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--:-- Sean Rameswaram: Welcome to Today Explained. I'm Sean Rameswaram, and we're going to hear from... Knock, knock. Who's there? New variant. No! Go away!
--:-- Sean Rameswaram: Coming up on Today Explained, Vox's in-house epidemiologist on the newest sub-variant BA5. It's surging, there are little to no restrictions. We are officially in the do-it-yourself phase of this pandemic in the United States. Oh, and Paxlovid might make you feel better, but watch out for that rebound. More on that too ahead on the show.
--:-- Sean Rameswaram: Support for this show comes from ServiceNow. AI is only as powerful as the platform it's built into, don't you know? That's why it's no surprise that more than 85% of the Fortune 500 use the ServiceNow AI platform. Didn't know that. While other platforms duct tape tools together, ServiceNow seamlessly unifies people, data, workflows, and AI, connecting every corner of your business. And with AI agents working together autonomously, anyone in any department can focus on the work that matters most. I've never met an AI agent. Learn how ServiceNow puts AI to work for people at servicenow.com.
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--:-- Sean Rameswaram: Today Explained, Ramas Verum here with Karen Landman, MD, VOX. Karen, it feels like we're once again at one of those points in the United States, at least, where everyone you know has COVID or knows someone who has COVID? What is up with the latest COVID?
--:-- Karen Landman: Yeah, so we are seeing a different pattern over the last month or so with the latest sub-variant of Omicron that's hit the scene. That's the BA5 variant. Now the dominant strain in the U.S., according to the CDC. It's not only more vaccine resistant, but it's also more highly transmissible than other versions of coronavirus.
--:-- Sean Rameswaram: Now, we've been dealing with Omicron variants since the holidays last year. You remember with the very first wave of Omicron that really ruined holidays for a lot of folks. And tried to destroy my wedding. But this is the first Omicron variant that has happened concurrently with a rise in hospitalizations of people with COVID. So it's caught the attention of a lot of folks. How worried are you at this moment, Dr. Fauci, about the BA5 variant?
--:-- [Audio clip of Dr. Fauci speaking]
--:-- Dr. Fauci: Well, it's something we absolutely need to take seriously. Those data are not as straightforward to interpret as they used to be, in part because there's a lot of immunity. And there's also, you know, a new treatment on the scene that has been a real boon for keeping folks from being hospitalized and dying, especially super high-risk folks, but has also raised a lot of questions for a lot of people. COVID symptoms, they might actually return for some after taking the antiviral pills. The FDA now evaluating reports of a viral load rebound.
--:-- Sean Rameswaram: So for those of us who don't keep up with the latest news on COVID and have maybe lost the plot, what is the origin story of this BA5 variant?
--:-- Karen Landman: Omicron started with a really fast out of the gate. As Omicron cases sweep the country, the U.S. Surgeon General is warning we have not reached the peak yet. With lots of cases, lots of really sick people turning up in hospitals, and lots of deaths. That was over, you know, December and January of 2021-22. And then since then, we've kind of settled into almost what seems to be a steady state of transmission.
--:-- Sean Rameswaram: You know, it indicates that whatever is changing or happening in transmission, it's not resulting in lots and lots of morbidity and mortality and bad outcomes in people. Now, over that same period, we had lots of new variants. There were three other Omicron variants that followed that first one that really didn't seem to change a lot of the outcomes for COVID in Americans. But when BI5 came on the scene in early May, we started to see the proportion of folks hospitalized who had COVID tick up a little bit.
--:-- Karen Landman: The number of Americans dying of COVID is once again climbing, Up 10% in just the last week. Nearly 350 deaths reported every day. Anecdotally speaking, a lot of the people I know getting this new Omicron variant seem to be having a tougher go of it than the previous Omicron that we came to know and appreciate, the so-called chill COVID.
--:-- Sean Rameswaram: Did this new variant make chill COVID a lot less chill?
--:-- Karen Landman: I have not heard from either docs who are taking care of people with COVID in the hospital or in outpatient settings, nor from any of the science that I've seen that there's a different spectrum of symptoms with the new BA.5 variant. I have seen some data saying that it may be capable of killing respiratory cells a little faster than previous variants. And a hint from just one paper so this is a paper from a laboratory study so not definitive proof of anything it does to humans but some hint that it may lead to a higher number of viruses inside cells it infects.
