The Body Remembers: COVID-19, The Immune System, And You

IRA FLATOW: This is Science Friday. I’m Ira Flatow. Let’s talk about our immune system.

As we keep hearing, it is complicated, an elaborate cellular machine whose job it is to protect you from anything that, well, isn’t you, whether that’s invading bacteria, parasites, and of course, the virus that causes COVID-19. Your immune system has two departments, the innate response which happens immediately, and the adaptive response, the immune memory that our hunt for an effective vaccine hinges on. But if you tangle with the virus once, research is increasingly finding signs that your immune system will remember and protect you for at least several months to come.

Could it be longer? How does it happen? Let’s talk about it with my guests. Dr. Katherine J. Wu covers science and health for the New York Times, holds a PhD in microbiology. Welcome to Science Friday.

KATHERINE J. WU: Hi, It’s great to be here.

IRA FLATOW: Dr. Deepta Battacharya, Associate Professor of Immunobiology at the University of Arizona in Tucson– welcome, Dr. Battacharya.

DEEPTA BATTACHARYA: Thanks for having me, Ira.

IRA FLATOW: Let’s begin with Katherine. Walk us through the standard immune system responds to a new virus. What should happen when we encounter this coronavirus for the first time?

KATHERINE J. WU: Yeah, thanks for that question Ira. I’ll speak here very broadly, because every virus is going to spark something slightly different in the body. But for a typical respiratory virus, you should expect an immune response in two kind of orchestrated waves.

The first is full of immune cells that basically see the world in two shades, self or not self. If it falls into that latter category and we’re talking about something that has nothing to do with the body that these cells grew up with, they’re going to attack it pretty indiscriminately. That happens really fast.

That sort of buys the rest of the immune system time to mount a more specialized response in the form of T cells and B cells. B cells like are cells that produce antibodies, those really important disease-fighting molecules that everyone has been talking about lately. And those are super specific. I sometimes call those types of cells assassins, because they can really set their sights of the thing incredibly specific and go after it specifically.

IRA FLATOW: Katherine, do you want to tell us what is so unusual so far with how COVID-19 provokes the immune system initial response?

KATHERINE J. WU: The first thing I’ll say is, a lot of people do seem to be mounting what seems to be a pretty typical and protective immune response. The virus gets in. The body says, hey, you don’t belong here. We’re going to attack you and get rid of you.

You see those two waves come in, the innate system first, then the adaptive system. And the virus does end up cleared. People feel sick for a little while. They are capable of passing that virus onto others. And that’s when they should really be taking care of themselves, staying inside, and seeking medical attention, if necessary.

But then the virus leaves their body. And they seem to have the tools to be able to fight it off again. Now, whether that production is actually occurring still remains to be seen. We’re only eight months or so into this pandemic. But it is looking promising.

That said, that’s absolutely not the case for everyone. For people who do really poorly with this virus, it seems that their immune system is totally confused. The virus gets in.

The innate system starts to react, but then it kind of never stops reacting. And eventually, it just starts creating all this collateral damage that starts attacking healthy tissues and sort of takes the body down with the virus. And then when the adaptive immune system comes in, it seems like there is this total lack of coordination.

It seems like it’s firing on all cylinders. And it almost seems like the body can’t tell whether it’s fighting a virus, or a bacterium, or a fungus, or a parasite, like a worm. And its just throwing its entire arsenal of weapons at the virus. And that just wreaks havoc all over the body.

IRA FLATOW: Why does it keep fighting [INAUDIBLE]? What kind of memory do these antibodies and T cells offer?

DEEPTA BATTACHARYA: So as you said at the very beginning, what the immune system is really trying to do is distinguish self, things that are normal, from non-self. We encounter all sorts of things that are different than ourselves, things we eat, things we inhale. And we really don’t want the immune system overreacting to those kinds of things.

So the innate immune system has a series of molecules called pattern recognition receptors. And they’re looking for really common traits in viruses, or bacteria, or fungi, or parasites that then instructs the adaptive immune system, the B cells and the T cells, to make the right kind of response. So in a typical kind of response, then what happens is that there is this intense competition for the best B cells and the best T cells that recognize the pathogen at hand, in this case, SARS-CoV2. And then at the end of it, all you’re really what are the winners of that intense competition. And those can persist for quite long periods of time so that they can respond very quickly if you see the virus again.

IRA FLATOW: How long does this memory last for in our bodies?

DEEPTA BATTACHARYA: So at the very beginning, during this competition process, there is this massive wave of both B cells and T cells that are attacking the virus. And they’re not all that great. And so, again, through this culling and competition process, there is a massive wave of death of the cells that are not very effective at dealing with the virus so that only the best ones are left.

So during that process, there is a decline in antibodies. There is a decline in the number of T cells. And what really follows is the stable wave of memory cells that persist after that initial decline.

