Killing the cure: The Strange War Against Hydroxychloroquine

Killing the cure: The Strange War Against Hydroxychloroquine

By Meryl Nass, M.D.and Belinda Brown

The following is a deep dive into what appears to have been a concerted attempt to ensure that hydroxychloroquine would not be viewed as an effective treatment for COVID-19.

As Published on LifeSiteNews

PART ONE

The UK has had the ignominious triumph of having one of the world’s highest death rates. Some see the solution in continuing lockdowns, more testing and ultimately the vaccine. We argue that the solution lies in medical treatments, such as hydroxychloroquine or ivermectin rather than in vaccination.  But hydroxychloroquine was ruled out as a potential treatment for covid19 quite early on. This is despite the fact that, when used correctly, it is a highly efficacious treatment. Had it been readily available as a prophylactic or early stage treatment we would need neither lockdowns nor vaccinations and dramatically fewer people would have died. However this didn’t happen. Here we intend to explore why.

Hydroxychloroquine had repeatedly been found to be an effective treatment for Covid19. Didier Raoult was one of the earliest to discover its usefulness. He treated over 1000 patients  with azithromycin and hydroxychloroquine and almost 99% recovered. Other studies found its efficacy was increased when zinc was added into the protocol; there were fewer fatalities and patients were discharged home earlier. Harvey Risch, a Yale professor conducted a meta-analysis showing the key role it could play in an outpatient setting. This was recently confirmed by McCullough who showed how when started earlier it may reduce the progression of disease, prevent hospitalization, and is associated with reduced mortality. Most recently Zelenko has written on the dramatic improvements hydroxychloroquine can bring about in a nebulized form. A groups of scientists and phd researchers put together a ‘living review’, a database of all the papers on hydroxychloroquine which can be viewed here: https://c19study.com/ They suggest that had it been used over 1,344,703 lives could have been saved

Safety was also never an issue when used correctly. It had been used for 65 years by hundreds of millions of people in tens of billions of doses, prescribed without routine screening and given to adults, children, pregnant women and nursing mothers.  It is derived from the bark of the cinchona tree, which has been used for hundreds or thousands of years to treat malaria.

How did a cheap, safe, and highly effective drug, come to be seen as a potentially fatal medication, which you could lose your license for prescribing, your credibility for advocating and every time someone tried to talk about it, they would be banned, humiliated or described as ‘fake news’.

How did this happen? And more ominously, why?

The stage was set when the WHO Director General, Dr Tedros Adhanom Ghebreyesus at a media briefing (18th March last year) made it clear that the controlled trials which had produced the initial findings were going to be overridden by the WHO’s far more expensively produced results:

" Multiple small trials with different methodologies may not give us the clear, strong evidence we need about which treatments help to save lives. WHO and its partners are therefore organizing a study in many countries in which some of these untested treatments are compared with each other. This large, international study is designed to generate the robust data we need, to show which treatments are the most effective. We have called this study the SOLIDARITY trial. "

The idea that multiple small trials are not able to generate strong evidence is false. The Cochrane Library Consortium, the gold standard  in the research world, examined tens of thousands of comparisons between randomized trials and their non-randomized counterparts and found the two types of studies arrived at virtually identical conclusions.   

But WHO appeared determined to control the narrative and set up a $108 million dollar study with 12,000 patients at 500 hospital sites across 30 countries. They trialled hydroxychloroquine on 954 late stage patients. 64% of these were already on oxygen or ventilation. 

Using this study they were able to achieve very different results.

To understand how, you need to know covid 19 has three stages: viral replication which can develop into florid pneumonia and then multi-organ attack. Hydroxychloroquine tackles early-stage viral replication rather than late stage inflammation which requires a different approach. It is most valuable as an outpatient treatment preventing covid19 developing to a later stage.

By giving hydroxychloroquine to late-stage patients SOLIDARITY was setting up a trial which would be bound to have negative results.

However, more egregious was the dosage. While hydroxychloroquine is very safe when used correctly, like paracetamol it has a narrow toxic to therapeutic margin. In 1979 the WHO calculated that 1.5 -2 g of the “base” drug could be a potentially fatal dose. In the Solidarity trial patients were administered a dosage of 2.4 g (equivalent of 1.9 base) in the first 24 hours or 9.6 g in total over ten days

The only ‘safety’ information collected during the trial was whether patients required oxygen, required a ventilator, or died. This effectively masked the adverse effects of the drugs tested, obscuring whether mortality was due to drug toxicity as opposed to death due to Covid 19.

