Welcome to this special episode of The Podcast by KevinMD, where I interview two infectious disease physicians on the COVID Omicron variant. They share their unique perspective on this threat answer the following questions: How do these early days of the Omicron variant contrast with past variants? What do they think about the travel restrictions? How has the media covered Omicron? What are the best-case and worst-case scenarios? And about Omicron keeps them up at night?
Kevin Pho, MD: Please share your journey and story to where you are today.
Nahid Bhadelia, MD: My entire career is based on emerging infectious diseases in particular, focusing on viral hemorrhagic fever. So for the last 11 years or so, I ran a biocontainment care unit that backed up a maximum containment laboratory, the National Emerging Infectious Diseases Labs at Boston University. So a biosafety level 4 lab generally does work on exotic pathogens that we don’t have a lot of treatments around. And most of those pathogens to date have been viral hemorrhagic fevers. And then over the course of that period have been involved with outbreak response, initially with H1N1, then with Ebola, Marburg in some ways, and then Lassa fever and others in different parts of the world, including West Africa in 2013 to 2016, and then recently in both Uganda and Liberia right before the pandemic. And now, as with everybody else, I’m working on COVID-19. My research and work focus is medical countermeasures, diagnostic evaluation, and health systems preparedness for emerging infectious diseases.
KP: Of course, today, we’re going to talk about the new variant discovered a few weeks ago but recently came into the news over the Thanksgiving holiday, the Omicron variant. So tell us what we know about that variant now.
NB: The reason this variant came to attention really is thanks to South African researchers, really great genomic capacity there, surveillance capacity there. And the concern was that this variant that was first discovered November 9th, had these mutations that first of all, the number were immense, 50 mutations or more, 32 of them being in a spike protein, including some in furin cleavage site, the part of the spike protein that’s really giving the virus advantage in terms of the connectivity to the human, to the human cells. And with that … so that itself was concerning, the mutations from the analysis of South Africa show that there are those that we’ve seen on prior variants that increase transmissibility as I’ve just mentioned, but also others that we’ve seen in variants such as Beta that had immune-evasive, potential immune-evasive elements or characteristics as well.
The reason South Africa sounded the alarm is that they’re also seeing an increase in the number of cases at the same time. So there’s this epidemiological potential where it’s both the likely virus and the number they’re seeing in many different regions. Since then, we know that this virus has been found both in travelers and travelers not from South Africa or Southern Africa, in Belgium, in Hong Kong, in Germany, and in the U.K. now. And the reason the WHO has now termed this a variant of concern is that it’s not just the mutations, but the likelihood that in that small number of cases that they’re now looking at in South Africa, there’s a concern that there might be cases of re-infections that combine with the mutations themselves. But interestingly, to date, we haven’t been worried about many of these mutations that have had immune-evasive issues because they’ve never been able to compete with Delta.
It seems that Delta, the king of the hill with this higher transmissiblity, sort of always held steady and all the other variants that might have been scarier from the perspective of potentially rendering monoclonal antibodies not as effective, or reducing efficacy of vaccines more, haven’t been able to get a foothold because Delta is more transmissible. So this is of concern because if it truly is out-competing Delta and it has immune-evasive characteristics, then it’s really something that we should be paying attention to. I will just caveat all of it to say that this is all very early. It is a cause for concern, but definitely not for panic.
KP: Give us a sense of the South African population in terms of what percentage of the population has been immunized. And do we know that the people who got infected with this new variant were primarily immunized or unimmunized?
NB: So, about 30% or less are fully immunized in South Africa on average. So we don’t actually know right where this virus originated. It was detected in Botswana and South Africa. But the continent of Africa, in general, has seen about 7% fully immunized so far. And we know that in places that are under-immunized, where there are high rates of transmission, there’s always a concern that the virus will evolve more and new variants will appear. We don’t know if that’s the case with this particular variant. A couple of interesting scientific characteristics that might be of interest to your listeners. So this doesn’t seem to be an evolution from a Delta variant. So it’s not that it would evolve from Delta, when Trevor Bedford, who is really a great resource to follow from the University of Washington on this, did his analysis and shared some of this.
