Delay The Second Shot? (w/Dr. Marty Makary)

Dr. Z: Hey everyone, Dr. Z. I have Dr. Marty Makary here, author of “The Price We Pay,” which just won the business book of the world. What what did you win?

Dr. Makary: Business book of the year.

Dr. Z: Business book of a year? That’s like Pimp Of The Year. That’s huge.

Dr. Makary: Good to see you, Zubin.

Dr. Z: Well, so you’ve been all over the news. You’re obviously a public health-trained surgeon, Johns Hopkins. “The Price We Pay” was a great book because it talked about all the money games that we do in healthcare. And I’ll refer people in a link to the interview we did before, but we’ve done a bunch of talks. Right now though, you’re focused like everyone, including myself, on this coronavirus thing, particularly vaccines, man. What are you saying? You’re the editor-in-chief of MedPage Today, So you have a good platform to get your ideas out. Well, what’s the latest?

Dr. Makary: Well, Zubin, first of all, I’m really enjoying the public health side of things. I spend probably 80 to 90% of my time doing public health research. And right now it’s sort of like there’s so many things out there that need to be said that are not being said, that it’s a good time to use as many different platforms as possible to get the word out. For example, why have we seen a massive deceleration in cases in the last three, four weeks? Massive. I mean, it’s almost going to be half the number of cases that we had during the peak on January 8th. We’re probably starting to see herd immunity kick in. And when people say, “Hey, wait a minute, there’s only 26 million cases confirmed. So you can’t have that much natural immunity.” Well, guess what? We’re only confirming one in four to one in 10 cases. So 26 million is really 104 million to 200-plus million. And we may be starting to see herd immunity kick in. That’s the good news, if we can beat out these variants. And then why are we giving the vaccine to people who really should not be getting it right now? People who have had the infection in the past. And why are we giving two vaccines at a time when we’re significantly supply-constrained? I think if we can give out the vaccine smarter rather than giving it out to people already immune, people who already had the infection, who already got one dose, who are young and healthy and shouldn’t be first in line. Yes, all those people should get a two-dose vaccine regimen, but not right now. Not while old people are sitting ducks in this war, where we’re losing two or 3000 a day. So there’s a lot of inequity right now in this vaccine allocation. So I think it’s a time to really reevaluate.

Dr. Z: Yeah, this is worth discussing because, by the way, even just saying the words herd immunity are enough to get my entire Facebook channel canceled. So it’s ridiculous, Marty. Even just interviewing you is enough to get me canceled. You can’t even have a discussion anymore without the algorithm pegging you as misinformation.

Dr. Makary: The term is polarizing because it became politicized because it’s a terrible strategy. Herd immunity is a terrible strategy, and so people associate that term with the strategy. I totally am against that strategy. But the reality is if we can use a friendlier term, we are seeing slowing. We are observing slowing. How else do you explain a halving in the number of daily new cases in the last three to four weeks? Half, 50% reduction.

Dr. Z: Do you think that what happens is, so herd immunity and developing some community immunity threshold, and we’ll talk about the two-vaccine regimen too, I think that’s key. Do you think some of it is because we have this big surge in infections over the holidays when people got together, and those are starting to peter out? And then people auto-regulate their behavior so now they’re more scared, they’re putting masks on, they’re not going out, there’s less travel and connection, and that’s why we’re seeing the drop? Or do you think we’re actually starting to generate overall greater levels of community immunity?

Dr. Makary: Well, look, we definitely saw a bump for sure after each holiday and special occasion. But the reality is how do you explain a 50% reduction in the last three to four weeks? There’s only 330 million people in this country. When 100 to 200-plus million have some natural immunity, which by the way, the old guard medical establishment has been very dismissive of, basically telling people even if you had the infection, you’d still need to get two vaccine doses. But the reality is that immunity is pretty good in the short term.

Dr. Z: Yeah, so let’s get to that. So that’s interesting. So yeah, I agree. I think that there is an effect of this community infection rate, and I think there’s some preexisting immunity too, some T-cell preexisting immunity which we talked about early in the pandemic. It’s not as high as we might’ve hoped it was, but it’s there. And then the idea that you’ve got 22 million people vaccinated already, and so that’s adding a little bit to the community. Unfortunately, they’re not necessarily the highest-risk people that got vaccinated like you said. And this question-

Dr. Makary:  Hospital administrator spouses.

Dr. Z: Hospital administrator spouses. No, they’re really high risk because how will they get on their golden yacht if they’re coughing a little with an asymptomatic case of COVID? Because they’re asymptomatic because their metabolic health is great because they can eat nice ’cause they’re rich.