This toxic dosage was quickly identified by India’s official medical research agency, the Indian Council of Medical Research. They wrote to the WHO to alert them to the fact they were using doses 4 times higher than in India. Dr. Soumya Swaminathan, the WHO’s chief scientist and previous head of the Indian medical research agency should have been able to identify this herself. A previous trial in Brazil in March-April with a slightly higher dosage (12 g in ten days) had been stopped prematurely due to excess deaths and is currently being investigated. But the Solidarity trial’s HCQ arm was only permanently stopped after one of the authors of this blog post, on finding out these doses, threatened them with a manslaughter charge. Was there a connection? You can decide.

A similar strategy in the fight against hydroxychloroquine was the Oxford based RECOVERY (Randomised Evaluation of COVid-19 thERapY) clinical trials run by two Professors from the University of Oxford Peter Horby and Martin Landray. This was a large British multi-centre clinical trial of the sort generally believed to yield the most reliable evidence.

It also used 2400 mg of hydroxychloroquine in the first 24 hours for treatment of already very ill, hospitalized Covid-19 patients, a potentially lethal dose

Horby and Landry presented a number of arguments to reassure that the dosages were not toxic, not all of which stood up to further investigation. For example, they suggest that as no extra deaths had occurred in the first couple of days when the dosage was highest this was evidence that the dose was not fatal (see line 284). They ignored the crucial fact that hydroxychloroquine has a particularly long half-life, and cumulative dosing was the more relevant measure.  

FranceSoir concluded from their extremely detailed investigation of RECOVERY that many patients died of toxic overdoses of hydroxychloroquine rather than covid 19.  You can read more about it here and here.

While the hydroxychloroquine arm has been shut down  doctors are strongly encouraged to enrol all COVID19 patients onto the RECOVERY trial. In fact they recently recruited over just over 10,000 patients in January alone. They are also maintaining  the same minimalist approach towards safety which we saw earlier on: “trials are being run as simply as they can to reduce the burden on the NHS”. 

As Chair of  the New and Emerging Respiratory Virus Threats Advisory Group (NERVTAG) and a committee member of The Scientific Advisory Group for Emergencies (SAGE), Peter Horby is an extremely influential man.

A third mysterious event in pushing hydroxychloroquine out of the picture was the publication in the Lancet of a large international observational study based on 96 000 Covid cases (15,000 of whom received a chloroquine drug) which appeared to show that hydroxychloroquine and chloroquine were of no benefit and caused considerable harm. This was reported on here. The flaws in the study were so blatant that one of us critiqued it on the day it was published. Within days 146 researchers wrote to the British Medical Journal with concerns about its methodology and data integrity. It took two weeks for the Lancet to retract the study but by then the damage was done.

PART TWO

In part one we showed how the trials designed to test hydroxychloroquine appear to have been manipulated in a direction which was bound to produce negative results. In part two we look at the influence of these studies.

Large studies have a significant impact on medical knowledge even where they are seriously misleading. They are more likely to be published and to shape meta-analyses. The fraudulent Lancet study mentioned in part one is still extensively cited.

 But in the case of hydroxychloroquine there has been a determination to influence the way that hydroxychloroquine was viewed and used throughout the world in fundamental ways. 

Firstly, the WHO put pressure on governments and professional bodies to stop doctors prescribing hydroxychloroquine. Belgium, France, Italy were just some of the countries which banned its use for treatment of Covid-19. The Jakarta Post/Reuters reported on May 27 that WHO had instructed Indonesia’s health ministry to suspend the use of hydroxychloroquine for treatment of Covid-19.  Indonesia, the world’s 4th most populous country, had been using the drug early for all cases, independent of severity, with good results. Fortunately, Indonesia refused to comply.

Similarly, Costa Rica, which had a particularly low fatality rate, and was said to be the only country in Central America using HCQ for early treatment, considered stopping hydroxychloroquine as a result of pronouncements by the WHO

The FDA at first issued an Emergency Use Authorization for chloroquine drugs, and then suspended  this. Each of these moves served to restrict use of the drugin different ways.

The clamp down in the use of hydroxychloroquine in Switzerland created a natural experiment. For about 2 weeks after hydroxychloroquine use was halted, death rates approximately tripled, for about 15 days. Then, after its use was allowed again, two weeks later death rates from Covid fell back to their baseline. But this did not receive the attention which it deserved. 

Large outpatient studies were also suspended in response to these studies. 

For example, COPCOV, a large global clinical trial which aimed to enrol 40,000 healthcare workers in an outpatient setting, appears to have been temporarily halted after recruiting 226 participants. Investigators involved in the study argue that HCQ had the potential to save tens of thousands of lives. They attributed this suspension to ‘the fraudulent data [in the Lancet-published, later retractedstudy], unjustified extrapolation and exaggerated safety concerns’.

