Will the COVID Omicron variant change the world again? [PODCAST]

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“The variant keeps me up at night a little bit because it has 32 mutations in the spike protein, in contrast to the Delta mutation.

But it’s not just the mutations. In terms of biological plausibility, it’s plausible that it could be more evasive against immunity. Not just vaccines, but potentially reinfection.

What really worries me is seeing the signals line up in the wrong way. It first started in Botswana, but it’s surging not just in one part of South Africa, but across six different provinces in South Africa, all at once.”

Eric Feigl-Ding is an epidemiologist and health economist. He can be reached on Twitter @DrEricDing.

He shares his story and discusses the COVID Omicron variant.

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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.

Transcript

Kevin Pho: 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 KevinMD. Today in the show, we have Eric Feigl-Ding. He is an epidemiologist and health economist, and he’s a senior fellow at the Federation of American Scientists. Eric, welcome to the show.

Eric Feigl-Ding: Thank you so much for having me.

Kevin Pho: Can you briefly share your story and journey to where you are today?

Eric Feigl-Ding: I think it’s relevant that I was originally born in China, and I came to America when I was five years old. I grew up all-American, went to Johns Hopkins for my undergrad in public health, and then I went straight to my doctoral program in epidemiology at Harvard School of Public Health. Along the way, I picked up another doctorate in nutrition as well, but that’s a story for another day. And then I also started medical school, EU medical school, while I was a postdoc at Harvard School of Public Health, and then eventually I became faculty at Harvard Medical School, and that forced me to drop out of medical school. So that’s my brief academic career.

I’ve done a lot of academic research. I’ve done a lot of clinical trials and global health projects, and I have a lot of colleagues at WHO and other health agencies worldwide. When this pandemic first emerged, in January of 2020, I was really worried about it. But back then, people were still talking about, “Do we need to wear masks?” The early days of the pandemic, as I like to say. But I was incredibly worried, and I realized that slow action was really endangering the world, because the failure to act and failure to move is the greatest error of pandemic management. So I tried to warn the world with my “holy mother of God” warning, and yeah, the world has kind of played out in the worst possible scenarios. We’re in the wrong timeline, as you could say.

So I’ve been trying to keep the world updated on COVID, as well as running a few other global health projects, running a trial on COVID that’s finishing up soon in Mexico, and working with WHO and global leaders, trying to really help people digest, process, and act faster. And I have no idea why I’m still here after all these months. This should have been over by year one or year one and a half, but here we are, going into year two pretty soon.

And now we have the Omicron variant, the new variant of concern that literally popped up, I would say, before Thanksgiving. No one had even heard of B.1.1.529, which today just got its Omicron name, but now it’s shaking the world markets and really shaking how people live their lives. Within a span of literally two days, I think the world has changed because of it.

The variant, I would say, keeps me up at night a little bit, because obviously it has a lot of mutations, and some of the speculation so far has been, “Oh, it has a lot of bad mutations.” It has 32 mutations in its spike protein. Contrast that with Delta, which has 13, I think, mutations. So this is a lot more mutations. But it’s not just the mutations; that’s just in terms of biological plausibility that it could be bad. It’s plausible that it could be more evasive against immunity, against not just vaccines but potentially reinfection. And that’s actually what the WHO’s warning today about Omicron was, that it has reinfection potential, but it’s also potentially higher in infectiousness and severity. We don’t know.

But what really worries me is seeing the signals line up in the wrong way. By that I mean it’s surged in South Africa. Again, the story first started in Botswana, but it surged in South Africa, and it’s not just in one part of South Africa. It’s surged across six different provinces in South Africa, all at once. Normally, if it was a random surge in one spot, we could say maybe we did some over-testing. But no, this is across the board, across almost all provinces. South Africa positivity went from 1 percent to 30 percent, and in terms of the cases identified in one region, it’s basically been 75 percent Omicron. It’s been displacing Delta, and we have not seen a variant that has been successful in displacing Delta as a dominant variant anywhere in the world up until now. And the fact that it quickly displaces Delta is incredibly worrisome.

Some models, early models based on the early data, say it has a 500 percent infection advantage versus the original Wuhan, while Delta has about 2x. Now, I hope to God that early data is wrong, but whether it’s 500 or 300 or 200, that is still incredibly worrisome in terms of its infectiousness speed. And we should take the precautionary principle. That’s always been kind of my philosophy: When in doubt of certainty, lean towards what will save more lives, and lean towards containing this virus as quickly as possible, rather than let it spread and wait and see and collect the data of how infectious and severe it is, and then realize after the fact, “Oops, it was really bad, but oops, we didn’t act until now, while waiting for a significant p-value,” and then the world is endangered again. So I think taking the precautionary principle is really, really the best philosophy here, especially in the face of all this worrisome data.

