By Sept. 3, 2021, the COVID-19 pandemic had produced a staggering 220 million cases worldwide and claimed some 4.5 million lives. Just in Shelby County, there have been more than 127,500 confirmed or probable cases of COVID-19, and nearly 1,900 deaths.

But in these 18 months, uncertainty has been as prevalent and transmissible as the virus itself. Even now, as vaccines provide a shield often preventing the worst consequences of the virus, questions about the disease, its origins and safety measures ranging from inoculation to masking don’t always come with definitive answers.

The combination of a virus with chameleon-like tendencies – mutations and the variants they can spawn – and misinformation camouflaged as fact, often has left the public unsure where theory ends and evidence begins.

So in an effort to bring more clarity and delineation to bear, The Daily Memphian conducted extensive interviews on the pandemic’s past, present and future with two of Tennessee’s foremost physicians. 

One is Dr. Jon McCullers, who is on the Shelby County Board of Health and chief operating officer for the College of Medicine at the University of Tennessee Health Science Center. He has been a frequent voice in these pages since the first case here.

The other is Dr. William Schaffner, an infectious disease specialist at Vanderbilt University Medical Center, a regular guest on CNN and a source cited in many Daily Memphian stories.

DM: At this point in the pandemic, how would you characterize COVID-19 as an infectious disease — from a historical context?

Schaffner: I actually thought I would never see, in my lifetime, anything as severe as HIV infection, which spread around the world and profoundly had an impact economically and socially in our society. And knowing there could be an influenza pandemic, I didn’t think we’d see anything akin to 1918-1919.

But COVID has changed my mind. It’s blown me away.

I mean, it was within four months that COVID had landed on every continent, except maybe Antarctica. And it’s probably there now.

DM: And, safe to say, it’s not near over?

McCullers: We’re in our fourth wave nationally. I think we’re coming out of that fourth wave and because of the emergence of the Delta variant, and perhaps others, we’re going to see waves, and I’m expecting another in the winter that may be as bad or worse than this one.

So, we’re certainly not done with it and history tells us that’s kind of the pattern you see. And I expect it’s going to become an endemic disease after the big waves are over and we’ll continue to see big winter surges for some years to come.

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DM: And what about the historical context of the vaccines in terms of safety and effectiveness?

McCullers: We haven’t seen a vaccine that’s worked this well in a long, long time. I think the measles vaccine is probably the closest to it, but it’s a live vaccine so it’s a little bit different. It’s also historically safe. The measles vaccine has all sorts of side effects that we probably wouldn’t tolerate if they were in the COVID vaccine … the combination of effectiveness and safety, we’ve never seen before in a vaccine like this.

DM: Some people have been concerned about the rapidity of vaccine development, but these vaccines were not just produced out of thin air. There had been groundwork, right?

Schaffner: We had a backlog of science that had been developing over 15 years. When this new challenge arrived, we were able to focus on that science and in record time create a vaccine that exceeded our expectations.

Of course, my elation was matched by my disappointment because we have such a large proportion of the population that hasn’t taken advantage of this (as of Sept. 3, 50.4% of eligible Shelby County residents had received at least one dose).

I’m old enough to remember a huge smallpox scare. I grew up in metropolitan New York. I remember standing in line with my dad, for hours, because all the adults came and rolled up their sleeves to get this awful vaccine with all kinds of complications associated with it. I remember mothers bringing their children for polio vaccine. And now we have such a large proportion of our population stubbornly rejecting this vaccine, which is of such obvious benefit and is the root of curtailing the transmission of this virus.

I’m stunned by that. I don’t understand why so many of your and my fellow citizens in this state (49.9 % of Tennessee residents have received at least one dose), which is our home, still have not availed themselves of the vaccine.

DM: Do you get the sense that the side effects are much of a driver for why somebody won’t get vaccinated like maybe they remember having a bad reaction one year to a flu shot? Or do you think it’s more other factors?

McCullers: I don’t think it has anything to do with the actual side effects. People have a sore arm and maybe feel bad after the second dose for a day or so. That occurs with the flu shot, too, but maybe less so. I do think there’s fear of unknown side effects. People can worry about things that don’t exist and maybe won’t exist or are theoretically possible. And I think there’s a lot of deliberate misinformation out there, trying to make people think there is a potential for side effects that do not exist and are not biologically plausible.

