There was an interesting study out of Israel comparing natural immunity to vaccine-induced immunity for SARS-Cov-2. Generally it finds that natural immunity is more robust than vaccination, though the vaccine does still seem to yield some benefit to people with natural immunity. And it's not a small effect, we're talking seven-fold or thirteen-fold, depending on how you do the analysis. Note the three different comparisons:
Model 1 – previously infected vs. vaccinated individuals, with matching for time of first event
In model 1, we matched 16,215 persons in each group. Overall, demographic characteristics were similar between the groups, with some differences in their comorbidity profile (Table 1a).
During the follow-up period, 257 cases of SARS-CoV-2 infection were recorded, of which 238 occurred in the vaccinated group (breakthrough infections) and 19 in the previously infected group (reinfections). After adjusting for comorbidities, we found a statistically significant 13.06-fold (95% CI, 8.08 to 21.11) increased risk for breakthrough infection as opposed to reinfection (P<0.001).
Also:
Model 2 –previously infected vs. vaccinated individuals, without matching for time of first event
In model 2, we matched 46,035 persons in each of the groups (previously infected vs. vaccinated). Baseline characteristics of the groups are presented in Table 1a. Figure 1 demonstrates the timely distribution of the first infection in reinfected individuals.
When comparing the vaccinated individuals to those previously infected at any time (including during 2020), we found that throughout the follow-up period, 748 cases of SARS-CoV-2 infection were recorded, 640 of which were in the vaccinated group (breakthrough infections) and 108 in the previously infected group (reinfections). After adjusting for comorbidities, a 5.96-fold increased risk (95% CI, 4.85 to 7.33) increased risk for breakthrough infection as opposed to reinfection could be observed (P<0.001) (Table 3a).
Overall, 552 symptomatic cases of SARS-CoV-2 were recorded, 484 in the vaccinated group and 68 in the previously infected group. There was a 7.13-fold (95% CI, 5.51 to 9.21) increased risk for symptomatic breakthrough infection than symptomatic reinfection (Table 3b). COVID-19 related hospitalizations occurred in 4 and 21 of the reinfection and breakthrough infection groups, respectively. Vaccinated individuals had a 6.7-fold (95% CI, 1.99 to 22.56) increased to be admitted compared to recovered individuals.
Finally, they compare vaccinated plus naturally immune to natural immunity only.
Model 3 - previously infected vs. vaccinated and previously infected individuals
In model 3, we matched 14,029 persons. Baseline characteristics of the groups are presented in Table 1b. Examining previously infected individuals to those who were both previously infected and received a single dose of the vaccine, we found that the latter group had a significant 0.53-fold (95% CI, 0.3 to 0.92) (Table 4a) decreased risk for reinfection, as 20 had a positive RT-PCR test, compared to 37 in the previously infected and unvaccinated group. Symptomatic disease was present in 16 single dose vaccinees and in 23 of their unvaccinated counterparts.
This really piqued my interest, because I've been hearing quite a lot of nonsense dismissing natural immunity to covid. What I've heard ranges from wild speculation to non sequiturs to unscientific rejection of what we all know about the immune system. (It tends to sound like, "Meh, we just don't know yet!" As if we couldn't analogize from other respiratory viruses, even other coronaviruses.) A lot of people have been playing the role of naïve empiricists this past year and a half, pretending we can't know anything without direct observation of the specific question at hand. We actually have some powerful general scientific principles that can be applied here. Some are from the logic of evolutionary theory (we all still believe in that, right?). Others are from a basic, high school level understanding of how the immune system functions (and a basic understanding of how the mRNA vaccines work).
Here's my reaction: The paper's conclusion is exactly what we should have expected, at least directionally even if we can't predict the magnitude. The vaccines are scientific wonders, but the ones that are most common (the Pfizer and Moderna mRNA vaccines) are incredibly narrowly tailored. None of the live virus is present in the vaccine. It's just a strand of mRNA, basically some biological instructions that tell your cells to "make me some spike protein." This teaches your immune system to build antibodies for when the real thing comes along. I don't know exactly how pure the RNA sequence is in the vaccine, but I would guess that every strand of mRNA in a given formulation is making exactly the same spike protein. Don't get me wrong, this is great. It means when you do encounter the "novel coronavirus," it's not completely novel. Your immune system has some familiarity with what it's encountering and can fight it off, often without any hint of illness (though obviously we're now seeing a lot of breakthrough infections). But compare that to having a live virus replicating inside of you for weeks. In this latter case, your immune system isn't going to be narrowly tailored to one particular version of the spike protein. It's going to cue in on other pieces of the virus. If the spike protein mutates and you encounter this new strain of the coronavirus, that's okay, your immune system can recognize other signals that your body is being invaded and ramp up production of antibodies. Also, given the amount of exposure you have to the virus and its various proteins in the case of a live infection, you should expect that your body would spend more time and energy building up antibodies. I'm at the limits of my understanding of the immune system here, but I would suspect someone who just spent two weeks fighting off a live virus would have built up more antibodies than someone who's had two quick jabs of mRNA.