Similarly, another trial described as ‘The largest and most systematic outpatient trial leveraged by the US National Institutes of Health’ which planned to include an estimated 2000 outpatients with early covid-19 was stopped for good after only 20 had been enrolled in a month.

This was particularly damaging to the potential use of hydroxychloroquine, as it is in an outpatient context that it has its most valuable role to play

And so the systematic exclusion of hydroxychloroquine from the COVID19 medical landscape progressed.

The most-consulted US medical encyclopedia, UptoDate, advised physicians to restrict hydroxychloroquine to only clinical trials, citing the FDA.

Sanofi announced it would no longer supply the drug for use with Covid, and cancelled its clinical trials  including one for outpatients, which should have been a key area of research.

Sanofi also began acting like a regulator, writing to health professionals in Australia to remind them that hydroxychloroquine was not approved for use outside a clinical trial. Sanofi also started collecting information on all off-label use of hydroxychloroquine in New Zealand and Australia, providing mechanisms for people to make anonymous reports.  

If anyone should wonder why Sanofi, a drug manufacturing company, should become a surveillance/ enforcement mechanism to frighten medical providers from using the drug for COVID19, it is worth noting that Sanofi, partnering with GSK, subsequently received a potential 2.1 billion dollars from the US government for 100 million doses of coronavirus vaccine. Perhaps that is where the answer lies.

And in what appeared to be a strange war against hydroxychloroquine, in Taiwan, a country which fared remarkably well in the battle against covid19, a factory essential to the production of hydroxychloroquine was burnt down

The barrage of negative publicity which the studies on hydroxychloroquine precipitated influenced what was published. When publishing empirical research, it is easier to publish positive findings. But when it came to hydroxychloroquine there was a bias towards publishing negative results. Studies from North America were almost four times more likely to report negative results than studies from the rest of the world combined.

Richard Smith, former editor-in-chief of the British Medical Journal (BMJ) helps us understand why: ‘Medical Journals are an extension of the marketing arm of pharmaceutical companies,’. He was backed up by Richard Horton: ‘Journals have devolved into information laundering operations for the pharmaceutical industry’.

Richard Horton was the editor in chief when the Lancet published the fraudulent research on hydroxychloroquine. He should know.

The treatment of hydroxychloroquine by social media companies provided a study on the operation of ‘fake news’.  YouTube CEO Susan Wojcicki said: ‘YouTube will ban any content containing medical advice that contradicts the World Health Organisation (WHO) coronavirus recommendations’. While this sounds reasonable on the face of it, the fact remains that the WHO’s pronouncements were not reliable. When those with power control the narrative it is more difficult to decipher the truth.

An example of this censorship occurred when a group calling themselves “America’s Frontline Doctors” gave a press conference and livestream talks about the Covid-19 pandemic and the need for physicians to be able to prescribe HCQ freely.  While the media sparsely attended the press conference, the livestream got millions of views. Within hours, their livestream was banned by Google, YouTube, Facebook and Twitter. While they can be found again on YouTube, they have been subject to character assassinations, and accused of having a political agenda. It is hard to see what they gain from exposing themselves to criticism and public humiliation except the knowledge that they have done their best to save other people’s lives.

There was a pattern of targeting doctors who spoke out in favour of hydroxychloroquine. Professor Didier Raoult, an authoritative microbiologist and one of the world’s most published scientists, wrote the original paper which put hydroxychloroquine on the map. As a result, he was subject to a significant level of attack. For example, when the New York Times Magazine did a feature on him, what they ultimately produced was a detailed hit piece. In the US, Raoult is now considered an unreliable crank

Vinay Prasad MD explained how ‘Over the last few months, I have seen academic articles and op-eds by professors retracted or labelled “fake news” by social media platforms. Often, no explanation is provided. I am concerned about this heavy-handedness and, at times, outright censorship’. 

PART THREE

In part one we looked at how trials of hydroxychloroquine appeared to have been designed to achieve negative results. In part two we looked at how these trials influenced strategies in the treatment of COVID19. Today we consider why hydroxychloroquine was subject to such an unprecedented attack?

Initially there may have been political motivations.

As it was the year of the US elections there was no shortage of people ready to criticise Trump’s poor handling of the pandemic. Firstly, he was attacked for downplaying the severity of it and then for his over-enthusiastic embracing of a potential cure. This was seen to be a risky strategy which could (and did) lead some people to self-medicate. As a result, Trump’s approach elicited a strong negative reaction from some members of the medical profession.

However, it also seems possible that had Trump been able to successfully promote hydroxychloroquine this would have transformed him into a hero. And there were many forces which wanted the President out.

