is extremely small. So that’s problem number one but our clinical teams are using masks that are referred to as N95 and they will exclude 95% of the particles above two tenths of a micrometer or 2,000 nanometers in size. Now this is extremely small. I mean, we’re talking much smaller than the width of a human hair. So that’s problem number one, which is why there was this run on disinfectant products very early on because what goes up, must come down. Gravity is a very jealous, jealous force of nature and it doesn’t let anyone escape its grasp, at least on planet earth, and so even the small viruses will eventually settle out.

So that’s why it’s important to wipe down surfaces, though we now know that surfaces are not as significant of a contributor as we once feared, but they can and do contribute so it’s still a good idea to keep your surfaces clean but we know now that it’s likely the asymptomatic individual or presymptomatic if you will, that is walking around shedding those viral particles outside of their leaking mask or they’re not wearing their mask properly and they fail to wash their hands before they interact with any portal of entry to the human body.

Those portals of entry are your eyes, because the virus can enter via our tear ducts, our nose, so when you rub your nose because it’s itchy that can do it, or if you just eat something that’s contaminated, the virus can get liberated and infect your salivary system and that can effectively transport itself to your lungs and so, you know, all of these routes of entry we have to block so the virus can’t get in. And that’s hard to do and that’s why we have in this country, you know, 22 million and change infected so far, why South Carolina had 5,000 people convert to SARS-CoV-2 positive status on Friday. And the rule I always use is that the people getting tested are probably one fifth of the numbers of individuals who are becoming infected on any given day. So that 5,000 is probably 25,000 people in South Carolina were infected on Friday.

[00:25:09] Lynch-Reichert: Wow. Can I ask you why you call it, what’s the difference...

[00:25:16] Schmidt: SARS-CoV-2 is the virus...

[00:25:18] Lynch-Reichert: Yeah, COVID. Okay.

[00:25:18] Schmidt: And COVID is the disease.

[00:25:22] Lynch-Reichert: Ah! Thank you for that, thank you so much. I wondered about that.

[00:25:26] Schmidt: You know, the science community is, are very sticklers for names so I try to use the name. Well, so everyone has a common vocabulary, so we all know what we’re talking about.

[00:25:41] Lynch-Reichert: Right. So can I ask you then with children, and I know you’re not a clinician, but why does it appear the virus is less robust in children? Is that a fair statement to make and is that because the children’s immune system is either stronger or is more flexible?

[00:26:04] Schmidt: Candidly, the scientific community is still investigating that question. That’s one of the great mysteries. We do know that young people can develop a special condition that COVID is just as lethal in them as it is in adults. We just don’t understand why COVID is a much more mild infection, I think that was the word you were looking for, mild... a milder infection in kids versus adults. It’s true that the immune system of young people is much more robust, I mean that’s effectively what the immune system is designed to do. It’s supposed to look at new things, ask the question ‘does this belong to you or should I throw it away?’

And our immune system has been adapted to make certain that we make it into our reproductive years, because if you don’t make it to your reproductive years, your genes won’t be deposited into the next generation. So evolution works against those diseases that kill you before you've had your first set of kids. So our immune system has been sort of having this tug of war with infectious diseases. You know, evolution is the great leveler. It’s both the leveler for the virus and a leveler for the human race and you know, we’ve all heard the expression adapt or die, and you know, the human race has really adapted and we’re making certain that we’re not going to allow folks to die on our watch.

[00:27:58] Lynch-Reichert: Right. That brings up a point I heard - Sanjay Gupta, the neurosurgeon who actually does a lot of medical discussions on TV, asking about... when folks are asking about what should we know about the variants with the virus, and one of the things he noted, which I think goes along with what you’re saying, is that virus wants the human being to live so it can remain as its host... so the virus can remain in the body, so what can you tell me about... what can you tell our audience about the variants that are occurring now and what do they mean?

[00:28:46] Schmidt: Well first and foremost, remember that science is based on observation first and foremost. So what I can tell you with great confidence is that there is no evidence at this point in time that the variant causes a more severe illness or a greater risk of death. Our medicines are still working, our strategies for limiting spread are still working, and perhaps more importantly, there was a paper published pre-print on one of the pre-print servers, that at least for the Pfizer vaccine, this new variant, the vaccines and - it was really a very simple and elegant experiment.