Dr. Makary:  Well, hospital administrator spouses over the age of 65, they’re the ones I support getting the vaccine. One dose right now. The other ones, we’ll have to have a separate conversation about.

Dr. Z: So let’s talk about the single-dose thing because you mentioned variants, and all of this makes sense in the absence of variants. When we start seeing variants with some degree of resistance to vaccine, not frank “vaccine escape” yet, but just resistance. The problem Offit would bring up say is if you just get one dose, you’re not generating as much immunogenicity as natural infection in the trials. And so as a result, you’re setting yourself up for possible viral replication in the setting of some pressure to evolve away from vaccine, instead of suppressing at a level that will actually prevent replication. So do you worry about that with a single-dose vaccine regimen?

Dr. Makary:  The question is not should we have a single-dose regimen. The question is should we delay that second dose further out, and if so, will it be more effective? Now, I’m plunging into this controversy knowing that I’m gonna be mislabeled as a one-dose, single-vaccine advocate. And I’m not. What I’m saying is let’s look at the data. The Pfizer data is now public. By the way, why the heck does the FDA not make public the applications once they get them? When they got the Pfizer application, that afternoon they should’ve made it public in my opinion. Sorry, I just believe in transparency.

Dr. Z: I agree.

Dr. Makary:  They release it after they authorize it. Once they did, we looked deeper and guess what? 91% effectiveness of the vaccine seven days after the second dose, when we know that second dose hasn’t kicked in yet. It just doesn’t physiologically. So that 91% protection you see after four weeks after the first dose of the Pfizer vaccine is the efficacy in the short term of the first dose. The Moderna trial, the study that just came out, 80% efficacy in a month after the first dose. The UK has now said officially, try to wait 12 weeks for your second dose. Other vaccines, are they more effective if you wait or are they more effective if you give a second dose within a month? In general, to quote Dr. Pollard in the UK, head of the Oxford Vaccine Group, “In general, vaccines work better the longer you spread them out.” HPV works better at one year than when you give the second dose at one month. Other vaccines, the same. So the question is as we’re significantly supply-constrained, why would you choose to protect 50 people with 95% protection when you could protect 100 people at 91% protection? Or thereabouts. That is the ethical question right in front of us, and this directly translates into public policy, what we tell our patients, what we do for ourselves, and what we say in social media.

Dr. Z: Yeah, I think this makes a lot of sense, because what you’re making a distinction is there’s the practical supply constraint right now. So if the goal is generate as much community immunity as rapidly as you can, and actually that’s gonna have an anti-variant effect. So if we’re worried about variants taking hold, as many people as can be immunized quickly means less replicatable real estate for a virus to get a foothold and to generate new variant, et cetera. So that’s gonna be a key component of it. As far as immunogenicity goes, that’s interesting point that some of those vaccines, like you said, HPV, you space longer out. I’m gonna talk to Offit on Friday, so I’ll ask him these questions. I think it’s worth asking because this has been an interesting discussion. This is the kind of discussion we oughta have because it’s a mix of policy, like the effector organ of science. You can talk about the science all you want, but if you can’t execute it, then what does it matter? And this idea of who should be getting it, and in what, like today I’m supposed to get my second dose of Moderna. And I know you’ve gone on record-

Dr. Makary: Don’t do it.

Dr. Z: Yeah, I know, just don’t do it. But the thing is, I don’t think they’re gonna give it to a new patient. They held it back specifically for a second dose for healthcare workers. I know you’ve gone on record and said you’re not going to get the vaccine until the supply constraint, did you get it or no?

Dr. Makary:  No, my personal risk is too low and I don’t see enough patients to really be a transmission risk. And our protocols are so good in surgery that I’m not gonna get it until every high-risk American has been offered it first in principle. And I don’t blame people who are getting it, healthcare workers who have received it. That’s what they were told to do. That’s what they did. But in principle, I’m trying to say, “Look, 80% of the deaths are on people over 65.” Let’s hit them first with a simple age-based allocation strategy. There’s less decision paralysis at the hospitals and at the state level. And they can roll out vaccines faster that way. That’s why Israel has vaccinated over half its population.

Dr. Z: That’s right. And I think there’s a lot of validity to that angle in the sense of pragmatism and also saving lives. So if you’re purely looking at saving lives, who’s dying? It’s the people over 65 that are at high risk.