See this Nature article explaining why the Delta variant is so much more transmissible:
Shi’s team and other groups have zeroed in on a mutation that alters a single amino acid in the SARS-CoV-2 spike protein — the viral molecule responsible for recognizing and invading cells. The change, which is called P681R and transforms a proline residue into an arginine, falls within an intensely studied region of the spike protein called the furin cleavage site.
Sometimes people forget, or pretend to forget, that evolution is a thing. Evolution isn't like organic chemistry or knowledge of the immune system, where you have to know how actual, specific biological systems work (T-cells and such). Evolution has its own simple, mathematical logic, absent of any specific details. (Though certainly the details enrich one's appreciation of the concept.) Given that there are replicators trying to pass their genes into the future, and given that those replicators vary from each other in ways that modify their probability of success, we should expect some versions of those replicators to proliferate and others to die off. If there is a mutant form of covid that is good at evading the mRNA vaccines (say, by having a mutant version of the spike protein), we should expect that mutant to proliferate. Maybe someone who knows more about this can contradict me. Perhaps the Delta variant's spike protein is no more likely to evade vaccine-induced immunity than the Alpha variants, it's just that the mutation makes it more infectious in general? But it does seem like we're creating a world that would select for mutant spike proteins. Biologists should be standing up and declaring that what's happening with the Delta variant isn't a surprise.
All of this has me thinking, Why in the hell are we talking about a booster shot of the same vaccine that was developed in January of 2020? Given that someone was able to develop a working vaccine based on first principles basically on their first try, where is the vaccine that's tailored specifically to the Delta variant? The lesson coming out of this past year-and-a-half is that it's relatively easy to tailor an mRNA vaccine to a new virus. So let's have that lesson inform vaccination policy (including the approval process for new vaccines and vaccine recommendations from the CDC). If we're seeing evolution in the direction of altered spike proteins, let's have a more robust ecosystem of vaccines. How about, if you've already had the mRNA double-jab, the recommendation should be to get the Johnson & Johnson vaccine (which is not an mRNA vaccine). Or how about variolation? Let's see a proliferation of attenuated virus vaccines. The mRNA vaccines were a great way to buy some time and protect the most vulnerable individuals (at least temporarily), but we should expect a rapidly evolving virus to outfox it. I'd also like to see population-level serology sampling to determine the prevalence of antibodies, and furthermore to determine what kind of antibodies people are getting. Which proteins are our immune systems zeroing in on? And can we use this study of natural immunity to inform the development of vaccines? Can an mRNA vaccine hold the instructions for multiple proteins? Perhaps for multiple variants of multiple proteins? You know, so 180 million Americans (many times that number worldwide) are not all susceptible to a single mutation on a single protein. Even if you're still a total covid-hawk who viscerally rejects the notion of letting the virus run its course, the Israeli paper should be informing your opinion of what kinds of vaccines to pursue.
(By the way, it seems that Geert Vanden Bossche alerted us to this possibility. See his interview with Bret Weinstein here. I can't quite buy his conclusion that we shouldn't engage in a vaccination campaign during a pandemic, at least I think that's what he's saying. It's like saying "We shouldn't use this life-saving medicine because there's a finite supply that will eventually run out." I think the correct take-away is that we'll have to keep adjusting the mRNA vaccines to new variants, or eventually switch to attenuated virus vaccines.)