--:-- Sean Rameswaram: But this is not proof of anything. So I just, I want to be cautious about how we talk about what might be different in the lab between BA5 and other variants and what that actually translates to and what it causes for people.
--:-- Karen Landman: But I have not heard a difference in symptoms or severity just as a consequence of changes to the variant itself. What I will say is that the further out any person is from their last boost, whether that is due to an infection or due to a vaccination or booster shot, the more likely they are to have a more severe set of symptoms.
--:-- Sean Rameswaram: Which is to say that the older boosters are still effective against this newer Omicron variant? I mean, the short answer is yes, but it's actually a complicated question in several ways.
--:-- Karen Landman: Let's talk real quick about those neutralizing antibodies again. Oh, yeah. Those are the circulating antibodies that you get after an infection or after vaccination that are kind of imprinted on whatever it was you got in the vaccine or whatever variant you were infected with. Unlarge and in charge, baby.
--:-- Sean Rameswaram: We see that even though in the lab they're less effective against the BA5 variant than they are against previous variants, either of Omicron or, you know, even, like, for example, Delta variant. Well, medium, I guess. They still are effective to a degree in protecting people from severe disease.
--:-- Karen Landman: Oh, my God! Oh, my God! What they might not be effective against is protecting people from becoming infected to begin with. So, you know, you might still turn up with an infection, have a positive test, have some symptoms, but you're still very, very unlikely, you know, if you have that level of neutralizing antibodies to end up in the hospital or die from your infection.
--:-- Sean Rameswaram: Medium is good enough. Oh, yeah. Now, I know that the FDA and CDC are interested in getting some boosters that specifically target Omicron. Moderna is saying the picture of what the fall boosters look like might be starting to shape up. They have new data this morning at looking at a combo booster that protects against both Omicron and the original strain of the virus.
--:-- Karen Landman: But these boosters aren't expected until fall at the earliest. And by then we will surely have new variants, right? Is that really going to help? If you look at how quickly waves of variants rise and fall, both in the United States and elsewhere, I mean, we're going to be well done with BA5 by the time these vaccines, these boosters become available in the fall.
--:-- Sean Rameswaram: And on to the next one. And who's even to say whether that next one is going to be an Omicron variant? I mean, there's nothing to suggest that right now. So I don't want to sound like I have information other people don't. All the variants of concern or of interest worldwide that I'm aware of right now are Omicron variants.
--:-- Karen Landman: But I think the lesson that we've learned over the last two and a half years is that, you know, there are new variants brewing right now in people all over the world. And preparing to deal with the variant that is currently in circulation is a losing game on its face. We're just not going to be able to play catch up in that way.
--:-- Sean Rameswaram: And so focusing on broader strategies for minimizing spread while we're in kind of a question mark phase, while we don't know what a new variant is going to do. And, you know, focusing vaccine efforts on products that are going to be more effective at protecting people from the endpoints they really care about, you know, even if that includes infection and certainly when that includes long COVID, not just hospitalization and death.
--:-- Karen Landman: So we want to try to focus vaccine protection less on variants and more on sort of a longer term product that would protect against all future iterations of this virus. And I think at this point in the United States, a question a lot of people have, because we do have so much that looks like herd immunity, a question people have is, can I get this new COVID? How protected am I from my previous COVID?
--:-- Sean Rameswaram: We did an episode back in June called How Often Can You Get COVID? And we spoke to the people studying the question, and it seemed like the answer was, we don't really know, but you do have some immunity for a while, but it's all about your risk tolerance, et cetera, et cetera. Does this new variant change things for vaccinated people?
--:-- Karen Landman: It does, because what we see from Omicron infections is that when you get infected with an Omicron variant, it means that if you later get infected with, I don't know, if you run across a Delta variant, your Omicron infection kind of boosted you. It's protective against that. But if you then get infected with another Omicron variant instead of an earlier variant, you're not that well protected.
--:-- Sean Rameswaram: So Omicron doesn't really boost for its own variants as well as it does for other variants, which is a little weird. That's interesting. Research will help define this a little bit more going forward. It may be that the immunity that it provides lasts less time. It may be that it really depends on a very specific feature of whatever the Omicron variant that it encounters is.
--:-- Karen Landman: So we may find that it's better at protecting against some Omicron variants than others. But that's, I think, what's raising some experts' concern that we may have even less long-lasting immunity from infection-related boosts than we did from previous infections. So an infection with an Omicron variant now may only give you a few months of protection, whereas infection with Delta last year might have given you, I don't know, six, eight months of protection.
