COMMENTARY

COVID-19 Data Point to Two Possible Realities -- Which Is It?

F. Perry Wilson, MD, MSCE

Disclosures

April 28, 2020

Find the latest COVID-19 news and guidance in Medscape's Coronavirus Resource Center.

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, once again recording from my office at Yale University.

It is breathtaking how much we are learning — and how quickly — about the novel coronavirus. I continue to be awestruck by the power of the worldwide 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 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 is a virus with a disturbingly high death rate, on the order of 1%-3%, slowly marching its way through the population — a steamroller. The other is 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 United States, 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 two undocumented cases of COVID-19 for each documented case.

That's not enough; that's steamroller COVID. It means that 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 preprints 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 10 to 1.

This is windstorm COVID — blowing through the country at rapid-fire pace, leaving some destruction, but, thankfully, passing quickly. This is the COVID that allows us to open up more quickly, assuming that 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 currently regulated 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 million 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 due to random chance.

A 95% specific test would lead to a conclusion that at least 15 million 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 that 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 that 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.

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

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