And the worst data is that in Hong Kong, they caught two cases only by an extreme amount of quarantine and PCR testing. They found one case after two PCR tests, and one case after eight days and four PCR tests that finally turned positive on the fourth test. And both of those Hong Kong cases were fully vaccinated with Pfizer, albeit they were six-months-old Pfizer-vaccinated individuals. They didn’t do boosters yet. The Israel case was also vaccinated. But the most worrisome is the Belgium case. That young woman wasn’t vaccinated, but she never traveled to sub-Saharan Africa. She had just returned from Egypt via Turkey. Neither of them is in sub-Saharan Africa or even remotely close in distance to South Africa in any way, but yet there she caught it. Which means that Omicron is already out of southern Africa. It’s already spreading around the world, and we are just playing catch-up.

For example, with the Hong Kong cases, the first case traveled out of South Africa on November 11th carrying the virus. We’re on, what, November 26th, 27th, as we’re recording this now. So the virus has had a good two weeks to already spread around the world, and that’s what makes us worry. Just before our call, the Netherlands quarantined two flights from Cape Town and Joburg carrying 600 people, and they tested 100 people so far and already found 15 cases of COVID. They’re still trying to confirm whether it’s Omicron, but it’s highly likely that they’ll find a couple dozen cases, and among them, I bet half of them are likely Omicron at this point, given that Omicron is 75 percent in certain provinces in South Africa. So the cat’s already out of the bag.

Travel restrictions are good only to a certain degree, if you can pinpoint where they are. But if it’s already left southern Africa, like the Belgian case has already shown, I think what we need more than travel restrictions is quarantine upon international arrivals, in the United States or any other country, where the government should quarantine international arrivals and test them. Whether they quarantine at home or in a hotel, you have to have state quarantine and have enforcement around that, and test throughout quarantine, because only with testing throughout quarantine are you finding cases, as Hong Kong has taught us. So we have to take a really radically different approach if we want to keep this Omicron variant contained.

Kevin Pho: How do these first few days of the Omicron variant contrast with the first few days of the Delta variant?

Eric Feigl-Ding: Well, the first few days of the Delta variant were very different, because Delta emerged in India, in rural India, and of course India does not have good testing. I equate India to Botswana, because B.1.1.529 originally started in Botswana. We think that’s where it was first identified, but they don’t have good testing there. It wasn’t identified until tracing from South Africa retroactively found it. But in India, Delta spread for, like, a month or two before it actually hit the world stage. So people said, “Well, look, Delta was already spreading for two months.”

Yeah, the thing is, what really was the critical point was, remember back in spring, April, May, June, in April, when Delta really was causing the calamity in Delhi, New Delhi, and then international travel brought it further around the world. It was those early days: Had there been action, we could have contained it. But by then, we had no international arrival containment. People were flying in from India to Toronto airport and walking off the airplane without any testing or quarantine whatsoever, and many countries did that, and hence it spread around the world.

I think we need to learn from that lesson that you can’t just, if there’s a flight from an epicenter, travel bans are one thing, but again, given what we’ve seen, I don’t think just restricting to southern Africa flights is enough. We need to test all international arrivals. That is what we really have to do, and that’s, I think, our lesson from Delta: unless you do that international arrival testing, at least at minimum upon-arrival testing and upon-arrival repeat testing, like several days after your arrival. That would really catch a lot of cases that we missed, just due to the nature of the incubation period taking a few days to build up. So I think that is the lesson we should learn. Screwing around and delaying and sitting on our hands, waiting for the right data from your own government before you act, I think is really, really a lesson that we should soak in, and act quickly for this Omicron.

Kevin Pho: You mentioned that the cases in Hong Kong were in fully vaccinated individuals, albeit six-plus months. What do we know about the infections in South Africa? Were they primarily also in fully vaccinated patients?

Eric Feigl-Ding: Many of them are not vaccinated. I don’t have the exact number; I just remember reading that the majority of the cases in South Africa, and we’re up to several hundred now, were unvaccinated. Granted, South Africa, you know, I think Botswana could definitely use our vaccine, but South Africa is not supply-blocked. It’s vaccine-hesitancy-blocked. Just like in the United States or many other countries, there’s a lot of vaccine hesitancy, and that’s what’s blocking the uptake.

