If we have more recent episodes on COVID-19 or hydroxychloroquine, we'll include them

in the description.

[ intro ]

Allright, Everyone is talking about antimalarials

and how they're a promising treatment for COVID-19—let's make the case…

some people are too excited about this,

it's going to end the pandemic,

if only the scientists would get out of the way.

Some people, on the other hand,

are reflexively saying that they definitely don't work.

But science does not work that way,

and when initial anecdotes look promising…

that's when we investigate further.

What these drugs are not is new.

They've been prescribed for malaria and autoimmune conditions for decades

and those are two VERY different things.

but if you take a closer look at the chemistry involved,

you can start to understand how they can do so much.

But that doesn't mean we know they work for COVID-19.

Or even if they do.

There are good reasons to think they might,

but like with many things surrounding this illness,

there's a lot we need to figure out.

The two medications making international headlines

are hydroxychloroquine and chloroquine.

That “quine” in their names comes from the fact

that their chemical structure is similar to quinine—

or, as some call it, “kwih-nihn”.

And if you've heard that name before,

it's probably because humans have been using it to treat malaria for centuries.

But quinine shortages during WWII prompted German and US chemists

to look for alternatives.

So, they turned to chloroquine —

quinine's chlorine-toting cousin —

which was first synthesized in the 1930s.

And since that has some pretty unpleasant side effects,

the less-toxic hydroxychloroquine was introduced in the 1950s.

Now, the parasites that cause malaria are very different from the virus that causes

COVID-19,

Like as different as diseases can get from each other.

and both might seem totally unrelated

to the autoimmune conditions like lupus that these drugs are regularly prescribed for.

But, once you understand what these antimalarials actually do to cells

— including their ability to fend off parasites and treat autoimmunity —

their ability to fight a viral infection actually makes a lot more sense.

Let's start with the parasites —

because these drugs were developed as antimalarials.

Despite the long history, it's not 100 percent clear exactly how

these drugs treat malaria, though we know the big picture:

they kill the parasites.

The first reason they can do that is because of their chemical structure,

these compounds can get all up in fatty molecules called lipids.

And the membranes that surround cells and their inner compartments

are made out of lipids, so chloroquine and hydroxychloroquine

can go almost wherever they want in your body,

including into red blood cells.

You know what else likes hanging out in red blood cells?

The parasites that cause malaria!

and, It just so happens that chloroquine and hydroxychloroquine

are also weak bases.

In other words, they like to snatch up protons when they can.

Like, the hydrogen ions that make solutions acidic.

and, once they do this, they lose their ability to pass freely across membranes.

They're no longer all lipid soluble like they used to be.

All that means that these drugs can get into acidic places,

but they can't get out of them.

So they accumulate in the parts of cells that are acidic,

since those areas have more protons up for grabs,

and once the drugs bind protons,

they can't move back out so easily.

It's pretty cool chemistry.

And experts think this is ultimately how they kill malaria parasites.

A bunch of the drug ends up trapped in a stomach-like compartment

within the parasite and interferes with the parasite's ability

to break down poisonous substances.

And boom! — you got yourself a dead parasite.

But Killing malaria parasites is not all these drugs are good for, though.

Since (they) chloroquine and hydroxychloroquine get into cells in general

—not just the ones infected by parasites—

they can have a lot of other effects in the body, including ones to the immune system.

That's why they work well in a variety of autoimmune conditions.

These conditions manifest in tons of different ways,

but all of them are caused by the immune system going haywire

and attacking the body's own cells.

And while, much like with malaria,

we don't fully understand how these drugs help,

we do know that they can help calm the immune overreaction.

A big part of that probably comes from their effects

on compartments inside your cells called lysosomes.

A lysosome's big job is to gobble up and destroy rogue proteins

and other compounds that might be harmful to the cell.

And because they have all those bits of rogue protein,

they're able to help some of our immune cells tell other immune system cells what

to do.

Basically, the smaller chunks of material they break down become antigens:

compounds that tell the immune system's soldiers what to go attack.

It's thought that, when a person has an autoimmune condition,

the lysosomes inside certain immune cells produce antigens

that tell the immune system's soldiers to attack the wrong thing, the body's own cells.

But these antimalarials can interfere with that.

Since lysosomes are slightly acidic,

hydroxychloroquine makes its way inside of them and gets stuck there.

This ends up taking a lot of hydrogen ions out of the lysosome fluid,

making it less acidic.

And once the pH of the lysosome gets nice and basic,

it can't function the same way.

Which ultimately means there are fewer lysosomes

generating antigens

that tell the immune system to attack the person's own cells.

But, this doesn't just happen in the cells involved in self-directed attacks.

