The Coronavirus Conspiracies
Claim: Hydroxychloroquine is the cure!
This is the claim that Hydroxychloroquine is the miracle cure, and the evil doctors are suppressing the truth.
This drug looked promosing when the idea was first introduced. Everyone had a ray of hope that this already FDA approved anti-Malaria drug might be able to be repurposed for covid-19. Everyone was optimistic from science advocates to even Donald Trump. The problem arrose when it turned out that this once promosing candiate after further investigation proved not to be the micale it was originally thought.
After this you have the scientifically minded moving on, while those who don't understand science latched onto this drug and touted it as the miracle cure, even saying that it does work and it's all a cover up.
Let's start with the institutions who's job it is to understand the science.
The World Health Organisation discontinued their Hydroxy study writing:
"WHO today accepted the recommendation from the Solidarity Trial’s International Steering Committee to discontinue the trial’s hydroxychloroquine and lopinavir/ritonavir arms. The Solidarity Trial was established by WHO to find an effective COVID-19 treatment for hospitalized patients."
"These interim trial results show that hydroxychloroquine and lopinavir/ritonavir produce little or no reduction in the mortality of hospitalized COVID-19 patients when compared to standard of care. Solidarity trial investigators will interrupt the trials with immediate effect. "
"This decision applies only to the conduct of the Solidarity trial in hospitalized patients and does not affect the possible evaluation in other studies of hydroxychloroquine or lopinavir/ritonavir in non-hospitalized patients or as pre- or post-exposure prophylaxis for COVID-19. The interim Solidarity results are now being readied for peer-reviewed publication."
You might think that this last paragraph is the "uh huh!" moment, but this is just how science works. Science doesn't conclusively say this does or does not work. Studies are building blocks of which the scientific consensus is built upon. It's a scientific approach to not assume that because your study is failing to find utility in a drug, that someone else won't.
The FDA originally approved the drug for emergency use, but then later issued this statement and retracted that energency use:
"The agency determined that the legal criteria for issuing an EUA are no longer met. Based on its ongoing analysis of the EUA and emerging scientific data, the FDA determined that chloroquine and hydroxychloroquine are unlikely to be effective in treating COVID-19 for the authorized uses in the EUA. Additionally, in light of ongoing serious cardiac adverse events and other potential serious side effects, the known and potential benefits of chloroquine and hydroxychloroquine no longer outweigh the known and potential risks for the authorized use"
Additionally, the National Institue of Health has also halted their study:
"A clinical trial to evaluate the safety and effectiveness of hydroxychloroquine for the treatment of adults hospitalized with coronavirus disease 2019 (COVID-19) has been stopped by the National Institutes of Health. A data and safety monitoring board (DSMB) met late Friday and determined that while there was no harm, the study drug was very unlikely to be beneficial to hospitalized patients with COVID-19. After its fourth interim analysis the DSMB, which regularly monitors the trial, recommended to the National Heart, Lung, and Blood Institute (NHLBI), part of NIH, to stop the study. NHLBI halted the trial immediately."
"The data from this study indicate that this drug provided no additional benefit compared to placebo control for the treatment of COVID-19 in hospitalized patients."
Let's take a look at some unfortunate examples of science being done badly.
A study from the International Journal of Antimicrobial Agents titled Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial has been described by the International Society of Antimicrobial Chemotherapy as:
"The ISAC Board believes 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."
"Given his role as Editor in Chief of this journal, Jean-Marc Rolain had no involvement in the peer review of the manuscript and has no access to information regarding its peer review. Full responsibility for the manuscript's peer review process was delegated to an Associate Editor."
"Although ISAC recognises it is important to help the scientific community by publishing new data fast, this cannot be at the cost of reducing scientific scrutiny and best practices. Both Editors in Chief of our journals (IJAA and Journal of Global Antimicrobial Resistance) are in full agreement."
This study has some serious problems. You can read a critique from the Science Integrity Digest, as well as many heavily critical comments from PubPeer. For example, this is a non-randomised study with a tiny sample size. There are questions about missing patient data, inconsistencies from pre-print and the published paper, it was peer-reviewed and published in a single day, and the editor in chief of the journal it was accepted in, is an author on the paper.
Here's another bad paper, this one retracted from the Lancet:
"Important scientific questions have been raised about data reported in the paper by Mandeep Mehra et al—Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis 1 —published in The Lancet on May 22, 2020. Although an independent audit of the provenance and validity of the data has been commissioned by the authors not affiliated with Surgisphere and is ongoing"
The paper has now been retracted.
This paper in the New England Journal of Medicine finding no risk of ACE inhibiters titled Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19 has since been requested to be retracted. It now has.