Even before the WHO got to work on Solidarity, President Trump had, on the basis of findings from smaller clinical trials, obtained free drug donations for the Strategic National Stockpile of hydroxychloroquine and chloroquine, which were made available for distribution to state governments. By the end of May pharmaceutical companies had donated more than 150 million doses, enough to fully treat more than 15 million people as part of their efforts for the ‘prevention and treatment of the coronavirus outbreak’.  

However, Rick Bright, an Obama appointed official, personally opposed widespread distribution of the donated hydroxychloroquine and chloroquine, by insisting that it be registered for Emergency Use Authorization only (EUA). This greatly restricted its usage to only hospitalised patients, while preventing distribution to the outpatients with early disease in whom it would be expected to do the most good. This was not necessary as it was a properly licensed drug. This usage particularly discriminated against elderly residents in nursing homes who would no longer be able to access it as a prophylactic treatment.

This was a charade to confuse doctors.  FDA participated in the charade, issuing advice that use of the drug required a level of monitoring that could only be accomplished in a hospital. So, even though doctors could legally prescribe it off-label, they became aware that if they did so, they would likely be sued for malpractice if something went wrong.

However clumsily some may feel that Trump articulated his plan, it would have been able to save thousands of lives.

But perhaps more pertinently the fingerprints of big pharma were all over the decisions made.

One of the earliest studies initiated in response to Trump’s plan found that patients receiving hydroxychloroquine were more likely to die than those receiving regular care. However it was soon acknowledged that this was due to the severe stage of illness, and the fact that those in the group who received the drug were much sicker than those who did not. As The study noted, ‘hydroxychloroquine, with or without azithromycin, was more likely to be prescribed to patients with more severe disease…Thus, as expected, increased mortality was observed in patients treated with hydroxychloroquine both with and without azithromycin’. The study was not peer reviewed, nor did it include azithromycin and zinc although previous studies suggested this combination produced the best outcome. One could argue that the trial appeared to be designed to ensure that hydroxychloroquine would come out badly.

One of the co-authors had been involved with Gilead which was produced remdesivir, a competing covid19 drug.

Perhaps more telling are the various links with vaccine producers. In fact, it is the Bill and Melinda Gates Foundation (BMGF), the byword for vaccines, who were the experts when determining the doses of hydroxychloroquine. It was they who had developed a model of chloroquine penetration into tissues for malaria. At the expert working group they explained that they would have a post-exposure prophylaxis clinical trial protocol for hydroxychloroquine in the coming week, but we have not been able to find this.

Either way the BMGF were influential.  At the first meeting where the WHO working group discussed the potential role of hydroxychloroquine in the treatment of covid19 five out of 25 of the meeting’s participants were from BMGF. When it came to decisions about the dosage for the disastrous SOLIDARITY trials a representative from the foundation was one of only four participants involved

Similarly, BMGF heavily funded the Recovery trial

As advocates of vaccination conflicts of interest were inevitable.  But if the dosage decided on for the hydroxychloroquine trials was a mistake it has cost us very dearly and served BMGF very well.

Big Pharma are extremely heavily invested in the UK public health decision-making system from the top down.  In the light of what we already know it would appear that their financial interest in vaccine production takes priority over a desire to save individual lives.

For example, many might wonder why Neil Ferguson, with his poor record of disease modelling, might be allowed to be so influential. But as someone who consistently over-predicts the scale of danger and is Acting Director of the Vaccine Impact Modelling Group, (funded by BMGF and GAVI, The Vaccine Alliance) he could undoubtedly play a useful role.

The British Government is also the largest funder of GAVI, The Vaccine Alliance. The links between big pharma, the WHO and our health strategies have been documented in detail here and here. When a floundering UK government is so heavily invested in a vaccine industry the potential financial gain from a successful vaccine roll out, rather than health and wellbeing of the people, is shaping  everything which the government chooses to do.

When looking at public health decisions it becomes apparent that these have been shaped by big pharma in a way which will inevitably lead to vaccines. PCR testing has been used to artificially ramp up the rate of infections, lockdown has destroyed the economy, and potential cures such as hydroxychloroquine (and maybe more recently ivermectin) appear to have been strategically removed. As a result, we are pushed into a corner from which vaccines appear to be the only escape.

What can we learn from this sorry saga of hydroxychloroquine?

The WHO and other national health agencies, universities and charities have conducted large clinical trials which appear to have been designed so hydroxychloroquine and its cousin chloroquine would fail to show benefit in the treatment of Covid-19, perhaps to advantage much more expensive competitors and vaccines in development. In so doing, these agencies and charities have de facto conspired to increase the number of deaths in these trials.  In so doing, they have deprived billions of people from potentially benefiting from a safe and inexpensive drug, when used properly, during a major pandemic.  This might contribute to prolongation of the pandemic, massive economic losses and many increased cases and deaths.

