A small Israeli study published as a preprint on medRxiv indicated that some of the new coronavirus variants may put people who have been vaccinated at higher risk of a “breakthrough infection.”
MedPage Today‘s Editor-in-Chief Marty Makary, MD, MPH, of Johns Hopkins in Baltimore, discusses the study with Vinay Prasad, MD, MPH, a hematologist-oncologist at the University of California San Francisco and a member of the MedPage Today Editorial Board.
Following is a transcript of their remarks; note that errors are possible.
Makary: So Vinay, I don’t know if you saw it but a lot of panic over this study out of Israel that looked at infections after vaccination. I mean it’s kind of nuts, making headlines all over the place. Did you catch this?
Prasad: I caught a bit of it, Marty. I caught a bit of it.
Makary: So it’s pretty interesting, what they suggested in these headlines is that the South African variant may be piercing vaccinated immunity with the Pfizer vaccine. You know, I took a look at that study on the preprint and I would not recommend it to my worst enemy. It is a bear to get through. The only critical data points are buried so deep in there. Even Dr. Fauci said publicly that it was a very difficult study to read and to interpret. So I felt a little validated by that.
But there were eight cases of people getting a positive test after the Pfizer vaccine. In all eight cases, it was before that optimal period of immunity, 2 weeks after the second dose. And eight of those cases were with the South African strain. One was not with the South African strain. And so they made a conclusion that it may be that the South African strain is more likely to sort of pierce vaccinated immunity.
But to me, the big question is, were any of those people sick? And they suggested that they were asymptomatic or mild, but they didn’t give any descriptions. Now, if you’re going to put a study out there, that’s going to make headlines, that you’re going to publish in a complicated statistical format on a preprint server, please, for the love of humanity, give me the eight data points I’m dying to hear about. And that is, are these people sick? I mean, am I missing something?
Prasad: I agree with you, Marty, wholeheartedly. The goal of vaccination, of course, is to eliminate deaths from SARS-CoV-2 and bad medical complications from SARS-CoV-2. We don’t want people on the vent. We don’t want people on oxygen. We don’t want people with long-term sequelae of SARS-CoV-2. We don’t want people to die of SARS-CoV-2. But the goal of vaccination is not necessarily to eliminate every mild case. I mean, that would be great. But you don’t have to have that for this to be a game-changer vaccination.
And so, just as you say, if somebody says vaccines aren’t working, I would say, are people dying? Are people intubated? Are people suffering? Or are people having mild symptomatic infections? And if the answer is you’re only having mild symptomatic infections, I’ll take that as a success.
SARS-CoV-2 would never have been on the radar if it was only mild symptomatic infections. It’s only on the radar because of the bad things it does. And the moment we can defang the virus and get rid of those bad complications is the moment we can go back to normal. We don’t need to worry about PCR positivity. We have to worry about people living long and good lives. And that’s true in all walks of medicine, especially with the vaccine.
It’s easy to go in the media and fearmonger about variants. Variants, variants, variants. It gets publicity, it gets press. But the harder thing to do is to say, where are we really? How many hospital beds are occupied? How many people are dying? How sick are the people who are presenting with SARS-CoV-2? Those are better metrics of what the pandemic is doing.
Makary: And to be clear, none of the patients in that Israeli study — none of the eight people who tested positive after their second dose but before the 2 weeks after their second dose — none of them had serious illness. It was either asymptomatic or mild. It appears as if most were asymptomatic.
So if these are almost incidental findings of viral particles that lit up a PCR test, we’ve now created this worldwide concern in every media outlet that a South African strain could evade the Pfizer vaccine. And look, the media has run inappropriately with many studies I’ve put out for my research team. So I don’t necessarily blame the investigators. But the key points that people are not sick, or there’s no serious illness, they’re not going to the hospital, and that these may be incidental positive tests, I would think that’s a relatively important fact to get out there.
Prasad: Absolutely, Marty. Marty, as you know, the original sin of the media in this pandemic was in January and February of 2020. They went on and kept repeating that the flu is a bigger threat than SARS-CoV-2. And since that moment, they have done nothing but pay penance for that by trying to err in the other direction: that everything is catastrophic and the sky is falling.
And the truth is often you need to look at these facts independently and make your own judgment. And you’re asking the right question, which is — it’s not enough to show me that people have breakthrough PCR positivity, or even mild infections — I want to know how many people have severe infections. And I want to know about infections that occur after the full course of vaccination — as you point out, the cases that break through even though you’ve been vaccinated and you have gone 14 or even 21 days after dose two, where you’re having maximal humoral immunity against the virus.
