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

Sure it’s still a thing out there you can catch,
Sure it’s still a thing out there you can catch,

but most people seem tired of hearing about it.
but most people seem tired of hearing about it.

But not only is COVID not going anywhere –
But not only is COVID not going anywhere –

for some people,
for some people,

infection is followed by a protracted,
infection is followed by a protracted,

debilitating condition known  informally as long COVID.
debilitating condition known  informally as long COVID.

The good news is that scientists  are hard at work on solving that.
The good news is that scientists  are hard at work on solving that.

And while we don’t know  what causes long COVID yet,
And while we don’t know  what causes long COVID yet,

we’re getting closer to  understanding what’s involved,
we’re getting closer to  understanding what’s involved,

which points at ways to treat it.
which points at ways to treat it.

Today, let’s talk about one area  where we’ve made some progress.
Today, let’s talk about one area  where we’ve made some progress.

And it has to do with sticky notes on your DNA.
And it has to do with sticky notes on your DNA.

[Intro Music]
[Intro Music]

Symptoms of long COVID vary  dramatically between individuals,
Symptoms of long COVID vary  dramatically between individuals,

but depending on who you ask,
but depending on who you ask,

it’s defined as experiencing  signs of illness somewhere
it’s defined as experiencing  signs of illness somewhere

between 4 weeks and 3 months
between 4 weeks and 3 months

following infection with the SARS-CoV-2 virus.
following infection with the SARS-CoV-2 virus.

These effects can be devastating,
These effects can be devastating,

and have dramatic effects on  a patient's quality of life,
and have dramatic effects on  a patient's quality of life,

including their ability to work.
including their ability to work.

Now, there is a flurry of interest in this topic –
Now, there is a flurry of interest in this topic –

which is great!
which is great!

and you can find scientists looking at everything
and you can find scientists looking at everything

from the heart to the brain to the lungs
from the heart to the brain to the lungs

to the everywhere.
to the everywhere.

But a few research groups
But a few research groups

are thinking smaller.
are thinking smaller.

Way smaller, down to the fine print
Way smaller, down to the fine print

and the genes that dictate  our response to infection.
and the genes that dictate  our response to infection.

While most every cell in your body
While most every cell in your body

has the same sequence of DNA in its nucleus,
has the same sequence of DNA in its nucleus,

there are a lot of ways for the cell
there are a lot of ways for the cell

to decide what genes to use when.
to decide what genes to use when.

They don’t all get used the same  amount, or at the same rate.
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.
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,
You’re probably going to reference  some important sections more often,

and skip over others that  are less relevant to you.
and skip over others that  are less relevant to you.

You might even use sticky notes
You might even use sticky notes

to mark a page you want to come back to often.
to mark a page you want to come back to often.

Well, cells have their own version of  sticky notes in their genetic libraries.
Well, cells have their own version of  sticky notes in their genetic libraries.

Genes may get marked up with tags
Genes may get marked up with tags

that tell the cell’s machinery to  use that gene more or less often.
that tell the cell’s machinery to  use that gene more or less often.

This is the basis for the science of epigenetics
This is the basis for the science of epigenetics

a way for the cell to modulate genetic information
a way for the cell to modulate genetic information

without changing the sequence of DNA.
without changing the sequence of DNA.

The kind of epigenetic sticky note
The kind of epigenetic sticky note

we’re going to be talking about  is called DNA methylation.
we’re going to be talking about  is called DNA methylation.

The best-understood version of methylation
The best-understood version of methylation

usually adds a tag to quiet the gene down,
usually adds a tag to quiet the gene down,

causing it to be read out less  often than it would otherwise.
causing it to be read out less  often than it would otherwise.

And we have good reason
And we have good reason

to think the virus that causes COVID-19
to think the virus that causes COVID-19

may affect epigenetic signals in our cells.
may affect epigenetic signals in our cells.

Back in 2017,
Back in 2017,

before anyone had ever heard the word “COVID”,
before anyone had ever heard the word “COVID”,

researchers were looking into the epigenetic  effects of SARS and MERS infections,
researchers were looking into the epigenetic  effects of SARS and MERS infections,

which are both coronaviruses,
which are both coronaviruses,

like SARS-CoV-2.
like SARS-CoV-2.

It's unlikely that the virus is moving genetic sticky notes itself
It's unlikely that the virus is moving genetic sticky notes itself

Rather, the thinking seems to be
Rather, the thinking seems to be

that our own bodies produce more or less
that our own bodies produce more or less

of the products of certain genes
of the products of certain genes

to make infection less severe.
to make infection less severe.

In long COVID,
In long COVID,

research is starting to suggest
research is starting to suggest

that the changes to these signals persist
that the changes to these signals persist

when the body should have scaled  them back after infection.
when the body should have scaled  them back after infection.

And here’s the thing –
And here’s the thing –

we can read these epigenetic signals.
we can read these epigenetic signals.

So if we can identify genes whose signals
So if we can identify genes whose signals

are consistently changed in  patients with long COVID,
are consistently changed in  patients with long COVID,

we might be able to both  diagnose long COVID more easily,
we might be able to both  diagnose long COVID more easily,

and shake those genes down
and shake those genes down

for answers about how to treat those patients.
for answers about how to treat those patients.

A research group based in Sweden
A research group based in Sweden

has studied DNA methylation
has studied DNA methylation

in the blood cells of patients with long COVID.
in the blood cells of patients with long COVID.

