— Bob Wachter, MD, breaks down the science

by Serena Marshall and Lara Salahi 

While natural immunity from previous COVID infection is of scientific interest, it’s also a political talking point that some have seized on to sidestep vaccination.

What does the science show when it comes to the duration of natural immunity? And how does natural immunity compare to vaccine-acquired immunity?

On this week’s episode, Bob Wachter, MD, of the University of California San Francisco, answers questions about immunity and how to stay protected.

The following is an abridged transcript of his interview with “Track the Vax” host, Serena Marshall:

Marshall: Some people are deciding whether to get vaccinated and they’re seriously weighing options of whether they’re better off developing or getting natural acquired immunity. That means getting the virus instead of the shot. It kind of sounds like chickenpox parties of 2021.

Wachter: Yeah, it’s a bad call, and it might not necessarily be a bad call if COVID was more benign. But when you can get your immunity via shots that are essentially perfectly safe, and are free, versus get it from an infection that has killed almost 800,000 Americans, and for those that it hasn’t killed has put a fair number of them in the hospital, and for those that didn’t go to the hospitals, still a decent number will turn out to have symptoms that last for months and may have long-term effects that we don’t understand, that’s not even a close call in terms of two alternative strategies.

Natural immunity is a thing. You do get some measure of immunity from an infection, but on this one, you have a pretty clear decision to make whether you get it from a vaccine or get it from an infection, and you want to get it from a vaccine.

Marshall: So, explain for us why the immunity, maybe from the infection, is different than the vaccine immunity.

Wachter: Well, it’s probably not. It’s a matter of the degree of immunity and sort of the breadth of the immune response. But, conceptually, I tend to think about them as being not all that different.

Your body has never seen this virus or the main protein on the virus, the spike protein, before. That’s why it was called the novel coronavirus. And until it sees it, it doesn’t know how to respond to it in terms of its immune response.

So, there are different ways of getting your immune system to be primed to attack this virus. And one is to see the virus and respond to it, sometimes successfully, sometimes unsuccessfully, and another is through vaccines, and vaccines work through a number of different mechanisms.

You know, the literature that you cited, Serena, as I read it, it sort of feels like there are arguments in both ways that the immunity you get from an infection might be similar to that that you get from a vaccine or might be somewhat worse. My own bias and reading the literature is that it’s patchier, it’s less predictable. And in the grand scheme of things, probably works less well. In either case, it doesn’t matter that much.

Marshall: I know, I was gonna say, I’m so glad you brought up that research because I really want you to dive into it for me. Because I feel like we’ve had so much back and forth on this … that we’ve heard, if you’ve had COVID you can still get reinfected. And if you get the vaccine it’s way better, but then new research seems to suggest the immunity lasts the same amount of time. So, what did that study out of Israel say? And why is it different from the CDC study?

Wachter: Well, the CDC study is fairly convincing that the immunity you get from natural infection is less powerful in orders of magnitude, I think it was five times less powerful than that you get from the vaccine. And the Israeli study seems to indicate that the immunity from natural infection worked well, and people were somewhat more resistant against another infection than after the vaccine.

But I guess my point is, it doesn’t matter whether you say that the immunity from natural infection is a little better or a little worse than the immunity you get from a vaccine. In either case — and I suspect that when the research finally settles out — it’s going to turn out to be that the immunity from the vaccines is better and lasts longer on average. But let’s say they’re equal.

The problem is equal is not great because we know that immunity for vaccination begins to wane at about 5 or 6 months, and you need a booster. Now, the people who got their immunity from the vaccination, if they’re like me, will go ahead and get a booster and get their immunity back up to a rate that’s very, very protective of both infection and serious infection. I worry about the people who got their immunity from an infection because that wanes. I’m guessing they’re not going to get a booster or they’ll not get a vaccine because they didn’t get one in the first place. And they are going to sit there and believe that their immune system is ready to fight off another exposure to COVID.

And maybe it’s not in bad shape after 4 months or 3 months after the infection, but for a lot of these folks that are now a year out, year and a half out, I think they are quite vulnerable to another infection. They have no protection at all or minimal protection. So, it doesn’t matter that much what the comparative level of immunity is.