Big pharma does not work in our interests. Some of those involved in this scandal appear to be financially motivated and these motivations shape policy decisions in ways which, certainly in the case of COVID19, are ultimately destructive of human health. Furthermore, their own agenda, wittingly or not, shapes the decisions and outputs of those further downstream.

We need some form of deregulation where as individuals we have greater control over our own health decisions. The risks involved are unlikely to be greater than the risks involved in entrusting ourselves to those who are influenced by financial interests when they make decisions about public health. Their recent track record speaks for itself.

Arbiters of ‘fake news’, wittingly or not, act as advocates for those with the funding and clout to produce the reports, studies and trials which make their case. While there is a great deal of fiction on the internet, fact checkers themselves do not have the authority to determine the ‘truth’ and in fact were recently pulled up for their censorship of a post about hydroxychloroquine. In the case of hydroxychloroquine (and more recently ivermectin) anonymous fact checkers claim more authority for the results of large clinical trials which can produce seriously misleading information.

By preventing the off-label use of hydroxychloroquine for early stage covid19 huge numbers of the elderly and those with co-morbidities, with men disproportionately represented among them, have died. This is genocide by default.

In this strange war against hydroxychloroquine it is not just hydroxychloroquine ‘they’ are attacking. This is a war against us. 

To read the original article, please visit

https://www.lifesitenews.com/opinion/hcq-behe

The Hydroxychloroquine Saga

The Hydroxychloroquine Saga

by Rick Bradford

Has much of the world failed to benefit from an effective, early-stage treatment for COVID-19, because early trial results were misleading? There may be a number of drugs we could ask this question of; here I look at hydroxychloroquine.

The Early Indications

Hydroxychloroquine is not an exotic new drug with which doctors and medical authorities have little experience. On the contrary, it has been used widely for decades to treat malaria, lupus and rheumatoid arthritis. It came to public attention as a potential treatment for COVID-19 early in 2020, not least because of President Trump’s espousal of it.

In the period March – July 2020, attention focused on the WHO-led multinational Solidarity Trial and the UK’s own Recovery Trial which addressed the efficacy of hydroxychloroquine against COVID-19.

The Chief Investigators of the Recovery project released a press statement on June 5th 2020 which stated simply, “no clinical benefit from use of hydroxychloroquine in hospitalised patients with COVID-19”.

On July 4th 2020 the Solidarity project discontinued the hydroxychloroquine and lopinavir/ritonavir trials. The interim trial results showed that hydroxychloroquine and lopinavir/ritonavir produced little or no reduction in the mortality of hospitalized COVID-19 patients when compared to standard of care. The Solidarity Trial found that all four treatments evaluated (remdesivir, hydroxychloroquine, lopinavir/ritonavir and interferon) had little or no effect on overall mortality, initiation of ventilation and duration of hospital stay in hospitalised patients.

The Recovery and Solidarity trials were exclusively carried out on seriously ill patients in hospital, rather than the early-stage patients for which there was existing evidence that hydroxychloroquine might be effective. A drug which acts against the pathogen is most relevant when the pathogen is multiplying. In the later stages of COVID-19, the illness becomes an immune-system-driven inflammatory condition, and by that time the original pathogen has already done its damage. Could it be that the negative results of the Recovery and Solidarity trials were due to their deployment to patients in an inappropriate phase of the disease? Certainly, Professor Didier Raoult from IHU-Marseille, and an early leading proponent of hydroxychloroquine, was not impressed with the Recovery trial, accusing it of being “the Marx Brothers doing science”.

In passing I note that a further multinational trial, REMAP-CAP, was also deployed only to seriously ill patients with severe pneumonia admitted to an intensive care unit (ICU). I have found no results from this study. On June 3rd 2020 it was suspended following the scare from a now infamous Lancet paper by Mehra et al which claimed the use of hydroxychloroquine increased death rates (the paper was retracted a few days later). I presume that trial was never restarted.

Another criticism of the Recovery and Solidarity trials which has been made is of the dosage regime, with the doses appearing to be substantially greater than standard practice when the drug is used against malaria, lupus or rheumatoid arthritis (see, for example, “Killing the cure: The strange war against hydroxychloroquine“).

Recent Evidence that Hydroxychloroquine is Effective Against COVID-19

Care is needed here. To recommend a particular drug to medical practitioners requires a randomized controlled trial (RCT). However, before one goes to the expense and trouble of carrying out a controlled trial there must be some prima facie evidence to suggest a positive outcome is likely. Is there such prima facieevidence that hydroxychloroquine is effective when used in the right dosage on patients in the right stage of the disease?