They went to people who were vaccinated with the Pfizer vaccine, they allowed the vaccine to become effective in those individuals, they drew their blood, isolated their serum, so now we have this serum from vaccinated individuals and then they created the variant in the laboratory, so they now have the variant and then they added the serum to the variant and they asked the question, ‘would the serum still neutralize the variant rendering it noninfectious?’ And the answer was yes! The vaccine still works, and that paper was posted last week so we now know that the variant, at least for the two emergency use authorization vaccines here in the US, the Moderna vaccine will likely work, and we now have data that the Pfizer vaccine does indeed still work against the variant.

Now the variant is in the spike protein and the spike protein is the antigen that the vaccines employ to educate our immune system and the variation in between what was originally circulating in our community and what is now in there is a simple amino acid change. It went from an asparagine to a tyrosine. So those of you who are students of biochemistry know that an asparagine is a very different looking amino acid than a tyrosine. But it really didn’t do much to the spike protein in terms of its activity against the spike protein antigen in total. Because the other thing that we know about from immunology is that the protein is viewed by the immune system and it’s sliced and diced up into 10 to 12 [unintelligible]. So that’s what our body makes antibodies against, so we know that the N to Y change in this new variant is at amino acid 501. So that’s a big protein. 10 goes into 500 a bunch of times and that’s not at the end [unintelligible].

So our immune system has many opportunities to look at this protein and one of the clever things about the vaccines that are being developed using the spike protein – they're messenger RNA vaccines that Pfizer and Moderna have offered us and so what happens is they’re injected, everybody knows you get a shot, it goes into your muscle cell and what happens is your muscle cell looks at the piece of message – and remember messenger RNA is merely a set of instructions, it just tells our cells ‘make this protein.’ So our cells being good, make the protein, they put it in the membrane, and the protein is just hanging out. But our immune system looks at it and says, ‘this don’t belong here’ so it immediately begins to say ‘we’ve got to get rid of it’ but it’s anchored in the membrane. So they come in and do a search and destroy and they destroy that muscle cell which is effectively why the vaccines sometimes hurt is because they’re doing a search and destroy on you but they’re educating our immune system.

So our immune system is effectively developing the next component, namely - in addition to making an antibody it’s also educating the adaptive arm of our immune system, namely our T cells, and it’s the T cell, that germinal center - and those of you that are vaccinated have probably been asked by your clinician ‘did you feel your lymph nodes being enlarged?’ and if you were vaccinated in your arm, the lymph node is under your armpit, and you can actually feel when you’re getting a vaccine if the germinal centers are being activated and that’s the draining lymph nodes. You'll effectively feel a little tiny lump telling you it’s working; the lump will go away but that’s how you know this sucker is working and that you’re developing immunity.

When you get boosted, and that’s the other take home message – get your first shot but then your immune system needs that boost and that boost that you get for Pfizer in three weeks and Moderna in four – it's very important to remember to get boosted. Your doctor, your healthcare team will remind you when to go back to get your second shot, and get your second shot, and that will continue to make certain that when you’re shown the virus out in the wild, your immune system will immediately say ‘hey this don’t belong to me, time to dispatch it, throw it away, kill it dead’ and then that’s what will happen and you won’t get SARS-CoV-2.

[00:35:39] Lynch-Reichert: There’s so much to ask you on this and unfortunately, we don’t have a whole lot of time so I’m going to veer off and ask you

[00:35:45] Schmidt: Sure!

[00:35:46] Lynch-Reichert: As a microbiologist. For some, the idea of this virus was a complete and horrible surprise, but you deal with the potential of viruses as part of your research all the time. What are your concerns about potential viruses in the future. Are the types of pandemic humans suffered in 1918 and 2020 an indication that these viruses come in some sort of hundred-year cycle, or have we just been lucky?

