William Blair Investment Management Research Analyst Camilla Oxhamre Cruse, Ph.D., and Global Strategiest Olga Bitel

COVID-19: The End Game

September 28, 2020 | 36:34

Almost two years after the COVID-19 outbreak, much is still unknown. Why are heavily vaccinated countries such as Israel and the United States seeing record cases? Will children drive infections as we open up? And how will the economy stay on course? In this episode, Hugo speaks with William Blair Global Research Analyst Camilla Oxhamre Cruse, Ph.D., and Global Strategist Olga Bitel, about what’s next in the COVID crisis.

Meet Our Moderator

Hugo Scott-Gall, Partner

00:43 Introduction to episode and guests.
01:37 What can we learn from what is happening in Israel?
07:29 Will Europe and the U.S. experience a similar timeline as Israel?
11:20 How will children be affected?
13:22 How has the post-pandemic euphoria of the early summer months shifted?
16:25 What are the permanent psychological effects of this kind of pandemic?
21:01 Discussing herd immunity.
23:50 The new variants and potential risks.
26:02 Will this optimism extend into a real innovation period?
28:55 How will the economy be impacted tomorrow and into the future?

Hugo Scott-Gall: Hello and welcome to today’s podcast. You’re familiar with our COVID-19 science and economic series. And today we are going to give you another installment in that. We are going to really look at the next phase of the COVID pandemic. To discuss that I have with me one of our global health care analysts, Camilla Oxhamre Cruse who has a Ph.D. in infectious diseases. Also with me is our global equity strategist Olga Bitel who has a Ph.D. in pretty much everything else. Olga and Camilla, welcome again.

Olga Bitel: Thank you, Hugo. We’re delighted to be here.

Hugo Scott-Gall: Okay. So, lots of things to talk about with regards to the next phase of the COVID pandemic. I want to start with countries. And I’m going to start with questions to you Camilla. Which is Israel, U.K., U.S. — different things going on in each of those countries but they’re all pretty interesting in terms of infection rates, mortality rates, what we’re learning about vaccine efficacy. So, maybe we could start with Israel. Israel has been one of the vaccine success stories in terms of percentage of population vaccination and speed of vaccination.

And yet Israel seems to be having — or not seems to be, factually has a pretty sharply rising infection rate. Which implies therefore a lot of breakthrough cases, a lot of people with vaccines are getting infected. So, starting with Israel what can we learn from the last few months about what’s happening in Israel?

Camilla Oxhamre Cruse: Thank you, Hugo, it’s a good starting point. As you said Israel has been a little bit of a guinea pig when it comes to vaccination of COVID. And it’s been really a forerunner for the rest of the world. And I believe that we have a lot to learn from Israel. So, what do we see there? As you said, we have seen a sharp increase in number of cases in the last couple of months in Israel. And we have since July, also seen an increase in hospitalization. But let’s break down the numbers a little bit further.

So, if you look at the largest health care provider in Israel called Clalit, they have vaccinated approximately three million people in Israel. Of those three million, 600 of those have suffered severe breakthrough cases since June. So, that’s much less than 1%. Of these 600 people that have suffered severe breakthrough cases, 75% of those are above 70 years old. And they were vaccinated five months or longer. So, what does that tell us? Well, first of all, the number or the percentages of breakthrough cases—real breakthrough cases—is extremely rare. And it’s primarily happening to the elderly generation.

So, people that are 70 years old or that they have underlying diseases. And it also tells us that there’s something going on with the protection of the vaccine over a long time.

So, around five or six months it seems like the protection we get from the vaccines start to wind down a bit. Why is that? It’s actually quite expected to see some sort of wind down of the protection. Because after a while the body feels that the acute phase of whatever sort of pathogen it has experienced is kind of, it’s past beyond that. And the neutralizing antibodies that are circulating in our body is then normally starting to decline. Because quite honestly, we can not have a huge amount of circulating neutralizing antibodies for every pathogen that we see through our life, in our blood stream. They would completely clog our circulation.

So, the body naturally winds down the neutralizing antibodies that is circulating in the system. But it doesn’t mean that we don’t have any protection at all.

