COMMENTARY

Is Eradication of COVID a Pipe Dream?

F. Perry Wilson, MD, MSCE

Disclosures

August 11, 2021

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This transcript has been edited for clarity.

Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I'm Dr F. Perry Wilson of the Yale School of Medicine.

There was a time not so long ago when COVID was not a thing. Most of us have resigned ourselves to the idea that we will never again truly be free from SARS-CoV-2. Sure, we might get case rates down very low or population immunity high enough that the illness becomes relatively mild, but it will always be there, appearing in our electronic health record test results along with the other endemic respiratory viruses — flu, parainfluenza, etc.

Eradication of COVID — the complete removal of the virus from the world — seems like a pipe dream. At least, it does to me. But not to Nick Wilson and his team from New Zealand, who have this piece appearing in BMJ Global Health urging us all to consider a worldwide effort to eradicate COVID.

They are not just talking about elimination here, where you get case rates to zero in certain geographic areas and remain ever-vigilant for the occasional outbreak, to which you react rapidly (think of our approach to measles). They mean eradication. Gone. Not existing worldwide. Think smallpox and.... That's it.

In fact, there are two viruses that humans have eradicated: smallpox and rinderpest. But the latter is a cattle disease. We are a hair's breadth away from eradicating polio, with two of three circulating strains gone, but we aren't there yet.

The authors use those metrics — smallpox and polio — as markers in the epidemiologic sand, and try to put SARS-CoV-2 somewhere along the spectrum.

To assess how "eradicatable" (to coin a word) the virus is, they use a set of criteria from a 1999 paper. There are seven major factors.

1. A Highly Effective and Safe Vaccine

Smallpox had one. Polio, not so much, given the occasional spread of vaccine-derived virus. COVID vaccines, they point out, are somewhere in the middle — highly effective, but with concerns about durability of protection. But, they argue, vaccines will get better, pointing out that intranasal vaccines (none are yet approved) might be game changers from a public-health standpoint.

2. Lifelong Immunity

If you get smallpox, you never get it again. Same with polio, probably. COVID? Not sure. Clearly, people have repeat infections, but it does seem rare. Of course, we're only a year and a half into this thing. That's far from a lifetime.

3. Absence of a Long-term Carrier State

This is a critical one. Viruses that can hide out in our DNA for years or decades only to re-emerge (think varicella) make eradication basically impossible. Fortunately, as is the case with smallpox and polio, SARS-CoV-2 has no known long-term carrier state.

4. An Easily Recognizable Clinical Syndrome

You need to know where infections are happening. Smallpox was obvious. Polio, not so much — lots of asymptomatic infection. COVID, probably in the middle.

5. An Easy Way to Diagnose Infection

Again, to target your eradication resources. For smallpox, this is trivial; you can diagnose it with your eyes alone.

Source: Wikimedia Commons

Polio, not so much; it requires a laboratory test. COVID also requires a test, though our testing is getting better and more efficient.

6. The Absence of an Animal Reservoir

Here's where I begin to get really concerned. Neither smallpox nor polio has nonhuman reservoirs, meaning that if you can vaccinate all the humans, you can eradicate the disease. SARS-CoV-2, though, can clearly infect animals. The authors argue that this isn't so bad, suggesting that companion animals are unlikely to transmit to humans and that "wild animal infections are rare." OK — but, I mean, the whole thing started with an animal-to-human spillover, right? Even if you have concerns about the Wuhan lab, it's clear that coronaviruses do just fine in a variety of animals that come into contact with humans.

7. A Genetically Stable Causative Agent

Again, smallpox was easy here. It's a DNA virus — far more stable than RNA viruses. Poliovirus is an RNA virus with a mutation rate of about 1 per 2200 bases. SARS-CoV-2 may be about two orders of magnitude slower than that, which bodes well for eradication. But, obviously, the high infectiousness and worldwide spread is allowing many variants to emerge.

The authors argue that the virus may achieve peak fitness in the near future, so we don't have to worry too much about mutation. I'm not sure this is right. While you may achieve peak fitness in terms of binding to cellular receptors, the use of vaccines will create some selective pressure for vaccine escape mutants, as they will be more fit. That said, those escape mutants would have less affinity for the cellular receptors, so maybe there is something there.

Taking stock in the end, this seems like a really big lift.


 

Smallpox comes out looking like the dodo bird: absolutely perfect for worldwide eradication. Polio is obviously more challenging, and the fact that we've gotten so close with that virus should provide us some hope. But SARS-CoV-2 really strikes me as a different beast. While biologically, maybe eradication is conceivable if we have a truly massive worldwide effort, let's not forget that worldwide eradication is not just a biological but a political process. The authors note this — but remain hopeful. Maybe I'm more cynical because I live in the United States. Maybe everything is better in New Zealand.

For me, eradication is aspirational. On the road to eradication is elimination, which is potentially achievable, though that too will take something we are not particularly good at: broad and deep cooperation within and across nations.

F. Perry Wilson, MD, MSCE, is an associate professor of medicine and director of Yale's Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and here on Medscape. He tweets @fperrywilson and hosts a repository of his communication work at www.methodsman.com.

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