"Because all the authors were not granted access to the raw data and the raw data could not be made available to a third-party auditor, we are unable to validate the primary data sources underlying our article, “Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19.”1 We therefore request that the article be retracted. We apologize to the editors and to readers of the Journal for the difficulties that this has caused."
Another study in the preprint server for the British Medical Journal titled Hydroxychloroquine plus azithromycin: a potential interest in reducing in-hospital morbidity due to COVID-19 pneumonia (HI-ZY-COVID)? has the following description:
"The authors have withdrawn this manuscript and do not wish it to be cited. Because of controversy about hydroxychloroquine and the retrospective nature of their study, they intend to revise the manuscript after peer review."
In a New England Journal of Medecine study titled Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid-19, they write:
"Of the 1376 patients, 811 (58.9%) received hydroxychloroquine (median duration of treatment, 5 days) and 565 (41.1%) did not. Among the patients who received hydroxychloroquine, 45.8% received it in the 24 hours between their presentation to the emergency department and the start of study follow-up, and 85.9% received it within 48 hours after presentation to the emergency department."
"In this analysis involving a large sample of consecutive patients who had been hospitalized with Covid-19, the risk of intubation or death was not significantly higher or lower among patients who received hydroxychloroquine than among those who did not"
"Clinical guidance at our medical center has been updated to remove the suggestion that patients with Covid-19 be treated with hydroxychloroquine."
From Recovery Trial:
"A total of 1542 patients were randomised to hydroxychloroquine and compared with 3132 patients randomised to usual care alone. There was no significant difference in the primary endpoint of 28-day mortality "
"preliminary results from the RECOVERY trial are quite clear –hydroxychloroquine does not reduce the risk of death among hospitalised patients with this new disease"
In the Annals of Internal Medicine titled Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19.
"56% (236 of 423) were enrolled within 1 day of symptoms starting. Change in symptom severity over 14 days did not differ between the hydroxychloroquine and placebo groups (difference in symptom severity: relative, 12%; absolute, −0.27 points [95% CI, −0.61 to 0.07 points]; P = 0.117). At 14 days, 24% (49 of 201) of participants receiving hydroxychloroquine had ongoing symptoms compared with 30% (59 of 194) receiving placebo (P = 0.21). Medication adverse effects occurred in 43% (92 of 212) of participants receiving hydroxychloroquine versus 22% (46 of 211) receiving placebo (P < 0.001)."
"Hydroxychloroquine did not substantially reduce symptom severity in outpatients with early, mild COVID-19."
I should add that there have been a few critical comments on the above paper which are worth reading.
I've investigated this and there is an element to validity to the claim in premise. I've dug around and found the source of this to not be so sturdy.
This comes from five places as far as I can see.
Here's the description:
"COVID-19 is an aggressive and contagious virus, found to have high mortality especially in persons with comorbidities (Age>60, hypertension [HTN], diabetes mellitus [DM], Cancer, and otherwise immunocompromised). Zinc is a supplement with possible antiviral properties, having been shown to have effect in the common cold, many of which are due to coronavirus. In addition, elderly patients and patients with co-morbidities have high incidence of zinc deficiency. We are repleting zinc in all patients and studying its direct effect in combination with hydroxychloroquine, and an antibiotic, either azithromycin or doxycycline to see if there is enhanced treatment efficacy in early COVID-19 infection and assess the safety of these two regimen."
Estimated study completion date: December 31st.
"No Study Results Posted on ClinicalTrials.gov for this Study"
This isn't a complete study. It hasn't been peer-reviewed, it's not in pre-print, it isn't even a study yet.
This one's description:
"Healthcare professionals mainly doctors, nurses and their first degree relatives (spouse, father, mother, sister, brother, child) who have been started hydroxychloroquine(plaquenil) 200mg single dose repeated every three weeks plus vitaminC including zinc once a day were included in the study. Study has conducted on 20th of march. Main purpose of the study was to cover participants those who are facing or treating COVID19 infected patients in Ankara."
Estimated study completion date: September 1st.
"No Study Results Posted on ClinicalTrials.gov for this Study"
Again, this isn't even a study yet.
3 - A pre-preint study from the British Medical Journal titled Hydroxychloroquine and azithromycin plus zinc vs hydroxychloroquine and azithromycin alone: outcomes in hospitalized COVID-19 patients.
Again, pre-print studies should be taken with a grain of salt as they haven't gone through peer-review yet.
