Conversation

Nicholas A. Christakis
@NAChristakis
Let’s talk about natural immunity (NI) versus vaccine-induced immunity (VI) to SARS2. This has become controversial. If you survive COVID19 infection, what does that mean, immunologically and practically (given current state of knowledge and current state of the pandemic)? 1/
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Nicholas A. Christakis
@NAChristakis
This is a SUPER long thread (with recent research) on a topic that has become weirdly politicized (as I learned – though I should have known with anything COVID19-related! – after my recent interview with
@SamHarrisOrg
youtube.com/watch?v=vod4aO). So buckle up. 2/
youtube.com
What Have We Learned from the Pandemic?: A Conversation with Nicholas...
In this episode, Sam Harris speaks with Nicholas Christakis about the lessons of the COVID pandemic. They discuss our failures to coordinate an effective res...
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Nicholas A. Christakis
@NAChristakis
Bottom line: natural immunity is probably *somewhat less* effective at preventing serious COVID19 compared to vaccine immunity, or possibly *just as* effective. But this depends on many details: how sick you got, your age, the variants in circulation, and follow-up duration. 4/
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Nicholas A. Christakis
@NAChristakis
Plus (and this is crucial) in order to get NI, you must survive an infection! It’s not a rational plan to say “I’ll just get immunity naturally rather than get vaccinated.” The whole point of vaccination is to give you immunity without running the (non-trivial!) risk of death. 5/
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Nicholas A. Christakis
@NAChristakis
So, *given current variants*, and given the follow-up times so far available (less than a year), I would say VI is better than NI for two reasons: 1) you don’t have to run risk of death to get it, and 2) if you get VI, it’s probably slightly better than NI. 6/
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Nicholas A. Christakis
@NAChristakis
This conclusion depends a lot on what any new variants do to us. For instance, while VI might be better than NI for the original strain, that might not be the case for newer strains. This means the story may change as the variant landscape changes, or with new booster shots. 7/
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Nicholas A. Christakis
@NAChristakis
Information on the efficacy of natural immunity is also crucial to things like allocating scarce vaccines in poor countries (why jab already immune people?) and to issues like social restrictions (if naturally immune have good protection, they should not be restricted). 9/
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Nicholas A. Christakis
@NAChristakis
Benefit of NI is old topic. In antebellum NOLA, people who were immune to yellow fever – by having survived this deadly disease which could kill 8% of population – had special status (they were “acclimated”). academic.oup.com/ahr/article-ab Now we just get a vaccine for this scourge. 12/
academic.oup.com
Immunity, Capital, and Power in Antebellum New Orleans
Abstract. Antebellum New Orleans sat at the heart of America’s slave and cotton kingdoms. But it was also the nation’s “necropolis,” with yellow fever routinely
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Nicholas A. Christakis
@NAChristakis
Still, to be clear, and based on the review below, I think that those with (documentable) natural immunity should be treated as if they have been vaccinated and should not be discriminated against. 13/
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Nicholas A. Christakis
@NAChristakis
However, from a public health policy point of view, this might not be easy to implement, and it might not actually be optimal from a collective viewpoint (it’s logistically easier to just try to vaccinate everyone, for instance). 14/
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Nicholas A. Christakis
@NAChristakis
With that preamble, let’s look at current research: 1) head-to-head epidemiological studies of NI vs VI, 2) epi studies of NI, 3) epi studies of VI, 4) in-vitro studies of natural vs vaccine-induced antibodies and of cellular immunity, and 5) studies of having both NI and VI. 15/
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Nicholas A. Christakis
@NAChristakis
This
@CDCgov
review, based on then-available evidence & conditions, concluded that 1) mRNA vaccines lead to more consistent and higher initial antibody response, and 2) NI had efficacy against infection of 80-93% at six months, probably somewhat lower than VI (Pfizer) of 91%. 17/
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Nicholas A. Christakis
@NAChristakis
In general, antibody titers rise more rapidly and reach higher levels among those with more serious COVID. In a sense, a vaccine can therefore emulate a more serious case of COVID, but without the risk. This may be one reason VI is indeed better than average NI. 19/
