COVID Reinfections

The latest talk in the world of COVID is BA.5. In combination with BA.4 and BA.2.75 (which inexplicably someone gave the name “Centaurus”), these are the latest Omicron subvariants. They share many features with Omicron but have variations in their genetic code that render them distinct. BA.5 has become the dominant variant in the U.S. (we think, based on fairly limited data). This fact implies that it must be either more transmissible than earlier variants or better able to evade existing immunity, or both. Without these features, it wouldn’t become dominant — a new dominant variant needs some advantage. Beyond the survival advantage, our (again, overall limited) evidence suggests that the variant is similar to the original Omicron (or BA.1, or BA.2) in terms of severity. The presence of BA.5 has raised significant concerns — in some of the messages I get, I would say this borders on panic — about reinfection. Omicron in general, but perhaps the new variants even more so, show some immune evasion. We know already that COVID reinfection during the Omicron wave was much more common than during the Delta or Alpha waves. This has translated, in popular discussion, to questions like “Are we all just going to get COVID every three weeks now?” and “I heard that vaccines and prior infection do not protect you at all anymore.” You know how we can better answer these questions? Data. Let’s go. Can reinfections happen? Yes. Before getting into data, we should be clear on what we mean here. By “reinfection,” I mean a second (or more) COVID infection. A first infection after vaccination is a “breakthrough.” Both these post-vaccine breakthrough infections and reinfections were much more common in the Omicron wave than in prior waves. The evolution of the virus meant that antibodies developed in response to earlier variants, either through vaccine or infection, provided less immediate protection. However: both vaccines and prior infections continue to provide very good protection against serious illness and death. How common is this reinfection? It’s difficult to know for certain given the data we have. I’ll talk below about data on the protective effect of prior infection, but that’s a slightly different question. To get a vague sense of the extent of reinfection in at least one population, I surveyed all of you (newsletter readers, Instagram followers, etc). I got over 21,000 responses. On one hand, this is a totally non-representative sample. On the other hand, it’s representative of you! The graphs below show reported infection counts — for individuals and a sample of their children — in this group. Of course, a random sample would show up with different numbers. What I believe is useful here, though, is to illustrate the balance of one versus multiple infections. Again, this is in a select group and may leave out people who are more or less vaccinated, or with varying demographics. About 60% of adults who responded here had had COVID at least once, but only about 6% reported having it more than once. When asked about their children under 18, about 53% of kids had had it, but only 4% more than once. Again, I do not want to suggest these data are some kind of representative random sample. In this group, though, repeat infections have happened but they are not the mode. How much protection is provided by prior infection/vaccination? A somewhat terrified question I get a lot: “Am I totally unprotected even if I had COVID before?” My sense is that some of this fear stems from the feeling that everyone has already had COVID, so all the infections we hear about must be reinfections. That’s not true, though. When we dive into the data we have, it becomes clear that prior infection does provide a lot of protection, even in the current wave. One way to see that is using data from the U.K. and from New York State, both of which report the number of first infections and reinfections separately. Let’s take the U.K. data first. On July 8 (the most recent fully reported day as of this writing) the U.K. Health Security Agency estimated 17,179 first infections and 4,607 reinfections, so about 21% of total infections were repeat infections. This number isn’t very meaningful on its own; to interpret it, we need to know how many people are at risk for the two categories. Imagine that in the population, at the moment, 21% of people have had COVID sometime in the past. If we then — this week — saw that 21% of cases were reinfections, that would mean that infection this week was equally likely regardless of whether you had COVID before. This 21% of the population makes up 21% of infections. On the other hand, if (say) 90% of people had COVID before, then the fact that only 21% of infections were among this population would suggest that prior infection is very protective. In more technical terms, it’s extremely important to pay attention to base rates. In fact, estimates from the U.K. indicate that about 90% of the population have had at least one infection. Using an analog to a “vaccine efficacy” calculation, this would suggest that having had COVID before reduces your risk of infection by about 95%. It doesn’t reduce it to zero, but it’s a huge change. The New York data shows a similar number — about an 88% reduction in risk. These numbers are back-of-the-envelope calculations that are subject to concerns about who has been infected before, their risk factors, and so on. But we see similar things from new published work out of Qatar. This paper used the entire population of Qatar to analyze the protection provided by prior infection and vaccination against COVID. It is important to note that the country has a very young