"In univariate analyses, zinc sulfate increased the frequency of patients being discharged home, and decreased the need for ventilation, admission to the ICU, and mortality or transfer to hospice for patients who were never admitted to the ICU. After adjusting for the time at which zinc sulfate was added to our protocol, an increased frequency of being discharged home (OR 1.53, 95% CI 1.12-2.09) reduction in mortality or transfer to hospice remained significant (OR 0.449, 95% CI 0.271-0.744). Conclusion: This study provides the first in vivo evidence that zinc sulfate in combination with hydroxychloroquine may play a role in therapeutic management for COVID-19."
4 - A pre-print study from preprints.org titled COVID-19 Outpatients – Early Risk-Stratified Treatment with Zinc Plus Low Dose Hydroxychloroquine and Azithromycin: A Retrospective Case Series Study
"Conclusions: Risk stratification-based treatment of COVID-19 outpatients as early as possible after symptom onset with the used triple therapy, including the combination of zinc with low dose hydroxychloroquine, was associated with significantly less hospitalizations and 5 times less all-cause deaths."
It's worth mentioning other than the obvious nature of being pre-print, that the comments on this study are mixed, with some being sceptical of potential bias and mising information, as well as many implications of selection bias.
5 - The only peer-reviewed study on the list is from the Intermational Journal of Infectious Diseases titled Treatment with hydroxychloroquine, azithromycin, and combination in patients hospitalized with COVID-19.
"In this multi-hospital assessment, when controlling for COVID-19 risk factors, treatment with hydroxychloroquine alone and in combination with azithromycin was associated with reduction in COVID-19 associated mortality. Prospective trials are needed to examine this impact."
Now this might seem promising but unfortunately this study doesn't look too good.
The four studies linked at the start: "Hydroxychloroquine, an antimalarial and immunomodulatory agent and a safer analogue of chloroquine, has demonstrated antiviral activity against SARS-CoV-2"
3 are in vitro studies meaning not on actual people, and the fourth doesn't apply to Covid-19.
Those minor issues aside, the main contention here comes from the related links. This paper has some criticism behind it.
"The process of allocating patients to treatment groups results in the “neither drug” group having a disproportionately high share of patients with cardio-vascular comorbidity. The Arshad (2020) study finds that the Hazard Ratio for cardiovascular comorbidity is 1.062 (from Table 2 of Arshad, 2020) and is not statistically significant. Similarly, it finds that the Hazard Ratios for COPD comorbidity and Hypertension are not statistically significant. Other studies have shown the increased risk of death due to cardiovascular comorbidities to be around 300% (see, for example,Dhakal et al., 2020), not 6%, so the (not statistically significant) 6% is just not plausible. Other implausible results are that having a BMI of 30 or higher reduces that patient’s risk of death by 22%, and being white increases it by 74%.
Another major flaw in the study is that it makes a substantial adjustment to the death rate if the patient receives ventilator support. A hypothetical thought experiment reveals the inappropriateness of such an adjustment. Consider a treatment protocol A which results in all the patients on that protocol requiring ventilator support, and which is being compared with a treatment protocol B in which none of the patients require ventilator support. If the actual death rate for protocol A was twice the actual death rate for protocol B, after making the Hazard Ratio adjustment of 2.159 for ventilator use (from Table 2), protocol A would be judged to have a lower death rate than protocol B. This is clearly not an appropriate result.
As a result of the flaws in the analysis the conclusions reached in Arshad 2020 are invalid."
In another letter to the editor, another researcher compares their similar results to this study:
"Some important weaknesses of the analysis by Arshad have been pointed out (Lee et al., 2020) but not all of these apply to our study. Our propensity scores include some of the potential confounders that were missing in the analysis by Arshad (e.g. calendar day of admission, disease severity, cardio-vascular disease (CVD), baseline plasma CRP); second, we have excluded people receiving other drugs which could have biased the effect of hydroxychloroquine when used in combination."
"These results from two different real-life settings (Italy and USA), are conflicting with those of two large randomised trials (
Horby et al., 2020, World Health Organization, 2020). Although unmeasured confounding remains the most likely explanation for the discrepancies, a robust meta-analysis is still lacking and we question whether hydroxychloroquine should be further tested. When best to start treatment is also a question that needs to be addressed in ad-hoc randomised studies."