--:-- Sean Rameswaram: The answer to that question is I think going to determine the shape of the pandemic going forward. And we don't know it yet. We don't know it yet. Classic pandemic, right? That kind of how it do. Where there is room for confusion and inconsistencies, pandemic's going to come through. More with Vox's Karen Landman in a minute on Today Explained.
--:-- Sean Rameswaram: Support for today's show comes from Adio. What is Adio? Adio Adio is an AI native customer relationship management system built specifically for the next era of companies. They say it's extremely powerful, adapts to your unique data structures and scales with any business model. According to Adio, Adio takes less than a minute to set up. And within seconds, you will have your email and calendars synced. You'll see all your relationships in a fully fledged platform, they say, all enriched with that actionable data.
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--:-- Sean Rameswaram: Explained Explained That's kind of how it do. Today Explained, we're back with Dr. Karen Landman from Vox, and we wanted to talk about this one thing that was supposed to be a game changer in the panty, Paxlovin. This is not meant to nip your symptoms in the bud and get you back to the party. This is meant to keep older and other high-risk, especially unvaccinated, but also vaccinated high-risk folks out of the hospital and alive.
--:-- Karen Landman: But here, too, there have been some complications. We got to talk about endpoint. If your endpoint is preventing severe disease and death in high-risk folks, it's still doing great. There's no indication that it has fallen off in any way, even with BA5 on the scene. But what it is doing is proving to be kind of incomplete treatment for controlling symptoms.
--:-- Sean Rameswaram: You probably heard that Anthony Fauci himself had what's called rebound symptoms after taking Paxlovid. And then on the fourth day, just to be absolutely certain, I tested myself again. And I reverted back to positive by the antigen test. So it was sort of what people are referring to as a Paxlovid rebound.
--:-- Karen Landman: And so he started this five-day course of Paxlovid, which means I think it's three pills twice a day for five days. And then a couple days after that, he tested positive and actually developed worse symptoms than his first set of symptoms. And then over the next day or so, I started to feel really poorly, much worse than in the first go around.
--:-- Sean Rameswaram: But he basically just took a second course of Paxlovid and did fine, as do most people who have these rebound symptoms. But he didn't go to the hospital and obviously had no severe outcome from the infection, as do, to my knowledge, all people who have had rebound symptoms after a Paxlovid course.
--:-- Karen Landman: Part of fine-tuning a new drug is figuring out how it works in the real world. In Pfizer's trial, only maybe 1% or 2% of people had rebound symptoms after five days of Paxlovid for an early COVID infection. But it seems just from the anecdotal reports I'm seeing and hearing, it seems like in the real world, there's probably a higher proportion of people who are experiencing that.
--:-- Sean Rameswaram: But wait, Karen, are you saying that Pax Lovit essentially for some people gives them an additional bout of COVID? It's not that the Paxlovid is giving them an additional bout of COVID. The original COVID that they had is giving them persistent symptoms that the Paxlovid was not enough to completely turn back.
--:-- Karen Landman: There's some question about why that is. You know, people are worried. Does that mean that if I take these five days of COVID and my symptoms come back, is it a super COVID? Is that COVID sort of stronger than it was before because it overcame those first five days or is something else going on?
--:-- Sean Rameswaram: And I think some early data I've seen some single patient studies that suggest that's not what's going on, that it's really just that the viral infection requires a higher dose for a longer time or even just the same dose for a longer time in order to get into all the cells where the COVID might have gotten into.
--:-- Karen Landman: So I think it's probably just a matter of the science of pharmacokinetics and how drugs get into your body cells and take action and how they get eliminated by your body. You know, drugs act differently in different people because our metabolism of drugs is different. And so I think we'll probably end up seeing the dosage that's recommended of this drug change as we learn more about how many people are experiencing this and who might need a little bit more of the drug in order to completely treat the viral infection with COVID.
--:-- Sean Rameswaram: But it sounds clear that Paxlovid has done more good than bad and it's not going anywhere. I think it's done a lot more good than bad. I mean, when you think about what, quote, bad Paxlovid might have done, okay, it has some side effects. They're generally pretty minor. I hear most about the metallic taste in people's mouth for people, but otherwise, it's generally pretty well tolerated.
