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Reinfection, Variants and Stumbling Blocks to COVID Herd Immunity

With new SARS-CoV-2 variants cropping up, the questions of COVID-19 reinfection, and the role of vaccination to reach herd immunity, have become more important than ever. In the second part of this exclusive MedPage Today video, Monica Gandhi, MD, of the University of California San Francisco, talks with MedPage Today Editor-in-Chief Marty Makary, MD, of Johns Hopkins University in Baltimore, about the new variants and what they could mean for herd immunity.

Following is a transcript of their remarks; note that errors are possible.

Marty Makary: Hi, I’m Marty Makary. I’m here with Dr. Monica Gandhi, a professor of medicine and infectious diseases physician at UCSF. Monica, great to be with you.

Monica Gandhi: Thank you so much. Nice to be with you.

Makary: People sort of use the argument that there is no data selectively and to manipulate a narrative to fit their own conclusion. For example, some might say there’s no data on long-term natural immunity from COVID-19. Well, there’s no data on long-term vaccinated immunity beyond 300 days.

Gandhi: Right.

Makary: Absolutely, now that the vaccines are just out.

Gandhi: Sometimes it’s only for 2 weeks for people because those vaccine trials got published 2 weeks after the second dose, for a median… that was the minimum time, so we don’t have long-lasting immunity data on the vaccines at all.

Makary: A study just came out of the U.K., 6,614 people followed with COVID-19. Less than 1% developed COVID infection or reinfection.

Gandhi: Right, healthcare workers, exactly. That was not only an impressive study, but it’s mirroring what we see in the world, with 100 million cases and counting, if in fact reinfection was a prominent part of this disease. Now, let’s admit it, we’ve been a year and what? Like this is more than a year in, we would be seeing reinfection after reinfection after reinfection. The fact that there have been 6 or so documented re-infections, it’s so rare and we kind of knew that even 6 months in, because you would have just seen reinfection after reinfection, and then you just showed that study with 6,000 people, reinfection is so rare.

Then it just makes sense. That has made sense for RNA viruses and DNA viruses for many years, so it should never have been… and then you can’t say we don’t have long-term studies, so that’s why we can’t prove it. Well, this is a new virus. We could only have 8-month studies, and the Jennifer Dan study went out to 8 months, and you also have to postulate from the half-lives, like these memory B cells weren’t even starting to decline. Like it’s probably going to be either lifelong or very long, like 10 years.

Makary: Why is it that some people get reinfected with — I don’t know if reinfection is the right term — the seasonal coronavirus, the four seasonal coronavirus that circulate year-to-year? Are those true reinfections? Has the immunity worn off or are they mutating a little bit around the prior immunity like people do with seasonal flu?

Gandhi: Yes, this is a great question. We have seen that all the RNA viruses, which is actually different than DNA viruses, which are more stable, have this ability to mutate. Their spike proteins, because they’re the ones that are interfacing with the cell and getting in, have the most evolutionary pressure to mutate. Of course, remember the influenza virus has two spikes, H and N, which is why we have an H1 and an N1, or an H2N3. It has two spike proteins and so there is a lot of variability, that antigenic variability, that it can occur with the spike proteins of influenza, which is why every year we’re doing different viruses.

The same is true of coronavirus. The corona means “crown” in Latin and it does have a spike protein, of course. We all now are very familiar with how it has a spike protein, so it’s that protein that’s going to have the most antigenic variability, so it is going to mutate. It is mutating. That’s all we’ve been talking about for last month, are these new variants.

These more mild coronavirus infections, very mild coronavirus infections, that cause colds, you may have a T-cell response that protects you. But with time, because we’re not immunizing people against those coronaviruses, because it’s no point in immunizing people who get the common cold, then you’re going to have more and more selective pressure to mutate, and then you may evade the immune response.

That’s why these new variants with this SARS-CoV-2 are important and we want to get to mass vaccination quickly because there will be a time that there’ll be enough configuration change of the spike protein that your robust T-cell response to this variant won’t be as good against this variant. We don’t want to mutate our way out of these vaccines being effective when we have these great vaccines and we’re in a public health emergency. That’s why there’s nothing else that anyone should be talking about except for how to get these vaccines out to people.