Our memory cells our memory b-cells, t-cells are still active. And they still recognize the pathogen upon exposure and start a biological reaction. But it can take a little bit longer time. However, for those people—the elderly generation—naturally have a lower immunological response to vaccines. So, the average protection for severe COVID hospitalization is approximately 92% to 96%, depending on what vaccine you got. But that is the average, right? For the elderly population that normally has a lower immunological response to the vaccine, that could be more 70% or 80%.

Now if that starts to wind down you start ending up in more dangerous territories, right? And that’s why we see these severe breakthrough cases, primarily in the elderly generation.

Primarily in those that received their second shot five months or longer ago. So, it makes rather sense to me, that we’re seeing this pattern. And therefore, I think, that it also makes sense that we’re now talking about giving the elderly generation and those that are at higher risk, a booster shot during the fall. And I think that we’re already seeing this in Israel and it will happen in the U.S. and U.K. as well. And I think that this will simply be the normal route to have a booster. It doesn’t necessarily have to be every six months going forward because what also happens when you get the booster, it trains the immune system a bit further to recognize the antigen.

But I do think that it’s fair to assume that maybe once a year we’ll get a booster shot for COVID. Much as we get a booster shot for the influenza virus every year. So, I think that this is just something that will be part of our life going forward.

Hugo Scott-Gall: So, what’s happening now is not surprising to you?

Camilla Oxhamre Cruse: I think it makes sense that the protection we get from the vaccine is winding down. No one could predict exactly how long it would take, five months, or eight months, or a year. I think that, that was the biggest question mark. But that the protection was going to wind down a bit particularly for the elderly generation. I don’t think that that is a huge surprise.

Hugo Scott-Gall: So, I hear you, Camilla. I hear you that what’s happening in Israel is—the precise timing is difficult to predict—but overall, this is to be expected. So, therefore, does that mean what’s happening in Israel is going to happen in bigger economies? In the U.S. and in Europe and in U.K. And so, as we think about U.K. and U.S., the U.K. has perhaps been the boldest in saying actually all restrictions—anything to do with lockdowns is currently gone. There are some remaining quarantine rules. If you test positive, you have to isolate in your immediate household.

But overall, the U.K. has gone almost fully open and has seen a rise in infection rates but actually not the same rise in hospitalization rates. The U.S. is not quite as open as the U.K. but that varies. The U.S. has seen rising infection rates, Delta variant. And the hospitalization rate has risen actually faster than the U.K. in terms of the relationship between infection rate and hospitalization rates. So, that’s something I want to discuss with you. But I guess the first question is one of those clumsy questions I ask where there are two things going on. But the first question is, is Israel a lead indicator? Is what’s happened in Israel about to happen in Europe, including the U.K., U.S.? And so are we looking at a difficult September, October, November into the autumn, the fall or winter where actually where you’ve got a deterioration in the climate as well. We’re going to see rising infection rates and rising hospitalization rates due to vaccine efficacy waning.

As well as those economies being quite open and you’ve got colder air as well. So, question one: Israel’s the lead indicator there’s worse to come for those that vaccinated after Israel. Question two is really to talk about U.K. versus U.S. Differences of vaccination rate but not huge. I think it’s around 10% of the population has a second dose difference. So, I think the U.K. is 10% higher than the U.S. But the hospitalization rate is very different. So, that’s the sort of second question. But the first one really is about what to expect next few months in the major economies, certainly in the West due to failing vaccine efficacy.

Camilla Oxhamre Cruse: Right, that was a lot.

Hugo Scott-Gall: I know it’s a lot, sorry.

Camilla Oxhamre Cruse: Let’s try to break it down one by one.

Hugo Scott-Gall: Yeah, yeah.

Camilla Oxhamre Cruse: Let’s start with Israel as a lead indicator, which I think is a great question and I think it’s a good topic. Yes, I do think that Israel is a lead indicator. And I do think that the pattern we are seeing in Israel—if you don’t do anything sort of we will see pretty much the same thing in U.K. and rest of the world.

Or rest of the developed world that has a large number of vaccinated people. So, it will mean that the vaccination protection in the elderly generation will start to decline. And in association with that we will see a larger number of a hospitalization sort of despite a double vaccination. If you look again at the data in Israel, the number of severe breakthrough cases is still very, very low. I want to point that out. The vaccine is very, very good. But it will just become a little bit less good. And in particular for that part of the population that is older and has a weaker immune response to a vaccine. It can put that part of a population at risk.