--:-- Karen Landman: Metallic taste? I haven't heard about that. I have heard that people about an hour or so after taking it it tastes like they sucking on a penny. It just kind of a gross metallic taste in their mouths. It probably a function of one of the component drugs of Paxlovid and it just kind of an annoying and sort of gross side effect.
--:-- Sean Rameswaram: But, you know, compared to being hospitalized, I think it's highly tolerable. I think probably the biggest concern of harm with Paxlovid is that it gives people confidence that they're treated, and they may therefore go back to mixing with other people in a way that if they do relapse, if they do rebound on their COVID infection after taking Paxlovid without realizing it, they could transmit COVID to other people without realizing it.
--:-- Karen Landman: I think we really cannot expect perfection from medicines here. I think we need to manage our expectations and understand what it is we're actually trying to accomplish with these medications. I know we'd all really love to make COVID go away and not be a concern at all. And we all wish we had a magic pill that would do that. And maybe one day we will, but I think it's a lot more likely that we're going to make smaller incremental progress in reducing the virus's disruption of people's health and people's livelihoods by finding medications like Paxlovid that do a lot to reduce hospitalizations and deaths, even if they have some problems with finding the right dosage, even if it takes some time for us to find the exact right dosage and fine-tune things early on.
--:-- Sean Rameswaram: Could things get worse, Karen? It felt like we were trending better for a minute there, but now maybe not so much.
--:-- Karen Landman: Really hard to say, and since we can't say definitively that it's going to get better from here, I think we have to be prepared for worse. You know, Omicron is genetically really different from the variants that came before. When you look at the genetic tree, all of these other variants kind of cluster on one side, and then Omicron is just sticking way out. It's like somebody grew a third arm. It's just not right.
--:-- Sean Rameswaram: There are a lot of mutations that caused Omicron to emerge. And, you know, those mutations we think happen largely when you have people who are very immunocompromised and infected for a very long time with COVID. And as the virus replicates in their system, it just accumulates more and more and more variants and then eventually spreads to other people.
--:-- Karen Landman: This is sort of how the model for how we think these new variants emerge. And there's no reason to think that's not currently happening and that we might not see a completely different variant emerge within months or years. It's a little hard to say right now with confidence that we're not going to see things get worse with this particular pathogen ever.
--:-- Sean Rameswaram: However, it's also important to keep in mind that not all mutations that happen to a virus benefit the virus. Sometimes those mutations benefit us. But we've all learned not to make any promises about what will happen with viral evolution just because we've been surprised so many times in the past.
--:-- Karen Landman: So we got to be prepared for anything. We got to be prepared for anything. And yet it feels like what we sense more and more from the public in terms of this pandemic is apathy. And it's not just apathy from the public anymore. It's apathy from governments to do anything. And then when people are actually scared, you have the government saying, oh, yeah, we'll get you something about that current variant in the fall, which only leads to greater apathy.
--:-- Sean Rameswaram: I mean, how confident should we feel that public health will have the response it needs to if this does get worse? You know, to my mind, the things that are going to save us, us individually, the people listening, the people in their families, the people they care about, their neighbors, their communities, what's going to save us from this is not going to be a magic pill.
--:-- Karen Landman: I mean, it may be some fine tunings in vaccines, but what will save us is awareness that things are changing. And a willingness to do what we need to do to respond to that. And, you know, I realize that apathy, it's pretty normal to start feeling like, you know, when things are terrible for a long time, that the terribleness is just the long-term way things are going to be. So why bother?
--:-- Sean Rameswaram: But the reality is that this is coming in waves. And right now we're seeing a wave that we don't know how severe it is. But I think if we think of our response to this less as either we care or we don't care and more as we care all the time, but we just fine tune our behavior and that's OK.
--:-- Karen Landman: There can be times where we walk around in a mall without masks and it's pretty safe. And also there may be people for whom it's okay to have different behaviors than other people. I think if we communicate to folks that they don't have to have an N95 on at all times for the foreseeable future, it might be a little easier for them to hear the alarm when it is sounded.
--:-- Sean Rameswaram: Dr. Karen Landman, she's Vox's in-house epidemiologist. You can read her work at box.com. Our show today was produced by Tori Dominguez with a big assist from Miles Bryan. It was edited by Matthew Collette and fact-checked by Laura Bullard. Paul Mounsey engineered. I'm Sean Rameswaram for him. It's Today Explained. Thank you.