Makary: Why are we learning this from Israel? Why can’t we have a simple policy? And I had a piece on MedPage Today a few weeks ago about this, where anybody who has a weird case gets sequenced. Okay, anybody who gets an infection after vaccination gets sequenced. Anybody who’s reinfected from natural immunity gets sequenced. Anybody who dies at a young age — you know, anything atypical — sequence those people instead of all of this sort of random sampling sequencing, which, it is important to have that component as well. But this is the critical information.
And the CDC has the vaccination file of every American with the date. And they have the genetic sequencing data. Merge those two files. I’ve been urging people there, merge those two files and they say, “Oh, well, it lives there, and it lives there, and the contractor, and there’s the funding.” I mean, this is like the most critical pieces of information we need right now.
Prasad: I’ll say this, Marty. I agree with you and I’ll put it to you this way. America to me has always meant that when it comes to science and medicine, that we are second to none, we’re the best. And if you want to be the best when it comes to pandemics, you need to do some things that we didn’t do. One is, you need to collect data systematically and merge it and make it broadly available. That’s what you’re getting at. And that can be sequencing data for breakthrough infections, which absolutely needs to occur. But there are many other types of data that should have been like that all along. We would have benefited immeasurably if we organized a systematic sampling around this country and documented zero prevalence over and over again, getting time courses of zero prevalence.
We have very little idea of what the epidemic patterns were in this country, beyond the cases that present to healthcare settings where we were able to test. Exactly as you say, we’ve not systematically collected information on genotypes. We cannot, in many cases, tell you what the frequency of particular variants was in a population at a moment’s time. These are all detriments, and for a nation as terrific as ours when it comes to science and technology, not doing this seems like an unforced error.
Makary: Do we have a pandemic public health emergency when the vast majority of seniors are protected, the vast majority of people over 50 are protected, and the virus is circulating among young people at low levels? Because I think this is exactly what we’re about to witness in May. And I could almost see a national argument ensuing, where some people will say, “Hey, the case numbers, it’s like a stock price that could bounce right back up to where it was,” and other people will say, “No, wait a minute, most of the country is immune, including almost everybody vulnerable.” I mean, the U.K. now has vaccinated 92-plus percent of people over age 55.
Prasad: We would have been much better had we done one dose in more people first. But I guess I would say to you that the moment every eligible adult who wishes to be vaccinated has gotten that opportunity to be vaccinated, the moment we shield older individuals who suffer the greatest consequences of SARS-CoV-2, the moment that hospitals empty out, the moment the deaths drop, I think you’re going to be seeing a situation where the calls to reopen are vast and people will want to get back to life.
And I suspect you’re right, that there will always be a few cases of SARS-CoV-2. I don’t think it will ever go away. I think it’s an endemic virus. I think those cases are likely to occur in people who have not been vaccinated for whatever reason — their choice, or unfortunately, a medical comorbidity — and people who have been vaccinated but are otherwise immunocompromised. People who receive B-cell ablative therapy or older individuals. I think it’s likely to have some seasonality to it. Every winter there may be older Americans who fall ill with SARS-CoV-2 in a nursing home or the other.
But I think the moment we will be beyond the pandemic is when we start to think of SARS-CoV-2 as just another respiratory virus that we deal with the same way we’ve dealt with the flu year after year. And I think that’s where we’re going to be. I’m optimistic as you are that by the summertime we’ll be in a good place.
Makary: And given the politicalization of the pandemic, as you know, Vinay, it’s like you quickly get lumped into one extreme, right? And no one is suggesting we blow it off, or we not be careful. Young people need to be careful, especially if they have a chronic condition. We’ve all as doctors got to stay on point on that message, as long as it’s out there. But the situation you just described where the hospitals are mostly empty from COVID and nobody’s dying from COVID, but it’s still circulating at low levels among younger people: we are there now in the United States in certain regions. Different parts of the country, it’s basically a different pandemic. It’s almost like different countries in terms of what is going on in the pandemic. I mean, Michigan and South Dakota, total polar opposites. New Mexico, complete polar opposite from Massachusetts in terms of how they’re doing right now. But Alaska has not had a COVID death in 3 weeks. North and South Dakota combined had one COVID death in the last 2 weeks. I think Utah and Oklahoma just hit zero deaths.
Prasad: And we’re doing quite well in San Francisco.