Dr. Makary: Yeah, look, and things are different from the spring. Remember in March and April, we were giving people a lot of infections. We were transmitting a lot of infection. A lot of people came to the hospital and got the infection. That’s different now. Our protocols are much better. Now, look, if you’re an at-risk ICU worker, take 10 vaccines for all I care. That person probably should be in the formal two-dose protocol. But the vast majority of healthcare workers, one dose is pretty good, And we should probably take it in turn with an age-based allocation. By the way, I love Offit and I respect what he has to say. But a couple of observations. Number one, in general, the US experts have been in a bit of an academic ivory tower disconnected from the fact that on the ground we’re rationing a scarce resource. That’s the first disconnect. The second is there’s a massive disconnect between UK doctors and US experts. A massive disconnect. They have official guidance from the experts and endorsed by the government saying try to delay your second dose out to 12 weeks. And they may increase it further. In general, they’ve done better as an expert group. they’ve approved the Oxford-AstraZeneca vaccine. We haven’t. We’re sitting on it, hoping another trial rolls in. They do rolling reviews. We don’t do rolling reviews at the FDA. Our experts have been dismissive of the effectiveness of a single dose. They are talking a lot about it. They did the steroid trial. US experts said it didn’t meet our elaborate standards. Of course, that trial ultimately proved that steroids reduced mortality by over 1/3. There is a massive disconnect across the Atlantic Ocean between UK experts and US experts. So just something to keep in mind when you hear US experts speaking.

Dr. Z: I think that’s really interesting because you know that in the UK, since they have nationalized health, they think in a systems approach much more I think than maybe the academic ivory tower, sort of fragmented approach we have here. So maybe that’s a component of it. But these are the conversations we need to have and we need to be debating publicly, assuming Facebook doesn’t cancel us for even talking any of this stuff. But then I say this because Facebook recently penalized me for things that they wouldn’t even explain what they were. They just go, oh, we’ve shut down this account, we’ve closed this. And I’m like, “Why?” They won’t even tell you. And I think if we’re gonna have discourse about anything, you better have an open platform to be able to do it. Especially when misinformation is spreading so fast. If you can’t actually counter it with rational discourse. So I mean, so what what is your call-to-action on what we should do then? Should we just say spread it out to 12 weeks, give it to old people first, stop giving it to hospital administrators? What’s your plan?

Dr. Makary: Well, Zubin, I’ve dodged the AI algorithms over there at Facebook for now, although I’ve had some close calls. And AI cracks me up because people always say, “Oh, in healthcare, you need AI.” And AI can help with this and AI, and I tell them, “Look, we don’t need AI. We just need I right now.” We just need basic I. No one has ever died from missing their second dose, for delaying their second dose. Let’s use I, and let’s recognize that we can double our vaccine capacity instantly if we look at the data on how effective the first dose is, and delay that second dose until we have the capacity to immunize more people. That’s number one. Number two is let’s stop immunizing people right now that had the infection. If you had the infection confirmed, you’ve got natural immunity at a likelihood greater than the effectiveness of the vaccine. It’s greater than 95%. And matter of fact, the study out of the UK two weeks ago showed that out of 6,600 healthcare workers who had COVID, less than 1% developed a reinfection. We don’t see reinfections. I know it doesn’t meet all the fancy criteria of the “New England Journal of Medicine” and “JAMA,” that there’s not been a randomized control trial showing that reinfection rates are low. We haven’t randomized two similar identical countries, studying the reinfection rate in one versus the other country that didn’t have any. In fact, it didn’t meet the elaborate standards of the journal. I love it. Today I was submitting something, You can’t start a sentence with a number, right? How dare you? You bad, bad researcher. You have to spell it out, but you can’t have a number to start a sentence.

Dr. Z: You should respond with a bulleted number list. One, you guys are idiots. Two, STFU. Three.

Dr. Makary:  I mean, we need to just look at observational data. We’ve not seen massive rates of reinfection in Italy or in Wuhan or the rest of Europe or the rest of the world or in New York or in the entire country. Now, maybe that’ll change with the Brazilian strain. There’s laboratory evidence that it might be starting to mutate around your body’s immunity and around vaccinated immunity. That’s something we’ll keep an eye on. But we’ve got a vaccine right now, and we’ve gotta make real-world decisions. My parents are high risk. They can’t get their hands on the vaccine. Meanwhile, some 26-year-old who interjects Botox for a living got it from their friend because there was an allocation for healthcare workers, even though that person already had the infection and they’re being called now for their second dose. This is insanity. We don’t need AI, we just need I.