In the study, published in the  journal Clinical Epigenetics in 2022.
In the study, published in the  journal Clinical Epigenetics in 2022.

they found several genes and groups of genes
they found several genes and groups of genes

with changes in their methylation after infection.
with changes in their methylation after infection.

These included some seriously tantalizing hits:
These included some seriously tantalizing hits:

genes involved in regulating ACE2,
genes involved in regulating ACE2,

the now-famous protein
the now-famous protein

that the SARS-CoV-2 virus
that the SARS-CoV-2 virus

uses to invade cells.
uses to invade cells.

Some genes were also involved  in histamine signaling,
Some genes were also involved  in histamine signaling,

which lines up with the evidence
which lines up with the evidence

that some antihistamine medications
that some antihistamine medications

can benefit long COVID patients.
can benefit long COVID patients.

Most intriguing,
Most intriguing,

some of these methylated genes
some of these methylated genes

were related to taste and smell,
were related to taste and smell,

which makes sense given
which makes sense given

that one of COVID’s signature symptoms
that one of COVID’s signature symptoms

is loss of those senses.
is loss of those senses.

Before we get too excited, though,
Before we get too excited, though,

this was a small study with  only 10 long COVID patients.
this was a small study with  only 10 long COVID patients.

So while it isn’t as robust as we would like,
So while it isn’t as robust as we would like,

that’s unfortunately the case for  a lot of COVID-related research
that’s unfortunately the case for  a lot of COVID-related research

because it’s just so new.
because it’s just so new.

Another research group,
Another research group,

this one based in the US,
this one based in the US,

looked at patients recovering from COVID
looked at patients recovering from COVID

in a pair of papers between 2021 and 2022.
in a pair of papers between 2021 and 2022.

They had a total of 102 participants
They had a total of 102 participants

with COVID in their first study,
with COVID in their first study,

and followed up one year later with 15 of them
and followed up one year later with 15 of them

who reported symptoms of long COVID.
who reported symptoms of long COVID.

They also found changes in DNA methylation
They also found changes in DNA methylation

that persisted after infection…
that persisted after infection…

but in pretty much totally different  genes than the Swedish study identified.
but in pretty much totally different  genes than the Swedish study identified.

Their previous study had found about 1500 genes
Their previous study had found about 1500 genes

whose methylation status changed
whose methylation status changed

during acute COVID-19 infection.
during acute COVID-19 infection.

Of those, 71 remained altered a year later.
Of those, 71 remained altered a year later.

Broadly speaking, those genes tended to be related
Broadly speaking, those genes tended to be related

to inflammation and response to infection.
to inflammation and response to infection.

Basically, a totally different group of genes
Basically, a totally different group of genes

than what the Swedish team found,
than what the Swedish team found,

although at least some of those  genes had similar functions.
although at least some of those  genes had similar functions.

Unfortunately,
Unfortunately,

not all of the studies on  methylation and long COVID
not all of the studies on  methylation and long COVID

have supported a connection between them.
have supported a connection between them.

A third study found no difference in methylation
A third study found no difference in methylation

between people with long  COVID and people in remission.
between people with long  COVID and people in remission.

These studies were all on the smaller side,
These studies were all on the smaller side,

with tons of differences between the patients
with tons of differences between the patients

who participated in them.
who participated in them.

But just for fun,
But just for fun,

let’s revisit a few of the methylated genes
let’s revisit a few of the methylated genes

that those studies did find.
that those studies did find.

Because they do all seem relevant to long COVID
Because they do all seem relevant to long COVID

if larger studies can validate their involvement.
if larger studies can validate their involvement.

For example, the US-based group
For example, the US-based group

says that the pattern of  gene expression they found
says that the pattern of  gene expression they found

could help to explain the increase
could help to explain the increase

in cardiovascular events that follows COVID-19.
in cardiovascular events that follows COVID-19.

And the Swedish group identified  genes related to ACE2,
And the Swedish group identified  genes related to ACE2,

which interestingly lines  up with an idea out there
which interestingly lines  up with an idea out there

that patients develop antibodies
that patients develop antibodies

to their own ACE2 after infection,
to their own ACE2 after infection,

which might contribute to  inflammation occurring in long COVID.
which might contribute to  inflammation occurring in long COVID.

Even more interestingly, this group also noticed
Even more interestingly, this group also noticed

that their patients had some  similar self-antibodies floating
that their patients had some  similar self-antibodies floating

around to patients with MECFS –
around to patients with MECFS –

what you might know as chronic fatigue syndrome.
what you might know as chronic fatigue syndrome.

And they noticed epigenetic changes to  those self-antibody receptors as well.
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,
I don’t want to get too excited  about such a small study,

but the evidence for a link between long COVID
but the evidence for a link between long COVID

and chronic fatigue syndrome
and chronic fatigue syndrome

is piling up everywhere you look.
is piling up everywhere you look.

And what’s better than understanding one disease?
And what’s better than understanding one disease?

Understanding two.
Understanding two.

So while it’s early days for this research,
So while it’s early days for this research,

there’s a lot going on in the world  of COVID-19 epigenetic studies,
there’s a lot going on in the world  of COVID-19 epigenetic studies,

and studies of COVID-19 in general.
and studies of COVID-19 in general.

But as we discover more about  how this spiky little virus
But as we discover more about  how this spiky little virus

is messing with our sticky notes,
is messing with our sticky notes,

we can hopefully find ways to get  our DNA textbooks back in order.
we can hopefully find ways to get  our DNA textbooks back in order.

Which is something that’s worth learning,
Which is something that’s worth learning,

even if you’re tired of hearing about COVID.
even if you’re tired of hearing about COVID.

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