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.

Is it safe for vaccinated people to go maskless?

In the US, the Centers for Disease Control announced that it’s safe for people who’ve been fully vaccinated to dance through the world naked–

Sorry. Not naked. Maskless. Which after a year and more of pandemic feels like the same thing. So this might be a good time to ask, What the hell’s going on? 

Let’s turn to an article in the Conversation that breaks it down manageably. It’s not a long article or a difficult one, and it’s well worth reading, because I’m going to boil it down until all that’s left is a thick syrup.

First, the vaccines we have for Covid are more effective than anyone had the right to expect. Much more effective. But they–or at least most of them–don’t provide sterilizing immunity. (There’s a chance one does but we’re not there yet.) 

To translate that, they don’t stop the virus from entering our systems, they only stop them from getting us sick. That’s less than ideal because it leaves open the possibility that we can pass on the disease.

Irrelevant photo: cornflowers

At the moment, it looks like the vaccines make fully vaccinated people less likely to spread the disease, but the numbers aren’t in yet. They’re outside, running around in the wet grass and refusing to come in for dinner. Or supper. Or whatever you call that meal. And Covid numbers are particularly hard to call home. It has to do with the disease’s habit of spreading while people don’t have symptoms.

Never mind that, though. What we need to know is that it’s hard to make those numbers behave and that scientists are working on it and that dinner’s going to be cold. Nothing’s certain, but a couple of studies hint at fully vaccinated being able to spread the disease–which means they’re able to spread new, more infectious variants. 

That is highly inconvenient but it doesn’t mean that vaccination’s pointless. Vaccination protects the vaccinated person, and it may mean they’re less likely to spread the disease. Less likely isn’t the same thing as incapable of, but it’s an improvement over what we had at this time last year.

The article (remember the article?) ends by saying, “The . . . relaxed guidelines on masking are meant to reassure vaccinated people that they are safe from serious illness. And they are. But the picture is less clear-cut for the unvaccinated who interact with them. Until near herd immunity against COVID-19 is achieved, and clear evidence accumulates that vaccinated people do not spread the virus, I and many epidemiologists believe it is better to avoid situations where there are chances to get infected. Vaccination coupled with continued masking and social distancing is still an effective way to stay safer.”

Boiled down to a thick syrup, that says masks still make sense. 

 

An update on viruses and human DNA

A study published in the Journal of Virology found no evidence that Covid integrates its genetic material into human DNA. An earlier study had found it doing that in petri dishes, but in real life–

Okay, think of this as computer dating. You exchange a few messages with someone, maybe you have a Zoom date. You establish that they can hold a coherent conversation and that they’re not a cat (that’s either good or bad, depending on who you are and what your preferences happen to be). Then you meet and think, I can’t spend an hour with this person, never mind my life. 

That’s what it was like for the Covid virus. In the petri dish, mingling genetic materials looked like a good idea. In person though? 

Nope. 

Some viruses do fall in love with us, and human DNA is a palimpsest of useless bits of genetic material left behind by bugs we danced a couple of numbers with back–oh, it might’ve been as early as when life was simple and we still had hairy bodies. The bits of genetic code don’t make us sick. They don’t make us better. They just sit there remembering old times.

That integration is called a chimeric event. And a palimpsest is something with layers of meaning, buried history, like a canvas that’s been painted over but the old brushwork is still there, under the surface. That bit of not particularly useful knowledge comes to us courtesy of the Cambridge Dictionary. https://dictionary.cambridge.org/dictionary/english/palimpsest

For anyone who’s spooked by the idea that MRNA vaccines might integrate themselves into our DNA, this new study should be good news: Covid doesn’t seem to love us. But for anyone trying to figure out why some people test positive for Covid long after they’ve gotten rid of the infection, it may not be good news. Chimeric events had been suggested as an explanation. Take that away and we’re left with the possibility that they might be getting reinfected and the question of whether they continue to be infectious.

 

How to vaccinate 108% of your population

The island of Nauru has injected 108% of its adult population with at least one dose of the AstraZeneca vaccine.

How’d they do that? They included foreign visitors, coming up with a total of  7,392 people. The island has been free of the virus, but every visitor brought the risk of an outbreak, so this comes as a real relief.

 

Online gamers researching Covid

Thanks to game designers embedding a citizen science project inside a game called EVE online, players are helping researchers learn about Covid and the immune system. The idea is to look at the blood cells of people who have Covid and eventually sort out why some people get severe cases and how Covid makes us sick. 

Thousands of gamers have been looking for patterns in groups of cells and have fed 120 million data submissions into Project Discovery. That amounts to decades of data analysis, and each submission also teaches the program to learn the process so that it can be automated in the future. 

The game’s popular, something I can prove by telling you that I’ve never heard of it.