It really seems to be from an earlier strain, even from early 2020. And the concern is that this might have been a virus that evolved in a single person over time. We’re seeing high rates of viral evolution, immunocompromised patients who may have a longer period of time, and the ability to clear these viruses. So there might be mutations within that one individual. And so that’s sort of the concern, majority of the cases in South Africa, actually that they’re currently detected with Omicron are all unvaccinated still. In fact, the Belgium traveler that I mentioned was unvaccinated. There are people who are vaccinated, the travelers in Hong Kong were vaccinated, but as far as I know, asymptomatic or minimally symptomatic, we don’t really have a lot of information, but the cases in South Africa, Kevin were mostly unvaccinated.
KP: So the fact that this variant may not have come directly from the Delta variant, but an earlier version of that. From a practical standpoint, what exactly would that mean?
NB: Well, I think that it’s still, I think people would argue, it means that it’s not just a continued transmission. It’s also protecting vulnerable folks who may be at risk because there’s this high community transmission. I think it basically means that it tells us something about how many parts of the world still don’t have enough genomic surveillance. And the fact that this could have gone undetected potentially longer than we think, that it’s been around. So it’s not that it just evolved. It might have been around for a bit longer. And the question is, if it was, that it really talks about our ability to be able to detect these types of new variants in parts of the world where there isn’t enough lab testing, just for diagnostics clinically, but potentially also genomic surveillance. And it shows the importance of trying to increase that capacity.
KP: You wrote in one of your tweets, that if there is significant immune evasion with this new variant, we have the technology now, and boosters can be updated. So talk a little bit more about the vaccine response to this variant.
NB: The way that both immune response and the vaccine responses work so far, is that you have both an antibody response and a T cell response that lasts longer, and both the antibody response and T cell response attack the virus in many different parts of the virus itself. To date, we’ve seen many variants sort of have the capacity potentially to decrease antibody efficacy. That means that you may not be as protected against infections, but just given how many places the T cell response identifies the virus, not many of them have been able to completely evade immune evasion, all that to say that there is concern that given how much this virus has the potential of these mutations, you could see a decrease in vaccine efficacy. In general, no variant to date has been able to completely evade the immune system.
So you don’t go back to basically zero is what I’m trying to say, but if there is a significant decrease in efficacy and protection to infection and including in some people who are older or potentially vulnerable, as we’ve seen with Delta also hospitalizations, we would have to update the boosters specifically to all those … the mutations and the variant that we’re seeing currently. What Pfizer and Moderna have said is that Pfizer has said it would take them about a hundred days, Moderna about 60 days once they’ve confirmed over the next couple of weeks, that this is a variant through laboratory analysis, through work with viral neutralization or pseudoviral neutralization, they’re able to show that the vaccine is losing efficacy, right against this variant. It would take them about that long to bring it, to be able to use it, to a point where it can be used clinically.
Then there is a regulatory question. We know the FDA last spring actually did pass some guidance, that there might be some leeway to be able to adjust these vaccines, similar to the way that we adjust flu vaccines, where you don’t have to go through a full trial every single time. So there might be that delay. They probably will need about two to three months to actually get the manufacturing of those new doses out. So we’re looking at, if in two weeks, we discover that there really are differences in that vaccine efficacy, and they’re considerable. Then we’re looking at months down the road, five months, six months down the road that we might have a booster that specifically addresses this variant. But, so I want to put that into perspective because people are going to be asking this question, “Well, why would I take the vaccine now?”
Well, first we actually don’t know whether there is a decrease in efficacy or not, because what you see in a laboratory doesn’t always translate into clinical factors or clinical evidence. But two, you won’t lose complete efficacy of the vaccines we have currently. So what I would recommend is people still get both the primary series. And as we’ve seen from the Delta variant, that booster that jump in antibodies may be protective. And so people should both get their primary series and the booster now, because that will, from what we’ve learned from variants in general, will provide some protection.