Makary: If you had to sort of ballpark guess when people may need to come back for another vaccine to address a mutated strain that may have mutated around the current vaccine, would you say 3 years, 5 years, 10 years?

Gandhi: It actually depends on how fast we can obliterate this particular SARS-CoV-2 pandemic into oblivion — not into oblivion, but into herd immunity. It depends on how fast we get out of this vaccine, because the less that you have circulating, just by definition…. This is true of HIV. This is true of every virus. The less you have circulating in existence, then the less chance it has to shed from people’s nose for a long time, like in an immunosuppressed person, for example, and then mutate. It depends on what we do right now, but it could be like that we have to get these vaccines every 5 years or every 10 years.

Makary: Dr. Gandhi, quick question for you here. When are we going to hit herd immunity and have we considered the number of people previously infected? If the trackers are saying… say the Johns Hopkins tracker today is about at 24 million confirmed cases cumulatively nationwide. We’ve been diagnosing, what, 1 in 4 to 1 in 10 cases, during the history of the pandemic in the U.S.? Is that about right?

Gandhi: Yes, you’re right. Of course, we don’t diagnose many of those who go undetected. Exactly right.

Makary: 24 million, just extrapolating, means 100 million to 200-plus million have had the infection in the past. Am I missing something, or do many more people have natural immunity from prior infection than folks realize right now?

Gandhi: I think you’re not missing anything and Dr. [Paul] Offit is saying the same thing from the vaccine committee, that he is estimating that 20% to 30% of Americans have had COVID-19 infection, and of course then would have immunity because, like we talked about, even asymptomatic infection can give durable immunity. So, yes, I think a lot of people already have it.

Makary: Dr. Scott Gottlieb, who I follow religiously and I think has been terrific with this, he has suggested that in the Midwest, and others too, in the Midwest, one of the reasons we may be seeing slowing right now is the sheer number of people who have had it. I get so frustrated when I see the media read off the trackers as, “This is the number of cases today.” Those are the number of confirmed cases, not the number.

Gandhi: Exactly right. We’ve never had a campaign in history where we test this much for any infectious disease. It’s not like we test people for HIV this much. We never tested people for measles. We don’t test people for influenza. You have to be sick to come in and that’s because of asymptomatic spread. We do a lot of testing, but there are many people who have not gotten tested who didn’t feel well who had COVID-19 because it has such protean clinical manifestations.

Makary: We’ve seen a spike after Thanksgiving, we’ve seen a spike after Christmas, and now we’re sort of on a decline… hopefully a rapid decline, but assuming that… people are people and we’ve seen this behavior now play out for 9 months. Assuming we have a steady decline and not a rapid decline, a lot of people will have had the infection by, say, the end of February and going into March. Is it possible that we could hit herd immunity by March because of the sheer number of people that have had the infection previously, and then you add to that some vaccinated immunity?

Gandhi: The estimates are like unclear what it would take to get to herd immunity, but everyone keeps on using this 70% number because of extrapolation from other infectious diseases and extrapolation from the R0 of this virus, but it doesn’t actually factor in the natural immunity. Let’s just say 70% is that number. We want to get there as soon as possible. People are miserable and so I would…

If we, to be very strict about it, said 30% of people have had natural infection in this country — and it’s probably more like what you’re intimating — we’d have to get 40% more to get to with our vaccines, and yes, we’re going to keep on having natural infection by definition because this virus is circulating at such high levels.

But I’d rather, like anyone would, we’d rather get there by vaccines because we have them. It’s safer. You don’t want people to get sick, and so I think I can’t say this enough, like drop everything and vaccinate. Do nothing else, but vaccinate. Nothing else will get to normal. We have the vaccines. Let’s get vaccines into people’s arms and get to 70% as fast as possible. Do I think we can get to 70% by July? I do. We have to do better with the vaccination, but I think we can get to 70%, herd immunity, by July of 2021.

Last Updated February 03, 2021

Source: MedicalNewsToday.com