Welcome to an expedited episode of The Podcast by KevinMD. Jeremy Faust is an emergency physician who can be reached on Twitter @JeremyFaust and on Instagram @JeremySamuelFaust. He also publishes the newsletter, Inside Medicine.
Kevin Pho, MD: Hi, and welcome to the show where we share the stories of the many who intersect with our health care system but are rarely heard from. My name is Kevin Pho, founder and editor of Kevin MD. Today in the show, we have Jeremy Faust. He is an emergency physician at Brigham and Women’s Hospital in Boston in the division of health policy and public health and an instructor at Harvard Medical School. He has been the first or senior author on research manuscripts published in the Journal of the American Medical Association, JAMA Internal Medicine, the British Medical Journal, and the Annals of Emergency Medicine, where he serves as an associate editor for news and perspectives.
His writing has appeared in The New York Times, The Washington Post, The Boston Globe, The Atlantic, and Scientific American, and he now writes Inside Medicine on bulletin.com. You surely have seen him on television as he has appeared on CNN, MSNBC, BBC, NBC, ABC, and NPR. He is also the co-host of the award-winning medical education podcast, FOAMcast. Jeremy, thank you so much for joining me on the show.
Jeremy Faust, MD: It’s great to be with you.
Kevin Pho, MD: So we are now speaking on Saturday evening, December the 11th. How worried should we be about the Omicron variant?
Jeremy Faust, MD: Right now, the DEFCON situation is very tenuous. It’s really difficult to know where we’re headed. In the past couple of weeks, we certainly have gone from seeing something that looks scary on paper in terms of it might be more infectious, to seeing that really take over in many areas. So in terms of people who are unvaccinated, I’d be very worried because this virus is now even more contagious, it looks like, and it’s going to find those people.
The question we really don’t know yet is for those of us who are vaccinated or people who have a history of infection and vaccination. How worried should those people be? And I think that it’s really an open question. And anyone who tells you that it’s doomsday is prematurely panicking. And anybody who tells you you don’t need to worry is prematurely telling you something that we just don’t know yet.
Kevin Pho, MD: There are some reports in South Africa that say that Omicron may be less virulent than the Delta variant. What are you hearing about Omicron in South Africa?
Jeremy Faust, MD: I do have friends who work there, and it’s true. We’re hearing that. But what I would say is that everyone has two concerns. Number one is their lag, meaning does this virus infect people a little bit sooner and therefore we see a case spike earlier than we might have seen in previous waves? Several days really now, we will finally start to see a real uptick in severe disease and hospitalization, and death. That’s one thing we do not know yet, and we’re hoping that that’s not what is happening.
The other thing that we know is that we’re not hearing a lot of the same story that would be very alarming. So, for example, I was being told, okay, every single patient I ever see is vaccinated. Maybe they’re boosted, and they are getting Omicron, and they’re in the ICU, and they’re very sick. It wouldn’t take many of those anecdotes to actually move the needle for me and really be concerned.
On the flip side, we haven’t heard that, but it’s asymmetric because we don’t yet know if the numbers are adding up the way they have in the past, so we can say, okay, we know what we’re dealing with. So, unfortunately, it’s frustrating because if the anecdotes were in the bad direction, we’d have to take it so seriously. But the anecdotes being slightly in the better direction, we have to be careful not to dance in the end zone too soon, if you will.
Kevin Pho, MD: So you mentioned about vaccine response, and I’m reading The Boston Globe, and there’s a headline “Pfizer Boosters Provide Omicron Protection, Study Finds.” I know this data has been released within the last few days. So what exactly is the data when it concerns the vaccine’s effectiveness against Omicron?
Jeremy Faust, MD: It’s really important, and we’re learning this, but the thing that I want people to always check for when we’re talking about this is what is meant by effectiveness or efficacy, but really effectiveness is the real-world term. And there is a major difference between effectiveness against getting infected and effectiveness against other outcomes like severe illness, long-term effects, hospitalization, and death. And that’s really important because we could have a vaccine that has zero effectiveness against infection. And that sounds really scary, and Omicron could end up being close to that for some people. We don’t know. But that same vaccine could still be providing 90 or 95 or 100% protection against these other feared outcomes, like longer-term effects, hospitalization, and death.
