Yes, mRNA Vaccines Work—&, It Appears, Work Much Better than I Thought
At the moment, COVID-19 is recorded as the cause of death for about 1/100 of the 0.4% of 19-64 year-olds who die each year—and failing to get your mRNA vaccine quadruples that. But it really looks like unvaccinated 19-64 year-olds have a greater risk of death not 0.016%/year higher than the vaccinated, but fully 0.12%/year higher. And the presumption has to be that there are an extra 6.5 19-64 year-olds who die from something else that they would have successfully fought off, had they gotten vaccinated and so had suffered under less of a metabolic burden from fighting COVID…
Am I wrong? Vaccine skepticism really, really, really should not be a thing.
Receiving the mRNA vaccination for COVID-19 is very strongly and causally associated with lower mortality from COVID: only ¼ of those who would die from COVID otherwise die if they were smart enough to get vaccinated.
But there are more correlations in the system:
Is receiving the mRNA vaccination for COVID-19 associated with lower non-COVID mortality because it indicates that you are a sensible person who can actually undertake to take reasonable care of your health?
Is it associated with higher non-COVID mortality because people in bad health have more powerful incentives to actually get vaccinated?
Is it associated with lower non-COVID mortality because COVID-19, even if it does not kill you, is a substantial drag on your metabolism and so opens your way to other things that do kill you?
Well, clearly (2) is not dominant: for every four people who die if they do not get the vaccine, only three people die who do.
Laura Semenzato & al.: COVID-19 mRNA Vaccination & 4-Year All-Cause Mortality Among Adults Aged 18 to 59 Years in France <https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2842305>: ‘A total of 22,767,546 vaccinated and 5,932,443 unvaccinated individuals were followed up for a median (IQR) of 45 (44-46) months. Vaccinated individuals were older… on average, more frequently women (…51.3%]…vs… 48.5%) and had more cardiometabolic comorbidities… (9.3%… vs…7.8%]. During follow-up… 0.4%… and.. 0.6%… all-cause deaths occurred in the vaccinated and unvaccinated groups…. Vaccinated individuals had a 74% lower risk of death from severe COVID-19… and a 25% lower risk of all-cause mortality… with a similar association observed when excluding severe COVID-19 death. Sensitivity analysis revealed that vaccinated individuals consistently had a lower risk of death, regardless of the cause…
So is it (1) or (3)? Sample selection for intelligence in a life-preserving sense, or reduced metabolic load?
Probably both play a role, but reduced post‑infection disease burden is the more plausible dominant channel. There broad, cause‑specific reductions across major ICD‑10 categories. It would be very hard to explain all of these reductions solely by health‑preserver selection.
And we do, by now, know a lot about SARS‑CoV‑2 infections. They do elevate medium‑to‑long‑term risks across organ systems: cardiovascular, thrombotic, metabolic, neurological, and still others. This is consistent with a persistent metabolic and inflammatory burden. Such a burden could easily raise non‑COVID mortality.
Complementary data show vaccination lowers the risk and persistence of post‑COVID conditions (including in breakthrough cases), reinforcing the pathway whereby fewer or milder infections reduce later non‑COVID mortality. Thus there is a very clear channel here: Reducing infection and severity, vaccination plausibly cuts these downstream hazards. This aligns with extensive evidence on long COVID’s multi‑system consequences, and elevated post‑acute event risks.
While residual confounding can’t be completely ruled out (but when can it?), the preponderance of evidence does suggest the primary driver of the roughly 25% non‑COVID mortality reduction is fewer and less severe infections—and thus a lighter post‑infectious physiological load—rather than vaccinated individuals simply being “more sensible.”
So right now 1/5 of the American population is unvaccinated. Just doing the arithmetic: At the moment, COVID-19 is recorded as the cause of death for about 1/100 of the 0.4% of 19-64 year-olds who die each year—and failing to get your mRNA vaccine quadruples that. But it really looks like unvaccinated 19-64 year-olds have a greater risk of death not 0.016%/year higher than the vaccinated, but fully 0.12%/year higher. And the presumption has to be that there are an extra 6.5 19-64 year-olds who die from something else that they would have successfully fought off, had they gotten vaccinated and so had suffered under less of a metabolic burden from fighting COVID.
How did we get into this mess?