Dr. Z: We need I. So I think what you nailed is exactly the frustration. So you have this misallocation of the resource, a lack of just general intelligence. So I absolutely agree that if you’ve already had COVID and there’s a scarcity of vaccine, you let someone or you allocate that vaccine to people who haven’t had COVID, because that’s gonna be the highest bang for the vaccine. I absolutely agree that here we are going, “When are our high-risk parents gonna get this vaccine?” You wanna hear a funny story? So I was doing the live show for my supporters yesterday, and my mom texts me during the show. And never ignore a text from your mom, dude. It doesn’t matter what you’re doing. You and I could be talking right now, I’m gonna interrupt it. So I look over at the text and she says, “Hey, you’ll never believe what happened. Your dad and I got a text from the doctor’s office and they said we have a small allocation right now. If you come to the parking lot, we’ll give you this vaccination.” They’re in their 70s and 80s. And they ran and got the vaccine. And you could see the audience was just like, “Watch his face.” I was just like , yeah. Like this huge relief. ‘Cause I was feeling guilty because, and I’ll tell you why I got the vaccine, Marty, if you wanna hear it. And this is an emotional reason. I have a factor V Leiden and prothrombin 20210A. So if I get infected, chances are I might get a blood clot. You never know, I’m probably okay. I’m 47, but still. I do see patients at UNLV, but not as many as a full-time practitioner does. And I have guests in the studio, so I’m always mindful of that. But the main thing was I had heard that locally, the system that was giving out the shots, 30 or 40% of healthcare professionals were declining the vaccination, and the shots were sitting there in their allocation for the tier that I was in. And I said, if these people are saying no, I’m not taking a vaccine from someone else. I’m gonna go get it. I got it, immediately felt guilty because my parents couldn’t get it. And they’re at vastly higher risk. And then so the huge relief when they just luckily got it yesterday shouldn’t be luck. It should be that we have systems to do this.

Dr. Makary: I don’t blame anyone who’s gotten the vaccine or two doses, even if they shouldn’t have gotten it, because I blame the CDC. I blame our medical establishment. I blame all the people sending the message. I blame the hospital leaders who are saying, well, it’s just too much work and too much money for us to set up a little community vaccination table in our lobby. We don’t get paid for it and we don’t have the staff, even though they’re the largest employer in the state. And so for that reason, we’re just gonna give it to anybody who works from home, including 23-year-old grad students at Columbia University.

Dr. Z: But they’re perfectly okay suing the crap out of low-income patients for not paying their bills.

Dr. Makary: Yeah, that’s another topic. By the way, we’ve shut down a lot of the practice of hospitals suing patients. It’s been a nice follow-up to the book.

Dr. Z: That’s great. That’s really great.

Dr. Makary:  It’s been encouraging to see that.

Dr. Z: That’s really great.

Dr. Makary:  The last thing we want is a food fight over this sort of polarizing language that somebody is all good or all evil. We all want what’s best for people. There’s been bad guidance out there. Let’s not blame people who got a vaccine. Let’s just evolve our strategy as the data comes out. We have more data now than we did three weeks ago, and it’s becoming more clear. That’s why the UK is issuing this strong guidance, telling people to delay their second dose.

Dr. Z: Well, what do you think of the Johnson & Johnson one-dose option here?

Dr. Makary:  Well, look, it’s probably true that any vaccine that you give a second time is gonna augment your immunity a little bit. That’s probably true if you just think in terms of the immune system of any vaccine. Then the question is at what point are you getting pretty good protection? With influenza, we say that’s about 40 to 60%. Imagine back when we had the stated goal of getting a vaccine with more than 50% efficacy. That was the bar that the FDA had. By the way, in terms of the FDA, why the heck does Moderna have to apply to put 15 doses in a vial instead of 10 doses?

Dr. Z: I know, it’s just, what the heck.

Dr. Makary:  With that, anyway, separate topic. So we have a stated goal of getting a vaccine that was gonna be 50% effective. Imagine somebody, imagine a scientist came on The ZDoggMD Show and made an announcement to the world, “I have discovered a vaccine and it is 80% effective, and even 91% effective four weeks later. And by the way, if you give it a second time, it’ll boost it up to 95 and maybe increase the durability.” You’d say, “Okay, you know what? Forget the second part. Let’s just give this out to as many people as we can, and then talk about the second dose.” Wouldn’t we?