"Also, in the accompanying editorial, Lee et al reviewed important potential limitations to the Arshad et al study (Lee et al., 2020). We underscore the concerns raised that bias may have been introduced into the study’s design by reserving the combination of hydroxychloroquine and azithromycin for patients with “minimal cardiac risk factors.” Additionally, Lee et al discuss the possibility that there may have been palliative intent in the selection of neither hydroxychloroquine nor azithromycin for patients who were more ill"
"Finally, Lee et al note that 78.9% and 74.3% of the patients in the hydroxychloroquine and combined hydroxychloroquine and azithromycin groups (respectively) received steroid therapy, while 35.7% of patients in the neither group received steroid therapy. Given promising results from a recent multi-site randomized study in the United Kingdom supporting a mortality benefit of dexamethasone, this confounding variable is of substantial concern"
"These potential confounding bias concerns regarding Arshad et al highlight the important role for randomized clinical trials as the gold standard study design for evaluating the benefit of COVID-19 therapeutics"
One of Hydrxychloroquine's biggest cheerleaders has been Donald Trump. On Twitter he wrote:
"HYDROXYCHLOROQUINE & AZITHROMYCIN, taken together, have a real chance to be one of the biggest game changers in the history of medicine. The FDA has moved mountains - Thank You! Hopefully they will BOTH (H works better with A, International Journal of Antimicrobial Agents). be put in use IMMEDIATELY. PEOPLE ARE DYING, MOVE FAST, and GOD BLESS EVERYONE!"
On YouTube he said:
He touted "strong powerful signs" that it will work. He said "I've used it for certain reasons, what have you got to lose?"
On another occasion he said:
"You'd be amazed at how many people are taking it, especially the front line workers, before you catch it. Front line workers - many many are taking it. I happen to be taking it."
When asked about the evidence for prevention we get the very scientific response:
"Here you go, you ready? Here's my evidence. I get a lot of positive calls about it." He then goes on to say he's only seen one negative thing and of course it's political again him, because the world revolves around Trump apparently.
Here's the danger. He has influence and many followers. People can and will self medicate if they're freaking out and their political hero starts talking about a miracle drug. In a Guardian article, a husband and wife self medicated on Chloroquine after hearing Trump rave about it.
"A Phoenix-area man has died and his wife was in critical condition after the couple took chloroquine phosphate, an additive used to clean fish tanks that is also found in an anti-malaria medication touted by Donald Trump as a treatment for Covid-19."
"“Trump kept saying it was basically pretty much a cure,” the woman told NBC."
Of course this is stupid, but this is the danger of unscientific claims made to a huge number of influential people.
Just 5 days earlier from the date of this article trump is quoted as saying:
"But the nice part is, it’s been around for a long time, so we know that if it — if things don’t go as planned, it’s not going to kill anybody."
That obviously didn't work out very well. It's not the same drug, but your average person especially the influential don't know that.
Recently he's again endorsed Hydroxychloraquine:
"Based on a lot of reading and a lot of knowledge about it, I think it's could have a very positive impact in the early stages, and I don't think you'd lose anything by doing it."
A woman lost her husband so maybe there is a risk of loss over self medication.
A viral video also circulated recently (end of July) from a woman named Stella Immanuel who Trump rewteeted claiming Hydroxychloraquine is the miracle Trump said it was.
"Nobody needs to get sick. This virus has a cure - it is called hydroxychloroquine, I have treated over 350 patients and not had one death,"
If you need to know about her credibility, here's a little summary:
"Five years ago, she alleged that alien DNA was being used in medical treatments, and that scientists were cooking up a vaccine to prevent people from being religious."
"Some of her other claims include blaming medical conditions on witches and demons - a common enough belief among some evangelical Christians - though she says they have sex with people in a dream world."
"They turn into a woman and then they sleep with the man and collect his sperm… then they turn into the man and they sleep with a man and deposit the sperm and reproduce more of themselves," she said during a sermon in 2013."
"After Facebook took down the America's Frontline Doctors' video on Tuesday, she declared that Jesus Christ would destroy the social media giant's servers if her videos were not restored to the platform."
I don't know about you, but she doesn't seem all that logical or reliable. Actually, she seems quite... quite mad.
Topping this off, here is a TSIA article from MedPage Today titled: No Evidence That Doctor Group in Viral Video Got Near COVID 'Front Lines'
From the available evidence used to support people's assertion that Hydroxychloroquine works, or works in combination with Zinc are two incomplete studies, two pre-prints, and a study heavily cricised for being biased. Not to mention fake viral videos.
On the other hand you have multiple insitutions and other studies concluding that the drug isn't worth studying any more.
You also have a number of retracted papers which also get cited as proof.
For this reason, until further information is released, I rate this between misleading and speculative. Maybe we will have good news on a miracle combination, but the evidence so far does not support this.
Maybe future studies will show utility of Hydroxychloraquine in combination with another drug, but right now the evidence points the other way. There is a lot of annecdotal evidence and speculation, but that's not enough for me.