And really, that’s the stage we’re at right now. And it’s a little bit difficult to predict exactly how long it will last. But not we take some lessons, say, from the first SARS coronavirus, I think we can expect those will persist for at least a few years.

IRA FLATOW: You know, it sounds like the immune system is really, really complicated. Katherine?

KATHERINE J. WU: I think that’s very fair to say. And Ira, what you said earlier actually struck me, because I think what a lot of people have been noticing recently is that dip in antibodies which has made a lot of people concerned about, oh no, what’s happening to our antibodies, what’s happening to our B cells. But what’s important to keep in mind is that, even if the weapons themselves disappear– and here, I’m referring to those antibodies that can maybe block the virus from entering a cell. What’s important is that the body may have the ability to retain the potential to produce those antibodies again. It’s like checking to see if the weapons factory is still working and not keeping as much track of the weapons themselves.

I’ll also point out that it’s pretty easy, at least relatively speaking, to measure antibodies in the blood. You really just have to take a blood sample and look for those proteins. When you’re talking about B cells and T cells, it becomes a whole nother ballgame.

You’re dealing with live cells that can be kind of finicky if you want to grow them up in the lab and see what they recognize. That involves all kinds of tricky scientific tools and really, really specially trained personnel. Also some cells hide out in tissues or in the bone marrow. And those are not really easy places to look.

IRA FLATOW: Well, then how much should we depend on counting the antibodies that are left in our blood as a sign that we have an immunity?

DEEPTA BATTACHARYA: Well, I think for research purposes, certainly. I think what we want to do is get a range of outcomes across different population, because it’ll instruct, how often would we need to get a booster vaccine? When do we need to start worrying about new epidemics? Those are the kinds of things that I think that need to be doing sampling.

Does every single person need to do that? No, absolutely not. I think we’ll be able to get some trends from sampling, and research, and getting some ideas as to how long the typical response is, and then getting a range around those as to how long we can expect any given person to be immune.

IRA FLATOW: This week researchers published what looks like confirmation that at least sometimes a person might be infected a second time by SARS-CoV2, or at least a slightly different strain. Is this bad news about our immune memory for coronavirus? Katherine?

KATHERINE J. WU: I do not think this is bad news. I actually think this is somewhat expected news. And depending on how you look at it, I could even cast this as good news. Considering how many millions of infections we’ve already seen from this virus– and that’s just confirmed infections– having one confirmed reinfection so far, that’s pretty impressive.

But what’s really important to note here is that it looks like his body was kind of doing its job, actually. This is not evidence to me so far that people are doomed to suffer repeat bouts of really severe disease over and over. It seems like the first time this man was infected, he experienced mild symptoms, probably evidence that his body was fighting the virus off. He recovered. And then several months later, he was infected again by a very similar-looking virus. But this time, he didn’t have any symptoms.

Being infected a second time and having significantly reduced symptoms or no symptoms at all, that’s a huge win. That could still be really good news for immunity and evidence that his body was doing what it’s supposed to do. And I think we will need many, many, many more cases that have some similarities to this to start noticing actual trends. The next person who has a confirmed reinfection may look extremely different from this. And there are many, many different directions that a second immune response to the same virus can take.

IRA FLATOW: This week, the FDA gave an emergency use authorization for convalescent plasma, using antibodies from people who have already recovered from the virus. But in the process, the FDA vastly overstated the known effectiveness of this treatment. What can we say at this point about this approach, Deepta?

DEEPTA BATTACHARYA: I mean, antibodies are really best if they’re already there. If you give the antibodies or convalescent plasma early, it can be somewhat effective. If you give it later, it’s much less so, because then the issue is a little bit different. Then it’s damage from the virus itself. It’s damage from the immune response to your organs. And then antibody is really not so useful anymore.

I think this has been one of the challenges, is that we really haven’t had a controlled trial in a way that would allow us to measure when is it effective, what types of plasma are the most useful, how many antibodies need to be in the donor’s plasma for it to be effective. And we just haven’t gotten any of those answers. And so I think that convalescent plasma was a fine option based on what we’ve learned from decades of viral immunology at the beginning, but this isn’t really a permanent solution. I mean, it was really meant to be a stopgap. I don’t think any of us felt this was, like, the end solution.

And in fact, there are many better, I think, more uniform treatments that are heading into trials now called monoclonal antibodies, where it’s just you put one type of antibody. You know exactly what it does. You know that it prevents the virus from getting into cells.

And there is a number of companies that are really struggling to actually enroll proper numbers of people in those trials for a therapy that I think is, frankly, much more likely to work consistently than convalescent plasma. And so I think the thing that I worry about the most is that the convalescent plasma emergency use authorization will just open the floodgates. Everyone will use this as a front-line therapy. It’s sort of middling in its effects. And then perhaps most damagingly, it really impairs the ability to run those monoclonal antibody therapy trials.