But I think we can’t quite elucidate whether it’s evasive, but every vaccinologist and immunologist I’ve talked to believes that it will be evasive. And again, I think the best word is that it’s evasive, not escape, like some people say, vaccine escape, which, to some lay public, people think, “Oh, efficacy goes down to zero.” I think it’s more like there’s going to be a 10 or 20 percent hit to the efficacy, but I think the efficacy against hospitalizations is still going to be good. We’ve seen hospitalization efficacy not really waning that much, only like 5 percent over six months. It’s the infection efficacy that really drops, from a combination of waning as well as Delta. Delta is probably a quarter of the efficacy drop that we’ve seen, and the other three quarters of the total drop, from, say, 95 percent to 50 that we see against infection now, is due to the actual waning.

But I think boosters will be good, because boosters don’t just restore your antibody levels to a fresh two-dose. From zero to a fresh two-dose, you get about 700 antibody levels, and over six months, you drop to about 300 to 400. But a booster at six months boosts you not back up to 700, but up to 2,000, like 2,000, 2,500. So that is a much higher level, orders of magnitude higher, in terms of antibody levels and therefore efficacy. That’s why we’ve seen that the actual infection protection, three doses versus two doses. Now, three doses versus zero doses, it’s even higher, like 95 or so. But against two doses, you’re still seeing 80, 90 improvement in efficacy, and really high hospitalization improvement in efficacy, over 95.

So I think, three doses, we should really reclassify the third dose not as a booster. “Booster” makes it sound like it’s optional, like, “Oh, it’s kind of if you need it.” But boosters, I think, are really, really key, because it triples the antibody levels from your fresh two-dose. Right now, I think we should adopt Israel’s philosophy that you’re not fully vaxxed until you’re three-dose vaxxed. The U.K. is starting to adopt that. A few other countries stopped adopting that. The U.S. should adopt that soon: that if you’re two-dose and more than six months, or even more than four months, out, because efficacy starts dropping pretty sharply even after four months, if you’re more than four months or six months out, you should be classified as only partially vaccinated with just two doses. We need a third dose.

And how long will that last? I don’t know, but a lot of immunologists say at least nine months, if not over a year, we should be good, given that we are no longer at 700 but over 2,000. But we really need to reclassify fully vaccinated for the sake of international travel, fully vaccinated travelers, as well as vaccine passports and other safety precautions that require fully vaccinated people.

Kevin Pho: When can we expect the data to come out articulating the efficacy of the current vaccines?

Eric Feigl-Ding: Well, I think they’re first going to do laboratory studies. In laboratory studies, the first fast way is to look at pseudovirus neutralization. So they’re going to create a pseudovirus in a lab, and then they’re going to run it. They’re already doing these experiments right now in South Africa and elsewhere. They’re going to run it against either convalescent plasma, convalescent serum from people who previously recovered, or against vaccinated serum. And again, I think now, compared to before, they’re going to really classify fully vaccinated or recently two-dose vaccinated serum.

And then they’re going to look at the neutralization reductions of this virus versus an older strain, like, for example, Delta or Beta or Alpha or 1.0. And then they’re going to look at how much relative fold drop in neutralization there is against Omicron versus against those others. So they’ll have a head-to-head comparison in these pseudovirus laboratory experiments against vaccinated or convalescent blood samples.

Kevin Pho: You wrote in one of your tweets, which I found very interesting, “Maybe this variant is Mother Nature’s revenge on humanity for not helping Africa enough with vaccines.” Tell us what you meant by that.

Eric Feigl-Ding: Yeah, it was late at night, I couldn’t sleep, and I was just really frustrated. Obviously, vaccine equity, as we know, is a serious problem, because wealthy countries have an overabundance; we can’t even use them all, and they’re expiring. But sometimes in Africa, among poor countries, you have high-, upper-middle-, lower-middle-, and lower-income countries. For these lower-income countries, the percentage of them that’s been fully vaccinated is incredibly low. Almost none have been fully vaccinated, and the vaccinations that they have done so far, it’s very, very slow, because they can’t afford to purchase on the world market. They only rely on COVAX donations. And with COVAX, the problem is that it’s mostly based on donations and fire-sale pricing.

So basically, if, for example, the world demand for vaccines goes up again due to boosters, and this is why WHO has been against boosters, which I don’t think is the best policy, given we know that boosters are really important for protection against hospitalization as well as infection, the issue is that when there’s high demand and insufficient supply, what happens is that the pharma companies stop donating to COVAX. Basically, if they have someone who they can sell to for money at full price, they would rather do that than sell or fire-sale at a heavily discounted price to COVAX. And a lot of these lower-income countries, they’re kind of like tranches, right? The COVAX donation mechanism is the lowest tranche, in which, once there’s an excess and these vaccine companies can’t sell all of them at the full price on the world market, then it goes to COVAX, and then it goes to poor countries.