population — only 9% of people are over 50, and 89% are expatriates from other countries. The researchers’ key graph is below, showing protection provided by various experiences against symptomatic infection and severe infection, with BA.1 or BA.2. (This paper predates BA.5, so of course things could be slightly different now.) Overall, the authors observe that prior infection is quite protective, and even more so with two or (better!) three vaccine doses. They estimate that prior infection plus three doses is 74% to 77% protective against symptomatic COVID, and 100% protective (again, young population) against severe infection. Of note here is also that two doses of vaccine — which at this point would have been quite far in the past — are protective against serious illness but not against symptomatic illness at all. What I take from this is that if you have had COVID before, and especially if you’ve been fully vaccinated, you have significant protection against symptomatic COVID. It’s not 100%, but it’s really quite high. What do we not know? There is much we do not have detailed information about. Based on some preliminary data out of Denmark and from our general understanding of illness, we expect reinfections to be on average less serious. (There was a preprint about the VA that suggested otherwise, but it is problematic; see discussion here.) However, this understanding is incomplete, and for questions about, for example, long COVID, we are in the dark. We do not understand well the likely gap between COVID infections if people are reinfected. There are a lot of assumptions made that people are protected for 90 days, but there seem to be exceptions to that, although they are probably rare. We also don’t have a good sense of variation across individuals. If you haven’t gotten it yet, are you somehow magically immune? (Probably not.) These are all questions I wish we had better data to answer, and I remain astonished that this many years into the pandemic, the U.S. still has not managed to create a better data infrastructure. For a long time I reacted to that by saying I hope they develop it soon (like here, here, and here). But at this point, I’m going to just say it’s too bad we do not have it and leave it at that. The bottom line, with our imperfect data: Reinfection is possible, and has become more common over time. However, prior infection does provide some really substantial protection. Most infections you are hearing about are still first infections. What should you do about this? There is a glass-half-full take here, which is that reinfection may be less common than you fear. But this discussion also forces the realization that reinfection is possible, and even if you had COVID before and have had all your shots, you could get it again. With this realization, we renew questions like “Should I fly now?” or “What about indoor dining?” In the past, many of us were looking at data on case rates to inform decisions like this. I will level with you: that isn’t going to work now. The testing and surveillance situation in the U.S. is not good, and we really have no idea what case rates are. This is frustrating, but it seems to be where we are. The combination of this fact and the realization that reinfection is possible means that it may be time to make a less contingent, more permanent, set of choices. You are now in a world where COVID is some risk more or less all the time, and you probably will not have much more than a vague sense of the size of the risk. Given that, what kind of long-term precautions do you want to take? One category of behaviors that I think are straightforward for many people: get vaccinated and, especially if you are older and higher-risk, keep up to date on boosters. If you get COVID, stay home. Get appropriate treatment if you get sick. These actions will go a really long way toward preventing serious and life-threatening illness. Vaccinations will also lower your risk of getting COVID at all. More complex are a set of choices about activity restrictions, masking, and testing. To some extent, your choices here can limit the risk of getting COVID, but they also entail some downsides. I’m talking about choices like indoor dining, movies, concerts, airplanes. Do you do these? And if you do these things, do you mask? How will you approach testing? You have been thinking about these choices all along. The difference I see now is thinking about these choices as almost permanent, or at least long-term. Not “Should I travel by plane this week, given the COVID rates?” But rather, “Am I comfortable with plane travel knowing the risk of COVID is present?” Not “Should I wear a mask in the movie theater this week?” But rather, “Will I generally mask at the movies?” Not “Should we rapid test before this particular gathering?” But rather, “Will we generally be rapid testing before we get together?” I don’t imagine everyone will come down in the same way on these questions. Comfort with COVID risk differs for many reasons. But at this point I think the question you need to ask is: What behaviors am I willing to undertake long-term to avoid infection? This question is sort of a bummer, since it recognizes that there isn’t some moment when COVID will be gone, but it also lets you off the hook from re-making these choices every time. Could things change? Of course. A new variant with a different profile or that causes more severe disease could alter our calculus. But none of the variants so far (knock on wood) have this feature. For now, make your decision once, knowing that the risk of reinfection is there but that it is perhaps lower than you feared.

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