I’ll buy that 3 months after your infection or 3 months after your vaccination, you’re reasonably well protected against another infection and a serious infection. But the question then is what happens as it wanes, as both of them will. And for the person whose immunity came from an infection, they are going to grow increasingly vulnerable over time and ultimately be at high risk of getting slammed.

Marshall: Before we dive in a little bit deeper into the over time and the waning immunity — if you have had COVID and it’s been 3 months later, then the research is now showing your chance of redeveloping COVID in 3 months is about nil, similar to a vaccine. Is that what I’m hearing?

Wachter: Well, it’s that your level of protection is very high. There certainly are cases of people who get reinfected within a few months. Those have certainly been reported. They’re not very common. So I tend to think of them as being in similar boats …

Marshall: Sort of like breakthrough infection?

Wachter: Yeah, there’s similar boats as if you’ve got a vaccine, and I think the research is still too immature to know for sure whether the infection-related immunity is going to last a little bit longer or the vaccine-related immunity [will].

But at the end of the day, it doesn’t matter that much. The point is that you have growing vulnerability after a period of a number of months. And that you really need to bolster your protection, particularly if you are going back to life as you knew it in 2019. So, my fear for the person whose immunity came from infection is that they think they’re protected. They’re probably not wearing masks. They’re probably not being very careful. They have made a choice, I think a very bad choice, not to get vaccinated in the first place. And over time, they’re becoming more and more vulnerable to getting hit with another Delta infection.

Whereas for the vaccinated person, I think it’s more likely that they’re going to recognize they’re becoming vulnerable, just as a person who got an infection is, but recognize that and do something about it. And the do something about it, is to take a booster.

Marshall: What about if you have had the infection and you check your antibody levels and you’re like, oh, they still seem relatively robust and it’s been a year since infected. So, therefore, I don’t need a COVID booster yet, but I’ll check them again in another year and then decide.

Wachter: Yeah, well, in this case, it wouldn’t be the booster, you’re talking about sort of their primary vaccination. I think that’s going to be an interesting strategy, and I would not dismiss that strategy out of hand. And I don’t think the strategy is very different, whether you’re talking about a vaccinated person and he or she deciding whether they need a booster, or a person who had a previous infection trying to decide whether they should get vaccinated.

I mean, I think there is pretty good evidence now that the level of your antibodies correlates pretty well with your true infection risk. And it would not be an irrational strategy for someone who’s had an infection to say, I’m going to check my antibody levels and if they’re high, then I’m going to consider myself reasonably well-protected and I’m going to wait on getting my vaccine.

Now, I think they would be better off getting the vaccine. I wouldn’t argue with them if they just got a single shot. Because the level of immunity that you reach after a single shot, if you have a prior infection, is sky high and every bit as good as the other person who’s not had an infection who gets two shots. I think that would be reasonable.

I think the argument is similar for a vaccinated person. For now, I think the best strategy at a public health level is to say to everyone, you’re 6 months out or more from your vaccines, go ahead and just get a booster. It’s essentially benign. It’s free. It’s the right thing to do. But it wouldn’t be surprising to me over the next 6 months if we examine an alternative strategy that says, after 6 months, you should get your antibody levels checked. And if they’re fallen, it’s time for a booster. And if they’re still high, you can wait.

So, it’s not an irrational way of approaching it, but I think at a population level, you’re trying to make recommendations for hundreds of millions of people. I think the best recommendation for the infected person is to go ahead and get a vaccine. And the best recommendation for the person who’s had their vaccines is to go out and get a booster at the appropriate time.

Marshall: You just said something, Dr. Wachter, that made me wonder. You said the person who gets the first shot is pretty much equally protected if they’ve had COVID as the person who gets two shots who never had COVID. So, in that scenario, then could it be mandated that if you’ve had COVID, at least one shot means you’re fully vaccinated?

