Chloroquine and the Cheeto-in-Chief

I’ve been steering clear of COVID-19 since my last post about it. Not least because the outbreak has been progressing much as predicted, the same conspiracy theories I nailed continue to do the rounds and I didn’t feel I had much to add.

In a fascinating intervention over the weekend Donald Trump made clear that he thinks two antimalarial drugs, hydroxychloroquine and chloroquine, should be deployed – and quickly – against SARS-CoV-2. (I’ll just refer to ‘chloroquine’ as a catch-all from now on out of sheer laziness).

This provoked an immediate furore of criticism – the New York Times‘s ‘Trump’s Embrace of Unproven Drugs to Treat Coronavirus Defies Science‘ is typical – and as might be expected Bloomberg is probably the most negative saying he’s ‘pushing an unproven drug‘ leading to cases of poisoning.

And then some utter, utter douche nozzle decides to self-medicate with a fucking fish tank cleaning chemical that contains chloroquine phosphate, thus taking himself out of the gene pool permanently. That was blamed on Drumpf too. But anyone stupid enough to do that wouldn’t have been living much longer anyway, I reckon.

Has Cadet Bonespurs overstated the case for these drugs against coronavirus? Of course he fucking has. Did he chose it just because it was used to treat the disease his current wife was named after? Who knows. It’s Trump. Were you expecting a nuanced, well informed, scientifically literate argument? Dream on.

That’s not the point. The point is this is a classic case of playing the man, not the ball.

The media are asking the wrong question. The question isn’t “is Trump a maverick riding roughshod over experts” – I think we can guess that one – or even the more nuanced “in an emergency how much data should medics require before they use a medicine?”.

Rather than attacking the man and cherry-picking arguments to bolster your antipathy to him, surely the only relevant question is:

Might this work? Even a little bit?

Let’s break that down a tad. The less rabid criticisms are based around a lack of data supporting this intervention – there hasn’t been an RCT but let’s ask a more fundamental question. Does this have any prior plausibility – or – could this conceivably work?

If there’s no plausibility you can get all the data you want, it’s still Tooth Fairy Science – or studying a phenomenon that doesn’t exist. You could accurately study how much money she leaves to kids in different socioeconomic groups or geographies – but that wouldn’t make her any more real. Same can be said of any ‘scientific’ study proving the efficacy of homeopathy…

But this isn’t Tooth Fairy Science. Chloroquine and hydroxychloroquine have a long history, originally as antimalarials (not so much now) but still for other uses too. These drugs are not particularly subtle and many of their uses have been supplanted by newer, more targeted formulations. And yes, they can have serious side effects, especially in overdose. They have many contraindications too.

But we know about those so they can be avoided with careful prescribing by physicians, combined with preventing idiots self-medicating.

The point is these medicines also have well-established, broad-spectrum efficacy against RNA and other enveloped viruses – such as the coronaviruses.

But they are now off-patent, widely available and cheap to manufacture as a generic. A more cynical observer than I might conclude that at 4 cents a dose globally (or even the shocking $5 in the US) – there is little upside here for the big drug companies – but let’s park that and look at the established facts and science regarding these agents’ mode of action.

When a virus invades a host cell it needs a way in, a way to hijack the host’s cellular machinery to replicate itself, and a way out to start the cycle all over again.

When the coronavirus (and, indeed, many other viruses) enters a host cell it’s does so via an envelope called an endosome. Chloroquine has been shown to stop this endosome becoming acidic – which means the endosomal proteases that cleave the viral glycoprotein segments won’t work. They require an acidic pH. So – put simply – these drugs are proven to stop these types of virus unpacking themselves, which they need to do to infect the host cell and get jiggy.

No mutation will change this. And this is one of the main tricks that gives this class of drug broad antiviral effectiveness. This is basic biochemistry and nothing to do with this particular virus. (It’s mode of action as an antimalarial is totally different, by the way – it has many tricks up its sleeve). Another that’s being speculated about is its role in clathrin inhibition – which would inhibit the endocytosis of any nanoparticle, not just CoV. In terms of its mode(s) of action it’s a sawn-off shotgun, not a rifle.

But that’s not all. These drugs also have immunomodulatory effects. When coronaviruses kill they don’t do it directly. It’s the body’s overreaction to the insult that causes a cascade of cytokines and other non-specific immune responses that does the damage – the things the body does to repel foreign invaders before it builds a specific immunity to a given pathogen.

These drugs limit the cytokine storm. This is well-established; the critics say “not against coronavirus” but this is not true. The argument seems to be “so you’ve proven this gun kills a Black Angus but you’ve never tested it against a Texas Longhorn so it’s not proven”. This is patent nonsense.

There are already six articles in peer-reviewed journals and 23 ongoing clinical trials in China demonstrating chloroquine seems to be effective in limiting the replication of SARS-CoV-2.

And many others regarding its effectiveness against other coronaviruses and multiple similar RNA viruses going back decades.

There is rationale, pre-clinical evidence of effectiveness and evidence of safety from long-time clinical use for other indications to justify clinical research on chloroquine in patients with COVID-19.

Yes, of course clinical use should either adhere to the Monitored Emergency Use of Unregistered Interventions (MEURI) framework or be ethically approved as a trial by a national body or the WHO. Safety data and data from high-quality clinical trials are urgently needed. But these drugs are already licenced with multiple off-label applications.

What the nay-sayers seem to be ignoring is this is a crisis of global proportions. These are medicines with prior plausibility against coronaviruses (and many similar RNA viruses) proven to slow the rate of infection and curb some of the most lethal features

It seems to me that the principal objection is to the messenger, not the potential for these medicines. Which is a tragedy. I’m sure the conspiracy theorists will claim that darker forces are in play given there is little financial upside to this for BiG pHarMa because… Monsanto, Soros, Deep State Paedo Lizard People…

By all means call the Tangerine Shitgibbon a twat, attack everything he says – but don’t let your antipathy to him cloud your judgement. Think infinite number of monkeys – purely by random chance he might get something accidentally right one day. Yes, more tests yada yada – but we need to do something and fast.

Too many people are dying. It’s time for action, not politics.