And my point about this is that a lot of these sub-Saharan African countries have not gotten enough, obviously, and sub-Saharan Africa is oftentimes a breeding ground for a lot of variants because of HIV. One of the first cases, I think the first case in Botswana that was identified was in an HIV-positive person. And one thing we know about what drives variants is not just the total number of warm bodies that the virus has; it’s immunocompromised people. We’ve seen it time and time again. We have MGH, Massachusetts General Hospital, a New England Journal case of someone with immunocompromise, and the virus literally went through several generations in the person’s body and hypermutated by the time this person died, many, many months later.

But we know immunocompromised individuals are like a breeding ground, because they can’t fully extinguish the virus with their own immune system, and so it creates several selection pathways for the virus to perfect itself in terms of evasiveness and infectiousness. And so sub-Saharan Africa has a lot of HIV, as you know, and that creates a perfect breeding ground among the immunocompromised. That’s been a lot of the worry. Africa has been, it’s kind of like a double whammy, because we kind of neglected HIV as well as neglected COVID vaccines for sub-Saharan Africa. So we have this perfect breeding ground, because we haven’t really mitigated or squashed this virus as much as we could, and here is the fruit of our bad karma. And hence, my analogy was Mother Nature trying to exact its revenge, because humanity has neglected sub-Saharan Africa in many ways. And that’s the ultimate irony and sadness of all of this.

Kevin Pho: We’re talking to Eric Feigl-Ding. He is a health economist and epidemiologist, and he is a senior fellow at the Federation of American Scientists. Eric, you’ve been following this pandemic very closely from the beginning. Now, given the Omicron variant, what do you think is our best-case and worst-case scenario?

Eric Feigl-Ding: The best-case scenario, look, I think there is no fate but what we make. There are so many diverging scenarios. In the perfect world, we would squash it as quickly as we can, vaccinate the hell out of the world, so we can really create a really high seawall. I like to use a seawall thing, because right now we’re giving the virus speed bumps, or earthen dams, against these waves. On a good day, we can hold back against it with our vaccines and our laissez-faire, half-serious mitigations around mask-wearing and ventilation and testing, contact tracing, which we don’t really do that well anymore, or do that well, period, in the U.S. On a good day, we’re going to hold it back. But when the waves come, like the winter wave that’s already coming, it’s already hitting northern U.S. states and obviously hitting Europe, it’s not enough, and you have to add other mitigations, multilayer mitigation. Some people call it the Swiss cheese model, where you have to layer all of them together in order to stop the virus. And I think that is the best approach, but we’re not doing that enough.

This is the pandemic of not just a virus, but a pandemic of failed leadership during a virus, up and down. Because, you know, I think the best analogy is, what people ask: What is causing this? I think causality is very tricky. Take someone who has a heart attack. What caused it? Was it because the ambulance came too late? Was it because they didn’t take their cholesterol medication to prevent their heart attack? Or was it, you know, they couldn’t afford the cholesterol medication? Or they couldn’t afford to see a doctor, or they couldn’t afford good health insurance? All that causal chain led them to have their heart attack and die. I would say the virus is only one part of the chain. The lack of good pandemic response and mitigation and aggressiveness against the virus has been the other, because many governments are pursuing this: “Let it spread; let’s go for natural herd immunity.”

To some degree, yes, if you infect everyone, eventually cases will go down. I call it the burn-through, just like in a forest: Eventually a forest fire will end when it burns all available brush, right? But that is not the price, that is not the pathway we should use to extinguish a wildfire or a pandemic. Letting it burn through, it’s not just deaths and hospitalizations; it’s also long COVID. Long COVID is neurological, as well as subclinical, like, for example, kidney damage from reduced glomerular filtration rate. That’s subclinical. It doesn’t always lead to end-stage renal, but it will have domino effects for many, many years that you don’t see yet. I think that long COVID thing has been completely neglected by a lot of people who say, “Well, cases are down, hospitals, oh, you know what, infection’s OK. Cases, you know, it’s OK as long as they don’t go in the hospital. It’s fine.” It’s not fine.

Because I also want to remind people that there was a study in Britain of 80,000 people, 15,000 with COVID, and among those ventilated in the hospital, they lost seven IQ points equivalent. Among hospitalized but not ventilated, they lost about five IQ points equivalent. But even if you were never hospitalized, but you had symptoms, you lost anywhere from one to four, or three or four, IQ points. That is actually a lot, considering that lead poisoning in children is about two points, and we as a society do not accept lead poisoning in children as an acceptable, tolerable consequence of leaded water, right? But yet we’re doing that and allowing that with COVID as it burns through our population, and it’s incredibly tragic.