Wachter: It’s tricky to sort of come up with what the best mandate strategy would be. There were a lot of discussions in the federal government about whether the person who had documented prior COVID, which is its own challenge — a lot of people think they had COVID and maybe didn’t if they didn’t have a good test. Everybody in the past year and a half who’s had any upper respiratory infection or a flu believes they had COVID and a fair number of them did not — so if you had truly documented COVID, I think you can make an argument based on the literature that you are well-protected after a single shot.

The problem is to try to figure out how you would operationalize a mandate that said, okay, you’re good to go with only a shot, but then you have to show proof that you really did have COVID. I think the simpler and more straightforward strategy is to require that people have both shots. But at an individual level, it is not an irrational decision for someone who had a prior episode of documented COVID — you’re sure you had COVID — to go ahead and get a single shot rather than two shots.

Marshall: Now for somebody that didn’t have COVID, though, the risk that they’d be taking of doing a … I guess a COVID party … to get that natural immunity, it carries its own risks. We kind of highlighted them at the beginning, but can you dive into that differential? People are worried about the shots impacting things like fertility. That’s been completely debunked, but they still have that fear over the vaccine. So, break down for us, Doctor, what the actual risks are from a vaccine versus getting COVID.

Wachter: Anybody who had questions about the vaccine 1 year ago, when they first came out, and said, I want to give it some time: Well, a year has gone by. And hundreds of millions of people in the United States, and now billions around the world, have received the vaccine.

And what we know is, particularly … for the Pfizer and the Moderna [vaccines], which are the main ones we’re talking about in the U.S., the risks are infinitesimal. The fertility thing turns out to be nonsense and just wrong. The risk of an anaphylactic reaction occurs in about one and a quarter of a million people. And I don’t think there’s been a death from it yet.

The risk of myocarditis, which is real, occurs in one in a few tens of thousands of people, mostly younger men. And the cases tend to be mild and go away on their own. And I don’t believe there’s been a death in the United States from that.

And that’s about the sum total of the risks that we know about from the vaccine. On the other hand, what we know about the risks from the virus are nearly 800,000 Americans dead, millions of people hospitalized, millions of people with long COVID who continue to have symptoms months out.

The long-term side effects of having had COVID are still a little bit up in the air. We don’t know what the long-term implications on your heart and your brain and your kidneys and your other organs are. So it’s not even a close call in terms of, if your two ways of getting a measure of immunity is infection versus vaccine, it’s not even a close comparison on what is the best and safest way to do that.

Marshall: You did just say that the unknowns for COVID long term, long impacts on the heart, brain, etc, are unknown. But some would argue the long-term impacts of the vaccine are unknown. So, if you’re thinking of immunity and you’re like, oh, I already had COVID. So that’s why I’m not going to get it. And I’ll wait and see if I can check my antibodies or I just will hope that I have long-term immunity. Why would that be the right case or not the right case?

Wachter: Yeah, I mean, I guess you never absolutely know with 1,000% certainty that something couldn’t emerge. But in the history of vaccination, there is not a case where a new long-term risk emerged that had not become clear after the first few months. It’s just, when there are risks from vaccines, they occur in the period soon after you got the vaccine. Sometimes right after you get it, sometimes weeks or maybe a month or two.

I guess anything is possible, but there’s no precedent for long-term effects of the vaccine, in terms of the ways the vaccines work. In terms of there being long-term consequences of a viral infection, a viral infection, particularly one that can set up not only ongoing infection with the virus, but then an immunologic reaction in people that sometimes continues to smolder for long periods of time, when we see these kids who have this immune reaction that is often quite disabling, so it’s not at all without precedent that people can have long-term effects of a viral infection.

I mean, look at Lyme disease. Look at certain kinds of hepatitis, look at HIV. Now, all the viruses are different, but in one case … first of all, in the vaccine case, there’s no evidence after hundreds of millions of people have gotten it and have been followed for over a year in many cases. And there’s no precedent with other vaccines.

And in the case of COVID, you do have some evidence … you have a fair number of people that have long COVID who still have symptoms months out. You have studies that show some effect on the heart and on the kidneys and on the brain in a small but meaningful percentage of people. And you do have precedents for ongoing effects of viral infections for different viruses.