KP: Over the last 36, 48 hours, the world has responded with travel restrictions with South Africa. Is that enough? And if not, what more needs to be done?
NB: You know, travel bans are interesting. They, at best what they can do is help slow the spread. If you catch the variant or a virus or a new threat early enough. In this case, I think that, sure they may offer some benefit of slowing, if it’s early enough, but we’re already finding that many countries have the variant there. Right. The U.K., as I mentioned, seems to have found one, Germany this morning found one. And so the likelihood that this is not already within our borders, it’s growing slim, I got to say by the hour. And so we really got to figure out what our goal is with these travel bans. And the flip side of that is that South Africa raised the alarm. And so let’s say countries that have that capacity, genomic capacity, if you punish the country that actually first detected a variant are you setting an example that actually decreases willingness, a country’s willingness to share future data.
And that’s a big concern, particularly when you weigh the risk versus benefits, right, of these travel bans. And it’s interesting because the Biden administration statement was, Americans can still come back from those areas as long as they’re tested and vaccinated. And one wonders, why can’t we just do that for everybody, require testing and vaccination from everybody, right? And rather than imposing just blunt travel tools, just require everybody has a vaccine, everybody’s tested before getting on a plane, or right after getting off a plane. And that might be … and we should do that regardless for everybody who’s coming from anywhere else. If we really truly want to use, slowing through travel restrictions, that would be a more effective way than just focusing on one part of the world. At least that’s my thought.
KP: What keeps you up at night about the Omicron?
NB: We were getting to a point in this pandemic where, with both the levels of vaccination, which aren’t uniform, where there’s parts of the world, right, only 7% of the low-income countries have gotten one dose, but in major parts of the world here in global north, you’re looking at either through vaccination or unfortunately through infection, you’re achieving some level of immunity, and it seemed to be enough, particularly with boosters to get us over this hurdle. We have a surge ahead of us. We’re nowhere near being done with the pandemic, but there could be a site seen potentially in the future, where you in the spring with enough vaccination passes, winter surge in travels in cold weather. And with oral antivirals in hand, you could have gone to a point where you could have disconnected infections and hospitalizations, and that’s enough.
And we may still do that. We don’t know yet to the point where you could return to some level of normalcy, right? That’s really what we’re all aiming towards. And that eventually we … and quickly we should do that globally as well. This very clearly, even if Omicron doesn’t turn out to be as big of a threat as we’re currently sort of concerned that it might be, right. It raised the concern of what we’ve already always said, which is that we’re all connected. And if there is continued transmission elsewhere, that there is a potential for new variants down the road that could decrease efficacy enough so that people, even with three doses, you might need another booster that specifically is adapted to these new variants that come along. And so, you might have a period of time where you still have a portion of the population that’s vulnerable. And that’s what worries me, is that we’re going to be in this cycle for a long time. Even if Omicron doesn’t turn out to be the reason why, until we get global coverage of vaccination for COVID-19 or SARS-CoV-2.
KP: And my final question, what are some of your take-home messages that you want to leave with the KevinMD audience?
NB: Humility. I got to tell you I’ve been part of the pandemic response world for a while. I’ve been … I was part of West African Ebola epidemic response for a long time, a year and a half I was in and out. And the one thing that COVID has taught me is humility, about these pathogens and how quickly they can evolve. We can know some things and we can know many things based on prior knowledge, but we can still be thrown for a loop. So to never speak in … at least I have, my personal lesson out of this is to never speak in absolute speak as we seem to be always be thrown behind, in preparedness because of it.
Kevin Pho, MD: Next on the show, we have Paul Sax. He’s also an infectious disease physician and CNN contributor. Paul, welcome to the show.
Paul Sax, MD: I’m a CNN contributor when they run out of superstars to have on their show, and they go down their list, and they find me. So thanks for inviting me, Kevin.
KP: No problem. Thank you so much for being on this show. Can you briefly share your story and journey to where you are today?