Dr. Z: Yeah, it makes sense. And that’s why I think the Johnson & Johnson thing is interesting. One interesting spin on that, because it’s an adenovirus vector, you do wonder, they’re doing second dose trials now to see does it make it better. You wonder if you’re actually gonna develop immunity to the vector, and so your second dose can be less effective at getting that DNA into cells. So there some interesting ins and outs. But it doesn’t matter. The bottom line is what you said. Look, the amount of vaccine efficacy that we’ve been blessed with in these vaccines is absurdly high compared to what we all hoped. In the beginning of this thing, man, I was like, “We’ll get 30% efficacy if we’re lucky ’cause it’s a coronavirus.” These things are squirrely. And already you can see it’s variating its way down to 50%. 50%, that’s amazing. And you’re still preventing severe disease in most of these cases, which is all you really care about. Like, “Oh, I got an asymptomatic case.” It’s like, yeah, well, as Doc Vader says when he talks about patient satisfaction, “Did you die?” Did you die.

Dr. Makary:  Yeah, I mean, why are we just talking about efficacy in terms of people who didn’t get the infection? Why is that our endpoint? Shouldn’t it be how many people survived? How many people lived? I mean, nobody has died for missing or delaying the second dose. In the trials, no one who got a vaccine died, period. Now, subsequently there is at least one reported case in Europe of somebody who died at three weeks, but nobody from missing or delaying the second dose. So look, if even those who get the infection have some partial immunity and a downgrades the illness to a mild or a moderate case from a severe case, that’s a win. That’s not a failure. And so I think we need to put this in context. I was doing some research, Zubin, for the piece on people who had COVID should not be getting immunized right now, as long as we’re supply-constrained, for “The Washington Post.”

Dr. Z: Wait, wait, wait, stop, stop, stop, stop, stop. You said something that disagrees with me. You did research before you spoke? What’s wrong with you, Marty? I did it it backwards. I should have just blurted something out-

Dr. Makary: And then confirmed the bias. Confirmed the bias with the cherry-picked studies. So tell me, so you were researching this thing for that piece in “The Washington Post” about people who’ve already had COVID.

Dr. Z: So I found this study, it was in 2005 it was published, where they looked at the few living survivors from the 1918 Spanish flu. These are people who were alive when they did this study in 2005. 32 people they found. They actually took their blood and checked their immune system, and they had functioning memory T cells that produced neutralizing antibodies against the Spanish flu virus, eight, almost nine decades later. And people are saying, “Oh, we don’t know. there’s no data on natural immunity.” Now, granted, that was the influenza virus. This is coronavirus. But still, the other studies now are showing that even if you live with somebody who had the infection and you didn’t develop symptoms, chances are you’ve got memory T cells that are functioning.

Dr. Makary:  Yeah, it’s funny because those outliers are superstars genetically as it is. So it may be they just have better T-cell memory. But I don’t think so, I think you’re right. I think that we have this very robust immune response to these infections. And now, the the measured immunogenicity in the trial data, but again, we don’t really know. What are the neutralizing antibody correlates of immunity? We don’t fully know. We can look out in the world and go, oh, hey look, your pool guy’s here. Where’s your mask, Marty? That’s what I’m gonna ask.

Dr. Z: Important work. So this is critical work.

Dr. Makary:  This is critical work. The key thing is the immune memory is gonna be strong, and it’s gonna be these things that we don’t typically measure in standard assays. The other thing is, I made this horrible mistake, Marty, and you know what this mistake is. I watched the news yesterday, and-

Dr. Z: You mean the entertainment industry.

Dr. Makary:  Sorry, the entertainment industry, the clickbait entertainment algorithm industry. I partook in it, and this is what I saw. ‘Cause I never watch actual TV news, because why would I do that? I have the internet where I can be misguided in words and little video clips instead of an anchor on CNN. So I go on YouTube and I watched the news agencies’ clips. Oh my God. If I were a little old lady sitting in my house watching that, I would think the world was ending. I would think that there was no immunity to COVID, the variants were all gonna kill us. Every piece of positive news that they put out is followed up by but we’re all gonna die. And I feel like they’re preying on our negativity bias as humans, how we’re wired to detect threat. And it’s really harming our ability to actually proceed with effective measures because everyone’s so pessimistic.

Dr. Z: It’s been sort of a scientific exercise to make projections up until this point. And actually, you you’re able to do it with some degree of precision if you really read up on everything and talk to the experts. But right now there’s a big unknown, and that’s the variants. Putting those aside, because that could be a game-change if they mutate around natural or vaccinated immunity. Assuming that we are able to get ahead of that and not fall behind the eight ball, given the current rate of deceleration, the sheer number of Americans who have natural immunity, probably somewhere over 100 million. Let’s say roughly 30 to 50%. you add to that another 100 million that have been vaccinated, which we’re gonna hit that number in March given the current rates. We could see a really low threat by April, and some restoration of normal life. Now, a lot of people will be timid and understandably so, but I mean, we might see a rapid deceleration, barring the threat of new variants, and that’s good news. That is something that’s at hand. We’re close to it. And I couldn’t disagree more when I hear the establishment experts say we have to vaccinate 75 to 80% of the public. Have you heard this?