In the early months of the pandemic, I repeatedly heard commentators (covid hawks all) dismiss the idea that naturally occurring immunity could lead to herd immunity. The same people would often insist that we could only get there through vaccination. (See this incredibly bad-faith piece in the Atlantic, and my commentary on it here. ) It was thoroughly confusing. Say you had a society of people with enough vaccination coverage that it had herd immunity. These commentators were apparently saying that if you swapped out the vaccinated people for people with natural immunity, the virus would come back and start spreading again? Or perhaps they were simply saying that the concept of herd immunity arose in the context of a vaccination campaign. This is a historical claim about the origins of an idea, but it's completely irrelevant to the claim about whether herd immunity from natural infection would work. Or perhaps if asked directly they would have conceded that, yes, a sufficient level of natural immunity would provide herd immunity, but it would come at too great a cost along the way? Or as a matter of historical fact, it had never happened? (Though wouldn't it happen in this case, with covid being so infectious? And wouldn't it be fine if the non-vulnerable, who basically experience it as a mild flu or cold or as nothing at all, all got the virus while the vulnerable were being isolated and protected?) No version of the "herd-immunity-from-natural-immunity-wouldn't-work" claim actually makes much sense. I think these people were actually so confused that they themselves didn't even have a clear idea what they were claiming. They had so little patience for the notion of simply tolerating the virus that they shut off and began lobbing whatever rhetorical fodder was within reach. They were jack-knifing from one idea to another without acknowledging the change in direction.
I can't help but feel a little vindicated by the study linked to at top (I'll happily retract that statement if the result doesn't hold up, though). A lot of people were suggesting that natural immunity to covid didn't exist at all, or was very short lived, or at any rate we couldn't count on it for protection. I knew this was nonsense at the time. If there were no natural immunity at all then sick individuals would simply never recover, they'd just keep getting re-infected by the virus circulating in their body. (Like, what model of the immune system did these people have? You will eventually fight off the viruses that are inside your body, as I think they would have conceded. But then you'd promptly be reinfected if new particles of exactly the same virus entered your body from the outside?) This was the dog that didn't bark, as in they would have been shouting from the rooftops if they found substantial numbers of reinfections. But reinfections were exceedingly rare. If the result of this study holds up, I'd like to hear some kind of correction from this crowd. A big, fat, blubbering apology to the Great Barrington Declaration crew would be in order. The greater robustness of natural immunity means their prescription is even more attractive.
All those people who are saying they don't need the vaccine because they've already had covid aren't wrong. The Israeli study suggests they'd cut reinfection risk in half by getting vaccinated, but that's on top of immunity that's extremely robust. Most people would probably think it's sufficient and see no need to dredge the depths for tiny incremental amounts of covid protection. There is some finite risk of undiscovered dangers with the mRNA vaccines, which I discussed in my previous post. I personally don't care for this "unknown unknown" type of argument, and I don't think the VAERS data on reported vaccine side-effects is showing a real signal. But I can respect someone who has a different cost-benefit calculation than mine or who reads the evidence differently from me. I have far less respect for the condescending attitude of the vaccine scolds. "Just get the jab, you backwards rube! Learn about the science!" Clearly the cost-benefit calculus differs for different people. It depends on their risk factors; if you're in a high-infection-fatality-rate demographic you should get vaccinated. If not, it may not be worth it. I have just enough reservations that I'm not super-thrilled about my young children getting the jab. (BTW, it is the official position of the U.S. public health establishment that very young children shouldn't be vaccinated. According to the CDC, as of this writing the vaccines are only recommended for children above the age of 12. Even if that changes tomorrow, the current recommendation is completely defensible.) Given that vaccine-induced immunity is going to wane anyway, given that they're not going to get very sick from the virus, and given that they're likely to encounter the it eventually, it's probably best that they encounter the real bug and acquire robust immunity while young. It's unlikely that the vaccine is "protecting" them in that sense, just delaying their development of a truly robust immunity.
The Israeli study is just one paper, so I don't want to put too much stake in it until someone replicates it. If it fails to hold up, maybe I'll leave the post up but just strike through a bunch of the above text. That being said some of the points I made above are independent of this particular study's results. There is no question that natural immunity is real and at least comparable to vaccine-induced immunity. That's a substantial update compared to what people were saying last year.
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A further note on the matching, from the body of the paper. Here's regarding model 1:
These groups were matched in a 1:1 ratio by age, sex, GSA and time of first event. The first event (the preliminary exposure) was either the time of administration of the second dose of the vaccine or the time of documented infection with SARS-CoV-2 (a positive RT-PCR test result), both occurring between January 1, 2021 and February 28, 2021.
Therefore, matching was done in a 1:1 ratio based on age, sex and GSA alone. Similar to the model 1, either event (vaccination or infection) had to occur by February 28, to allow for the 90-day interval.
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