The COVID-19 pandemic has been a golden opportunity for quackery and conspiracy theories, such as the willful misinterpretation of a study in order to claim that the influenza vaccine makes people more susceptible to SARS-CoV-2, the virus responsible for COVID-19, or that 5G networks and glyphosate somehow make the infection more deadly. Pseudoscience like this is to be expected from cranks, of course; so it is no surprise that antivaxxers, anti-GMO cranks, and other conspiracy theorists are fusing their favorite pseudoscience and conspiracy theories with conspiracy theories about COVID-19 in order to create meta-conspiracy theories. Unfortunately, the COVID-19 pandemic has also revealed just how weak the allegiance to evidence- and science-based medicine is among physicians, who have embraced unproven treatments, in particular chloroquine and hydroxychloroquine, the latter sometimes with azithromycin. True, President Trump and his allies have been promoting the use of hydroxychloroquine with minimal evidence as the latest bright shiny object that let Trump’s magical thinking run wild with the hope that a magic bullet had been discovered to get us out of this crisis. However, before that it was Chinese and European physicians who had embraced the idea of using hydroxychloroquine to treat COVID-19, none more prominently than French brave maverick doctor Didier Raoult, who is now not reacting well to criticism at all. In fact, he just doxxed a French physician and critic and threatened to sue him, as you will see.
Didier Raoult: Bad science on hydroxychloroquine and azithromycin
Although there are other opportunistic doctors touting their “experience” with hydroxychloroquine to promote it as a “miracle cure” for COVID-19, as I discussed when I argued that the FDA’s emergency use authorization for hydroxychloroquine was a very bad idea, the evidence base for using hydroxychloroquine comes mostly from Raoult’s group, and the three studies from his group are horrible studies. The first of his trio of scientific crap was an unrandomized study that claimed that the combination of hydroxychloroquine and azithromycin eliminated the virus completely compared to controls or hydroxychloroquine alone. Its flaws were so numerous and manifest as to make the study painfully uninformative. Indeed, based on the shenanigans Raoult engaged in with the data, plus his history of fabricating data, I now suspect, but obviously cannot prove, scientific fraud. Even the International Society of Antimicrobial Chemotherapy (ISAC), which publishes the journal that published this study, backed away, even going so far as to state that the article “does not meet the Society’s expected standard, especially relating to the lack of better explanations of the inclusion criteria and the triage of patients to ensure patient safety.” Muddying the waters is a second statement issued a week later, apparently at the behest of Elsevier, that seems to soften the criticism and points out that the journal’s peer review process had been followed, even as it suggests a possible joint investigation with Elsevier.
The second study in the trio was a single arm case series that consisted of a huge percentage of COVID-19 patients treated with azithromycin and hydroxychloroquine who were not very ill at all. Only 15% of them even had fever, even though data from around the world show that 90% of symptomatic COVID-19 patients have fever during the course of their illness. Basically, the vast majority of these patients were patients who would have been sent home and told to self-quarantine, with instructions to call or go to the emergency room if they get significantly worse and especially if they start experiencing shortness of breath. Raoult claimed that the combination of azithromycin and hydroxychloroquine was very effective in clearing the SARS-CoV-2 virus, but there’s no way of knowing if these patients wouldn’t have cleared the virus anyway. It, too, was a singularly uninformative study.
The third study is no better. As of last night, Raoult has published only an abstract and a data table for 1,061 patients treated with his azithromycin/hydroxychloroquine combination, with no full manuscript yet. Of course, this dataset suffers from even more issues than his previous papers, as there are no methods to look at, and we can’t look at his study design in depth or his inclusion/exclusion criteria. Taking the results at face value, between March 3 and April 9, Raoult’s group tested 59,665 specimens from 38,167 patients for COVID-19 by PCR. There were 3,165 patients who tested positive, of which 1,061 met Raoult’s unstated inclusion criteria and were treated with his azithromycin/hydroxychloroquine combination. The mean age of the patients was 43.6 years old, and 492 (46.4%) were male. The results further state that a “good clinical outcome and virological cure” were observed in 973 patients within 10 days (91.7%), with prolonged viral carriage in 47 patients (4.4%), with viral clearance in all but one by day 15. They further observed:
A poor outcome was observed for 46 patients (4.3%); 10 were transferred to intensive care units, 5 patients died (0.47%) (74-95 years old) and 31 required 10 days of hospitalization or more. Among this group, 25 patients are now cured and 16 are still hospitalized (98% of patients cured so far). Poor clinical outcome was significantly associated to older age (OR 1.11), initial higher severity (OR 10.05) and low hydroxychloroquine serum concentration. In addition, both poor clinical and virological outcomes were associated to the use of selective beta-blocking agents and angiotensin II receptor blockers (P<0.05). Mortality was significantly lower in patients who had received > 3 days of HCQ-AZ than in patients treated with other regimens both at IHU and in all Marseille public hospitals (p< 10-2).
