'Natural Immunity' to COVID-19: Taking Politics Out of Science

 "Natural immunity" to COVID-19 reinfection has become a political hot-button issue, due in part to groups such as the Great Barrington Declaration organizers. In the first part of this exclusive MedPage Today video, Monica Gandhi, MD, of the University of California San Francisco, discusses the evidence with MedPage Today editor-in-chief Marty Makary, MD, of Johns Hopkins University in Baltimore, and speaks about whether individuals who were previously infected with COVID-19 should be vaccinated when there are so many vulnerable populations who are still at risk of severe disease.

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: I have got so many questions for you, just with you being at the center of so much of this area. First of all, let's talk about natural immunity from prior infection, something that I think many experts have been dismissive of. Why are we vaccinating first-in-line people who have already had the infection? I'm still trying to understand why we don't clarify that they should step aside and get to the back of the vaccine line when reinfection rates appear to be very rare, and when they do occur, they're very mild.

Gandhi: Yes, so you're absolutely right about that. Immunity to natural infection is like something we learned on the first day of medical school, this is not mysterious. That's entirely how the immune system works and so we expected that you would get immunity after natural infection. Now we have incredible data on that, which we can talk about. But it is amazing that immunity became politicized to the degree it did, that people went so far as to say, "Don't consider that you're going to get immunity to natural infection," because of this Great Barrington-John Snow debate that came out, and neither one was correct.

There was probably a middle ground where it is accurate that protecting our elderly, and 40% of our deaths in this country were nursing home residents, was the most important thing we could do. It is correct that immunity develops and that it means a lot, and it is also correct that lockdowns have terrible economic effects on the poor and the young. This has been going on for a long time.

The Great Barrington Declaration was also incorrect in not saying that masks were a good idea because they didn't bring in masks or non-pharmaceutical interventions into their discussion. They actually, literally, said more like, "Let it rip," and certainly we want to protect people from severe disease.

Makary: Dr. Atlas had sort of suggested, possibly, that maybe that's a strategy, that we should sort of let it rip among those who are not vulnerable, and I think -- why is it, Monica, that if you believe in the scientific data that says natural immunity is highly protective, at least in the first year for which we have data, that that somehow is married to the idea of "let it rip," which I would never suggest?

Gandhi: Correct.

Makary: And I'm open to your thoughts. We shouldn't just let it rip.

Gandhi: We should never let it rip.

Makary: Absolutely.

Gandhi: Right.

Makary: But somehow if you believe in natural immunity, that has become sort of married to this idea that you should let it rip.

Gandhi: Those are completely de-linked concepts and that was the strange aspect, is that by saying from the beginning that you understand that pathogens confer often long-time immunity in a complex way with B cells, T cells, and antibodies to an infection, that should never have been married to the idea that you would want people to let this rip, that you didn't believe in non-pharmaceutical interventions. You didn't believe in masks, distancing, ventilation, hand hygiene, and ways to keep people safe.

I think it got married because of the extreme politics in our country, of which both sides are at fault. As you were intimating, my favorite paper had natural immunities which I will tout to the ends of the Earth because I just couldn't believe how well done it was -- it was this Science paper that was just published in November -- because it had the longest data.

This was Jennifer Dan and colleagues from UCSD, and showing that if you follow these 888 people with COVID-19 with a wide range of severity of illness, some hospitalized, some asymptomatic and mild infection, that you get profoundly robust antibodies, expected, memory B cells that don't even seem to have a half-life.

They just keep on going at the same level, so they're estimating it could be lifelong memory B cells, and then memory T cells that are so high that they emulate the half-life of what happens after a yellow fever vaccination with memory T cells. The yellow fever vaccination is once in a lifetime.

Makary: To our original question, should we be vaccinating people with natural immunity right now? What are your thoughts on that question and why isn't the CDC talking about this?

Gandhi: It could be because immunity to natural infection did become politicized and it could be that it became confusing... we can understand why that became controversial for some of the reasons we talked about before, so it is, they actually did talk about it. The ACIP, when they put out their recommendations on this right after the EUA of the Pfizer vaccine, which was, of course, the first one, it was a week ahead of the Moderna in mid-December. They had in their slide deck that if you have had natural infection you can wait 90 days.

Makary: Yeah. Where did 90 days came from? I saw that. It was almost like a footnote.

Gandhi: Yeah, and it was kind of tiny and it wasn't, like you said, advertised enough. The 90 days came out from as we've been getting the immunity data it's been getting longer and longer and longer by definition because SARS-CoV-2 has been around longer and longer and longer. Some of the first studies said 3 months, you get durable immunity. Just some of the first studies after 3 months. Then they said, "Okay, 90 days. You should wait." They didn't say it strong enough here. They said you can wait, because please give it to other people who need it more.

Then this recent data that's gotten a lot of attention, the Science paper, would suggest you could wait 8 months. It actually could, by the half-life extrapolations, it's suggesting you could wait many years. But at least if we want to be very strict about it, the Science paper went out to 8 months and you have profoundly strong immunity at 8 months after natural infection, very strong from all arms of the immune system, so you could at least wait 8 months.

So the CDC could say, very well grounded in excellent data, that you should wait 8 months. Just let everyone else get it first and then you can wait at least 8 months. They could very well say that on strong scientific data and it would help because people are estimating that at least 14% of the U.S. population and up to 20%... Paul Offit said maybe 20% of the U.S. population has had natural COVID-19 infection, which is not surprising. We've been the epicenter of the pandemic.

That would be a lot of people sitting aside and waiting for other people to have a turn. If we're getting to herd immunity by 70%, if 20% sit aside, then 50% need to get it to get to herd immunity. That makes this whole thing to get back to normal life faster, so I don't know. I would take that data and immediately issue a statement that, "Please wait your turn."

Makary: It's almost like antibody greed. It's like, "I've got 90% immunity, but before you're going to get 60% or any immunity, I want to take that up to 99%." I guess it makes sense if you're an older, at-risk person with kidney failure working in an ICU. That I could have some understanding for, but we're immunizing right now communication staff, accounting staff working from home, spouses of hospital administrators in their 30s and 40s.

We're sort of seeing the true colors of people come out at a time of rationing, which is really where we are. We are rationing. I think your point, though, or the point we're making together here, is very important for everyday practicing physicians that if people come up and ask you, "I've had the infection" -- confirmed, not one of these people, "I think I had it," which is half of America, and they may not have had it because a lot of the viruses circulate. If people have had it for sure, they've been confirmed to have the positive COVID test or the antibodies, they should step aside in the vaccine line in order for us to save the most number of lives.

Gandhi: They should step aside.

Makary: Yeah.

Gandhi: I think you're -- it is, especially healthcare workers, because the reason we've been working since the beginning of the pandemic and we don't have routine testing -- as you know, we work with masks, distancing, ventilation, but without weekly testing, for example, routinely is because we have committed to help others. That is kind of what you do from the very beginning of being a healthcare worker. It would behoove a healthcare worker, that was your point, and you're a young healthcare worker, to make that comment that, "I knew I had COVID. I actually got swabbed. It was back 6 months ago. I know Jennifer Dan says 8 months, so I'm going to wait."

Makary: Monica Gandhi, great to be with you. Great insights. Thanks so much for being with us.

Gandhi: Thank you so much.

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