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 which you react
rapidly to – 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.
First, 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.
Second, 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.
Third, 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.
Fourth, 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.
Fifth, 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.
Polio not so much – it requires a laboratory test.
COVID also requires a test, though our testing is getting better and more efficient.
Sixth, the absence of an animal reservoir.
Here’s where I begin to get really concerned.
Neither smallpox, nor polio have non-human reservoirs – meaning if you can vaccinate
all the humans, you can eradicate the disease.
SARS-CoV-2 though can clearly infect animals.
The authors argue 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.
Seventh, 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 some there 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 US.
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 out – broad and deep cooperation within
and across nations.