The Problem and A Solution: How Governments Have Failed at Addressing High-Pandemic-Risk Diseases Like COVID & What Can Be Done (Part 3 of 3)

Part 3 of a 3-Part Interview With Dr. Arijit Chakravarty, "5 Years of the COVID Pandemic"

What I find remarkable is not that [the Avian Flu] pandemic is imminent. It is that they have created conditions that make a pandemic not only plausible, but likely.

BM: Rather than enhancing our public health posture and scientific understanding of diseases, there’s been the opposite effect through growing vaccine hesitancy, mistrust of science, cavalier attitudes towards infections and diseases and the embrace of personalized perspectives on communicable diseases. Meanwhile, every day we grow closer to seeing a bird flu pandemic become a reality. What are your thoughts on this?

AC: I’ll take one step back. I see the bird flu situation a little bit differently. If you look at the 1918 influenza pandemic, the 1918 influenza virus has a segmented genome that can readily mix and match with other flu viruses. There were a couple of critical mutations that got picked up in that flu virus. People have done phylogeny, pulling bodies out of the permafrost and then sequencing the influenza genome from the victims of the 1918 pandemic. So, they were able to reconstruct the lineage.

What they found was that the emergence of that virus happened in stages. It most likely circulated for a period jumping from birds to pigs somewhere at the turn of the 20th century. It probably circulated in pigs for six to 12 years, and then at some point around 1918, literally months before the pandemic, the different pieces, the different segments of the genome got put together.

There are only a handful of mutations, I think two or three mutations, that gave the 1918 influenza its killing power, its pandemic power. But those mutations came together in pieces through the previous decade. It was really bad news that it was circulating in pigs, but very different from COVID. Influenza evolves very slowly. COVID, on the other hand, evolves rapidly and is very tolerant to mutations.

My point is that I think that H5N1 in dairy herds is really bad news. I think it’s unconscionable that they allowed this to happen, because they are essentially incubating a pandemic potential virus at scale, in multiple different live subspecies. However, I couldn’t predict for you when that pandemic would explode. It could explode tomorrow. It could explode six or 12 years from now. The fact that we are pretending like this is not a thing to me is just jaw-dropping.

There are whole plans around influenza pandemics. Governments have spent millions of dollars on preparing for the next influenza pandemic plans. What I never realized was that once they made these plans, they said, “Problem solved! We know what to do. We’re not going to do it, but we made the plan.”

I find that remarkable. The surveillance situation is just beyond bizarre. The idea that they are allowing the virus to spread among cattle, poultry and humans and see what will happen is terrifying.

If you look at what happened in 1918 at Camp Funston (today Fort Riley, Kansas) when the epidemic first broke out, the body count racked up fast. In two weeks, all hell had broken loose. And that was in an era when it would take people two or more weeks to get from one end of the globe to the other. If something like that happens now, out of a farm somewhere in Iowa or Kansas again, it will be a week or so before half the world is severely infected with this thing.

What I find remarkable is not that this pandemic is imminent. It is that they have created conditions that make a pandemic not only plausible, but likely. And then they have also gutted the public health infrastructure such that their plan on paper is not worth the ink they used. The whole thing is just a joke—I think we are worse off today than we were in 1918.

BM: You said earlier that although the COVID virus is a difficult virus to deal with, the possibility continues to exist to address it. Can you elaborate on this?

AC: It is primarily difficult to deal with because it has a lot of characteristics that make it tricky. One, it kills slowly. Two, it has a low infection fatality rate. Three, it is highly contagious. And four, immunity wanes very quickly.

All of that said, essentially the first obstacle we must deal with is the idea of pandemic denialism. We are like lemmings at this point. There is no real appreciation at the public level for the scale of threat we are facing.

The first thing that public health would need to do, long before we get to nasal vaccines, is to stop the lying. We need to tell people why it’s bad to get COVID repeatedly. Tell people why COVID can shorten one’s lifespan. I think most people who are alive today will face the reality that COVID is a contributing factor to their death. Do people know this?

 If you’re out there taking COVID seriously, and if you’re out there still trying to avoid repeated infections, you’re still doing the right thing.

You have a 65-fold increased risk of a heart attack on day zero of COVID if you are vaccinated (the number is approximately double that if you’re not). It is very likely COVID can contribute to cancer. COVID decreases your overall immune responsiveness. It’s very likely that COVID causes 50 other things. You can build these cases from [scientific] literature. In fact, there are so many papers on COVID that people can’t keep ahead of it, there are literally hundreds of thousands of papers on this topic. But I’ve never seen such a wide disconnect between what the public thinks and what science says.

COVID is not inconsequential, and our public health leadership has been complicit, actively participated in making people believe it’s just another run-of-the-mill respiratory virus. And that is problematic too. If people really understood the science behind all this, they would have a very different attitude.

