Self & Other · mRNA, and What COVID Taught Us
The Honest Accounting of Side Effects
This was not the vaccines failing. It was the virus changing in ways that the original vaccine, designed against an earlier strain, no longer matched as cleanly. The pattern is the same one we discussed in Chapter 4 with the flu: a vaccine against a moving virus eventually becomes less effective against new variants. The COVID vaccines, like flu vaccines, have been periodically updated to keep pace.
What the vaccines have continued to do, throughout all of this and across all variants, is dramatically reduce the rate of severe disease, hospitalization, and death. This effect has held up across years, across variants, across populations. Vaccinated people, even when they get infected, are far less likely to be hospitalized and far less likely to die. The exact numbers vary by variant and population, but the order-of-magnitude effect on severe outcomes has been consistent. By the most credible estimates, the COVID vaccines, in their first several years of deployment, prevented somewhere between fifteen and twenty million deaths globally that would otherwise have occurred. The numbers are imprecise. The order of magnitude is not.
The honest framing is that the COVID vaccines have been somewhat overpromised in one direction — they were never going to permanently prevent infection in a world of evolving variants — and dramatically underappreciated in the other — their effect on severe disease has been one of the largest medical interventions in human history.
The Honest Accounting of Side Effects
The COVID vaccines are, as a class, very safe. They are also not free of side effects, and being honest about which side effects are real, which are very rare, and which were exaggerated is part of what this chapter is for.
The common side effects — sore arm, fatigue, mild fever, headache, muscle aches, sometimes a day or two of feeling unwell — are not bugs. They are the immune system doing exactly what it should be doing, which is mounting a response to the protein the vaccine has just produced. We talked about this in Chapter 4 in the context of adjuvants and again in Chapter 8 in the context of inflammation. The temporary discomfort is the point. It indicates that the system has noticed and is responding.
Severe allergic reactions (anaphylaxis) to the mRNA vaccines occur, but at extremely low rates — roughly one in a hundred thousand to one in a million doses, similar to or lower than rates for other widely used vaccines. Such reactions, when they occur, generally happen within minutes of injection, are recognized quickly because vaccination sites are equipped to manage them, and are essentially always treatable. They are not the basis of a serious safety concern at the population level.
The most genuinely interesting and worth-discussing side effect is myocarditis — inflammation of the heart muscle — which has been observed at elevated rates after mRNA vaccination, particularly in young men in the sixteen-to-twenty-nine age range, particularly after a second dose, particularly with the Moderna vaccine compared to Pfizer. The condition is real. The cases were not denied. They were tracked, reported, and studied carefully.
What the data have shown is that vaccine-associated myocarditis is rare — roughly one case per fifty to sixty thousand vaccinated young men in the highest-risk group — and that almost all cases have been mild. The patients are usually hospitalized briefly, treated with anti-inflammatory medications, and recover fully. Long-term follow-up has, on the whole, been reassuring. A small number of cases have been more serious, and ongoing surveillance continues.
What is also true — and what is sometimes left out of the conversation — is that COVID-19 itself causes myocarditis at a substantially higher rate than the vaccines do. Several studies have estimated the COVID-induced myocarditis rate to be roughly five to ten times higher than the vaccine-induced rate, with the COVID-induced cases tending to be more severe. For young men weighing the risks, the comparison was never “myocarditis from vaccine” versus “no myocarditis at all.” It was “myocarditis from vaccine, mostly mild, against the substantially higher risk of myocarditis from COVID itself.” The vaccine, even given the rare cardiac side effect, came out favorably for almost every population.
Other reported side effects — from temporary menstrual changes to Bell’s palsy to various rare neurological events — have been investigated. Some were real and tracked. Some were not statistically distinguishable from background rates. The general framework that has emerged is the one any large-scale vaccination program ends up with: real but rare adverse events occur, are tracked, are weighed against the risks of the disease itself, and the overall calculation is updated as data accumulates.
The recommendations for COVID vaccines have been adjusted over time based on this evolving picture. Some doses were dropped from the recommended schedule for some age groups. Some were added. The frequency of recommended boosters has changed. None of this is a sign that the original decisions were wrong; it is a sign that the system is doing what science is supposed to do, which is update based on evidence.
What COVID Taught Us About Immunity
The pandemic was, among many other things, the largest natural experiment in immunology that has ever occurred. Hundreds of millions of people were exposed to the same virus over the same period. Billions of people received vaccines whose effects could be measured in real time. The data that emerged from this period has changed how immunologists think about several things, and a few of those changes are worth noting briefly.