I know a lot of us are, like, ignoring COVID now.

Sure it’s still a thing out there you can catch, but most people seem tired of hearing about it. But not only is COVID not going anywhere – for some people, infection is followed by a protracted, debilitating condition known  informally as long COVID.

The good news is that scientists  are hard at work on solving that. And while we don’t know  what causes long COVID yet, we’re getting closer to  understanding what’s involved, which points at ways to treat it. Today, let’s talk about one area  where we’ve made some progress.

And it has to do with sticky notes on your DNA. [Intro Music] Symptoms of long COVID vary  dramatically between individuals, but depending on who you ask, it’s defined as experiencing  signs of illness somewhere between 4 weeks and 3 months following infection with the SARS-CoV-2 virus. These effects can be devastating, and have dramatic effects on  a patient's quality of life, including their ability to work. Now, there is a flurry of interest in this topic – which is great! and you can find scientists looking at everything from the heart to the brain to the lungs to the everywhere.

But a few research groups are thinking smaller. Way smaller, down to the fine print and the genes that dictate  our response to infection. While most every cell in your body has the same sequence of DNA in its nucleus, there are a lot of ways for the cell to decide what genes to use when.

They don’t all get used the same  amount, or at the same rate. Think of it like a textbook that  you don’t read cover to cover. You’re probably going to reference  some important sections more often, and skip over others that  are less relevant to you.

You might even use sticky notes to mark a page you want to come back to often. Well, cells have their own version of  sticky notes in their genetic libraries. Genes may get marked up with tags that tell the cell’s machinery to  use that gene more or less often.

This is the basis for the science of epigenetics a way for the cell to modulate genetic information without changing the sequence of DNA. The kind of epigenetic sticky note we’re going to be talking about  is called DNA methylation. The best-understood version of methylation usually adds a tag to quiet the gene down, causing it to be read out less  often than it would otherwise.

And we have good reason to think the virus that causes COVID-19 may affect epigenetic signals in our cells. Back in 2017, before anyone had ever heard the word “COVID”, researchers were looking into the epigenetic  effects of SARS and MERS infections, which are both coronaviruses, like SARS-CoV-2. It's unlikely that the virus is moving genetic sticky notes itself Rather, the thinking seems to be that our own bodies produce more or less of the products of certain genes to make infection less severe.

In long COVID, research is starting to suggest that the changes to these signals persist when the body should have scaled  them back after infection. And here’s the thing – we can read these epigenetic signals. So if we can identify genes whose signals are consistently changed in  patients with long COVID, we might be able to both  diagnose long COVID more easily, and shake those genes down for answers about how to treat those patients.

A research group based in Sweden has studied DNA methylation in the blood cells of patients with long COVID. In the study, published in the  journal Clinical Epigenetics in 2022. they found several genes and groups of genes with changes in their methylation after infection. These included some seriously tantalizing hits: genes involved in regulating ACE2, the now-famous protein that the SARS-CoV-2 virus uses to invade cells.

Some genes were also involved  in histamine signaling, which lines up with the evidence that some antihistamine medications can benefit long COVID patients. Most intriguing, some of these methylated genes were related to taste and smell, which makes sense given that one of COVID’s signature symptoms is loss of those senses. Before we get too excited, though, this was a small study with  only 10 long COVID patients.

So while it isn’t as robust as we would like, that’s unfortunately the case for  a lot of COVID-related research because it’s just so new. Another research group, this one based in the US, looked at patients recovering from COVID in a pair of papers between 2021 and 2022. They had a total of 102 participants with COVID in their first study, and followed up one year later with 15 of them who reported symptoms of long COVID.

They also found changes in DNA methylation that persisted after infection… but in pretty much totally different  genes than the Swedish study identified. Their previous study had found about 1500 genes whose methylation status changed during acute COVID-19 infection. Of those, 71 remained altered a year later.

Broadly speaking, those genes tended to be related to inflammation and response to infection. Basically, a totally different group of genes than what the Swedish team found, although at least some of those  genes had similar functions. Unfortunately, not all of the studies on  methylation and long COVID have supported a connection between them.

A third study found no difference in methylation between people with long  COVID and people in remission. These studies were all on the smaller side, with tons of differences between the patients who participated in them. But just for fun, let’s revisit a few of the methylated genes that those studies did find.

Because they do all seem relevant to long COVID if larger studies can validate their involvement. For example, the US-based group says that the pattern of  gene expression they found could help to explain the increase in cardiovascular events that follows COVID-19. And the Swedish group identified  genes related to ACE2, which interestingly lines  up with an idea out there that patients develop antibodies to their own ACE2 after infection, which might contribute to  inflammation occurring in long COVID.

Even more interestingly, this group also noticed that their patients had some  similar self-antibodies floating around to patients with MECFS – what you might know as chronic fatigue syndrome. And they noticed epigenetic changes to  those self-antibody receptors as well. I don’t want to get too excited  about such a small study, but the evidence for a link between long COVID and chronic fatigue syndrome is piling up everywhere you look.

And what’s better than understanding one disease? Understanding two. So while it’s early days for this research, there’s a lot going on in the world  of COVID-19 epigenetic studies, and studies of COVID-19 in general.

But as we discover more about  how this spiky little virus is messing with our sticky notes, we can hopefully find ways to get  our DNA textbooks back in order. Which is something that’s worth learning, even if you’re tired of hearing about COVID. This video was made possible thanks to our supporters on Patreon.

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And, thanks for watching. [ OUTRO ]