These drugs can get into and mess with all of your immune cells.

Plus, they likely have other effects in immune cells that can calm them down.

So, they dampen the immune response in general.

Now, if it sounds like dampening the immune system would be,

y'know, actually very bad for a person who has COVID-19...

you might be wrong.

Here's the thing about a lot of deadly viruses, including coronaviruses…

it's not always the virus that actually kills.

don't get me wrong, these viruses definitely infect cells and kill them.

But it isn't always infected cells dying that kills a person—not directly anyway.

When those cells die,

your body realizes there's an invasion taking place.

So, it mounts a counter-attack using chemicals called cytokines,

which act as a call to arms to immune cells—

raising a battle cry that unleashes the full force

and fury of the immune response on the infection.

The effects of this are collectively called inflammation,

and it can do a great job of stamping out an invader.

The trouble is that massive amounts of inflammation

can damage healthy cells, too.

So if a viral infection gets really out of control and kills lots of cells,

the immune system's frenzied reaction may damage and kill even more cells,

which call in even more immunological attackers,

which causes even more inflammation.

If this whole process spirals out of control, it's called a cytokine storm.

It's basically the immune system equivalent of trying to kill a fly with a hand grenade.

And it's the collateral damage from that that ends up killing the person.

So it's thought that a drug like hydroxychloroquine,

which eases up the immune response, might be able to quell a cytokine storm.

At least, that's one hypothesis.

Another idea is that chloroquine and hydroxychloroquine make it harder for viruses

by raising the pH in cellular compartments they need to infiltrate and replicate.

Viruses tend to operate best when these compartments

are a little on the acidic side,

and antimalarial drugs tend to make things nice and basic.

There is already some promising research in cells and non-human animals

that suggests chloroquine can prevent viral replication

in SARS and other coronaviruses.

Even better, recent in vitro studies —

or experiments carried out in cells in a laboratory —

suggest it and hydroxychloroquine might work against SARS-CoV-2 specifically,

the coronavirus that causes COVID-19.

Based on this, it seems like these drugs could be super helpful —

and a super helpful drug is kind of on everybody's wish list right now.

But studies of drugs in cells in petri dishes or in other animals

aren't the same as clinical trials in people.

Just because something works in a controlled laboratory environment doesn't mean it's

going to be effective in practice or safe for everyone.

That's what clinical trials are for—to figure that kind of thing out, so we don't

end up killing people when we're trying to save them.

And while it would be amazing if these drugs help,

right now, we just don't have enough hard evidence

that these antimalarials are safe and effective for COVID-19

to start just like giving them to everybody..

Some preliminary data from China suggested they might help,

along with one very small trial out of France.

But some experts have pointed out that that trial

has methodological flaws and doesn't provide sufficient evidence.

And a similar trial from China found

there was no significant difference between COVID-19 patients that received hydroxychloroquine

and those who didn't.

Multiple researchers have now concluded that additional,

well-designed trials are needed before we can really say

whether altimalarials are actually safe and effective in fighting COVID-19.

And, I keep saying safe,

because even though these drugs are prescribed regularly for malaria and autoimmune conditions,

that doesn't mean they're safe to use in treating coronavirus infections.

We already know that not everyone can take these drugs safely.

Like, people who have a G6PD deficiency

can have a life-threatening reaction to chloroquine.

Also, these antimalarials might negatively interact with other drugs a person is on.

For example, studies have found that these antimalarials

seem to slow the breakdown of the heart medication digoxin,

which can cause everything from nausea and vomiting to irregular heart rhythms,

which can be fatal.

Plus, even in people who don't have specific reasons not to take them,

antimalarials aren't totally harmless.

Since they pretty much ubiquitously get into and mess with cells,

the dose really matters.

Like, for example, although chloroquine and hydroxychloroquine can be taken safely by

many people,

higher doses can lead to blindness and heart problems.

we don't know for sure whether this drug could make that specific infection worse,

or at what point in the course of the illness it might be best to take it.**

In the end,

it's very possible that at least one of these drugs really will be great for treating,

or maybe even preventing, COVID-19.

There are several clinical trials trying to figure all that out.

And I think everyone really, really hopes they work.

I mean, how amazing would it be if we already have something on hand

that kicks this virus's butt?

Something that we understand and is inexpensive to manufacture.

But until we know for sure, we shouldn't get our hopes up too much.

We have to let healthcare professionals and medical researchers

test this stuff carefully and rigorously.

They are the experts and they know what they're doing.

And we have to keep exploring other treatment options,

AS MANY OF THEM AS WE CAN.

So thank you to the researchers all over the place who are doing that right now.

Thanks for watching this episode of SciShow News!

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