PS: I’m an infectious disease specialist at Brigham Women’s Hospital in Harvard Medical School. And, you know I, after a brief flirtation with cardiology, like all of my co-residents, I decided that I better focus on this global problem that was HIV, and this was in the 1980s. And, but I’m a general infectious disease doctor as well. And of course, every infectious disease doctor is a COVID-19 specialist to some extent right now, because we have to be. So, that’s my story.
KP: Over the last 24 to 48 hours, of course, the new variant, the Omicron variant has been in the news. So what do we know today about this variant?
PS: Well, it’s first sequenced in South Africa. That doesn’t mean it actually originated in South Africa. Remember that our ability to find these variants is dependent, not just on where they arise, but also the sequencing ability of the scientists, and South Africa has very good sequencing capabilities. And they’ve determined that a variant was coming in and “replacing” the Delta variant, which had caused quite a bad surge of cases in South Africa. One important thing to note is that we really don’t understand why, but COVID-19 goes through these cycles where it ramps up rapidly. You know, everyone is panicking, and then for reasons that are not clear, it then starts to go away and a kind of two-month cycle. It’s very, very common to see that happen. And South Africa was at the end of its two-month cycle with Delta. They actually had very little disease activity.
Remember, it’s their summer right now. And so that’s why they’re able to detect this, because the cases started to go up again, and they sequenced them and found that they were very different from Delta. So what else do we know? We know that the sequence, the variant, the spike protein, spike antigen is dramatically different from the reference strains. And this has implications for our vaccines. That’s probably the most important implication as well as for monoclonal antibody treatments. And right now, we’re still in the information-gathering phase, to put it mildly, about the implications of these spike antigen mutations on both vaccines and monoclonal antibody treatments, as well as on transmissibility. Because you know, just to give us a little historical insight, Beta and Gamma variants were very much in this antigenic shift, that the spike protein had changed and a lot of concerns that our vaccines wouldn’t be as effective, but their transmissibility wasn’t enhanced and they really never went anywhere and then Delta just took over. So, it’s not enough just to be different antigenically. You also have to be highly transmissible, and we’ll see whether this variant falls into that category.
KP: The World Health Organization labeled this variant as a variant of concern. Now, what exactly does that mean? And where is that on their spectrum of worry?
PS: I would say it’s, at this point, a couple of days into its first identification, it’s appropriate to put it there. As you might know, from seeing virologists and other scientists weigh in, the response has been this is cataclysmic on one extreme. Our vaccines won’t work, to the other extreme, which is that, our vaccines probably will work, because our response to vaccines is not monoclonal it’s polyclonal. And it also includes cellular immunity. So we don’t know where in the spectrum, this is going to shake out. I think it’s just too early. And one thing I’ve learned after being wrong a few times is you do not make predictions about this pandemic confidently, because doing so is a big mistake. Because it is very … what has happened over this nearly two year period now.
KP: I’m looking at the front page of the New York Times website, and it says, “New variant of concern fuels global fear of another virus surge.” In general, what do you think about the initial reporting on this variant?
PS: The media is in the business of creating clicks and eyeballs on the page and selling. And so, it’s inevitable that they are going in their headlines to make it sound as alarming as possible. The good news is that some of the reporting is actually trying to be done cautiously. And when you read this finer print in most of these stories, they then come down to what you and I have been discussing, which is that we don’t know yet whether this is really going to be a huge problem or not. I do strongly support the fact that the WHO has called it out. I do strongly support the scientists in South Africa who reported it. I think this is great that they did that.
I am very saddened by the fact that reporting it might have this negative consequence for them, because of the travel restrictions, but it’s way too early to overreact. I would say, follow the news, scientists working on this very quickly. Even during the holiday, you heard about Moderna and Pfizer already thinking about tweaking their vaccines. You know that the scientists can’t wait to get their hands on some serum from patients who’ve been vaccinated to see whether there’s neutralization. I would anticipate we start seeing results from various studies on this, possibly within a week. And certainly, within a couple of weeks, it’s going to be very interesting.
KP: Various countries have initiated travel bans against South Africa. What do you expect the public policy measures to come down the line in the coming weeks to the American public?