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Nicholas A. Christakis
@NAChristakis
This also means that, if you want to rely on having been naturally infected to have good immunity, you had to have had a bad case of COVID19. Having had a mild case is unlikely to be as good as having had a vaccine. 20/
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Nicholas A. Christakis
@NAChristakis
Studies of NI can face a methodological problem. Most were done early in pandemic when testing was minimal, so asymptomatic cases were not detected. This means that the efficacy of NI was inflated since cases with weak immunity after exposure were not included in the studies. 24/
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Nicholas A. Christakis
@NAChristakis
A (controversial) November 2021 analysis of 187 US hospitals found that, among 7,348 (baroquely chosen) patients hospitalized with COVID-like illness, 5.1% of those with a history of vaccination actually had COVID and 8.7% of those with prior COVID had COVID again. 26/
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Nicholas A. Christakis
@NAChristakis
Said differently, the study found (in population of 7,348 hospital patients) that, of 413 cases of test-positive COVID, 324 (78%) were vaccinated & 89 (22%) had prior COVID. But in 6,935 test-negative control patients, 6,004 (87%) were vaccinated & 931 (13%) had prior COVID. 28/
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Nicholas A. Christakis
@NAChristakis
In essence, this is a “case control study,” meaning that cases of COVID are compared (in terms of prior exposure to vaccination/infection) to ostensibly *otherwise similar* ppl without COVID (the controls – ppl who were sick with respiratory disease in same place & time). 29/
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Nicholas A. Christakis
@NAChristakis
Choice of controls is *always* the crucial thing in such studies because it can drive the results (one can stack deck this way). Choice in this study (ppl hospitalized with COVID-like illness) seems OK. (But for a critique, see: brownstone.org/articles/a-rev via
@MartinKulldorff
) 30/
brownstone.org
A Review and Autopsy of Two COVID Immunity Studies ⋆ Brownstone Institute
I have never before seen such a large discrepancy between immunity studies that are supposed to answer the same question.
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Nicholas A. Christakis
@NAChristakis
There are many strengths to this Israeli study, including the fact that it was a population-based cohort study that used an electronic database to capture both the relevant exposures and the outcomes. 32/
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Nicholas A. Christakis
@NAChristakis
But there were many technical limitations too that worried me. There was evidence of imbalance in relevant covariates (e.g., the vaccinated people had more chronic diseases, despite matching on age, sex, and SES). 33/
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Nicholas A. Christakis
@NAChristakis
Also, many cases were dropped due to lack of suitable matches. In key analysis, we go from 673,676 vaccinated & 62,883 naturally immune subjects to 16,215 of each. No data re these ppl is given. Comparison is made in a particular group where there is “support in the data.” 34/
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Nicholas A. Christakis
@NAChristakis
Also, maybe vaccinated people took more social risks and this is why they had more infections? Or those with prior infection, having seen COVID up close, exercised more caution during follow-up? We cannot be sure. Of course, that is whole point of vaccination: to set us free. 35/
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Nicholas A. Christakis
@NAChristakis
In 11,405 health care workers, protective efficacy of prior infection against symptomatic infection was 86% (95%CI 77-92%). In the absence of prior infection, vaccine efficacy (of these *non-mRNA* vaccines) against symptomatic infection during delta wave was 32% (24–39%). 38/
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Nicholas A. Christakis
@NAChristakis
One odd finding in this study is the very low vaccine efficacy, which worked in favor of natural immunity benefit. This may relate to vaccines used, because other work finds higher efficacy (e.g., in UK, the AZ vaccine had 67% efficacy against delta (nejm.org/doi/full/10.10). 39/
nejm.org
Effectiveness of Covid-19 Vaccines against the B.1.617.2 (Delta) Variant | NEJM
Original Article from The New England Journal of Medicine — Effectiveness of Covid-19 Vaccines against the B.1.617.2 (Delta) Variant
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Nicholas A. Christakis
@NAChristakis
This Indian study also found evidence that having both infection and vaccination was superior. Vaccination combined with prior infection provided 91.1% (95%CI 84.1%-94.9%) efficacy in preventing subsequent COVID infection (i.e., VI+NI > NI) 40/
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