So right now, I think it’s pretty clear, based on the genetics, the laboratory data we’re now seeing in terms of how well does the virus bind or evade the antibodies from people who’ve recovered from COVID, people who’ve been vaccinated and boosted? I think that drawing those lines, we’re beginning to be able to do that in a way that we say, okay, look, we’re concerned that the effectiveness of these vaccines against an infection is likely far, far lower than anything we’ve seen so far, even worse than Delta.
But what we don’t know at all is what that means for severe disease and worse. That matters, and I think that we have occasionally lost the thread there, even during the Delta era, where we saw a really big decrease in the vaccine effectiveness against infection in, for example, young people, but we never saw a budging in that protection from the two-dose series. The two-dose series may have maxed out the protection that young people who are healthy get from these vaccines, because it’s so good.
Now in older people, we didn’t see that. We began to see from Israel and other datasets that both happened, more infections and even among the infected, an uptick in severe disease. So we don’t know. I just want people to be very careful whenever they are thinking about this question to look at what’s being measured.
Kevin Pho, MD: Now there are some people who say that fully vaccinated now means three shots. What do you think about that?
Jeremy Faust, MD: I think that’s a convenient talking point. It’s something that sounds very settled. I don’t share that view, and I’ll tell you why that is. First of all, I think that these vaccines were clearly studied in some of the best randomized controlled trials that have been ever done and certainly under the circumstances. And these were designed to look for the outcomes that we all are aware of, the severe disease, symptomatic disease, and they’re performing in the way that they were meant to. So I don’t know how you can add to that when there are certain populations who clearly only get a benefit for preventing infection.
Now look, preventing infection in some people is very, very important. There’s just no doubt about that. But there are others for whom that’s just not the case. And I also think that if we understand that these vaccines are not going to keep us from getting infected over and over again, that we’re not going to reach COVID zero through these vaccines, it really becomes a bit of a problem to say that it’s a three-dose series, because what you’re really saying is okay, every single person in the developed world now needs three doses, no matter what. And that has equity issues, no matter how you slice it.
We’ve already seen, in the equity quotient, if you will, in the booster campaign, massive equity problems. And this is something that happened during the initial series, so we’re just perpetuating that. So I get really worried that because, for example, the Hispanic and Latino community had a slower uptake of the vaccine, it’s caught up over time slowly but surely. It’s still not as good as it ought to be, but it’s caught up. Now with the booster campaign, you’re saying to people, well, you were slow, so you don’t get to be boosted, and that also means you’re not fully vaccinated now.
So now in a way, because of our structural problems, we are going to be perpetuating this. I think that’s a real problem when, in fact, you realize that really what we’re after is keeping people safe, and whether or not they’re infected is not necessarily always synonymous with that. So I’m actually really worried that that talking point can backfire in ways that we have not yet really contemplated.
Kevin Pho, MD: So I have a question about vaccine equity. Do we not have enough vaccines to do both boosters plus give enough vaccines to countries that don’t even have the primary series yet?
Jeremy Faust, MD: Well, I’m not an expert on that exact issue, so I would defer to people who do speak on those issues frequently. And quite frankly, I reach out to those people and ask that exact question, and their answer is no, that’s not the case. If not today, then tomorrow. There’s a ripple effect. So, for example, certainly a vaccine that’s on the shelf at your local Walgreens or CVS is not going to be suddenly transported to Beruni, where they just started vaccinating people a couple of months ago, I think finally. We understand that.
At the same time, we know that the vaccine manufacturers understand their supplies, they understand their supply line. So knowing that the United States and Europe are going to start boosting everybody, you know that at some point there’s just downstream, they keep going to the same places over and over again. So in this case, demand creates the supply problem, not supply creating the demand problem. But again, I don’t study that issue per se, but what I will tell you is that when I’ve asked that exact question to people, to WHO or people at MSF, Doctors Without Borders, they keep saying the same thing, which is yeah, not the actual stuff on the shelf right now, of course, but it’s the policy that got them there that we perpetuate that does lead downstream to those problems elsewhere.
And that’s a big, huge problem because look, maybe Omicron came because of that issue. We don’t know, but certainly a variant can come out of someone more likely if they haven’t received their primary series. So we have to think globally. I know that sounds like a cliche, but it’s actually really important.
Kevin Pho, MD: I’m a primary care internal medicine physician, and one of the most common questions I get is the effectiveness of natural immunity versus boosters. And I’m seeing data all over the place on this by proponents of the booster and against the booster. What’s your take on the effectiveness of natural immunity versus the vaccines?