This study suffers from the same issues that Raoult’s much smaller study. The overwhelming majority of patients (1,008, or 95%) had a low national early warning score (NEWS), with 97.4% of the patients with a “good clinical outcome” (not defined). The table shows patients taking beta blockers and angiotensin II receptor blockers having “poor virological outcome,” while patients taking metformin (used to treat type II diabetes), beta blockers (used for hypertension and angina, as well as certain cardiac rhythm disturbances), dihydropyridine derivatives (a class of calcium channel blockers, often used for hypertension, cardiac rhythm disturbances, and angina), angiotensin II receptor blockers, HMG CoA reductase inhibitors (statins), and diuretics (used to treat hypertension and heart failure) were more likely to have “poor clinical outcomes.” Of course, it is most likely the diagnoses for which these drugs are used, rather than the drugs themselves, that are responsible for the poor outcomes in COVID-19 patients, and there’s no indication that Raoult’s group tried to do any sort of analysis to tease out whether these associations were with the drugs themselves or with the conditions being treated with the drugs.
The bottom line is that this study is also uninformative. For one thing, a 0.5% fatality rate is at the low end of current estimates and might even be the “true” case fatality rate when all cases of mild and asymptomatic infections are included in the denominator. Consequently, this study certainly doesn’t show that Raoult’s treatment was responsible for the low mortality rate. When the overwhelming percentage of the patients you treat have mild or asymptomatic disease, then of course should expect to observe that the fatality rate among these patients will be low, no matter what you do. The reason Didier Raoult refuses to do a truly randomized trial is because he’s now a true believer in his combination, which has led him to conclude that it’s unethical to randomize COVID-19 patients to a placebo control group. Worse, French President Emannuel Macron has started emulating our President Donald Trump and become a booster for Raoult’s bad science. Whether it’s out of a misplaced nationalistic pride or other reason Macron has been talking up Raoult’s results, even though Raoult has produced no data sufficiently compelling to know if his combination is safe and effective or not, particularly given the high percentage of patients with mild or asymptomatic disease in his treatment group.
Didier Raoult: Brave maverick doctor
I’ve referred to Didier Raoult as a “brave maverick doctor.” It’s a term I use to describe a wide variety of arrogant cranks who think they have “The Answer” to a disease, even if the evidence says otherwise. Not all brave maverick doctors are quacks, but nearly all quack physicians are brave maverick doctors. In any event, “brave mavericks” are doctors who think they’re “bucking the system,” that they know more than other doctors (whom they view as hidebound and lacking in their imagination and intelligence), and that they are somehow special. This term definitely describes Didier Raoult, whose persona is downright Trumpian, pure bullshit artist. Prior to his promotion of hydroxychloroquine and azithromycin being picked up by President Trump, celebrity doctors like Dr. Oz and Dr. Drew, and a wide variety of right wing pundits, Raoult was pretty much unknown outside of France, other than in some international scientific circles. That’s why this post was of great interest to me, as it described his history. And what a dubious history it is, at least with respect to COVID-19. On January 23, 2020, Raoult was saying things like:
You know, this is a crazy world. The fact is that some people have died from the coronavirus in China, you know, I don’t feel so concerned. It’s true to say that the world has gone completely crazy, that is to say that if something is happening where there are three Chinese people who are dying and that becomes a worldwide alert, the WHO gets involved, it’s on the radio and on television. […] In other words, there is no longer any sense of lucidity.
Whenever there is a disease in the world we wonder whether we are going to have the same thing in France. It has become utterly insane. [ …] I don’t know, people don’t seem to have anything to worry about, so they try and find something to be afraid of in China, just because they are unable to face what they might be afraid of if staying in France. That’s it, this is not serious.
Eventually, he discovered hydroxychloroquine. One thing that bothers me is how few people know the origin of the idea that hydroxychloroquine might be effective against COVID-19. The hypothesis that antimalarial drugs might be effective treatments for COVID-19 originated in Wuhan, China during the early phase of the pandemic in January. There, Chinese researchers reported that none of their 80 patients with lupus erythematosus who were taking hydroxychloroquine went on to become infected with SARS-CoV-2. As a result of that and old evidence of antiviral activity for the drugs, they became interested in using these antimalarial drugs to treat COVID-19. (Never mind that immunosuppressed patients are exactly the patients most likely to assiduously follow the recommendations of public health authorities during a pandemic.) A number of clinical trials were registered, and, based on anecdotal reports and small clinical trials (nearly all of which are as yet unpublished), in February the Chinese government published an expert consensus recommending CQ or HCQ for patients with COVID-19. Soon after, a number of nations followed suit. Apparently Raoult found out about this, and suddenly, at the end of February, he posted a video entitled Coronavirus: End of the game, later renamed “Coronavirus: A way out of the crisis?”