Yes, there is. Lots of it. In fact, far more than is necessary to establish a prima facie case. It is this fact, against indications from the earlier trials, that motivated the writing of this short article. The number of studies emerging which examine the efficacy of hydroxychloroquine, sometimes in combination with other drugs, is substantial – far too many papers for me to review here. Fortunately, review articles are now appearing which bring the big picture together, although what is still needed is a definitive, rigorous meta-analysis published in a top journal.

What I shall do first is give the reader a brief impression of what data is around by looking at a small sample of studies. These alone are sufficient to provide a solid prima facie case. You will see that the evidence comes from all over the world. The weight of evidence that hydroxychloroquine, possibly combined with other drugs, is efficacious in the early stages of COVID-19 is very strong. I will give a status summary of all the studies available as of February 2021 after looking at a few individual studies.

Didier Raoult and the Marseille Team

Although invariably associated in the press with the name of the flamboyant Didier Raoult alone, the paper which was submitted to the journal Travel Medicine and Infectious Disease on May 27th and published online on June 25th 2020 included the names of 43 authors: “Outcomes of 3,737 COVID-19 patients treated with hydroxychloroquine/azithromycin and other regimens in Marseille, France: A retrospective analysis“. Extracts from the abstract are:

" In our institute in Marseille, France, we initiated early and massive screening for coronavirus disease 2019 (COVID-19). Hospitalization and early treatment with hydroxychloroquine and azithromycin (HCQ-AZ) was proposed for the positive cases. We retrospectively report the clinical management of 3,737 screened patients, including 3,119 (83.5%) treated with HCQ-AZ (200 mg of oral HCQ, three times daily for 10 days and 500 mg of oral AZ on day one followed by 250 mg daily for the next four days, respectively) for at least three days and 618 (16.5%) patients treated with other regimen (“others”). "

" The patients’ mean age was 45 (sd 17) years, 45% were male, and the case fatality rate was 0.9%… Treatment with HCQ-AZ was associated with a decreased risk of transfer to ICU or death (Hazard ratio (HR) 0.18 0.11–0.27), decreased risk of hospitalization ≥10 days (odds ratios 95% CI 0.38 0.27–0.54) and shorter duration of viral shedding (time to negative PCR: HR 1.29 1.17–1.42)… Although this is a retrospective analysis, results suggest that early diagnosis, early isolation and early treatment of COVID-19 patients, with at least three days of HCQ-AZ lead to a significantly better clinical outcome and a faster viral load reduction than other treatments. "

Although many patients were relatively young in Covid terms, 12.3% were over 64 (5.7% older than 74). Of patients given hydroxychloroquine, 359 were over 64; of patients given other treatments, 157 were over 64. There was a high level of comorbidity: cancers 4%, diabetes 8%, chronic heart disease 6%, hypertension 15%, chronic respiratory disease 9% and obesity 11%.

The vultures have been circling Raoult for some time. The New York Times did a hit piece on Raoult in which “Trump” occurred 11 times. The Guardian was delighted to give Raoult some publicity… when the story was that he was to be subject of a disciplinary hearing by his professional medical body. In the Guardian story, “Trump” appeared in the third sentence. Muddying the waters of a purely medical question with political partisanship is worrying. There were 42 other authors responsible for the paper as well as Raoult, but Trump was not one of them.

Bernaola (Madrid)

The paper “Observational Study of the Efficiency of Treatments in Patients Hospitalized with Covid-19 in Madrid” by Nikolas Bernaola et al was submitted to the medRxiv medical preprint archive in July 2020 (current peer review status unknown). It concluded: “In this multicenter study of patients admitted with COVID-19, hydroxychloroquine and prednisone administration was found to be associated with improved outcomes. Other treatments were associated with no effect or worse outcomes.” However, it sounds a warning note: “Randomized, controlled trials of these medications in patients with COVID-19 are needed to avoid heavy administration of treatments with no strong evidence to support them.”

