The future of mRNA vaccines

Covid may end up giving us an unexpected gift–a real one, not some snarky, I’m-saying-the-opposite-of-what-I-mean gift. All the work that went into developing the mRNA vaccines for Covid may soon translate into a flu vaccine that works against all 20 known subtypes of flu. It’s still in the testing stage, but it’s looking promising, and since flu can turn from annoying to lethal without having to file paperwork, this is no small thing.

In animal tests, it reduced symptoms as well as protected the little beasties against death. 

To be clear: protection against death is good. It’s not as good as 600% protection against illness, as we know from the Covid vaccines, which miss that 600% bullseye, but it’s a hell of a lot better than having zero protection against death.

The flu vaccines that are around now are seasonal: they protect against the recent versions but if some new strain that jumps unexpectedly from a bird or animal, adapts to humans, refuses to file paperwork, and turns out to be as potent as the 1918 flu–well, they’re not up to the job.

The 1918 flu? That’s the one those of us over a certain age learned to call the Spanish flu because it didn’t originate in Spain and because it’s important to have someone to blame, however inaccurately.

Thoroughly irrelevant photo: a neighbor’s dahlia

The developers of the new vaccine are currently designing human trials, and with luck the vaccine will be available by 2024.

Yeah, so what else can the technology do?

Since you asked, mRNA technology makes the creation of multivalent (be impressed with that word, please) vaccines relatively easy. 

Multivalent vaccines? They’re the ones like that flu vaccine that fore-arm us against bugs with pandemic potential, even when we’re not forewarned. 

The vaccine we really need these days is a pan-coronavirus vaccine, and one is moving into the human-trial stage. Or it’s fixin’ to get ready to think about moving into the human-trial stage. It’s close. In animal trials, three doses not only protected against severe disease, it also protected against infection and decreased the amount of virus the vaccinated animals shed, so they were less likely to pass it on.

Now we come to the hazy part: The article I read introduced it as a vaccine against coronaviruses in general, but the rest of the article focused on it as a Covid vaccine. I’ll leave you to figure out what that means. I’m short on time and can’t trace this one through the convolutions of the internet. 

The article did say, “The vaccine candidate is a combination of a nanoparticle antigen . . . along with an adjuvant—an ingredient that boosts a vaccine’s effects . . . . The adjuvant formulation, 3M-052-AF, significantly enhanced the immune responses in the animals when combined with the antigen.”

I’d translate that for you but I’m in so far over my head that not even the tips of my fingers reach the air. It does sound impressive, though.

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A Covid nasal vaccine is also in development, and it’s designed to piggyback on the immunity that previously vaccinated people carry. By coming in through the nose, it can work primarily on the mucus lining, which is where Covid likes to throw a housewarming party when it enters a body. If the vaccine works, it will be the emergency number you’ll want to call before the party starts, because you know what kind of neighbors Covid germs are. Loud music, fights, broken glass on the sidewalk. 

I could go on, but you get the picture.

In a trial, the spray protected previously vaccinated mice against both death and disease. It did zilch for unvaccinated mice. In hamster trials, it reduced transmission of the disease. It doesn’t use  live viruses, viral vectors, or adjuvants, and that may make the vaccine safer. 

Why? How much? No idea. Go do your own research.

So far, it hasn’t been tested in humans and the article I read was heavily spiced with the word may, so it’s not time to get too excited about this one. Although that hasn’t stopped me.

What about vitamin D and Covid?

Do vitamin D supplements protect against Covid? According to two studies, no. It makes sense that they would–vitamin D supports the immune system–but in a trial of 6,000 people vitamin D supplements made no difference in the number of either Covid or other respiratory tract infections. A second trial involved 35,000 people and tested vitamin D plus cod liver oil. Again, no noticeable difference emerged.

Both trials have their limits. In one, some people in the control group popped the occasional vitamin D supplement. In the other, most of the participants weren’t low on vitamin D at the start of the trial, so the real trial was with a much small group. And vaccines were rolled out during both trials, throwing the balance off. So don’t count them as conclusive, just suggestive.

The endless, depressing news about long Covid and (new word here) post-Covid

Having had Covid can–emphasis on can; it doesn’t always–leave people with nervous system  damage that messes with anything from their sense of smell to their ability to concentrate. It can increase their chances of having a stroke–not right away but eventually. 

It’s called neuro-Covid. Yes, folks, it’s another new word. Don’t say Covid hasn’t been generous with us.