PS: Well, the travel bans thus far have been really not so effective in controlling COVID-19, with a few notable exceptions. You’ve got countries like New Zealand and places like Taiwan initially, island countries that really put a very tight restriction on travel. And those are the exceptions to the rule, which is that travel restrictions have not worked at all. And so, in fact, they’ve sometimes have unintended consequences. When the travel restrictions happened in the spring of 2020 in the United States, American citizens poured into the country and brought with them a lot of COVID-19, because we were not prepared to do the kind of testing, isolation, surveillance that was required to make a travel restriction work, under those circumstances. And I fear the same thing is happening this time. The United States says, we’re going to start restrict travel from South Africa in three days.
So that’s three days for U.S. citizens to pour back into the United States. Is there a plan to have them all tested as they arrive? I know I haven’t heard of one. Is there a plan to have them isolate or mandate that they be isolated someplace? Not just like tell them, “Isolate.” I haven’t heard one. So yes, there are travel restrictions that have been put in place. I can’t help, but think that some of, it is political theater rather than real effectiveness in controlling this, and look, this virus is probably way more widespread than people right now know. I mean, already cases have been discovered in several other countries, no surprise at all. That’s just the way this virus gets transmitted. So I don’t know, I can’t imagine that the travel restrictions are going to be very effective.
KP: From your perspective as an infectious disease physician, what is your best case and worst case scenario when it comes to the Omicron variant?
PS: Best case scenario is that the vaccines are still protective, if not against infection, against severe disease. And that would be, the mechanism of that would be that our cellular immunity responds to a coronavirus infection now and keeps this thing mild and already there’s, if you want to be a glass half full person, the cases reported so far have been mild or asymptomatic. So, that’s one best-case scenario. Another best case scenario is that somehow this variant is not as transmissible. I doubt that one’s going to turn out to be true. And the third best-case scenario is that maybe these mutations have made it less pathogenic. So, that’s the best-case scenario. The worst-case scenario is that it’s basically so immune evasive, that our vaccines are essentially worthless in the face of this thing and that none of our monoclonal antibody treatments would work.
I do want to say, I should say parenthetically. I think that the biggest risk, based on what we know today, is our monoclonal antibody treatments. Some of them are probably not going to work against this variant. That’s what we’ve learned already. I mean, Imdevimab, which you may never have learned how to say, is now history because it doesn’t really work against some of our current variants. And it would not surprise me if we see a lot of this variant, it could actually mean goodbye for some of the monoclonal antibody treatments we have, but we’ll have to wait and see.
KP: I am going to see patients on Monday. They’re going to be asking me about Omicron. What are some of the messages that you want the public to know about it?
PS: You know, you’re already as a primary care doctor, you’re already strongly encouraging vaccination. I cannot stress the importance of that. I also think our messaging on boosters has been a little bit too soft, and I want to apologize for my dog barking there, but he’s very eager to make this message as strongly as I am. You know, if you’re an adult and you’re eligible for a booster, you should get boosted, because the vaccines, the way we gave them as two doses, so close together, you really see a clear decline in effectiveness.
And so with the third dose, you get antibody levels that are as high, or even higher than people who’ve recovered from COVID and been vaccinated. And those people are likely to be the most protected in the face of a new variant. So get vaccinated and if you haven’t had your booster yet, get a booster. They’re available for all adults six months after their second dose. And I should emphasize, there’s a smaller proportion of Americans, who’ve had the J&J vaccine. It’s now clear it’s less effective, definitely get another dose of an mRNA vaccine. The J&J vaccine is actually very widely used in South Africa, and it may have contributed to why they’re starting to see some case numbers go up.
KP: And my final question, what are some of your take-home messages that you want to leave?
PS: Too soon to panic about this. Good, that there’s global scientific collaboration, and stay tuned for more information over the next couple of weeks. This is really important and we’ll just have to wait and see.
KP: Paul, thank you so much for sharing your time and insight, and thanks again for being on the show.
PS: Thanks, Kevin. Take care.
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