DM: What’s your belief now as far as how all this started — did it begin in the animal world? Is it possible there was a breach at some laboratory? At this point, does it even matter to you how it started?

Schaffner: I think I don’t know but listening to my biology colleagues it is overwhelmingly likely that it came from the animal world.

McCullers: It’s very clearly a bat virus that adapted to be able to jump the species barrier into humans. We understand some of the mutations that are needed for that to happen.

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DM: And the lab theory?

Schaffner: A laboratory accident? Yes, that’s a possibility. But it’s not been demonstrated, and I don’t think we’ll ever know.

McCullers: The lab theory is possible; I think it’s unlikely. It’s much more likely this is just society being increasingly exposed to these viruses because we clear-cut the forest where the bats live and we’re building houses and farms there, and people go into bat caves and stuff and there’s just more opportunity for these viruses to jump across.

The laboratory they always point to is the Wuhan Virological Laboratory. That’s a BSL-4 (a lab with the highest level of biological safety) and it’s just not plausible that there was some lab accident in a BSL-4 that allowed this to happen. They would have had to be doing research that we’ve agreed internationally shouldn’t be done, and probably don’t have the capability to do.

Was there some other laboratory in Wuhan that could have been doing that? Maybe. It seems pretty farfetched to me. The people I know that know the scientists over there tell me they’re top-notch and you wouldn’t expect it to happen.

Does it make it impossible? No. Does it make it likely? No.

DM: So, if it’s natural transmission, animal kingdom to humans, what are the implications?

McCullers: I’ve been on the side of history saying we should be studying this. And we should be studying in the BSL-4 environment and trying to figure out the mutations of a bat coronavirus. There are hundreds of candidates out there that could do this, and we ought to be studying what it takes for it to cross over into humans. And then we ought to have surveillance, where we watch for those variants of concern —where they start to accumulate mutations that would allow them to cross, and when we find that we eliminate the source— by culling the bats or shutting down the markets where the bats are being sold. Or whatever the case is.

Right now, we don’t do that research because people are afraid it will escape from the lab. And because we don’t do the research, we can’t watch for it to happen, and we can’t prevent it from happening.

DM: What can you say in regards to transmission risk from one human to another?

Schaffner: What we do know, particularly in the Delta context, if someone was close to you for longer than 15 minutes, and both are unmasked, that positive (for COVID) person would exhale enough virus so that you would inhale it.

Whether or not it infects you, I don’t know. But given the contagiousness of Delta, that would be a high likelihood. And with Delta, one of the things we have learned is you don’t have to be face-to-face. On at least some occasions, you can be more distant (and still be infected). How that sorts out, I don’t think anybody knows.

It’s fair to say our friends the environmental epidemiologists think it happens more frequently than does the communicable disease epidemiologists, who still think close-in transmission is the highway and more distant airborne transmission is more the side street. But we all think it can happen.

DM: So, how much more contagious is the Delta variant to its forerunners, and how likely is it we get a variant that is even more contagious than Delta?

McCullers: It’s about twice as contagious. Will we get another more transmissible variant? Probably not. There are limits to how transmissible these things can get. Could I be wrong? Sure. I think it’s more likely we’ll see this thing mutate over time and still be transmissible, but not cause as much disease.

DM: And so, taking measures to slow transmission becomes that much more critical?

Schaffner: This Delta variant is spreading among the unvaccinated, principally. The vaccine skeptics keep pointing out the vaccinated can transmit this disease also. That’s true, but that doesn’t look at the magnitude.

Unvaccinated people are the main engine of transmission.

DM: And a person needs less exposure to the Delta variant than the Wuhan variant to contract COVID-19?

McCullers: If you have close contact with somebody that has the regular Wuhan strain, we think it’s about a 1 in 6 to 1 in 7 chance that you’ll get it from that close contact. Maybe that chance is 1 in 3 with the Delta.

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DM: And close contact would be less than six feet?

McCullers: Less than six feet for some period of time. And maybe that’s because if you said you’re breathing out a thousand particles per minute — and I’m just making up numbers here — maybe you need to be exposed to 10,000 particles in order to get that 1-in-7 chance. But the Delta’s more infectious so you only need to be exposed to a thousand particles. So, that’s how the math might work, but those numbers aren’t real-world numbers.