A study that looked at the cerebrospinal fluid and blood plasma of people with neuro-Covid found an overblown immune response in the group with the most serious symptoms: impairments in the blood barrier that could have been caused by a cytokine storm; antibodies that had turned on the body’s own cells; and an overactivation of the microglia, which are immune cells responsible specifically for the brain. People with serious symptoms also had a smaller brain mass than healthy people, especially in the area responsible for the sense of smell.

“The virus triggers such a strong inflammatory response in the body that it spills over to the central nervous system,” Professor Gregor Hutter of the University Hospital of Basel said. “This can disrupt the cellular integrity of the brain.” 

The researchers are hoping to find a test that could predict long Covid and neuro-Covid before they strike, and to identify targets for drugs to attack–in other words, to identify the excessive immune response at an early stage so they can put the brakes on it. 

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A different study shows that having multiple Covid infections increases the risk of long Covid and of other post-Covid health risks. This was a massive study–5.8 million people in the US Veterans’ Affairs database. Its limitation is that this is a population primarily of older white males, so diverse it ain’t. 

The study showed that, compared to people who hadn’t been reinfected, people with repeat infections are twice as likely to die prematurely and three times more likely to be hospitalized. Heart and lung problems were more than three times more common, and reinfection also contributes to brain conditions, kidney disease, and diabetes.

The risk could increase with each infection.

Are you depressed yet? Sorry. It’s not pretty out there and I would have to open the damn curtains. But since I have . . . 

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Another study came at post-Covid brain problems from a different direction. 

To back up for a minute and state the obvious: The problem with studying brains is that as long as their owners are using them you have to accept some limits on the ways you study them. You only have access to certain information once their owners to die, which most people are reluctant to do, even in the interest of science. So this set of researchers created brain organoids–little clusters of brain cells the size of a pinhead. If the organoids object to being messed with, they have no way of letting us know, so it’s open season and the researchers infected them with Covid.

Sorry, guys. For the greater good and all that.

The researchers found that an unusual number of synapses were eliminated.

So what? Well, synapses are the social media of the brain. They allow the neurons to communicate with each other. In the normal wear and tear that goes on inside a brain, a number of synapses will be eliminated, which may explain why I can’t remember what I did five days ago, not to mention the fingering for an F chord on the guitar: The downsizing committee up there decided I no longer need to know those things and got rid of the relevant synapses in the name of efficiency. I might still want to know that stuff, but it’s austerity up there in my skull and something had to go. I should be grateful my brain didn’t ditch everything I know about commas, because, hey, that’s important.

I’m aware that that last paragraph implies that who- or whatever I am exists separately from my brain, but let’s stay out of that rabbithole while I remind you that austerity is what Britain’s government–or what passes for a government when it’s not tied up with more important business–calls cutting public services. Calling it austerity, though, makes it sound like it’s good for us. Think of it as the kale of the political world.

So what the researchers saw happening in the infected organoids was something like what’ll happen in austerity Britain 2.0, which is Sunakian austerity as opposed to Cameronian austerity. When the promised spending cuts kick in, it won’t just be the F chord that goes, it’ll be the smell of lilacs and where I put my car keys and the oomph I need to get from one end of the official looking letter that just came in the mail to the other so I can figure out if I’m being evicted or asked to serve as the next prime minister.

Did I lose you in that last paragraph? Sorry. I was having such fun–

I’ll summarize in a marginally sane way: In infected organoids, an excessive number of connections were downsized–or as serious people would put it, eliminated. That’s frighteningly like what happens in Alzheimers, Parkinsons, and schizophrenia. 

It’s true that our brains are bigger than organoids, and with luck, more complex. But post-mortems on Covid patients (post-mortems, I remind you, are carried out on people who are no longer using their brains), as well as brain imaging on live patients, show that the gray matter isn’t as thick in people who’ve been infected, which hints at a loss of synapses. 

Keep in mind that we’re still in the land of hints, though, not definitive conclusions, and also that I’m not clear on whether the post-mortems and scans were carried out on people who’d had serious cases of Covid or simply from people who’d been infected.

For the researchers, the next step is to look at whether various drugs will inhibit all that downsizing. 

Some of us living in Britain want to know if some drug can stop the government from downsizing services that have already been downsized so radically that they’re held together by nothing more than thread and newspaper headlines.

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Will you forgive me if I toss in a bit of good news? Paxlovid looks like it decreases the odds of developing long Covid.

Pax-what? It’s an antiviral pill that reduces the chances of hospitalization and death in people who’ve been infected–and reduces the chances of long Covid by 25%.

That’s from a preliminary study–it hasn’t been peer reviewed yet, and its study subjects were (again) mostly older white males in high-risk groups, but the US National Institutes of Health plan to study the drug’s effectiveness on people who already have long Covid to see if it works after the fact.