And I think, in many ways, look, people were kind of really shocked by the market crash today, as well as the travel bans and this disruption of their holiday weekends here in the U.S., like, “This should be my shopping day. Why am I dealing with this stupid virus?” kind of thing, right? But if you want the peace of mind of not having to deal with COVID, the best way is to eliminate COVID as much as you can. And is it possible? Yes. Israel is not an island. It is not a dictatorship. It does not ban international travel, for the most part, until recently, against Africa. But Israel has had four days of zero COVID deaths and very, very low infections, because it took a very aggressive approach. Again, you’re not fully vaxxed until you’re three-dose vaxxed, for all adults.

And if we took only an aggressive approach, it’s like short-term pain for long-term gain. Right now, a lot of governments are kind of managing a pandemic like companies who only care about short-term quarterly earnings but don’t care about the long-term stability of the company. Many governments are kind of gaming for short-term political wins, as opposed to the long-term stability of their economy and the long-term stability of the society against disruption. And I think the best way for that is not relying on natural infection, or “focused infection,” as some people call it, many euphemisms, but really vaccination plus other multilayers of NPIs, non-pharmaceutical interventions, that will bring the cases down. And once you’re down, don’t let up. Just go lower, as opposed to releasing everything.

It’s kind of like if you have high cholesterol and diabetes, but then you go on a vegan diet for one month, but then after that month is over, you return to what you were doing with bacon and sausages before. Then you haven’t solved the underlying crisis that led to that in the first place, and things are going to revert, and it’s going to spiral out of control eventually again.

And I also want to remind people that reinfection is incredibly, incredibly serious. After 180 days, six months after you’re previously infected, there’s waning of protection against reinfection as well. It’s just like vaccines. That breakthrough reinfection is serious among those who previously got infected, and we should not rely on a natural infection-based strategy to stop the next wave. I think that is very stupid, and that is also very short term. It’s expedient; it’s very convenient to just let the virus burn, but long term, we’ll really suffer many cycles of this up-and-down roller coaster, and no one wants these roller coasters anymore. So I think mitigation, multilayered, and trying to go for as low as possible is the best approach.

Kevin Pho: And my final question: What are your take-home messages that you want to leave with the KevinMD audience?

Eric Feigl-Ding: OK, I think the take-home message, if I summarize, is that we have to rely on more than just two doses of a shot. We need a booster, but we also need ventilation, and on top of masks, not just cloth masks, but premium masks, KN95, KF94, FFP2 masks, and ventilation. In addition to mask mandates and vaccine mandates or vaccine passports, I think what’s even more important is ventilation standards in your schools and office buildings: that you should have HEPA filters on, in addition to opening the windows. We should have upper-air UV to disinfect the air if you can’t open the windows or you can’t install enough HEPA filters. I think we should have a lot of indoor air quality. I think indoor air quality for this airborne virus is really, really, quick or not, really, really important, to really change how we manage the virus going forward.

And all that together will allow us to stay safe, keep our kids in school, and not deal with crushing waves and potentially crushing new variants that will pop up. And of course, really, really vaccinate as quickly as you can, and really avoid infection. Also, relying on your own feeling of invulnerability, because, hey, you were vaccinated or you were previously infected, is not a good strategy. You should still take as many measures to protect you and your family, not just rely on the feeling of invulnerability because you were previously infected or previously vaccinated with two shots. Go for more protection. I think that is always the best precautionary principle. It will win the day if we adopt it.

Kevin Pho: And how can people reach you?

Eric Feigl-Ding: Well, they can find me on Twitter. I guess I leave my DMs open. I can’t answer everything, but my Twitter is Dr. Eric Ding, D-I-N-G, D-R-E-R-I-C-D-I-N-G. You can also send me some messages on my online forms, but you can also follow me on Substack, drericding.substack.com. But I think, look, just engage, and reach out if you have very, very interesting data you want to share. I oftentimes share a lot of data from readers and people who reach out to me, because I think the world needs to know. I think some of the best data comes from people from far-flung places who don’t necessarily have a voice, and I want to give voice to those who are voiceless in fighting this pandemic. So stay strong, and we’re in this together.

Kevin Pho: Eric, thank you so much for sharing your time and insight, and thanks again for being on the show.

Eric Feigl-Ding: Thanks, Kevin. Take care. Stay safe.

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