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. Last week, I had an interesting conversation with a friend of mine from college. Like many docs these days, I find myself doing my best to answer a lot of COVID-related questions from friends and family, ranging from straightforward stuff to edge cases that never seem to quite be covered by the CDC recommendations. But this one led to a question that I've actually been stuck on for a bit, and I want to share my thinking with you. My friend has not yet gotten vaccinated. He is not really anti-vaccine; he falls into the more common category of "wait and see" — nervous about some reported side effects, in no rush to get the jab. I try to meet people where they are when it comes to this — not overly dogmatic, just trying to honestly outline the risks and benefits. Like me, he's a forty-something guy without a high-risk medical condition. He understood that if he were to get COVID, there's a good chance it would be mild, a small chance it would be severe, and a very small chance it would lead to death. Fine. But then he said something I hadn't thought of. He asked, "And what's the chance that I'll get COVID at all?" That question had me stuck for a second. I mean, it has to be less than 100%, right? Nothing in medicine is 100%. So here's my best effort to answer the question. If You Are Not Vaccinated, Will You Get COVID-19? The first thing we need to think about is the much-vaunted herd immunity. For the people in the back, this is the concept that when a certain proportion of a population is immune to a disease, either through infection or vaccination, the epidemic essentially burns itself out. In other words, the "herd" protects those individuals without immunity. They may never get sick. The herd immunity threshold is tied directly to the basic reproduction number of the pathogen the average number of people each infected person subsequently infects in a totally vulnerable population. Estimates of the basic reproduction number of the original coronavirus strain was around 2.5. The alpha strain was about 50% more infectious than that, and the delta strain — on its way to being the next dominant strain in the US — is more infectious still. You can see that as we drive up that basic reproduction number, the herd immunity threshold increases. But here's the rub. It's a moral hazard. If everyone expects to be protected by herd immunity and chooses not to get vaccinated, no one will be protected by herd immunity. Assuming we don't get to the herd immunity threshold, will every unvaccinated person get COVID? Not necessarily. Some people will be naturally immune to any given disease; see the famous case of the Kenyan sex workers who are immune to HIV and the premise of every work of postapocalyptic fiction from The Stand to The Last Man on Earth. Are some people naturally immune to SARS-CoV-2? It's hard to say. There will certainly be people with genetic variants of the ACE2 receptor. In fact, some variants of ACE2 seem to convey some protection against severe malaria, leading to suggestions that selection for these variants might account for decreased COVID severity in certain parts of Africa. Genetic immunity is one thing. But the possibility that some of us have some acquired immunity due to exposure to prior common-cold coronaviruses is still out there. A study of US blood samples collected between 2015 and 2018 showed that 50% had T-cell reactivity against SARS-CoV-2, presumably from prior coronavirus exposures, though most of the activity was not directed against the spike protein, making the clinical significance of this finding unclear. Nevertheless, some of us might be harboring some antibodies and T cells that at least mitigate severe disease. That said, it may not be too many. SARS-CoV-2 attack rates in tight settings is pretty high — about 15%-50% within a household. And remember that Georgia summer camp with an almost 50% attack rate? These numbers don't suggest broad preexisting immunity. But they don't rule out that there are some people with some preexisting protection. The other way you might not get COVID is by already having gotten it. We know that SARS-CoV-2 can cause asymptomatic infections. We aren't totally clear yet whether those infections provide lasting protection, but they might. The CDC estimates that between February 2020 and March 2021, there were about 115 million infections in the US. Over that period, only around 26 million infections were detected. That suggests that there might be 80 million people out there — maybe a quarter of the US population — who had COVID and either didn't know it or didn't bother to get tested. Of course, the big unknown here is COVID variants. Will they break through prior immunity, whether acquired through vaccination or through prior infection? So far, the vaccines have performed admirably against new variants. So, what are we left with? If you don't get vaccinated, will you get COVID? I think the best answer we can give right now is... probably. Odds are, eventually you'll get it — perhaps from a currently circulating variant, perhaps from a future variant. But will every unvaccinated person get COVID? I don't think so. Some of them because they've already had it and don't know. Some of them because they are just lucky. And maybe, if we really push, because we can still end the pandemic before it infects every last human being — that is, if the vast majority of us decide to hedge our bets, avoid the moral hazard, and get vaccinated. Source