In the video, Raoult said:
- “From all respiratory infections, it is probably the easiest to treat.””
- “There’s no need to get excited.”
- “Be careful, there will soon be no more chloroquine in drugstores.”
The article lists numerous other examples of Raoult downplaying the severity of COVID-19, comparing it to seasonal influenza, and denouncing government actions to stop its spread as an overreaction. There’s also a recounting of his history of abusive behavior towards his underlings, charges of sexual harassment leveled at him, his history of being a climate science denier, and mismanagement at his institute. Meanwhile, evolutionary biologist P.Z. Myers has dissected in detail Raoult’s painful misunderstanding of evolutionary biology, while others have described a history of data fabrication by his group. Oh, and did I mention that he might be an antivaxxer? In 2018, he published a book entitled La vérité sur les vaccins. The title and the blurb for the book sure sound at least borderline antivaccine to me. The very best thing that can be said on this score is that Raoult strikes me as someone who exaggerates the risks of vaccines and buys into too much false balance with claims made by antivaxxers.
A French physician reacts
Raoult’s been doing real harm, and his fellow French physicians have become more vocal in their criticism. For example, yesterday a French physician at the Metz-Thionville CHR named Damien Barraud lambasted Raoult for “medical populism”:
“I haven’t seen a better description of what happened. Take everyone hostage and want to pass as the savior with the miracle drug that will save the world, by ignoring all the methodological and ethical rules yes, this is medical populism,” said Damien Barraud, guest on RMC this April 13.
“Outside of a protocol I don’t prescribe it, and I won’t prescribe it. And neither for me, nor for my loved ones, nor for anyone. (…) There is no reason to give it. You must have seen the alerts from the pharmaco-vigilance center of Nouvelle-Aquitaine and the ANSM pass over fifty cardiac accidents which occurred while taking this medication.”
“Very early on, from the start of the patient’s arrival and the communication from the IHU, some conventional doctors were asked to prescribe this. We had to (put a policy in place), hold meetings and waste time on some something that should not have happened because at this time there is for the time being no tangible proof of any effectiveness to have a beneficial effect in the patients in general “, he assured.
Here’s the full interview for those who understand French. It’s blistering:
We in the US have been unaware of just what a crank Dr. Raoult is, but his colleagues in France are trying to educate us.
Didier Raoult: Thin-skinned bully
Given how sharp Dr. Barraud’s criticism was and Raoult’s history of being thin-skinned and using his unfortunately not inconsiderable power to punish and humiliate underlings, critics, and others who displease him, it should come as no surprise that Didier Raoult did not react well to Dr. Barraud’s criticism:
Here’s the original French text:
Dr. Damien Barraud médecin réanimateur au CHR de Metz-Thionville, profite en ce moment d’un quart d’heure de gloire worholien en enchainant les interviews sur RMC, BFM TV et La Marseillaise.
Les propos qu’il tien dans ces interviews sont étrangement similaires à ceux tenus par le compte Twitter anonyme @fluidloading qui revendique être un médecin de la même région que le Dr. Damien Barraud.
Si ce compte Twitter est bien celui du Dr. Damien Barraud, nous somes heureux que dans les interviews données en son nom, ce médecin n’ait pas repris les injures publiques et les attaques diffamatoires que le propriétaire du compte @fluidloading se permet quotidiennement.
Nous espérons que, si le Dr. Damien Barraud n’est pas l’auteur des attaques portées par le compte @fluidloading, il s’en désolidarisera rapidement. Elles pourraient en effet justifier une plainte pénale et le lancement d’une procédure auprès de l’order des médecins. Poursuites que nous ne souhaitons pas lancer, car nous sommes aujourd’hui concentrés sur le soin des malades hospitalisés et suivis à l’IHU. Au-delà des polémiques nous espérons que le Dr. Damien Barraud trouvera le temps de se reconcentrer sur sa belle mission de médecin.
And here’s the translation (from a combination of Google Translate and me, although, surprisingly, I understood all but a few words of this):
Dr. Damien Barraud, critical care specialist at CHR Metz-Thionville, is currently enjoying a quarter of an hour of Warholian glory by doing serial interviews on RMC, BFM TV and La Marseillaise.
The comments he made in these interviews are strangely similar to those made by the anonymous Twitter account @fluidloading who claims to be a doctor from the same region as Dr. Damien Barraud.
