juliet

https://www.science.org/content/blog-post/covid-19-vaccinations-and-heart

First off, a note that posting will be a bit irregular this week, but I wanted to let people know that I'm definitely still around! So here's something to talk about:

There's a good new paper in JAMA Internal Medicine looking at a large recent data set in Covid-19 vaccinations in an older population. It's from the Veterans Administration, looking at about one million veterans who got a flu vaccine in 2024, and over three hundred thousand of them also got a coronavirus vaccine. Following up on these cohorts, the authors find that there was a 38% reduction in coronovirus-related major cardiovascular events in that latter vaccinated category, which is very nice to see. Even more interesting is that there was a 24% decrease in all-causes cardiovascular events (that is, including patients who were never diagnosed with a coronavirus infection during this period. That's quite impressive - comparable to the benefits of statins in at-risk patients (and it should be noted at the same time that the effects of statin therapy in otherwise healthy older patients do not seem to be particularly meaningful, although debate continues on that question).

As this excellent overview at Stat details, the most likely explanation for these numbers is a significant undercount of how many of these patients were actually infected with the coronavirus. But that's worth thinking about, too, because that leads one to the idea that many of them may have not felt all that sick (and never bothered getting tested for the virus as a result) but still had enough of an infection to raise their risk of cardiovascular trouble. And that makes a case for really getting those vaccination numbers up higher - the estimate from the paper's authors is the possible avoidance of 3,500 major cardiovascular events per million patients vaccinated in this population.

As the Stat article correctly says, this might surprise some people who associated the coronavirus vaccines (particularly the mRNA ones) with the side effect of myocarditis (particularly in young men). And that's a real finding - the vaccine did produce this in a small number of patients. But (and I've said this before), you know what gives people mycarditis at a significantly greater rate and in greater severity when it does occur, and not just in young men? Yeah: getting infected with the coronavirus. So it's still a very good tradeoff, and in this older population it's almost certainly an even better deal.

This will not sit well with the people who believe that the mRNA coronavirus shots have ravaged the world's population and are the cause of a whole list of diseases (cardiovascular death being a prominent one, for sure). You don't have to go far to find these folks - heck, some of them will be showing up in the comments to this post once they become aware of it, although I (as has been the policy here since the worst days of the pandemic) will not even let the most scurrilous of these even publish to the comments section in the first place. The signal/noise of the world is not improved by several paragraphs of poorly punctuated ranting about secret depopulation experiments, 5G nanobots, irreversible changes that make vaccine recipients subhuman and thus put the few, the brave, who haven't been vaccinated in the position of the Last Pure Humans on Planet Earth, and on and on. Nope, there's plenty of that crap out there already and I see no need to give it a platform here.

But the irony is rather thick: coronavirus vaccines not only keep people out of the hospital with severe viral infections - a fact that has been irrefutably proven in many large studies - but also help to keep elderly patients from dying of major cardiac events. Add that to the mounting evidence that the shingles vaccine helps to prevent dementia in these same age groups, and the recommendation has to be that older patients should be getting vaccinated far more often than they do. I'm not quite 65 yet, but I have taken all of these shots and will continue to get the updated coronavirus ones as they become available. Because I really think that it would be irresponsible to do otherwise.

https://www.science.org/content/blog-post/covid-19-vaccinations-and-heart

https://www.science.org/content/blog-post/hydroxyl-radicals-water-droplets-doesn-t-look-it

I’ve written more than once here (most recently last year) about the long-running controversy about what’s happening with very small droplets of water. There have been numerous reports of unusual chemistry under these situations, and I think it’s safe to say that one of the marquee candidates is the reported production of hydrogen peroxide, which is often based on mass spectral evidence. It has to be noted that further investigations did not support hydrogen peroxide generation per se, but numerous papers appeared hypothesizing that hydroxyl radicals were being produced instead.

But as that link above shows, there are more prosaic explanations, and one of these is contamination with traces of ammonia in human breath and from human skin. The ammonium hydrate species is very close in mass to an unusual M/Z 36 species seen in water mass spec under microdroplet conditions, a mass for which several cation-radical species have been proposed. But as the work referenced above shows, you may not have to go that far.

Now we have this follow-up paper, and it goes even further. The authors again are able to reproduce the mass spectra of the supposed hydroxyl-radical-containing water droplets, and reiterate the proposal that this is due to adventitious ammonia contamination. But they go further and produce actual hydroxyl radicals in the droplets through other means. Not the least of these is starting out with small amounts of added hydrogen peroxide, but they also use short-wavelength UV light and more. And each time the hydroxyl radicals are present, they attack any other organic compounds in the solution, as well they might.

Now, this behavior has long been expected of these reactive species, and in earlier papers there were reports of caffeine and melatonin molecules that were oxidatively modified under microdroplet conditions (with these M+17 adducts advanced as evidence that the hydroxyl radicals were indeed present). But unfortunately these can also be ammonium adducts from those ammonia traces mentioned above - the authors here show that collisional activation of these species shows loss of ammonia, for example. 

And it turns out that when you actually produce hydroxy radicals with an added caffeine analyte, the mass spectrum is hardly changed. That’s not because it’s unreactive - on the contrary, it reacts just fine but the product of that radical addition is not stable and converts to other compounds that have very poor proton affinity and are difficult to see under mass spec conditions. What you don’t get is that M+17 species, at least if you’re careful to exclude any sources of ammonia. When it does form (under adventitious-ammonia conditions), the introduction of hydroxyl radicals doesn’t really change its abundance, either.

On the other end of the scale, proteins and peptides are also reactive with hydroxyl radicals, and the products of these reactions have a much better chance of still showing up in the mass spectra. Using Lys-bradykinin as a model peptide, the new work shows that this molecule is indeed attacked by real hydroxyl radicals to make a variety of oxidation products (but none of them are M+17). And the fact that you don’t see such things under normal mass spec conditions also argues that hydroxyl radicals are not some inevitable consequence of mass spec microdroplets, either. Melatonin is also in this category - actual hydroxyl radicals attack it cheerfully, with several products (such as M+32), but no M+17 adduct is noted.

Here’s how the authors sum up:

The initial reports of spontaneous hydroxyl radical generation in water droplets have been the subject of significant controversy. Reasonable counterexplications have been offered and then disputed, because the original results could not be replicated. However, we reproduced the original results almost identically and demonstrate that the hydroxyl radical hypothesis is not consistent with any proper control experiments. It is also not consistent with radical chemistry in general, because analytes are not routinely damaged in the thousands of electrospray experiments conducted every day. The hypothesis is also not consistent with the binding energies, relative abundances, or dynamics of small water clusters.

Let's see what effect this has on the field. Previous experiences in the literature with closely-held hypotheses is not encouraging.

https://www.science.org/content/blog-post/hydroxyl-radicals-water-droplets-doesn-t-look-it