Jeremy Faust, MD: I’m not a great expert on this. I think that what I will say for Omicron is we’re already seeing that this concept of hybrid immunity, which that’s a combination of you’ve been vaccinated and you’ve also been infected with SAR-CoV-2, which is, of course, the virus that causes COVID-19. But that seems to be the strongest portfolio, if you will, against this virus, against this disease. Of course, the problem with that is that you have to have gotten coronavirus already. You have to have confronted COVID-19, and you have to have not had any of the downstream consequences that are so feared. So it’s a bit of roulette.
Now, of course, the roulette analogy is not quite apropos because in a game like roulette, literally if you lose, you don’t get anything for that. Whereas, at least in coronavirus world, if you lose, you get infected, you at least get something for it. You get that immunity. You get some degree of memory. So obviously for those people who have had both, that’s the strongest. Now that’s certainly with respect to the effectiveness, the contagiousness piece. I actually don’t know whether that’s the case for the severe disease.
I certainly think that the early Omicron story is concerning, which is that reinfection is really, really common. Look, the thing with the vaccines are is it’s a standardized dose. It’s a whopping dose of spike, and that seems to really provoke an immense immune response when we get the vaccine. We know that once we do that, our bodies also do develop what’s called a diverse repertoire. We anticipate mutations. We anticipate that something else might show up that’s a little different. It’s quite an amazing evolutionary thing that occurs.
And that can happen in natural immunity, but I think with the vaccines, it’s just a big standard whopping dose. And I think it’s likely to be sufficient, but I think that Omicron, again, we always have to be moving with the data, and we’ll see what happens in the next few weeks or months.
Kevin Pho, MD: So I know that we have a couple of antivirals coming in near horizon. Where are we in terms of therapeutics?
Jeremy Faust, MD: Well, one thing is that therapeutics are certainly the answer to the problem before you have a vaccine. So look, if you have an escape variant that the vaccines don’t work for, maybe the therapeutic can help you. That’s one reason to have them around. So again, I do worry sometimes that people go to therapeutics or they cling the therapeutics as a way to think to themselves, well, I don’t need to get vaccinated because I can always get monoclonals or I can get the Pfizer or Merck monoclonal pill.
And I think that two things have happened. I think with respect to Merck’s product, that’s molnupiravir, we certainly have seen early data that was really promising, which was then downgraded substantially recently. I think that was a big disappointment. So I think we’re waiting to see, again, in the post-vaccine era, in the Omicron era, where are we left?
Because we had this signal that was like, wow, decreased hospitalizations, maybe less depth. This is a big, big deal. But then it got downgraded. Now we have a variant. I’m very concerned. Same story for Paxlovid, which is the Pfizer product. I almost feel like the warranty expired already, but we’ll see what happens. Fluvoxamine remains such an interesting story to me. Again, fluvoxamine is an SSRI. It’s used for depression or anxiety, and it’s inexpensive. Why it works was a surprise to me. The mechanism basically has to do with inflammatories, which is why not all SSRIs work, because not all SSRIs have this property. But the data out of Brazil and elsewhere, pretty encouraging.
But again, same story. What happens now when you study in people who are vaccinated versus unvaccinated in the Delta or Omicron era? So I remain cautiously pessimistic is the way I put it that these things are going to make as big of a difference as we want right now, but I think we need to pursue them because we’re going to eventually find some winners here, especially inexpensive ones. And when that happens, I think it’s a huge arrow in your quiver to have.
Kevin Pho, MD: So I want to follow up on fluvoxamine because that’s certainly an inexpensive option that certainly can be used in a primary care setting when compared with the antivirals that are coming down the pike. Why aren’t we hearing more about fluvoxamine?
Jeremy Faust, MD: That’s a great question. It’s always really flabbergasted me too. Because when I first heard about fluvoxamine, it was really a long time ago. It was 2020. And at that time, we had hydroxychloroquine being floated around. We had colchicine being discussed. People were talking about azithromycin and ritonavir, all these different things that were studied. And of course, we actually had dexamethasone, which worked. So we have all these suggestions, which I think were really important ones, these repurposed medications, things that we had lying around. And, of course, ivermectin became a big one as well.
And of those, really obviously dexamethasone was shown in clinical trials to be effective for people with low oxygen, which I have to tell you the effect size surprised me. And I almost didn’t believe it at first, but the data are the data. Of course, we know that the internet and hucksters out there wanting a quick fix have been trying to sell some of these things like ivermectin and hydroxy, which is unfortunate. I wish they worked. We know they don’t.
