Back last summer, I was writing blog posts about possible side effects of mass vaccination. For readers who’ve shown up more recently and might have me filed as Defender of Vaccines, that might seem surprising, but remember, I’ve been in drug discovery for a long time now. All drugs, all therapies have side effects. It’s just a question of the risks and severity of those versus the benefits, and looking at either of those alone is a serious mistake.
One of the things I wondered about was Guillain-Barre syndrome. That’s because it’s already a known sequel to viral infections in general, and has also shown up response to vaccination. It’s an autoimmune disorder, which means that it’s going to be scattered around in the huge diversity of immune function from person to person, and it also means that it will be extremely difficult to predict who might be at risk. G-B involves an attack on a person’s own myelin sheaths around the nerves, which sounds very serious – and indeed, sometimes it’s severe enough that people need to be hospitalized while they recover. But fortunately the vast majority of patients do make strong recoveries – the immune response goes back down, and the body’s own remyelinating cells fix up the damage.
And now the FDA has issued a warning that there have been a few cases with the J&J vaccine. To the best of my knowledge, this has not been seen with the other vaccines, and that’s another illustration of the variability in the long tail of autoimmune side effects. You see these with small-molecules drugs as well, often when they can form covalent adducts and produce modified proteins that (in a few people) will set off the immune response, and this low-level idiosyncratic toxicity is a matter for constant surveillance.
Readers will recall the rare blood clotting problems seen with the AstraZeneca/Oxford vaccine, mostly in younger female patients. We now have more details on that, and this new paper seems to be the explanation. The affected people developed antibodies that respond to a particular 8-amino-acid region on the surface of the platelet factor 4 protein, in the same region that heparin binds to it. That sets off the same platelet activation cascade as heparin binding does, and thus the thrombosis effects that are seen clinically. The antibodies can also bind to existing heparin/PF4 complexes, which explains why heparin treatment makes things worse. Now, why just these particular people develop these particular antibodies, and why this seems to happen with the AZ/Oxford vaccine and not the others (to anywhere near the same degree, at any rate) are things hidden further down in the mysteries of human immunology. Meanwhile, the low-incidence side effect with the mRNA vaccines seems to be myocarditis, which has been noted mainly in male patients up to about 30 years old, generally after the second injection. This too is almost always a transient condition, fortunately, and is also down in the few-per-million range.
I know that these reports have many people with existing autoimmune disease concerned – that’s a completely rational thing to want to look into. I can only add, though, that the evidence is that coronavirus severity also seem to be greatly enhanced in people who have larger amounts of existing autoantibodies. All the medical advice I have seen so far is for people with autoimmune disease to indeed get vaccinated, and I agree with that as well.
That CDC link will take you through the sort of risk/benefit calculations that have to be done in all such cases. And since all of these side effects are in the few-per-million range, and since they all can be watched for, and can almost always be treated (or resolve themselves), the comparisons with the effects of the coronavirus pandemic itself are clear. It’s true that most people who catch the actual virus recover, but there certainly are deaths, even in the younger patients, and even more importantly, there are long-term effects. Reports of “Long Covid” have been growing with time, and there are now reports that the Altmann group at Imperial College has detected specific autoantibodies that are correlated with these long-running symptoms. (I’ll go more into that work when it gets published as a paper or preprint). Overall, the mortality/morbidity numbers are far worse with the actual disease – it’s no contest.
So as the CDC link shows, the choice is clear: mass vaccination does indeed have rare side effects, but mass infection with the coronavirus (which is the only other choice) is absolutely worse. And to reiterate a point that’s been made many times, the faster we can vaccinate people, the lower the chances we have of encountering a new variant form that will make everything even worse. We have to get as many doses out to the world as we possibly can, as quickly as we can.
Perversely, the current Delta variant may have done us a favor (although to be sure, I would rather it not have emerged at all). An earlier variant (Beta, the “351” strain) was actually better at evading vaccine protection than any of the others – not really to breakthrough levels, but certainly more than the rest. But it is disappearing from the world thanks to Delta being much more transmissible, and Delta is handled better by the vaccine-raised immune response. There are indeed vaccinated people who have come down with Delta infections, but the vast majority of cases are among the unvaccinated, a statistic that is seen most dramatically in areas where unvaccinated people are a minority of the population but are nonetheless the ones showing up infected.
No one has any idea of what the potential is for variant forms that could truly evade vaccine protection. Nor can we be sure about the potential for variants that are even more transmissible than Delta. And what we really, really don’t want is anything the combines those two properties. It would be very reassuring to show that you can’t have both those in the same strain, but we absolutely can’t say that yet. There are too many possibilities. We have to stop the virus from trying them, constantly and in every corner of the globe, if we don’t want to find out the hard way. Get vaccinated.
Update: as mentioned here, good faith discussion of all kinds on these topics is welcome in the comments section. Deliberately inflammatory posts, trolling, and conspiracy theories, however, will be deleted swiftly.
The post More on Vaccine Side Effects first appeared on In the Pipeline.