Tarek Sulaiman’s Team, Riyadh, Saudi Arabia

The Effect of Early Hydroxychloroquine-based Therapy in COVID-19 Patients in Ambulatory Care Settings: A Nationwide Prospective Cohort Study” was placed on the medRxiv preprint archive on September 13th 2020 with the names of 22 authors. From the abstract:

" This observational prospective cohort study took place in 238 ambulatory fever clinics in Saudi Arabia, which followed the Ministry of Health (MOH) COVID-19 treatment guideline. This guideline included multiple treatment options for COVID-19 based on the best available evidence at the time, among which was Hydroxychloroquine (HCQ). Patients with confirmed COVD-19 (by reverse transcriptase polymerase chain reaction (PCR) test) who presented to these clinics with mild to moderate symptoms during the period from June 5th–16th 2020 were included in this study. Our study looked at those who received HCQ-based therapy along with supportive care (SC) and compared them to patients who received SC alone. "

" All patients were presenting with active complaints; however, the HCQ groups had higher rates of symptoms compared to the SC group (fever: 84% vs 66.3, headache: 49.8 vs 37.4, cough: 44.5 vs 35.6, respectively). Early HCQ-based therapy was associated with a lower hospital admission within 28-days compared to SC alone (9.4% compared to 16.6%, RRR 43%, p-value <0.001). The composite outcome of ICU admission and/or mortality at 28-days was also lower in the HCQ group compared to the SC (1.2% compared to 2.6%, RRR 54%, p-value 0.001). Adjusting for age, gender, and major comorbid conditions, a multivariate logistic regression model showed a decrease in the odds of hospitalisation in patients who received HCQ compared to SC alone (adjusted OR 0.57 [95% CI 0.47-0.69], p-value <0.001). The composite outcome of ICU admission and/or mortality was also lower for the HCQ group compared to the SC group controlling for potential confounders (adjusted OR 0.55 [95% CI 0.34-0.91], p-value 0.019). "

CONCLUSION Early intervention with HCQ-based therapy in patients with mild to moderate symptoms at presentation is associated with lower adverse clinical outcomes among COVID-19 patients, including hospital admissions, ICU admission, and/or death.

Derwand, Scholz and Zelenko (USA Data)

The December 2020 edition of the International Journal of Antimicrobial Agents contains the peer reviewed paper “COVID-19 outpatients: early risk-stratified treatment with zinc plus low-dose hydroxychloroquine and azithromycin: a retrospective case series study“. The abstract reads:

The aim of this study was to describe the outcomes of patients with coronavirus disease 2019 (COVID-19) in the outpatient setting after early treatment with zinc, low-dose hydroxychloroquine and azithromycin (triple therapy) dependent on risk stratification. This was a retrospective case series study in the general practice setting. A total of 141 COVID-19 patients with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the year 2020 were included. The main outcome measures were risk-stratified treatment decision and rates of hospitalisation and all-cause death. A median of 4 days [interquartile range (IQR) 3–6 days; available for n = 66/141 patients] after the onset of symptoms, 141 patients (median age 58 years, IQR 40–67 years; 73.0% male) received a prescription for triple therapy for 5 days. Independent public reference data from 377 confirmed COVID-19 patients in the same community were used as untreated controls. Of 141 treated patients, 4 (2.8%) were hospitalised, which was significantly fewer (P < 0.001) compared with 58 (15.4%) of 377 untreated patients [odds ratio (OR) = 0.16, 95% confidence interval (CI) 0.06–0.5]. One patient (0.7%) in the treatment group died versus 13 patients (3.4%) in the untreated group (OR = 0.2, 95% CI 0.03–1.5; P = 0.12). No cardiac side effects were observed. Risk stratification-based treatment of COVID-19 outpatients as early as possible after symptom onset using triple therapy, including the combination of zinc with low-dose hydroxychloroquine, was associated with significantly fewer hospitalisations.

Brazil

Published online in October 2020 in Travel Medicine and Infectious Disease, the peer reviewed paper “Risk of hospitalization for Covid-19 outpatients treated with various drug regimens in Brazil: Comparative analysis” carried the names of nine Brazilian authors and one from the USA. From the Abstract:

Use of hydroxychloroquine (HCQ), prednisone or both significantly reduced hospitalization risk by 50–60%. Ivermectin, azithromycin and oseltamivir did not substantially reduce risk further….This work adds to the growing literature of studies that have found substantial benefit for use of HCQ combined with other agents in the early outpatient treatment of COVID-19, and adds the possibility of steroid use to enhance treatment efficacy.

Switzerland’s Natural Experiment

A rather stunning piece of evidence for hydroxychloroquine’s effectiveness comes from Switzerland, as explained in this article: “Covid-19: l’hydroxychloroquine marche, une preuve solide?” My French is not good, but I get “une preuve solide” right enough. Some background is required first.

On May 22nd 2020, the Lancet published a paper which has become scandalous. It claimed that hydroxychloroquine or chloroquine when used for treatment of COVID-19 decreased in-hospital survival rates. It met with a maelstrom of criticism, and was retracted by the Lancet just 13 days later on June 4th 2020. This is a most unusual occurrence. The newspaper FranceSoir described it using the term “fraudulent study” (l’étude frauduleuse). It has been claimed that its database did not actually exist.