Dr. Makary: Yes, I have. In order to get to herd immunity. No. Yes, we should, but we don’t have to in order to get to herd immunity. 100 million-plus people have natural immunity right now, and that is driving some of this slowing. And that’s good news.

Dr. Z: Yeah, and this is where you and Offit will definitely agree in that he said the same thing. By April, we’re gonna see this thing really start to tip because the combination of exactly that, natural immunity and vaccine immunity. And like you said, natural herd immunity as a strategy comes at a huge cost. You’re killing a lot of people, you’re causing some long-haul COVID which we still don’t entirely understand. A little bit of MIS-C in children which we don’t fully understand. And so that’s not a real strategy. But now out of no choice, we have that as a partial strategy, and vaccination as a very deliberate strategy. And I think the days of this thing are numbered, which means your and I ratings are going down, because people are gonna be like, “I no longer care about medicine.”

Dr. Makary:  Or the value of our information is expiring. It’s like MCATs. Three years, your MCAT expires. You no longer have the knowledge from studying for the MCATs. It just dropped off the cliff, and you are disqualified from applying to be a doctor.

Dr. Z: It’s brilliant. I mean, the thing has a shelf life, man. It’s like the expiration date on your milk. By the way, my daughter is obsessed with expiration dates because one time she threw up from some bad salmon or something. And so she has this conditioned fear. So she’s obsessively checking expiration dates. And I tried to tell her, your daddy eats things that are four months expired, and does it with pride. It’s called building your microbiome. It’s a key thing. I mean, sure, every now and again, he’ll shart a little. But it’s worth it.

Dr. Makary:  Maybe she threw up because it was too freshly caught. It was caught like 30 minutes before she ate it.

Dr. Z: I heard a school nurse, so she was at some swanky private school in Las Vegas, and back then when we did private school ’cause it was Las Vegas. And she said, the school nurse told me, yeah, there was a student complaining, came into my office with a stomach ache. And I said, “What do you think it was? What did you eat?” And he goes, “No, it’s what I didn’t eat. I didn’t have my wild grass-fed beef last night and now my stomach hurts.” And I was like, “So you have a grass-fed beef deficiency?” Really, this is how we’re raising our children.

Dr. Makary:  Oh, man. Hey, I love watching you and Vinay, man, Vinay Prasad. You guys have some great content, and the piece on No One Should Die Alone was so moving. It is a human rights violation for us to say loved ones can’t be with their family member when they, but you guys are doing great work and I’ve been loving every minute of it.

Dr. Z: Dude, you guys gave Vinay a platform on MedPage Today. It’s so funny how all these people congregate. I hope we’re not just forming an echo chamber, because we actually disagree about a lot of stuff. But it’s funny, we all are like, yeah, Vinay, Marty, let’s all hang out. And on MedPage, Vinay does his stuff. I mean, I read it and I go, I’ve changed my thinking about something, like I was on the fence about something.

Dr. Makary: Yeah, Vinay and you, kind of you with this too, like to challenge deeply held assumptions that really borderline on dogma. Things we need to question. And Vinay’s put out some really good pieces in MedPage. We love having him write for us, and we’re trying to push the field. I’ve got a piece coming out now, it should be out right now, on why we should be delaying that second dose for our patients and increase our vaccine capacity. And also, we’re trying to give people a forum so they don’t have to go through the clunky journals. Our study that was grant-funded as the largest study of COVID data to date, ever conducted in claims data. The ultimate analysis of risk factors for mortality has been under journal peer review for six months. And it’s not yet, now, it’s up on medRxiv, but MedPage Today was able to do a piece on it and talk about the preprint service. And Harlan Krumholz and I had a nice discussion about it. Does it make sense if you discovered the cure for breast cancer, does it make sense for someone to submit it in abstract form, wait six months for the national meeting, present it, have two months to submit it to a journal, put it under a six-month peer review, and then put it in a queue to be published three months later? Only for then some people to start picking it up and start talking about it. If you have the cure for cancer, tell people tomorrow, today. And that’s where there’s a lot of opportunity to change how we share information in medicine.

Dr. Z: Yeah, I think it’s really interesting. And of course the other side of that is the concern that you end up with a vitamin C-sepsis thing again, where you have science by press release, and then you do the follow-up randomized trials and it doesn’t pan out. But I think, especially in a pandemic-

Dr. Makary: ‘Cause the journals do that too.

