We Should Have Known So Much About Covid From the Start

[NYT’s David Wallace-Wells]: [..] The way most people think about a virus like, say, RSV, or chickenpox, is that a single exposure, while potentially worrisome, does deliver lifelong protection. Is it really the case that, as babies, we are fighting off those viruses hundreds of times?

[Immunologist and epidemiologist Michael Mina]:The short answer is yeah. We start seeing viruses when we’re 2 months old, when we’re a month old. And a lot of these viruses we’ve seen literally tens, if not hundreds of times for some people by the time we’re adults. People tend to think that immunity is binary — you’re either immune or you’re not. That couldn’t be farther from the truth. It’s a gradient, and your protection gets stronger the more times you see a virus.

Take chickenpox. As you say, people used to think that if you got chickenpox, you were good, you’d never get the virus again. But you can get shingles — [..]

[Wallace-Wells]: Which is caused by the same virus, though in older people.

[Mina]: It used to only happen when your immune system fell below a certain level: as you age, you lose your immunological memory and you can get shingles. But in recent years we’ve seen a massive shift in the age of people getting shingles. It used to be mostly people in their 70s or older. Now it’s hitting people in their 30s. And people started to say, well, that’s weird, what’s going on?

[Wallace-Wells]: Yeah — what is going on?

[Mina]: We used to think we just had this spectacular immune response when we first encountered the virus at, say, age 6, and that the immune response lasted until we were 70. But actually what we were seeing was the effect of an immune system being retrained every time it came into contact with the virus after the initial infection — at 6, and 7, and 8, and so on. Every time your friend got chickenpox, or your neighbor, you got a massive boost. You were re-upping your immune response and diversifying your immunological tools — potentially multiple times a year, a kind of natural booster.

But now, in America, kids get chickenpox vaccines. So you don’t have kids in America getting chickenpox today, and never will. But that means that older Americans, who did get it as kids, are not being exposed again — certainly not multiple times each year. And it turns out that, in the absence of routine re-exposures, that first exposure alone isn’t nearly as good at driving lifelong immunity and warding off shingles until your immune system begins to fall apart in old age — it can last until you’re in your 30s, for example but not until your 70s.

There’s a similar story with measles. There is no routine later-life sequelae, like shingles, for measles. But what we do see is that, in measles outbreaks today, there are some people who were vaccinated who get it anyway. Maybe 5 to 15 percent of cases are not immunologically naïve people, but vaccinated people. So — what’s up with that? We thought we had lifelong protection from childhood vaccination, but because there’s no more natural boosting of measles anymore, that protection wanes to some degree over time.

But to think about that in the context of Covid, for a minute — all of those subsequent exposures to chickenpox were basically invisible. You didn’t get sick the second or fifth or ninth time you encountered the virus. Covid is still making some people sick, on reinfection, if typically less sick.

And with Covid, we’re getting infected frequently. But there is also a very basic difference between a disease like Covid and a disease like measles or chickenpox. For measles or chickenpox to cause a symptomatic infection, it has to be brought into the body, through the upper respiratory tract and the lungs, into the bloodstream and the lymph. It doesn’t really even start replicating until it gets that deep into the body. And if it doesn’t get that deep, it doesn’t replicate. With a disease like that, our T-cells and B-cells, which were created during past exposure or by vaccination, typically stop the virus early enough that no replication happens and we don’t even notice it.

With Covid, when it infects you, it can land in your upper respiratory tract and it just start replicating right there. Immediately, it’s present and replicating in your lungs and in your nose. And that alone elicits enough of an immune response to cause us to feel really crappy and even cause us to feel disease. But it’s why we don’t see the severe disease as much, with a second exposure or an exposure after vaccination: For most people, it’s not getting into the heart and the liver and stuff nearly as easily. But it doesn’t have to. It’s still causing symptomatic disease. And maybe mucosal vaccines could stop this, but without them we’re likely to continue seeing infections and even symptomatic infections.

[Wallace-Wells]: This is a very different story about immunity than we were told through most of 2020 and into 2021, though. Back then, I think the conventional wisdom was that a single exposure — through infection or vaccination — would be the end of the pandemic for you. If this is basic virology and immunology, how did we get that so wrong?

[Mina]: The short answer is that epidemiologists are not immunologists and immunologists are not virologists and virologists are not epidemiologists. And, in general, physicians don’t know anything about the details. And the world has never before been forced to so directly grapple with these nuances.”

Full newsletter, D Wallace-Wells, New York Times, 2023.10.5