[00:36:17] Schmidt: that’s a long and complicated question. You’re asking why questions. We know part of the reason is in how. So the virus emerged in the bat and one of the things that the twentieth century and the twenty first century is responsible for is a great deal of habitat disruption and we know we have destroyed a lot of the natural nesting places of bats and so consequently bats have had to sort of get together and crowd amongst themselves and they are exchanging information and the viruses, by nature of the fact that they like to continuously mix things up, are always looking for a new host and just as we saw the emergence of this variant in the human race, there are variants that emerge all the time in bats, because we know it was associated initially with that wet market, but we’ll never know for certain, but we do know the virus was naturally occurring in the bat community and it emerged in the Wuhan wet market and Wuhan is again a very densely populated community and we know the virus is spread airborne, so people just talking, and consequently, they infected each other and again, being a very densely populated community, density is probably what drove the spread of the virus.

So we just have to be able to limit it and you know we did this experiment in the very early part of the pandemic when we had our mandatory shutdown in April and then we saw the first spike after memorial day and then we saw a moderate spike up in Clemson when Clemson went back to school in August and then we unfortunately saw the Thanksgiving spike, we’re now seeing the Christmas spike and probably by Friday, we’ll be seeing the New Year’s Eve spike.

[00:38:43] Lynch-Reichert: We have very little time, so while we have light at the end of the tunnel could you offer us your best guess at how long we are going to be in the tunnel?

[00:38:53] Schmidt: Well I’m glad you asked me that, Loretta. It’s really a function of us all rolling up our sleeves and when offered the golden ticket to all get our vaccines to quick like a bunny get your vaccine because the length of the tunnel is dependent upon how quickly we can all get vaccinated. Right now, in South Carolina, we have a population of about 5.1 million people give or take. We’ve only vaccinated about 1,300 of our citizens per 100,000. So that’s... we have to get to 90,000 per 100,000 to send everything back to normal. So we’re only at 1,300 so we have a ways to go. So that will determine how long this tunnel is.

So one of the statistics that DHEC publishes is the vaccination rate per 100,000. So just look at it, it’s a real simple number and we need between 80 and 90% of us to be vaccinated because – remember the mission of the virus is to find a host who’s not vaccinated, and it literally has to find a susceptible host. The more of us that are vaccinated, the harder it’s going to become for that virus to spread.

Right now, there’s very few of us who are vaccinated against this virus and consequently, the virus is finding an easy time to find a new host, hence 5,000 people got infected on Friday according to DHEC. That was confirmed diagnostic, you know, COVID tests, but in reality it was probably higher than that and so we really need to get those vaccines into people’s arms and so I’m hoping that DHEC and operation warp speed will really get to go to trans warp speed and really get us all vaccinated quickly.

[00:41:12] Lynch-Reichert: That sounds great and of course I want to remind everybody that MUSC indeed is a location for those vaccines. Of course, following very strict guidelines, but that is important that we all believe and trust and follow through. Dr. Schmidt, it has been a pleasure to chat with you today, I could talk to you for hours. You have labored long during this pandemic to research with the COVID-19 virus is, how it spreads, how to mitigate it, what the vaccine potentials are and how to protect ourselves and provide the support that provides us a better understanding of this new normal.

We are grateful to you for your expertise and your desire to make a difference in the lives of our community and the clinical care our citizens receive. Again, I just want to say that is the importance of the Medical University of South Carolina to our state and our community is we have folks like you doing the kind of passionate research without end that informs the translation of and innovation into great clinical care and we are very grateful to you for that.

[00:42:27] Schmidt: Well thank you Loretta, and you know this is a team sport. This wouldn’t be possible with my great colleagues in infectious disease and diagnostic microbiology and diagnostic immunology. It’s really a team sport and it’s very important that we appreciate each and everyone’s contributions. And you, the listener, have a great part to play in that you can continue to help us by wearing your mask, washing your hands and keep physically distant when you’re not with your immediate, closeknit group where you know their infection status at all times. So thank you Loretta, it’s been a great pleasure.

[00:43:12] Lynch-Reichert: You’re very welcome and that is great wisdom. And to our Science Cafe community, thank you for listening and please join us in making 2021 a year of renewed awareness and appreciation of the science behind the scenes that translates into robust health, wellness, and innovative discovery to enhance patient care. Please join us for our February podcast and feel free to email us to share insight, requests for research topics, or just to let us know how we’re doing. Until next time remember, at MUSC, science never sleeps.

Thank you.