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.
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