Dr. Z: Ah, tell me about that.

Dr. Makary: A lot of people forget, journals publish shit all the time. False stuff, retractions… That’s the thing. People hold up the journals as this safeguard. Do you think that journal, reviewing our study for six months, has the data set and is doing their own regression analysis? Do they interview the patients? Do they look in our cabinet? No, they’re reading a thing we write up. It’s like the FDA. They just read what we write up.

Dr. Z:  So you’re basically admitting to fraud here, Marty, is what you’re telling me is that you just wrote. But actually, okay, go ahead.

Dr. Makary:  No, it’s just that the peer review is also a bit of a scam in the sense that doctors are not paid for it. So it’s like we work like crazy, and then, oh, volunteer your time so our private company can make money from selling the copyrighted version of what we produce.

Dr. Z: The journals.

Dr. Makary:  And we’ll just sign the copyright over to them for free because that’s how it’s done. And by the way, it’s prestigious and you can get promoted for doing that process. What the? Pay the doctors. If you’re gonna have a peer review, pay ’em and turn it around in three days.

Dr. Z: Yeah, that’s brilliant. I mean, the whole thing is really backwards. It’s designed for a different era when a bunch of old guys sat around a table scratching their beards, and “Well, . Did you see this table? How about this table? What about the p-value?” And now it’s like we have a thing called the internet. We have actually citizen scientists too who can contribute quite a bit. It’s just how do you actualize that, and how do you make that actually work? It’s really interesting. So your study actually, the one that’s on medRxiv right now, you were looking at risk factors for coronavirus, and it’s really interesting what you found. Tell us what those top risk factors were, because I was kind of like, “Oh, I didn’t know that,” when it first came out.

Dr. Makary: Yeah, so interesting what was not really known, but was suspected a little bit. The number one condition that predicted COVID mortality with the highest associated risk was sickle cell disease.

Dr. Z: Wow.

Dr. Makary:  Makes sense from what you were saying about your Leiden deficiency. It is largely a vascular disease. COVID is largely a vascular disease. There was that paper in April in “JAMA” that said 40% of the deaths from COVID were vascular-related, either a pulmonary embolism or something vascular-related. And so we learned anticoagulation. And then after that was kidney disease. Now, that has a lot of public policy implications because as you may have seen from me speaking or shouting, I wanna say I’m sharing on Twitter. Twitter’s a nasty place. Everything seems like a shout.

Dr. Z: Talk to Vinay for five seconds about Twitter, and you will get him, Vinay is quite calm until he escalates. And then he is just cursing, it’s on Twitter, I can’t even, they make me wanna die. And I was like, “Vinay, Vinay, take a deep breath, brother.” You’re across the table from me. We’re in droplet range.

Dr. Makary: Yeah, I barely mentioned Twitter to him once, and he almost started picking up chairs and throwing them.

Dr. Z: Yeah, he’s off the top rope, ready to just come down. So tell me about your Twitter shouting.

Dr. Makary: Twitter’s nasty, it’s a nasty place. But 7,500 dialysis centers in the United States give the flu shot every year, efficiently and early, with a very high uptake rate among kidney disease patients. They’re set up to do this. Here is the number one most common risk factor, kidney disease, and we didn’t give the dialysis centers the coronavirus shot, the vaccine? I mean, here’s a clear, so I’ve been out there on Twitter, and I suggested to the Department of Health and Human Services, it’s not just CVS and Walgreens you guys gotta hit. Dialysis centers, 7,500 of them, and a whole bunch of nephrologists have been basically saying, “Yeah, just give it to us.” You wanna spend $400 billion setting up new sites? Give it to us at the dialysis centers and we will give it out reliably as they do every single year.

Dr. Z: Yeah, I mean, and again, our system failures in the US. There was a funny, I guess there was an SNL cold open, does anything in America work anymore? Hopefully this is a wake up that we do need some systems thinking. I always talk about, where is it? Here it is. I talk about the elephant and the rider, like our unconscious emotional mind, our thinking thoughtful brain, And these are humans and we’re systems And we’re always this kind of dyad. But what are they walking on is a path. A path is our systems design, our protocols, our financial incentives, our business structures, our peer review process, our dissemination of information. The Twitter, the Twitter, I said “The Twitter” because I’m old, Marty. And as a result, if we don’t design that path in a way that we want that elephant and rider to go down the least resistance path and it’s good for everybody, then we’re screwing up. And we don’t really do that very well in the US anymore. So hopefully we can get back on that.

