A Tale of Two Coronaviruses

The current data supports two interpretations of how coronavirus spreads. Determining which is correct is critical before society reopens.

It is honestly breathtaking how much we are learning, how quickly, about the novel coronavirus. I continue to be awestruck by the power of the world-wide scientific community focusing so intensely on this incredible threat.

But there is obviously a lot left to learn. There is a huge gap in our understanding about the epidemiology of the disease, and it is only now, finally, beginning to be filled.

The data we have available now are consistent with two different potential realities. Sometimes it feels like there are two coronaviruses out there – metaphorically – I’m not talking about genetic strains or anything.

One, virus with a disturbingly high death rate – on the order of one to three percent – slowly marching its way through the population – a steamroller.

The other, a virus with incredibly rapid community spread but with minimal impact on most people – save the unlucky few who have particularly bad outcomes – a windstorm.

We know that the documented, PCR-positive COVID-19 cases are just the tip of the iceberg.

We know that, as of now in the US 5.7% of people in that tip have died.

The question is how much iceberg is under the water. We’re JUST starting to learn that.

Last week, I was dismayed by a paper from Iceland that implied that there were roughly 2 undocumented cases of COVID-19 for each documented case.

That’s not enough – that’s steamroller COVID – it means a ton of people are still susceptible to the disease – no herd immunity is developing, the mortality rate is high, and we’re going to be stuck inside for a long time.

But recently a slew of pre-prints and press releases tell a different story. Using antibody tests, researchers are starting to sample asymptomatic people to figure out who had the disease.

There are some dramatic numbers.

In early April, German researchers published this study, which found that 70 out of 500 people tested in a hard-hit area had coronavirus antibodies – that’s 14%.

Translating that to the entire population put the ratio of undocumented to documented COVID-19 at about 5 to 1.

A much-criticized California seroprevalence study of 3300 individuals found that 50 were positive – just 1.5%, but in an area that hadn’t seen many symptomatic cases, putting the undocumented-to-documented ratio at 85 to 1.

More recently, Governor Andrew Cuomo reported that sampling of New York City grocery store shoppers (perhaps not the most random sample) has a seroprevalence rate of around 20%.

That implies an undocumented-to-documented ratio of ten to 1.

This is windstorm COVID. Blowing through the country at rapid-fire pace, leaving some destruction, yes, but, thankfully, passing quickly. This is COVID that allows us to open up more quickly, assuming antibodies are protective, which, let’s be honest, if they aren’t we’re sort of screwed no matter what.

So which COVID is it?

One critical variable here is the antibody tests themselves. No test is perfect, but in the case of COVID-antibody tests (which are not regulated currently by the FDA) the stakes for false-positives are particularly high. They are falsely reassuring – they will lead us to reopen faster than we should.

It’s easy to see why. Imagine you have an antibody test that is 98% specific. Only 2 out of 100 people will have a false positive. Well, right there you’ll estimate that 2% of the population has had the disease. If you did that in a random sample of America, you’d estimate that there have been 6,000,000 coronavirus infections, compared with the roughly 1 million we’ve detected, allowing you to comfortably cut the death rate down by a factor of 6, making us all feel a bit better.

But of course, that result was just do to random chance.

A 95% specific test would lead to a conclusion that at least 15,000,000 Americans have already been exposed, allowing you to take the observed death rate of 5.7% and cut it right down to a much more comfortable 0.3%.

See how easy this is?

So we have to be careful.

All that being said, I’m encouraged by the high seroprevalence rates reported from New York – it’s unlikely the test they used was only 80% specific, but to be fair at the time of this recording the test characteristics were not available.

So which coronavirus are we dealing with? The whirlwind many of us have already been infected with? Or the steamroller coming inexorably toward us? We don’t know.

But with adequate, high-quality testing, we’ll find out. Stay tuned.

This commentary first appeared on medscape.com