But the funny thing was with colchicine and fluvoxamine, there was early data that really was optimistic for me. Wow, this is actually working. These are small trials, but they’re really encouraging. Well, colchicine did not work out in the bigger trials. So, okay, that’s why you do the science. And fluvoxamine so far really looks good. But again, there’s some question about what are we measuring? Are we measuring whether patients get severely ill? Are they hospitalized? For how long?
So there’s a little bit of a difficulty there in terms of what we’re measuring, but why it is that fluvoxamine hasn’t taken off. Well, for one thing it’s cheap. So unlike the Merck and Pfizer products, no one’s really behind it in terms of trying to make a lot of money. And I hate to say it, but people have an aligned motive. Yeah, they want to help people, but they’re running these businesses. But why the internet didn’t go nuts with fluvoxamine, it bewilders me. It’s like, look, if you’re going to go nuts with one of them and tell me that this is the answer, why not choose the one that has actually some data to support it?
So look, I don’t want to tell everyone that it’s the cure, but I do think that it’s just interesting to me. As you said, if you’re going to pick a winner, pick the one that actually shows a glimmer of hope, which I think is where we’re at with fluvoxamine.
Kevin Pho, MD: Now with the Omicron variant that is emerging at the height of holiday season, what kind of advice and precautions are you giving to patients when it comes to holiday gatherings and travel?
Jeremy Faust, MD: This is really hard because two weeks ago I was saying, “Well, let’s wait two weeks because by mid-December we should have answers.” And it’s getting close to travel time. Got to know. I’m like, we got to get answers. I’ll tell you what I’m thinking about. I’m still open-minded about this. I’m still in play. So my family is flying to California. I have to work over Christmas, so I’ll stay here. And then we’re supposed to go to Mexico after that. And it’s day-to-day for me. Right now we’re planning to go, but if I learn something about my protection from the vaccine isn’t what I thought it was. If I get some information about my protection against the outcomes I’m really worried about, long-term effects, then I’m going to cancel those plans. I’m not going to do it. And I’m going to see, look, do we need Omicron specific variant?
We could get that in 100 days. And I know that sounds like science fiction, but we can do that. It’s an incredible achievement that these mRNA vaccines have done. Look, you’ll hear me dunk on these pharma companies sometimes, but I got to hand it to them on the mRNA vaccines. This is an incredible achievement, and that we can swap out the code and basically do a phase one trial, dozens of patients would need to be shown to have a good response, and then we could move forward with a rollout.
But to answer your question, I’m waiting. And that’s frustrating because people want answers, but I have to just be honest and say, it’s day to day. So if we don’t know and people have different risk tolerances, it begins to sound like last year to me. Look, wear your masks. I, of course, have been a major proponent of rapid testing as a way to keep people safe. Look, I know they’re not perfect, but I’d rather have an answer that’s almost certainly correct right now than no information for 48 hours, which happens with PCRs, especially when people start getting worried. So I think that a little bit more like 2020 than I was hoping, but at the moment, I have not canceled plans yet. But look, if something comes out tomorrow, I’ll do it. So I’m trying to keep an open mind.
Kevin Pho, MD: And my final question. What are some of your take-home messages that you want to leave with the Kevin MD audience?
Jeremy Faust, MD: Right now, I think that people need to understand that this virus is clearly mutating to become more contagious, and that is in its evolutionary best interest. That’s what viruses do. That is not the same thing as a virus having an advantage by making us more sick or breaking through our vaccines. There’s no advantage there. So we don’t yet know about that.
So what I really want your audience to know and to think is, do I care about infection or do I care about outcomes? Sometimes those things are totally interchangeable, like an infection is an outcome. You get infected. You have a long-term consequence. But as time goes on, I want people to really think about whether we’ve uncoupled that with our vaccines, with our therapeutics. And if we have, then we should really be watching a different set of outcome metrics.
So I want people to be willing to stand up their level of concern when something new and unknown comes along. But I want them to also be able to deescalate that when we learn more. Because look, we’ve been humbled by this many times in many directions, and I think that watching those issues in real-time and responding to the data is really our best chance to keep getting better at this.
Kevin Pho, MD: Jeremy, thank you so much for sharing your time and insight. Thanks again for being on the show.
Jeremy Faust, MD: It’s my pleasure.
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Hosted by Kevin Pho, MD, The Podcast by KevinMD shares the stories of the many who intersect with our health care system but are rarely heard from.