DM: And continued spread also means continued risk of new variants?

Schaffner: Most of the mutations are harmless, fall by the wayside. But every once in a while, by chance alone, you get a mutation or a series of mutations, that can survive on its own. Now, we’re looking for this around the world and new variants are being discovered.

For the most part, they’re not going to go very far, they’re not highly competitive. But in the United States or somewhere else in the world, another variant could crop up that is highly contagious and can evade the protection of our current vaccine.

DM: Let’s delve into masking and some of the controversy around it, some of the protocols that seem to defy logic and some of the risks people are willing to take.

Funerals, for example, are now mostly being conducted in-person again. Weddings, too.

And many people are again dining out, but the protocols around that seem odd. Like when people wear masks to enter a restaurant, but then when they get to their table and start to sip water, the masks come down. And you can hear people laughing about this, saying it’s like we’re supposed to believe the virus knows when it’s fair game to attack an unmasked person — in the entryway of a restaurant, but not once seated at a table and holding a menu.

So, it sort of feels like if we are going to do masking as a preventive measure, it actually needs to be more stringent. Otherwise, we should quit kidding ourselves that masking is really effective because, in reality, people don’t always mask in the way they would have to for optimal safety.

Your reaction to that?

Schaffner: There’s an element of truth there, but I’m gonna go down in the middle. You have the science, but you have to apply it in a way that’s acceptable to the population. You can’t do it in an ideal way.

In our current social environment, the family has decided to gather for this funeral. So, the decision was made this was important enough to come together. You weren’t going to just do it virtually. Once you do that, you’ve accepted a certain amount of risk.

Now, what can we do to minimize that risk? We keep the joint events as brief as possible. And if we’ve decided to have a dinner together, we’ve accepted the risk of taking off our masks. An entirely virtual event would have been much lower risk. In fact, you could even say that was safe.

So, you try to negotiate this in a way that is reasonably acceptable. My family is caring for someone that has a very high-risk condition. So, at the moment, we’ve pulled back and aren’t going out to restaurants. We did that before, but since this event, we’re being even more cautious.

McCullers: There’s a continuum of risk around the masking behaviors. If you and I are sitting really close to each other at a table and one of us has coronavirus and we take off our mask, you’re probably six-fold more likely to get infected. So, if you’re going into a restaurant, there’s a big difference between sitting at a crowded bar next to a bunch of people and sitting with your wife at a table six to 10 feet away from everybody else in the room. When I dine indoors, I make sure I’m at a table that’s away from everything else or I sit outside.

DM: Here’s another example: Two friends go to Chicago and attend a baseball game at Wrigley Field. Both are vaccinated. They ride the L after the game. It is jammed. Most people are wearing masks, but some of the young people coming from the game — and feeling no pain, by the way — are not. People seem to accept that as normal even though they are scrunched together on the train. Nobody says anything about it.

Not sure that would have been the case a while back, but people seem in a different place now. What do you make of that?

McCullers: I have not seen, anywhere in this pandemic, anyone who is willing to go up and confront maskless people. You might get into a fight, right? So I’m certainly not going to do that. If I go to Home Depot, I’m wearing my mask and most people are, but there are a couple who aren’t, and they’re your young people, usually. I’m not going up to them and saying, ‘Put a mask on.’ I’m just gonna walk the other way.

If you’re on the L, crowded together, that’s a high-risk situation so maybe that’s different. But again, I think people want to avoid conflict in these cases. Every viral video we see now is of the conflict escalating. I think you want to stay away from that.

Schaffner: There is COVID fatigue out there. There is no doubt about that. There is this yearning to go back to an old normal. And there has not been an acceptance among many that we’re moving into a new normal.

There is still this unwarranted hope that COVID will just disappear. And that’s not going to happen. COVID is with us the way flu is with us.

DM: So in terms of masking in schools, there’s some data from abroad that indicates, yes, masking helps slow transmission of the virus, but not near as much as you might expect. How does that influence how you view masking in the schools here?

McCullers: It’s a hard question to study. In order to study it, you have to look at a whole school vs. another whole school and do that with a lot of different schools and look at the rate. The problems are we know the mask is effective on an individual level, but what happens when you have multiple different kids and teachers and different interactions? And what are the protocols in place you’re studying, and how do you isolate and control for those different things?