If this Twitter account is indeed that of Dr. Damien Barraud, we are happy that in the interviews given in his name, this medicine did not take up public insults and defamatory attacks that the owner of the account @fluidloading allows himself daily.
We hope that, if Dr. Damien Barraud is not the author of the attacks carried by the @fluidloading account, he will quickly dissociate himself from it. They could in fact justify a criminal complaint and the initiation of a procedure with l’Ordre des Médicins. Pursuits that we do not wish to launch, because we are today concentrating on the care of hospitalized patients and followed at the IHU. Beyond the controversies we hope that Dr. Damien Barraud will find time to refocus on his beautiful medical mission.
Lovely. Dr. Raoult just doxxed Dr. Barraud in a despicable and passive-aggressive manner. “If Dr. Damien Barraud is not the author of the attacks” by @fluidloading, we hope that he will “quickly dissociate himself from it.” Particularly amusing is his “we’re too busy taking care of patients” shtick, a diversion beloved of brave maverick doctors the world over to excuse their lack of evidence for their treatments. He’s also destroyed another one of my irony meters, given that le Dr. Raoult seems to have plenty of time to do media interviews and appear on The Dr, Oz Show hawking his risibly bad science.
Raoult clearly meant to sic his 345K followers on Dr. Barraud on Twitter in retribution. Unfortunately, his threat to complain to l’Ordre des Médicins is not an idle one. As I discussed in February, in a time that seems fanciful in its normality from the lense of mid-April and the COVID-19 pandemic, l’Ordre des Médecins values “collegiality” and civility above all. It took the side of homeopaths against French physicians who signed a statement lambasting homeopathy as quackery and urging the French government to stop funding it, even going so far as to temporarily suspend the license of one of doctors who signed the statement. So it’s not at all clear that Dr. Barraud would be in the clear if the bully Dr. Raoult decided to follow through with his threats.
Hydroxychloroquine and azithromycin likely don’t work
Here’s the bottom line. Hydrochloroquinine, with or without azithromycin, almost certainly doesn’t work against COVID-19. That’s certainly the way that the evidence is trending, and it’s also showing evidence of harm. For instance, a Brazilian study was curtailed after patients in the high dose hydroxychloroquine arm started suffering serious adverse events, while a study from NYU found evidence of cardiac toxicity from hydroxychloroquine. Meanwhile, Sweden is reporting a similar experience, with several hospitals no longer routinely using these antimalarial drugs, due to adverse events. Meanwhile, in France itself, adverse events due to these drugs are leading doctors to rethink routinely using them.
That aside, my medical alma mater, the University of Michigan, recently published a blog post about its experience with COVID-19, including with the use of hydroxychloroquine to treat it. Basically, doctors at U. of M. have decided to stop routinely using hydroxychloroquine to treat COVID-19, because they have seen no evidence of efficacy but have seen toxicity:
Michigan Medicine just changed its guidelines on prescribing these drugs. There’s a lot of excitement about whether these already existing options for malaria could be useful in COVID-19, but so far that excitement hasn’t materialized in patient care data.
“Our infectious disease division and our antimicrobial pharmacists have reviewed all the available data and we found no convincing evidence that these drugs were effective in treating people with COVID-19,” Kaul says.
That’s consistent with what’s been observed firsthand in Michigan Medicine’s hospitals.
“We haven’t seen any clear evidence of benefit so we aren’t going to use hydroxychloroquine routinely anymore,” Chopra says. “We were initially recommending it to both inpatients and outpatients, but we’re no longer doing that routinely. That’s based upon the fact that we’ve been prescribing hydroxychloroquine for a few weeks, did not see therapeutic benefit, but did see adverse effects.”
Those side effects Chopra has seen in his patients include liver function toxicity, nausea and vomiting.
The evidence is definitely trending in the direction of the conclusion that these drugs don’t work and have more toxicity than benefit. Indeed, I’m now 95% sure that these drugs don’t work against COVID-19. Could I be wrong? Sure? Do I think I’m wrong? No, but I actually would like to be wrong about this. In any event, thanks to “brave mavericks” like Didier Raoult, Dr. Mehmet Oz, Dr. Drew Pinsky, Dr. Vladimir Zelenko, and sadly numerous others, bolstered by President Trump and his sycophants, toadies, and lackeys, hydroxychloroquine became the de facto standard of care without evidence. When they bypass rigorous science and rely on anecdotes and poor quality science, “brave maverick doctors” like Dr. Raoult do real harm not just to science, but to patient. It’s not Dr. Barraud who should be subject to lawsuits and criminal proceedings. It’s Dr. Raoult. Unfortunately, France being France, there’s no guarantee that it won’t be the other way around. The powerful bullshit artist might just win.