And therefore, I think that it’s logical that we’re now starting to talk about a booster shot for the elderly population. And the frail part of the population. So, that makes sense.

And already in the U.S. and U.K., we are starting to—we haven’t seen that starting to roll out—but I think it will start now September, October for the older generation. What we will also see in the fall and what we haven’t talked too much about, is the children. So, children up to now have been relatively protected because they haven’t been to school. They have sort of been a little bit in a bubble. And now schools are opening up again here in the U.K. and in the U.S.—sort of in-person school. So, we will see more cases among children.

One thing we know, the children are not reacting as severely as the elderly or the older part of the population. We will see cases of severe COVID in children. And the question is how we will react to that. We don’t have a lot of data yet on children because like I said, they have been in a little bit of a bubble up until now.

So, that’s now the trend that will be very important to follow. What will happen now that schools are opening up? How will the cases among children play out? I think that is another phenomenon this fall that will be very important to follow. And particularly since we will not only battle COVID this fall. We will probably also battle other respiratory infections, for instance influenza, SARS, RSV virus, et cetera. They will come back. We haven’t seen a lot of that all last year. We were relatively sparred from those kinds of infections because schools were pretty much closed all over in the developed world. But now that we opened up schools, we will see those other respiratory infections bubble up.

And how will our immune system response to potential double infection of COVID, influenza, COVID, RSV?

We don’t really now because we haven’t really seen that up until now. So, there’s still a lot of question marks. There’s still a lot of trends that we need to monitor. And to see how as a society responds to this fall and winter. So, I think that was the first part of your question, right?

Hugo Scott-Gall: Let’s bring in Olga because some things we’ve already discussed such as waning vaccine efficacy that creates a risk to older parts of the population. And you can attempt to mitigate that with boosters. If you can’t mitigate with boosters than you are either thinking about a lockdown or a lockdown for all the people saying, “Oh, you’ve got to be more careful.” Then you talked about the risk to children. As children go back to school, are they strong vectors and indeed with the Delta variant will it be greater risk to children’s health?

Which so far it seems that this has been a disease of the elderly and unwell versus the young. But I just wonder here, Olga, whether these sort of increased risks in most Western economies with potentially worse flu season because we haven’t had flu for a while. Don’t know how to make the right vaccines for it. Rising COVID infection rates may be from schools being back. And maybe rising hospitalizations, as per Israel, the need to get boostered. All of that may well have psychological implications that the idea we would put this behind us. And once we’re all vaccinated or everyone who wants to be vaccinated is vaccinated, that we can carry on as before.

That sort of hopeful scenario seems a bit less likely now than it did four, five, six months ago. There may well—and it’s just a question, there may well be some permanent changes in behavior as people have kind of got used to being cautious and maybe a bit afraid.

And talk around the need for a booster, rising infection rates. And we haven’t even really talked long COVID yet. This could mean that potentially economic activity is reduced. And maybe even permanently reduced. What say you Olga, to that?

Olga Bitel: Well, that is definitely a tall question. So, let me take it one step at a time, Hugo. The first point is definitely acknowledging that you’re onto something when we compare the euphoria of the introduction of the vaccine. Especially when we learned the high efficacy rates of the vaccines compared to what we had expected this time, last year. I remember Camilla vividly saying, a vaccine that is 30% to 50% effective is quite good. And obviously we got vaccines that had efficacy rates in the mid to high 90s. So, nothing short of stellar. And obviously the economic rebound that we saw subsequent to the roll-out of the vaccine has also been nothing short of stellar.

In the second quarter of this year, both U.S. and European economies recorded double-digit growth rates. So, for those that are interested in comparisons, there aren’t any. We’ve never grown this fast as a group since probably after World War II. But it’s too far to go back into the reliable records to really compare. So, the initial euphoria, to your point of COVID being over, is definitely behind us. In terms of the permanent shift in behavior and attitude. That is more difficult to call. And being that I’m a perennial optimist. Perhaps I’m biased in what I’m looking at. But prior pandemics—and unfortunately, we’ve had several.