IRA FLATOW: Oh, so it could get in the way of understanding what’s really happening?

DEEPTA BATTACHARYA: Yeah, absolutely. Not only because the EUA disincentives running a proper trial, but it also essentially would make someone ineligible to enroll in part of a monoclonal antibody therapy trial, because it just gets in the way. And the endpoints get in the way.

IRA FLATOW: This is Science Friday. I’m Ira Flatow. In case you’re just joining us, we’re talking about COVID-19 and our immune systems with New York Times reporter Katherine J. Wu and University of Arizona immunobiologist Deepta Battacharya.

Katherine, this is a point that we’ve seen hammered in over and over again, how complicated the immune system is. It’s clear we’re going to be seeing more headlines, maybe some appearing to conflict about the immune system as the fight against this continues. What are the most important things keep in mind as we proceed forward?

KATHERINE J. WU: What an easy question to answer. I’m totally kidding.

[LAUGHTER]

Oh gosh, all right, so a few takeaways from me so far– I think one thing to really keep in mind, immunity is not a binary phenomenon. We’re really talking about a spectrum of responses here. And a lot of times, when we talk about immunity in a more colloquial sense, we talk about it as, I am fully protected from x, y, or z. And I want to make sure that people understand that there is a lot in between being fully protected against a virus so that you’ll never be infected by it again and being completely vulnerable to suffer the same disease over and over.

Chances are that we are going to see SARS-CoV2 occupying something in the middle there. We don’t know exactly where it’s going to land. But I want people to set their expectations and also make room for some heterogeneity of responses. Some people are going to react differently to this virus.

And with so many people who have been infected so far, with likely some more to come, we are going to see a wide range of responses. And we’re going to see a lot of that range filled out. So people should not be worried when they see reports about reinfection.

People should not be worried if they see differences in levels of things like antibodies or T cells. How your body reacts will be different from how my body reacts. And that’s still all OK. Having an immune response that confers even a degree of protection is far better than having no protection at all.

Another thing to keep in mind is that the immune system can work for us, but it can also work against us, whether that’s because the virus is kind of messing with the immune system or because the immune system gets confused by something it is seeing that is brand new and is seeing for the absolute first time. Obviously, our immune system has evolved to protect us from disease. But as this virus has so clearly reminded us, there are a lot of ways in which that response can go awry.

And maybe in the future, as we keep dealing with this virus, we’re going to keep developing treatments that will help us temper those over-reactive responses or rev-up responses that might not be reacting soon enough or well enough. But it’s really a complex process. I think one thing to keep in mind is that, as we’re exploring treatments and vaccines, there are certain parts of the immune system that might be better dialed up and others that might be better dialed down. And we don’t have to paint the immune system with a single brush.

IRA FLATOW: Deepta– very interesting summation. What can you add to that?

DEEPTA BATTACHARYA: You know, what we’re learning is that it’s very possible to generate a protective immune response against it. In fact, almost everyone does. And so that is almost always one of the hallmarks of something that is susceptible to immunization and vaccination. And so I think that the early immune correlates that I’m seeing from the vaccines, the immunological behaviors that I’m seeing from people who have recovered from the virus make me think that this is something that it’s very possible to immunize our way out of.

And so it won’t happen immediately. There is a lot of logistical things. But you know, as long as we set our expectations, as Katherine mentioned, as that what we’re really trying to do is to limit the severity of disease, make this not so much of an issue, I think that’s a very achievable goal. And I think that a lot of the behaviors of how our immune system has been responding to this virus make me quite optimistic about that aspect.

KATHERINE J. WU: One other thing that I will add is the immune response that is produced to a vaccine will not necessarily look exactly like the immune response produced by a natural infection by the virus itself. That could actually be a really good thing, in this case. As we’ve seen, there is such a wide range of responses to this virus from the standpoint of the immune system in different people, with different conditions, with different backgrounds. But maybe being able to tailor and administer a vaccine that looks pretty much the same to everyone will really work in our favor. It may also remove parts of the virus that might be deliberately messing with the immune system to make it easier for the virus to gain a foothold.

So we have a lot of power here. By sort of observing these things from two standpoints, from natural infection as well as the vaccine, we can do some compare and contrast. And if things look different, people shouldn’t necessarily be alarmed. This may be a really good opportunity for scientists to really produce an optimal vaccine that will produce a lot of protection, and continue to tinker with those formulations as new generations of vaccines come in the future.

IRA FLATOW: And we have run out of time. I’d like to thank my guests. Dr. Katherine J. Wu covers science and health for the New York Times. She holds a PhD in microbiology. Thank you, Katherine.

KATHERINE J. WU: Thank you. It was great to be here.

IRA FLATOW: And Dr. Deepta Battacharya, Associate Professor of Immunobiology at the University of Arizona in Tucson.

DEEPTA BATTACHARYA: Thanks for having me, Ira.

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