But in the 13 days before the paper was withdrawn it did its damage: the WHO and many Nation States decided to ban the prescribing of hydroxychloroquine due to the scare caused by that paper. (The REMAP-CAP trial of hydroxychloroquine was terminated due to it.) Switzerland, in which hydroxychloroquine had previously been in widespread use, was one of the countries which introduced a ban – on May 27th. But, after the Lancet paper had been withdrawn, the Swiss rescinded the ban and the widespread prescribing of hydroxychloroquine restarted after 15 days on June 11th. This created a natural experiment of the efficacy of hydroxychloroquine. The result is shown by Figure 1 below.

Figure 1

The graph shows, in effect, the mortality rate of COVID-19 patients against date. To be precise, the ordinate is the nrCFR (New Resolved Case Fatality Rate), which is defined as the proportion of deaths among the resolved cases (dead or cured) in the seven days preceding the date in question.

The two vertical lines indicate the cessation of prescribing hydroxychloroquine (May 27th) and its reintroduction 15 days later (June 11th). Prior to May 27th, hydroxychloroquine was in widespread use and the death rate was reducing. A time delay between treatment change and any influence on death rate is to be expected. Thirteen days after the ban on hydroxychloroquine, the death rate leapt upwards to a level not seen since March. Thirteen days after the reintroduction of hydroxychloroquine, the death rate dropped equally precipitously back down to its previous low level. Une preuve solide, it would seem.

Stunning though that is, there is evidence that is perhaps even more stunning.

Covid Analysis Group

I had it in mind to look at how the overall death rates varied between countries according to their usage of hydroxychloroquine. But it’s been done already. A group of researchers calling themselves Covid Analysis Group have been publishing regular updates of exactly that data, the latest being November 14th 2020: “Early treatment with hydroxychloroquine: a country-based analysis.” The key result is shown in Figure 2. The analysis is very detailed. Figure 2 includes adjustments described in the web link, which also gives the raw data. I have not attempted to critique the data.

Figure 2 shows in green the death rate per million for countries with widespread early usage of hydroxychloroquine. The red lines relate to countries with limited early usage of hydroxychloroquine. The graph is so striking it needs no additional commentary. Virtually all the green countries lie at lower death rates than virtually all the red countries. Note the stipulation regarding the deployment of hydroxychloroquine in the early stages of the disease.

Figure 2

The most obvious concern is whether the countries plotted have been cherry-picked, since only a small sub-set of the world’s nations are included. The Covid Analysis Group addressed this issue:

Why is country x not included? Our goal is to identify countries that have taken a strong decision on treatment. Countries without clear decisions are much harder to analyze – to create any meaningful results we need to know the proportion of usage to some reasonable degree… Countries like Italy or Brazil have extremely mixed usage, with differences during major time periods of their outbreak and/or major geographic differences. Analyzing these countries would be much more complex.

The Totality of Available Studies at 26th February 2021

As of February 26th there were 259 studies, 211 which compare with control groups, and 187 peer reviewed. You can find them all listed on this very useful link. I quote that site’s summary of the totality of evidence:

Hydroxychloroquine is not effective when used very late with high dosages over a long period (Recovery/Solidarity), effectiveness improves with earlier usage and improved dosing. Early treatment consistently shows positive effects. Negative evaluations typically ignore treatment time, often focusing on a subset of late stage studies.

Figures 3, 4 and 5 below are lifted straight from that source. Figure 3 shows that all 27 studies which involved treatment during the early stage of the disease were efficacious, the average improvement being 65%. Figure 4 shows all the trials, on both early and late stage patients. Most show a beneficial effect, but a substantial number of late-stage studies produce a worse outcome than controls. Early stage treatment is therefore key, as has been consistently maintained by proponents of hydroxychloroquine in the medical community.

Figure 5 shows the distribution around the world of usage of hydroxychloroquine to treat COVID-19. Limited use is found across all anglophone countries.

Figure 3
Figure 4
Figure 5

Has the Efficacy of Hydroxychloroquine been Misrepresented?

So, has much of the world failed to benefit from an effective, early-stage treatment for COVID-19 because early trials of hydroxychloroquine were misleading? Based on the evidence now accumulating it would appear so. But one of the surprises, to this author, is that the negative view of the efficacy of hydroxychloroquine is highly country-specific, being universal across anglophone countries, whilst most other countries have continued to deploy it. The reader may speculate about the reasons for this.

Rick Bradford is an Honorary Senior Research Fellow in the Department of Engineering at the University of Bristol.

To read the original Article, please visit:

The Hydroxychloroquine Saga