The most comparable one I think to the current one, please Camilla, correct me if I’m wrong, happened in the mid to late 1950s. These types of pandemics usually last several years, two to two and a half years being the most common. And we have seen— we as economists, we as sociologists, we as anthropologists, have not seen any permanent shifts of behavior as a consequence of those.

Yes, there is a non-negligible cohort of people in almost every society that are more cautious. And that cautiousness gets perhaps more bid up, more exacerbated. Maybe it is as high as 20% to 25% of the population. And these people will remain more cautious, less mobile, less willing to engage and interact in a fuller lifestyle that they had before COVID. Perhaps longer than many of the rest of us. But we don’t have any evidence in societies that these shifts, once the pandemics are truly well behind us. Whether we reach herd immunity.

Whether the virus settles into a more dormant pattern. Whatever the case may be. Once the pandemic is truly behind us, that with a passage of time, sometime between six to 12 months thereafter, that people don’t really fully resume their economic and social activities. And the reason being is that biologically we’re social animals. We’re hardwired to interact. One of the most important things that we really need for not only survival but also thriving, is human touch, human interaction. And it’s okay to exchange ideas on Teams but it’s hard to reach over and touch someone on the shoulder on Teams, right? And so, that bit of human interaction is something that we’ll be missing in a virtual environment, in a self-isolation. And people willingly or not, will crave that. And so, once the pandemic subsides. Whether it’s another six months, another 12 months.

Hopefully even sooner than both of those. My optimist sense that is backed so far by the experience we’ve seen prior that within six to 12 months people will return to their pre-COVID living patterns.

Hugo Scott-Gall: Camilla, I often think of you as not quite as much of an optimist as Olga. And of course, you’re a Swede so, do you agree with that? Olga thinks we get used to and then eventually we just decide as a species just there’s no other way but to carry on as before. Do you agree?

Camilla Oxhamre Cruse: I think Olga has a very, very strong point that we are social animals. We’re social individuals. We want to have a—we need a physical interaction. But how that physical interaction takes places can, of course, can vary. Now we’re spending more time at home. So, maybe our physical or personal interactions just change. We spend less time at work. We spend more time at home. That can very well sort of—I think there will be a new normal. Exactly how that will look like, I can not necessarily predict. But to Olga’s point, what we saw here in the U.K. when they opened up the economy fully, opened all the nightclubs, all the restaurants, people went out in masses.

Masses. I think that’s the main reason why we’re seeing such a huge spread of the virus in the U.K. in July and in August is that they opened the economy fully. And people just craving that social interaction, and entertainment, and all those things that they’d been missing for such a long time. It’s been one and a half years. I think we will go back to some sort of normality. Will it be exactly as before? Probably not. We have been living with this for one and a half years. It’s probably going on for at least six months, maybe 12 months more. Of course, that will sort of change certain things. Is that necessarily bad for the economy?

I don’t necessarily think so. But it just might be slightly different. We find new ways of doing things. And new ways of interacting. And new ways of socializing that’s going to be slightly different.

Hugo Scott-Gall: Can we talk about a few more things? One is herd immunity. And the second is, new variants, further variants. So, I guess on herd immunity. I read something saying that in the U.K. something like, 94% of adults have some antibodies. And yet the U.K. infection rate is quite high, is pretty high globally. Is herd immunity, back when this all started, people saying herd immunity could come at 70%, 75%, 80%. That doesn’t seem to have happened. Is herd immunity just a red herring? The wrong way to think about this?

Camilla Oxhamre Cruse: Yeah, well to some extent yeah. Because it’s very hard to define exactly what is herd immunity? Because we’re dealing with somewhat of a moving target here. We’ve seen that the COVID-19 is changing. So, the herd immunity or what we need to accomplish to reach herd immunity is also changing.

And we have now seen a couple of new variants that we don’t know exactly how much more virulent they are. But it’s to say, there are more virulent. And of course, with more virulent variants we need to achieve a higher herd immunity to be able to fully protect ourself from these new variants. And also, so we are talking about the changing immunological response, we have seen that even if we get fully vaccinated. But that is also a moving target. And so, six months from your second dose you might not be fully protected anymore. And herd immunity is not one target. It’s more of a sort of moving target unfortunately.

And that makes it quite difficult to have that as our main goal and main focus to reach herd immunity. Because we don’t really know exactly what it means. And what we need to achieve to really get herd immunity. We’ve seen in other—take measles for example. So, it’s the most virulent virus that we know.