For example, I wear a mask when I travel to India. When I wear a mask and people ask me, why do you wear a mask? I say, “COVID.” And everyone says, “Is that still a thing?” And then people act somewhat worried because in India, when COVID hit the cities, you could smell the funeral pyres burning. Everybody knows that COVID is a deadly disease in India because we Hindus dispose of our dead in a way that’s not that discreet. In the West, the bodies go into the ground, so it’s much easier to literally cover it up. So, people to this day believe that nothing really happened, even though a million and more have died.

So, the lying must stop, is the first point.

The second point is if you want to control this virus, you have to deal with the threat that it represents. And the threat that it represents principally is the fact that it is evolving extremely rapidly. That rapid evolution creates a massive [probability of ] a mass death event later, which would happen very quickly and with very little warning. That risk, the possibility of such a turn of events, must be addressed even if it makes people uncomfortable. Otherwise, it will be difficult to mitigate COVID. The rapid viral evolution of COVID creates a massive tail risk for us, not only as individuals, but as a species.

Not only are we not taming the virus, but by playing roulette repeatedly, we will eventually hit that “outlier event.” But then they will say no one could have predicted it. This whole idea that somehow repeated waves of infection will make things better flies in the face of any rational science. The virus is not incentivized to become milder. And each time we afford the virus the opportunity to hit the jackpot, a combination of mutations that evade existing immunity with a high virulence, it could be catastrophic. Whether that takes two, four or 12 years, I can’t tell you. But I can tell you that this is not the way to solve this problem.

This whole idea that learning to live with the disease means permitting and encouraging its rampant spread and rapid evolution is just so many levels of stupidity that I don’t have a word for it.

BM: How do we solve the problem?

AC: First, we should talk about what the problem is. The first problem is that we are leaving a threat on the table that is completely undealt with, which is the risk of rapid evolution and a catastrophic event. The other problem that we have is that, by repeatedly reinfecting people with the virus, we don’t know all the long-term consequences (although the emerging evidence suggests that the long-term consequences will not be good). These are the risks of repeated exposure to the pathogen, and we need to be honest with people on these.

The good thing about COVID is that it has a lot of evolutionary vulnerabilities. So, if you really want to slow down the evolution of SARS-CoV-2, and if you set that as the public health objective, it’s quite doable.

One vulnerability it has is a narrow bottleneck when it goes from one person to another. It only takes about 10 viral particles, which means it finds it very difficult to optimize because it’s going from one person to the other. Although it exists within your body as a very wide range of viral particles known as quasispecies, it still is a very small sample of that that goes from one patient to the next. So, despite a wide genetic variability, only a handful go to the next person. That’s not efficient in promoting genetic variability.

The main way we are seeing large jumps in the evolution of these viruses is through a process called punctuated equilibrium [a term used in evolutionary biology]. This occurs in people with long-term infections such as those who are immunocompromised and the virus develops a chronic active state in the person. Long-term infections are much more efficient at generating better viral particles. And when these particles spread onwards from long-term infections they create the risk of a punctuated equilibrium event.

Punctuated equilibrium events, it turns out, are just really bad news from a public health perspective. The 1918 influenza pandemic was started by the product of a punctuated equilibrium event. The Black Death, the argument has been made, was caused by a punctuated equilibrium event. In other words, a large evolutionary jump can really create a lot of problems for human populations.

So, what you want to do is to stop those large evolutionary jumps for SARS-CoV-2. And the one obvious way you can do it is limiting onward spread and developing combination treatments specifically for long-term infections. This should have been done years ago. It’s not too late to do it now. Basically, we should identify people with long-term infections that are capable of infecting others. We should find ways to limit spread from them, and we should give them treatments that are specifically designed to bring the viral load down.

But you don’t want to just give Paxlovid to everyone with a long-term infection because they’re already harboring highly mutant forms of the virus. So that’s a great way to wreck your frontline treatment for the general population. Instead, you want combination treatments that are reserved for use with long-term infections.

Beyond that, you want to use a multipronged approach to reduce global viral load. Having more viruses around, at a global level, is a terrible idea because you’ve created a situation where there are probably more particles of this virus than of any other pathogen that humans have. On any given month there are hundreds of millions of people infected with trillions of viral particles. That is a recipe for disaster.

If you really want to bring the global viral load down, of course, then the most obvious way is to improve indoor air quality. It’s been well demonstrated by a lot of people that indoor air quality alone would get rid of a large chunk of the total viral load. It doesn’t have to get rid of spread as long as it brings the total viral load down. You can also do this by using other kinds of engineering controls such as monitoring air quality in a room. Much of that technology exists today. There are also far-UVC lamps that can be employed. Deploying HEPA filters, you could probably up the indoor air quality in every building in the US for the cost of an aircraft carrier. Sell a couple of aircraft carriers and upgrade indoor air quality. It’s expensive, but it’s on that scale that it’s doable.