Makary: Yeah, I saw that like three people were in an ICU in San Francisco with COVID a week ago in a city of like a million people. I mean, again, I’m not saying we blow it off and move on, and this is nothing. I mean, you know, not at all…
Prasad: But Marty, the right answer about SARS-CoV-2 was always, this is a serious threat, it’s unprecedented, we have to take it seriously, as well as the fact that life is a series of tradeoffs. And there are other things in our society to provide immeasurable good for people, including schools, upward mobility, the economy, other healthcare services, and SARS-CoV-2 was always a series of important policy tradeoffs.
And you’re absolutely right that I believe it has been politicized. I think everyone feels like they’re the one who didn’t politicize it and the other person did. But I think, to some degree, a lot of people have been complicit in the politicization of SARS-CoV-2. The moment we wed public health responses to political parties, I think it’s the degradation of public health and science. And I’m somebody who thinks of myself as a scientist, as a doctor. I’m not, I hate to say it, very politically active and I’m not politically interested or politically motivated. I’m trying to look at these things the way an empiricist does. The way somebody whose first commitment is to science and the truth looks at it. I’ve spent a lot of time in policy, like you have, and I know policy means hard choices, and the moment people present choices as if they’re not hard, as if there’s nothing you’re losing, I think they’re doing a disservice to that discussion.
Makary: Tell me if you ever hear our public health officials talk about suicide from kids being shut out of school, or the physiologic harm of profound isolation, or a precise prevalence estimate on natural immunity. I just feel like we’re constantly hearing about the war on viral replication and not hearing about some of the other stuff. But maybe that’s just what I’m listening to.
Prasad: Marty, I think many physicians who I talk to are frustrated by what you’re alluding to, which is that we’re not thinking about human beings in the totality of humanity, which means a few things. Obviously we don’t want anyone to get SARS-CoV-2, we don’t want anyone to get seriously ill with SARS-CoV-2.
We also acknowledge that young people who are pulled out of school for over a year, maybe you don’t see an immediate increase in suicide. I think there’s different studies and they’re different opinions there, but you do see anxiety. You do see weight gain, you do see changes in the behavior of children, and you hear this anecdotally. And I think there’s evidence to suggest that that’s true. You also see differences potentially in their life course. I mean, why do we have schools? Why do we invest so much in this public investment? Because going to school is the greatest thing that allows you to lift yourself up out of the neighborhood you’re born in and move into a better life for yourself. And many children, we are taking that away from them. That is a type of help.
I think people forget, they think this is just help versus book smarts. It’s not help versus book smarts. It’s help versus upward mobility and the chance to have a better life, which may in turn lead to increased longevity. And so I think thinking about these things in this narrow lens, as you put it, as a viral-focused model, means you miss things. And this is something that physicians, I think, invariably think about. We’ve all had patients where we know that the most important thing in their life might not be the cancer they’re dealing with, but might be the other things in their life. And if you’re a good doctor, you tackle everything. Every patient you look at holistically. And I think you’re right in the sense that I feel like much of the narrative has not been as holistic as it ought to be.
Makary: I got my first dose of the vaccine a couple of days ago. I’ll be getting my second dose in 12 weeks. I had to basically wrestle the scheduler on the mat to try to make sure that they understand I’m not coming [back] in 3 or 4 weeks. But I was excited to see that, speaking of obesity, since you mentioned it, Krispy Kreme donuts is giving out a free donut to anyone who gets a vaccine, but they’re giving it to people who get a first dose. So it’s good they’re not conditioning it on being fully vaccinated.
Prasad: I’ll say that, you know, the strategy that you have for yourself, which is you let a lot of people go first, Marty, and you are delaying your second dose to 12 weeks where I think you have some immunologic reasons why that might be, might be very good. I’d say it’s quite defensible. And, you know, I think we’re living in a world where people are going to pounce on you for even saying that. But I think your choice is perfectly defensible. I think it’s a very reasonable choice and it’s good of you to have given priority to people who are at higher risk.
Makary: I saw the New York Times had a lead article in their daily briefing on the first dose. More and more doctors have been recommending it, but it’s kind of going to be a moot point anyway, now that there’s enough supply. I mean, it’s basically a rationing strategy. So now that we’re going to have more supply than demand, it’s probably going to be a moot point now. So maybe we lost the battle, but maybe there’s a few other folks out there that recommended it.
Prasad: Well said.
Makary: Well, good to see you, Vinay. Great to be with you as always, good to hear your thoughts, and thanks for joining.
Prasad: Hey, thanks for the discussion.