Chloroquine is Donald Trump’s favourite COVID-19 treatment. Does it work?

This weekend, Donald Trump refused to allow infectious disease specialist Dr Anthony Fauci to answer questions related to hydroxychloroquine, an anti-malarial drug that has potential to be repurposed as a treatment for the novel coronavirus. Trump is a big fan, whereas Fauci has urged caution as the scientific community waits for more evidence on the drug’s efficacy. It’s not every day that a potential treatment for a virus becomes the partisan political issue du jour, but this is neither an everyday administration nor an everyday pandemic. So, what should we be thinking about chloroquine? To cut a long story short, not very much unless our doctor tells us to take it.

However, we’re all on lockdown with nothing else to do, and to make a long story longer, we first need to define what we’re talking about. A coronavirus is a family of viruses so named because they are spherical, with spike proteins protruding around their circumference, resembling the sun’s corona. As it happens, every other virus family that infects animal cells shares these physical corona-like characteristics (whereas viruses that infect bacteria look more like mean little alien spiders), and a more defining feature of coronaviruses is the large, single chromosomal RNA genome. This particular coronavirus is called SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) and the disease it causes is COVID-19 (coronavirus disease 2019). SARS-CoV-2 is named because, naturally, it’s the third coronavirus outbreak to cause similar symptoms, after the SARS and MERS (Middle Eastern respiratory syndrome) outbreaks of 2002 and 2012 respectively. So to summarise, the virus family is named after a shape it shares with all other animal viruses, the disease is named after the virus and the virus is named after the disease. SARS-CoV-2 is the third coronavirus outbreak that causes SARS, and we never name disease outbreaks after their location of origin unless we really, really feel like it. At a time when it’s never been more important to listen to the scientific community, one might be forgiven for asking what exactly they’re doing to make their message easy to understand.

Now, I know what you’re thinking – when Donald Trump waded into the discussion of potential treatments, surely he provided some much-needed clarity?

hillary
She doesn’t think so.

Chloroquine as a potential treatment for COVID-19 has some background behind it, but we’ll start when it entered the public consciousness in late March at a press conference where Trump first appeared to butt heads with Fauci. As Fauci encouraged caution, Trump confirmed that the drug had been ordered to be immediately deployed across America, claiming it could be a “game changer.” Characteristically of administration officials who know what they’re talking about but want to keep their jobs, Fauci wrapped his disagreement in language complimentary to the president. “There isn’t much difference in what we’re saying… it’s the difference between hoping it will work and proving it will work.” If the difference between hoping something will work and proving it will work, or the difference between deploying a treatment immediately and waiting for data showing its effectiveness seem quite a lot more significant than Fauci was making out, there’s not much to say except welcome to the world of Trump press conferences. Trump’s final comments on the matter, “I’m a smart guy and I have a good feeling about this” probably did little to assuage any confusion.

So crucially, is Trump right to have a good feeling? In the search for clarity, it’s worth looking at where he and Fauci actually agreed. Both cited the long history of chloroquine’s use as an anti-malarial as reason to believe it’s probably going to be found to be safe, and sure enough what little primary research exists has drawn the same conclusion. Worth noting is that this conclusion has an unspoken but very important caveat – when a prescription drug is said to be safe, that means with proper medical supervision. This isn’t that unusual, and most developed countries have an understanding that’s both cultural and enshrined in laws preventing drug companies from advertising directly to patients. Then again, most developed countries discourage heavily armed and emotionally unstable meth addicts from keeping tigers in their back yard. American culture prioritises individual liberty, and sure enough within a week of the press conference a man was dead and his wife was in intensive care; both overdosed on chloroquine phosphate they bought in the form of aquarium cleaner and used to self-medicate, citing the president’s advice.

So far this discussion has centred around the lack of clarity surrounding the treatment, and in normal scientific discussions the antidote for this is primary research. In this case, the primary research is actually thematic, since a lot of it was conducted by the bombastic French microbiologist Didier Raoult, whose institute is famous for publishing hundreds of original pieces of research a year and not allowing things like academic standards to get in their way. From questionable sampling practices to gels that appear to be outright falsified, journalist Leonard Schneider has gone into extensive detail on which studies contain dubious elements and which appear to be the result of outright academic fraud, and it’s probably not worth reading this article without reading his as well.

That said, there are a few reasons I’m probably more bullish on chloroquine’s potential than a lot of non-Trump people, Schneider in particular. He criticises Raoult for using many people in his studies who were not experiencing symptoms, but I kind of see the rationale. SARS symptoms are a function of interferon, a signalling molecule that infected cells send out, activating genes in neighbouring cells that can be protective and can cause inflammation, depending on the situation. One such pro-inflammatory gene is interleukin-6, which chloroquine suppresses. Severe SARS symptoms appear in cases after an interferon response which is delayed, but not when it is timely, and not when it doesn’t happen at all. Another mechanism by which chloroquine could help is by inhibiting some of the replication and assembly of the virus, reducing viral load. But when symptoms finally do start to become severe, viral load is on the way down too. So if chloroquine is going to be effective at all, it probably only is during the incubation period. Studies treating patients who already show serious symptoms would likely be a waste of time, because there’s not much of a proposed mechanism for it helping those people. To be kind to Trump, this also explains his desire to deploy the drug in as widespread a way as possible, as quickly as possible. After all, you want to give it to the most serious sufferers of COVID-19, but you need to give it to them before you find out who they are.

sarsifn1
From Professor Daniel Guerra’s YouTube channel, Authentic Biochemistry. There may not be much point in using a treatment that targets either the interferon response or the viral load once symptoms are already severe.

That’s the proposed mechanism, and as hard as it is to sift through bad science and science done in bad circumstances, the primary literature tentatively suggests that it works. A lot of the studies done in China have small sample sizes, which is understandable since they were conducted at the epicentre of what would become a pandemic. These studies tend to show either some effect or no effect, with little confidence in their conclusions, but on aggregate they are forming a consensus in agreement with Trump and Fauci’s instincts, that the drug is at least safe for use with COVID-19 patients. But if it’s a game changer, it’s doing a great job of hiding that from the researchers who have studied it so far. Much of the evidence coming out of China comes not as published trials, but in the form of consensus opinions from Chinese doctors and regulatory bodies that felt it helps – the anecdotal evidence Fauci warned against taking as gospel. The drug has been approved for widespread use in America, but is only to be used in clinical trials in Europe. To throw a spanner in the works, a single study with a miniscule sample size found – once the data were analysed by fresh eyes – that hydroxychloroquine had no effect on its own, but was effective when combined with the antibiotic azithromycin. Nobody can really explain why an antibiotic might have an effect on a viral infection, and Schneider is as dismissive about that as he has been scathing about everything else. The authors of that analysis suggested that co-infection could be what makes the symptoms worse. That’s speculation, but if you washed your hands before you started reading this it might be time to wash them again.

Chloroquine is Donald Trump’s favourite COVID-19 treatment. Does it work?

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