Dr. Makary: Yeah, and thanks for promoting civil conversations. I mean, I try to listen to every ZDogg episode with an open mind that you know what? This might challenge some deeply held assumptions that I have, and that’s okay. That’s the scientific process. But yeah, I would love to, medRxiv has done an incredible job during a pandemic. Gosh, can you imagine if we didn’t have medRxiv? I just saw Dr. Ho. So Fauci is kind of like the celebrity doctor. And to be honest with you, not a knock on him, he’s really a nice guy, but I don’t learn anything from anything he says. I don’t know if it’s just too general or whatever. Dr. Ho, Dr. David Ho at Columbia University, a famous virologist, he’s the dude. That’s the guy that I love to listen to. And he’s not slick on TV like Fauci. So of course the news organizations don’t have him on. There’s a certain TV style that they like. Ho it doesn’t have it. But Ho is a genius. I read everything this guy puts out. Look at what he put out. A paper that came out on medRxiv showing that the vaccines were less effective against the Brazilian and South African strains. The quote almost blew into the pool, but I’m gonna read it again. He said, look, “If the rampant spread of the virus continues and more critical mutations accumulate, then we may be condemned to chasing after the ever-evolving SARS-CoV-2 continually as we have long done for influenza.” I mean, this dude’s a prophet, man. I mean, those are not words of wisdom. That’s the decision tree we’re in right now, is are we gonna let this thing, these variants, dominate, or are we gonna get a hold and get a handle on this? And if we don’t, I mean, I think Dr. Ho is right.

Dr. Z: Yeah, actually, Offit did a good piece in” JAMA” about how we can better get a hold on these variants, and I think it was pretty valid. I’ll probably link to it at some point. So basically what I’m getting away from what you just said, Marty, is that the press “don’t love a Ho.” Is that what you’re saying? They don’t love that particular Ho. I mean, maybe there’s other eloquent Hos out there.

Dr. Makary:  I mean, there’s lots of those. The way you have a lab meeting is different from the way you talk on a 30-second sound bite on TV. And I’ve been trying to do some health promotion through the media just to try to get out some of these things I’m passionate about. But I think we could stand to learn a lot from Dr. David Ho and the researchers at Columbia University.

Dr. Z: I’m gonna listen to that ho a little bit more, Marty. I’m sorry, I just can’t resist. I’m basically a 12-year-old boy trapped in a 47-year-old doctor’s body. And I have a platform where I can say whatever I want till I get canceled. And I’m just pushing it right to the limit, Marty. And it’s so funny, we’re like evil twins of each other. Like you’re using MedPage which is this very reputable, august scientific thing. And then I’m just like, “Yo, it’s the ZDoggMD Show.” “I DON’T LUV A HO!” It’s very different.

Dr. Makary:  The ZDoggMD Show is on MedPage, and people get their benefits right there. So I mean, that’s probably what’s driving a lot of the traffic because-

Dr. Z: No, we’re co-affiliated. Yeah, I love It.

Dr. Makary:  I’m not sure they’re logging on for my articles since I’ve been known to start sentences with a number. Talk about cancel culture. The journals have been canceling researchers for decades if they start a sentence with a number. Shame on you. You should never do that.

Dr. Z: Oh, that is a perfect way to wrap up the show. Marty Makary, man, you always make me laugh. That’s why, look, I don’t care. You could be reading the phone book to me and I’d be like, “Uh-huh, uh-huh.” I love the way you communicate. And the thing is because your passion comes through, and the nice thing is you can disagree in a way that’s super polite, and you can agree in a way that’s super disagreeable. And that’s a key combination. I think it’s very important to challenge our assumptions any chance we get. So any other pitches before we go to the Z-Pac?

Dr. Makary:  Gosh, I love the Z-Pac. And I think maybe I could send you some of these pieces and we can post them.

Dr. Z: Hit me up on Link. Yeah, I can’t wait. So we’ll link to all your stuff, and by the way, if you guys haven’t checked out “The Price We Pay,” the book that Marty wrote, dude, it’s a transformative piece. I’ll link to the interview we did about it, because it just won business book of the year, and with good cause, because our healthcare costs affect all our business acumen in this whole country. It’s like an albatross around our neck. And then that’s not even talking about the human cost. So Marty Makary, man, it’s always a joy. So next time let’s do this again and let’s talk about something even more controversial, like, I don’t know, gout.

Dr. Makary:  We’ll talk about AI.

Dr. Z:  There you go.

Dr. Makary:  Or I.

Dr. Z: Just I, just I. We just want intelligence. I don’t care whether it’s a computer, a dog, or a human. Just something smart. Guys, I love you. Share the show, become a Supporter. And we are out, peace.