So if you’re at one school where all the kids seat six feet apart, but then they go to the lunchroom and they sit at tables without their masks to eat, then the seating six feet apart in the classroom might not have any impact because it’s going to be overshadowed by the lunchroom behavior.

And then you have another one where they make kids six feet apart and have lunch outside, then maybe you can get at the question of is the mask in the class gonna help? And there hasn’t been enough case study. We can say with like, flu, in Hong Kong, if you close entire schools then community transmission will be lower.

Schaffner: We can’t have perfection. And in order to create a low-risk environment, we don’t do one thing, we do a whole series of things. Think of them as a series of slices of Swiss cheese. Each slice is a barrier, but each slice has holes in it. So, you put in other things that partially covers up the holes. By the time you put in a whole series of things, you’ve got a pretty low-risk environment.

So, what’s the single thing that can be done with schools to have a low-risk environment? The answer: to have every adult vaccinated. That reduces transmission in the community. Number two, in the school itself, every adult should be vaccinated — whether you’re a school bus driver, a crossing guard, working in the cafeteria …

Number three, every child 12 and older should be vaccinated. And then good hand hygiene, good ventilation, social distancing and maybe provide lunches at the desk so they don’t all have to go to the cafeteria. And yes, wearing a mask is important. It’s another slice of Swiss cheese that clearly adds another layer of protection.

The mask should be routine in every school in the entire country.

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DM: How would you characterize the risk to unvaccinated children right now? And what do you think the chances are we get a strain in the future to which children are especially susceptible?

McCullers: We know that children are highly susceptible. It’s funny, back at the beginning of the pandemic, a lot of people like myself that study viruses, influenza … whatever, said young kids are going to have more virus, they’re gonna transmit the virus more easily than older kids or adults. That’s just every virus because kids’ immune systems are less developed. Kids are the main transmitters of influenza because they have higher social contact rate and they make more virus, and because of their immune system. We all assumed that would be the case for coronavirus and then all these data were coming out showing that kids weren’t getting sick, we weren’t seeing transmission in kids and people started to kind of doubt that and say maybe there is something different about the coronavirus.

For a long time, we really didn’t know. Well, now we have data coming out in the last six months that show that, indeed, the virus replicates to a higher level in young kids than it does in older kids and adults. Younger kids are much better at transmitting it to others in the household. Because they are almost all asymptomatic infections, we weren’t catching them.

DM: All things being equal, if you had eight people living in a 1,200-square-foot house and four people living in a 4,000- square-foot house, are you going to pass things around at a higher rate in the more crowded environment?

McCullers: You are, but there are interactions that come into that. If you have a 2-year-old, the 2-year-old is going to be in Mom’s lap. Maybe it’s a lot easier for the 8-year-old to go hang out in their room. But all things being equal, yes, obviously you have more space.

This is also something we’ve known for a couple of hundred years. There are all sorts of great epidemiological studies that were done in London tenement houses looking at crowded conditions and passing around of viral and bacterial infections. Same thing in the 1940s, there was a bunch of great studies looking at crowded public housing in Cleveland. They’re true with coronavirus, just like with every other virus.

DM: Is there anything besides the vaccine, and social distancing and masking, that provides any protection — anything like medications people may be on for other conditions? There has been stuff out there about statins perhaps making a case of COVID less severe. Is there anything you have seen that you put any stock in?

McCullers: There are certainly things that make it worse. Immunosuppressants makes it worse, clearly, so that’s on that side of the ledger. On the positive side of the ledger, there’s no data for anything working so far. So no vitamins or minerals. The statin one is interesting. And I’ve got some scientist friends that are big proponents of statins as a kind of positive immunomodulator of many different infections, including influenza.

We’ve done some research studies with statins and animal models and influenzas just because they tend to down-regulate some of the pathways the virus uses to cause damage. So that’s a line of inquiry that could be followed more. But there’s not data to suggest that it’s true. It’s more theoretical.

Schaffner: If there were something that provided a degree of protection, don’t you think everybody would know about it now? None of the postulated drugs have shown in rigorous studies to offer any degree of notable protection.