Justin Lessler, a professor of epidemiology at the Johns Hopkins Bloomberg School of Public Health, models disease transmission, and has been studying the novel coronavirus. A month ago, as the first confirmed COVID-19 deaths were occuring in the United States, I spoke with Lessler about some of the early findings about the disease. On Tuesday, I called Lessler again, to ask him how our understanding of COVID-19 has evolved in the past month, and how epidemiologists have changed their views of the pandemic’s likely effects. In our latest conversation, which has been edited for length and clarity, we discussed what we know about whether people who have been infected are now immune, the hope that warm summer weather will halt the disease’s spread, and why testing remains the only way to prevent further rounds of mass quarantines.

What sticks out to you the most, in terms of all the things we have learned in the past month?

One is something we have learned, which is that it appears that the social-distancing measures that we have been taking over the current period seem to be working in a lot of places. It’s a little early to say for sure, but hopefully the initial signals that maybe they’re working are an indication that they really are. In terms of what we haven’t learned, I think the amount of uncertainty that still remains on the true underlying burden is a bit disappointing. I had been hoping that we would have more of a sense of exactly how many infections there have been out there. I think that still remains the biggest unknown of the whole thing.

So, by “underlying burden,” you mean the number of infections?

Yeah. We know we’re seeing a particular number of deaths, and that’s a number we can be reasonably confident about. The number of people hospitalized is also something that we can be a bit confident about. But the number of confirmed cases—it’s unclear how much that’s telling us, because testing has been ramping up a lot over the past month or so, and a lot of those increases that we’ve seen in confirmed cases are just due to more testing. So the epidemic is progressing, and we are also testing more. Those are all the direct measures. But all of those measures come out of a pool of infected people that we don’t see, and we don’t know how big that pool is.

Is the reason that we don’t know that we haven’t ramped up testing enough, or is there something about the virus that has made it more difficult to figure that out?

It’s nothing specific to the virus, and it’s a little bit more than just testing. There are two ways you can get at that unseen pool. One is if you know how deadly the virus is, or how many people become clinical cases that you can detect, and we don’t really know that yet. The uncertainty in the mortality rate per infection I still think stands probably an order of magnitude between being as high as around one in a hundred, and as low as around one in a thousand. The other way you can get at it is if you’re able to go out and do not the type of testing most people are thinking of, which is virological testing to see if you’re infected right now, but serological testing, which tests for antibodies to indicate if you’ve ever been infected. Those studies are ongoing, but we haven’t started seeing many of those results yet. So we don’t really know how many people have been infected. But it’s the serological studies that are likely to answer the question more definitively, and sooner rather than later.

There seems to be an assumption that, once someone has the disease and recovers, they are likely to have some sort of immunity in the future. But at this point, how much do we really know about it?

We don’t know much in terms of the specifics of how the virus progresses. I mean, there has to be some immunity.

Why?

Because you cleared the virus somehow. You got the virus out of your system, and your immune system did that. How your immune system did that was by having an immunological response, and that was somewhat specific to the virus. So, for that reason, you have to have at least some immunity and protection from the virus. How much immunity and protection it is remains an open question. It could be what we call sterilizing or complete immunity, where you can’t even get infected with the virus, at one extreme. At the other extreme, it could just be very weak immunity that wanes quickly and maybe dampens symptoms a bit but doesn’t stop infection. So it’s clear that there has to be some protection, but the amount of that protection, how long it lasts, how important it is for interrupting transmissions—those are open questions.

If there is some immunity, would it exist only if you had shown symptoms, or would you have immunity if you had the virus and were asymptomatic?

You’d probably have some immunity either way. I think in most cases it’s likely that your immunity would be a little bit stronger if you had symptoms, because a lot of the symptoms you get for diseases like this are driven not by the virus itself but by your immune response. For instance, fever is something that’s driven by your body fighting the virus, not by direct action of the virus. And so it’s likely that people with symptoms may have a bit stronger immunity than people without, but the level of variation is something we don’t quite know. And there’s a lot of potential complexity there. Immunological interactions are complex things. In some cases it can even make second infections worse. We think that’s quite unlikely in this particular disease.

But the point is that there’s a lot of complexity in the way that immunological interactions work. Where I think we can be confident enough is that, over time, even if it’s not strong on the first infection, people will accumulate immunities such that they’ll be protected at least from severe outcomes from this virus on subsequent infections.

So if we were hoping for something, it would be that the virus spreads faster than we think, is less deadly than we think, and, once you’ve had it in any form, you have great immunity?

That would be the best scenario right now, that essentially there are many more people out there who have been infected now than we think, so that we’ve accumulated these high levels of community immunity, or herd immunity, that will protect us from subsequent waves.

Have we learned anything in the past month that makes that scenario more or less likely than when this thing first hit?

I think there are a few pieces of evidence that might point either way. I think it seems unlikely that it would be really, really widespread. I think there’s a moderate version of that scenario that’s still possible. But just take the number of deaths in a place like New York. The population is over eight million people, and just over eight thousand people have died. [New York City recently revised its death count to more than ten thousand people.] If the death rate is one out of a hundred, that implies that eight hundred thousand people have been infected, which is reasonable. But if the mortality rate is one out of a thousand, that assumes that eight million people have been infected in New York City, which is everyone. So if you scale those up by too big of a factor, you quickly get to a point where it implies that an unrealistic percentage of the city has been infected. So that sort of puts an upper limit on that scenario.