So, if I was a betting person, this is an easy bet. If I’m worried about long-term effects because I don’t know how things are going to play out, I’m much more worried about the virus than I am about the vaccine.

Marshall: Long COVID after natural immunity. Like, if you have immunity, you don’t have long COVID. Is that something that still can develop?

Wachter: Well, long COVID is defined as continued symptoms more than a couple of months out from your original infection.

Marshall: But does it have to do with your immunity level?

Wachter: No, it doesn’t. It doesn’t appear to. The fact that you had COVID and you’ve cleared it from your body and you no longer have active virus, you no longer have active viral replication, and you have whatever measure of immunity you got from your infection. But for reasons that we do not understand, a significant fraction of people — most studies say 10% to 20% — continue to have significant symptoms months out. And our best guess is that it has to do with your own immune system’s overreaction to the infection that continues to smolder than it has to do with the infection itself.

And, yes, it seems independent of the immunity. So, you’ve developed antibodies to COVID, you probably have some level of protection against getting another case, but there’s something about what the virus has done in terms of turning on your own personal immune system that is not getting along with your body.

And that is not something that we see with vaccination. So, vaccination, people sometimes feel crummy for a day or two or three, or, you know, on the outside five or six, but very, very little evidence, in fact no evidence, of people having long-term symptoms weeks or months after their vaccination.

Marshall: So switching gears here a little bit, Dr. Wachter. Oral antivirals to treat COVID are coming down the pipeline. When they get approved, or if they get approved, is it another tool to help build immunity? And could they lessen the immediate need for vaccination?

Wachter: No, they don’t do anything to build immunity. They actually attack the virus, you only use them after you’re already infected. So, is it a tool if someone gets infected? Which you would like not to have happen if you can possibly avoid it, but if you do get infected, it would be great to have a pill that we could give to someone while they’re having symptoms and they’re sick, but before they get super sick and need to go to the hospital or the ICU.

And so the best strategy is to go ahead and get vaccinated and try to prevent that from happening in the first place. But if you do get infected, particularly if you’re at higher risk today, the main tool we have that has been proven to keep you from getting super sick are the monoclonal antibodies, which are intravenous or subcutaneous. They’re kind of a hassle to use and very expensive.

It would be easier and far better, if you do get COVID, you do have symptoms, you get a test that’s positive, if you could go ahead and get started on a pill within a few days of your infection. At least the preliminary evidence from the Pfizer study showed that that decreases the chances that you’re going to need to go to hospital and die by 90%. And so it’s great.

But still, I want to be vaccinated. I’d rather not get COVID, rather not need the pill, but if you do get infected, it’s another piece of our ability to attack the virus, but attacks in a very different way. It’s not bolstering your immunity. It’s a medicine that’s attacking the virus.

Marshall: Okay. Well, turning back to vaccines. We know the recommendations are still to get fully vaccinated, but would it be better just to say boosters for everyone, vaccinated and unvaccinated with prior COVID infection?

Wachter: So, the question is, is it reasonable for you to get vaccinated? The answer is yes. Your protection will be far better. Does the evidence show that you might be able to get a good level of protection with a single shot rather than requiring the normal two shots? I think the evidence is pretty good that that would be a reasonable strategy.

What we don’t know about that strategy is how long your protection will last, whether it will wane faster than it would if you’d gotten the two shots. If it were me and I had had COVID and I was getting my shots, I probably would still get two.

But I don’t think I’d argue very strongly if a family member said I’d really prefer to get one and then see how things go. That’s not an unreasonable way of approaching it. What is an unreasonable way of approaching it is saying I’ve had my infection. I don’t want to get any shots at all.

Marshall: And are there any other tricks or recommendations you would give people who perhaps want to ensure they have the strongest immune response — we’ve heard it called super immunity against COVID — in any way outside of a vaccine?

Wachter: No, there really is no evidence of any medication or vitamin that makes a difference in terms of your immune system. People have talked about all sorts of things, but the vaccines work so magnificently well and are quite safe, that that is strategy one through 100. And anything else, the evidence is really not strong enough to recommend it.

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