We need to achieve over sort of some 96%, 98% immunity in order to achieve herd immunity. But you can easily sort of pop up local outbreaks when that herd immunity decline to just sort of below 90%. So, we see the virus then reemerge very, very quickly. It’s a moving target. I don’t think that it’s something that we entirely should rely upon and say, “Well, now we have reached herd immunity. We are done.” It doesn’t work like that. Herd immunity would be something that we then would have to sort of entertain forever. And given that we have now—we’re seeing also new variants.

And I think that, that’s also a topic that is very important, interesting to discuss. What these variants are and what they can lead to. So far, the new variants that we have seen has been more virulent. But they haven’t really been any changes regarding the immunological protection that the vaccine provides.

There was some talk, of course, that the virulent variants may be able to evade the immune system. I think that we now have seen enough evidence supporting that in a real-world setting, the vaccine is protecting us as well from the virulent variant as well as the other variants. But we are now changing the environment for the virus, right? So, we have an environment with a high level of spread of the virus at the same time as we have an increasing degree of vaccinated people. And what that means is that the virus has a lot of shots on goal of trying to evade the immunological protection that a vaccine provides. Evolution is the force of trial and error.

Trying to constantly to become better. Trying to evade obstacles. And now it has an obstacle. And that is the growing number of vaccinated or sort of people.

So, we are putting us obviously at a risk. And no one can really define exactly how big that risk is. But there is a risk that now that we have a huge number of spread of the virus. An increasing number of vaccinated people. That the virus gets a lot of chances of trying to evade that immune protection. And sooner or later we will see new serotypes, i.e. new variants that can evade a vaccine. We see that every year with influenza. So, it’s not really anything strange. But the time aspect is of course very important. If we see new serotypes a couple of years from now, we will be will prepared.

It will be to sort of change the vaccines and roll out new vaccine programs. Should we see that anytime soon I think that would be rather detrimental for the people and for the economy. So, that would be the bear case should we see any of these serotypes, new serotypes popping up. Obviously, we are standing with a completely new situation evidenced.

Hugo Scott-Gall: Just to finish up really on vaccines. As Olga said, pretty amazing the speed and the efficacy of these vaccines. With your broader healthcare analyst hat on, will this optimism extend into a real period of innovation? Will there be lots of spill off beneficial innovations around, not just vaccines but treatments, et cetera. You just said, look perhaps we’re in a slightly tricky phase where if the vaccine is not effective against new variants, in the short-term that could be risky. But in the medium term, are we looking at a spurt, a wave, a surge of healthcare innovation?

Camilla Oxhamre Cruse: Absolutely. Not just sort of in vaccine but of course what we’ve seen now with the development of MRNA vaccine is just completely new vaccine model that will be used not only for COVID but for a vast number of different diseases.

That would be a huge game changer. A huge game changer for influenza, for example. As we said before a good influenza vaccine is maybe provides 60% protection against the virus. Not particularly good if you compare to these new COVID vaccines where we are generating a 90% protection. So, I think that this will be a huge game changer for vaccine development in general. Will it spill over to other developments in health care? I think that the optimism—it is of course many factors involved in this. But I do think that we are standing somewhat at an inflection point.

We see so many elements of positive developments in research, in healthcare that together they will disperse a huge change in research. But also, in how we do and how we think about healthcare. So, the digitalization of the healthcare system.

The use of AI tools massively change how we do, how we conduct healthcare going forward. But also, how we do research going forward. So, that has brought a lot of enthusiasm about changes in the healthcare system that in terms sort of attract a lot of capital going into development and into the healthcare sector. So, there are a lot of possible forces with capital coming in, with research development, with clinical development. So, all together I think we’re standing at a very interesting inflection point now in healthcare that will drive massive growth over the next decade.

And we will see huge changes in the healthcare system. And how we think about disease. And we think about patients going forward. Patients will not be patients necessarily. Patients will be consumers. And that sort of this mindset change is quite interesting.

Hugo Scott-Gall: Definitely. Final question goes to you Olga. And two questions. Bad habits still going with the two-question format.