We still haven’t put in much into the whole problem of antivirals and better vaccines. When you look at it from that piece of it, there’s room to improve. Vaccines against non-spike proteins would have been a much better way to go about it. Having multiple viral proteins being targeted with antivirals, even as you’re improving vaccines, would be great.

This whole idea of nasal vaccines is a great idea and concept, but it’s technically very challenging. And when we put all our hopes on a single technological advance, we fall into the same trap. We did this five years ago. We haven’t learned the lesson. We should not have put all our eggs into the vaccine basket, but indeed we did, and here’s where we are. You could say maybe a nasal vaccine will fix this. I’ll bet you that it won’t, if you use it alone. Any intervention, if you rely on it alone, will fail because you’re up against evolution. So, a multipronged approach is what you need.

I think if COVID nasal vaccines show up, that would be great. But the idea that you can get an evolution-proof vaccine for coronaviruses, I find amusing. There’s no such thing as evolution-proofing anything.

Sotrovimab (brand name Xevudy) is a human neutralizing monoclonal antibody that showed activity against COVID. It was found by looking for sequences in the beta coronavirus family that were less prone to evolution. The reason you don’t hear about Sotrovimab anymore is because the FDA pulled the emergency use authorization after three months when they found it had no efficacy against Omicron. So much for your evolution-proofing.

I think the most important point is you want to maximize the diversity of neutralizing antibodies. What we did with Operation Warp Speed was the single stupidest thing we could have ever done, which is we concentrated all our efforts on targeting a single spike protein which we then targeted with antibodies. We predicted [in the fall of 2020] that the vaccines alone would not be enough to bring the pandemic to an end, and we predicted that the virus would rapidly evolve to defeat antibodies, and it played out that way.

If you want to avoid making that same mistake again, don’t put all your eggs in the neutralizing antibody vaccine basket or in the nasal vaccine basket. Don’t put all your eggs in the evolution-proof basket. It isn’t going to work. The story’s going to end the same way as it did last time.

But if you come in with a multipronged strategy where you limited onward spread from long-term infections, you develop combination therapies for long-term infections, you use the multipronged approach to reduce the viral load, including deploying things like HEPA filters and far-UVC and monitoring viral load in public spaces, now you have a fighting shot. If you then use a variety of different vaccines to really maximize the diversity of neutralizing antibodies at a population level, the odds of slowing viral evolution down to a crawl start looking good.

The bottom line is that if public health had stopped lying years ago and had been honest about the costs, and if public health had realized what the correct approach is, which is to slow evolution down, then we would have been in a situation today where public health was treating COVID as a disease that needs to be suppressed.

The whole [myth] from day one was that we would never eliminate or eradicate it, so, let’s let it spread as widely as possible. “Learn to live with it,” for other diseases doesn’t mean the same thing as we have applied to COVID. When we say we must learn to live with leprosy, we don’t mean let’s make sure everybody has leprosy. When we say we must learn to live with malaria, we don’t mean let’s make sure everyone gets malaria as often as possible, let’s keep mosquitoes lurking in our tanks outside our house. No one says you must learn to live with tuberculosis. Let’s let it spread as much as possible and see how that goes.

No, we suppress those diseases every step along the way. We suppress dengue. We suppress tuberculosis.

This whole idea that learning to live with the disease means permitting and encouraging its rampant spread and rapid evolution is just so many levels of stupidity that I don’t have a word for it.

One of the things I would say to you is it’s not so much eradication or elimination as it is just suppression. Suppressing disease is something we pay these people to do, and they do it for every other disease.

If they told us not to worry about tuberculosis because we can never eradicate it and let it spread, we would immediately ask them what are they doing with the money we give them. They should just do their damn job and suppress this disease like other diseases. And as I pointed out, there’s five or six things they could be doing tomorrow, none of which are hideously expensive, that would over time lead to suppression.

If you could get to the point where the disease is suppressed, where you have local outbreaks here and there, where you don’t have people getting it twice a year, you’re in a much better situation. There’s no disease in the world that we don’t suppress.

BM: Any final words, Arijit, as we conclude this fifth year of the pandemic?

AC: I hope we’re not doing this again in five years.

BM: I’ll take that as your final word!

AC: I think at the end of the day, it remains a solvable problem. It’s disgraceful the way that this has unfolded. And I think that if you’re out there taking COVID seriously, and if you’re out there still trying to avoid repeated infections, you’re still doing the right thing. It is still possible to avoid being infected, and a worthwhile goal.

This is part 3 of a three-part interview. Read other parts in the Related Posts Below.

"Five years of the COVID-19 pandemic: An interview with Dr. Arijit Chakravarty" by Benjamin Mateus is republished with permission from WSWS.Org.