But based on what you heard from Camilla around shorter-term risks maybe a more potent variant that can evade vaccines. Where it’s this game of cat and mouse. And the vaccines might lag. Are you still staying as optimistic around economic recovery? That’s question one. Question two is, because you’re an optimist. I think what we heard from Camilla was extremely optimistic about an innovation surge. Never let a good crisis go to waste kind of thing. Do you share that optimism? And see actual the potential for hard to precisely forecast, hard to precisely know, but spill off beneficial innovation coming out of this. So, that’s it, two questions.

Olga Bitel: Okay. So, the first one if I can put a time horizon on it. The first on is a bit of a shorter-term question. And the second one is more of a longer term where this will lead and where we settle out at. So, let me tackle the first one in turn.

So, economic recovery following the introduction of the vaccines and the reopening has been extremely strong. As strong, if not stronger than we anticipated. That recovery in and of itself—even if the virus had completely died away and we would be living in a post-COVID world, which probably most if not all of us are very eager to re-enter and to meet again. The economic recovery would naturally be fading from here. It is simply impossible for developed economies like the U.S. and Europe to maintain double-digit growth rates for anything like a multi-quarter time period. The more germane question, the relevant question.

We’re already starting to see that slowdown unfold. The relevant question for us and for the markets I suppose, is what is the cruising altitude for our economies? In other words, what kind of growth rate do our economies settle at? Are we going to go back to the pre-COVID? The last decade’s very mediocre growth rates of just around two percent?

And in the case of Europe, sub two percent? Or are we going to reach a higher cruising altitude of perhaps somewhere between two and three percent growth? Over a decade or even longer, that makes a tremendous difference in terms of our quality of life. And in the quantum of output, we produce. We’re talking about trillions of dollars in income, in consumption, in investments, et cetera. So, that distinction, the cruising altitude, the sort of steady-state growth rate. And the difference between two percent and three percent at an annual pace is not trivial. And that remains an open question. So, for the next six months we’re looking at a decelerating growth almost irrespective of what the virus does.

Obviously if the worst materializes and virus mutates in ways that are completely unpredictable at this point, such that we are forced to have some more forms of lockdowns because our hospital systems are inundated again.

This is very much not our base case at this point. It’s very, very bear case with a relatively low probability of materializing. But if something like that were to happen, obviously the economic recovery would stall out more substantially. But even in the absence of something like this, we’re still going to see a deceleration in economic activity almost across the board. So, that’s the near term. On the longer term, as you said Hugo, never let a good crisis go to waste. In this case that statement usually refers to governments or other public policy vigilantes to take up the baton and do something to promote some kind of development.

In this case I’m actually more optimistic because no further government action is required. Crises usually produce a bout of innovation. Any kind of crises. COVID was as pretty close to an existential crisis as we’ve seen in the recent history.

And there’s no doubt that it will spur the type of innovation that Camilla has talked about. Whether we see the benefits of this on the investment landscape or as patients within five years, or 10 years, or 20 years, remains an open question. But there are lots of companies and researchers that are already very excited about the fact that the sort of messenger RNA route of research, viral route of research has been massively underfunded in the U.S. and elsewhere for decades and decades as we pursued our knowledge of genes and genomics more broadly. And this area obviously has shown to be very, very exciting. And the kinds of lights of day that it will see.

And the kind of funding that it’s already getting will result in a step-change in terms of the discoveries that we’re on the cusp of. And maybe some that are maybe a little bit further away. And that is nothing short of revolutionary and exciting in my mind. So, very much echoing what Camilla has said.

And basically, need is the mother of all invention. And we definitely have the need. And increasingly we have the resources, the tools, and the personnel to bring those innovations closer to us as consumers and to us as investors, much, much faster than we’ve ever done before. So, this is very exciting.

Hugo Scott-Gall: Well, we’ve ended on a very positive note. Which is a necessary condition to appearing on the podcast. So, thank you both very much. I can’t even remember what installment this is. But we’ve done quite a few of these. And they are always very, very interesting. Camilla, thank you for your insights. Olga, thank you for your unbridled optimism. Hopefully this will be the last one we do on COVID. But I fear maybe it won’t. Anyway. Thank you both.

Camilla Oxhamre Cruse: Thank you.

Olga Bitel: Thank you.

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Hugo Scott-Gall, Partner

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