Coronavirus: Treatment is on its Way

by Jean-Pierre Kiekens – Oxford trained economist and former lecturer at the University of Brussels. The author also holds a degree in bio-engineering / agronomy from the same university.

Note: this article is available in French – l’article est disponible en Français.

Also, check a compendium of relevant latest news to the progress towards treatment.  

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Important Note: Regarding the Bloomberg story that a Chinese study found hydroxychloroquine inefficient, one needs to note that this study predates the knowledge of how chloroquine based treatment has to be used. Such treatment needs to be applied before an acute situation. At that point, as highlighted in the video clip below by Professor Raoult (with English subtitles), the virus load is about zero, and emergency room treatment with artificial ventilation is required. So the two treatments compared in the that study cannot really be compared. It’s just that knowledge is evolving.
 

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As a prelude to reading this article, you may want to watch this report by Dr Oz, providing an update on the situation, a brief interview of Dr Raoult, and interviews of two patients who took the chloroquine-based treatment. And please share the article on social media — Twitter, Facebook, etc. Thanks.


There is a shift of paradigm regarding how to deal with the raging coronavirus pandemic. Treatment is on its way. And it takes the form of a very cheap combination of an anti-malaria drug and antibiotics.

Here is the treatment now recommended by Professor Didier Raoult – the number one expert in the world in communicable diseases, according to expertscape.com – http://expertscape.com/ex/infectious+diseases –  and several of his colleagues.

– Hydroxychloroquine: 3 x 200 mg per day for 10 days
– Azithromycin: 500 mg the first day and 250 mg per day for the 5 following days
– A wide-spectrum antibiotic is added in the case of severe pneumonia

An electrocardiogram is recommended on Day 0 and Day 2, as a precautionary measure.

Source: https://www.maritima.info/depeches/coronavirus/marseille/66541/coronavirus-le-traitement-a-l-hydroxychloroquine-generalise-a-l-ihu-marseille.html

Chloroquine was discovered in 1934 by Hans Andersag and coworkers at the Bayer laboratories. It has been used for decades for the prevention of malaria. Hydroxychloroquine is a less toxic metabolite of chloroquine.

Researchers at the pharmaceutical company Pliva in Croatia, — Gabrijela Kobrehel, Gorjana Radobolja-Lazarevski, and Zrinka Tamburašev, led by Dr. Slobodan Đokić — discovered azithromycin in 1980.

Both drugs, and their safety profiles, are extremely well known by the medical profession.

See this March 24 video by Professor Raoult (video added to this article, as there is controversy about the safety of the treatment. English substitles are available for the video.



Both drugs are generic and are extremely cheap. The cost for a full treatment is less than US$20.

How the Treatment was Found

On February 25, Professor Didier Raoult announced to his students good news from China.

https://www.youtube.com/watch?v=8L6ehRif-v8

« The Chinese, who are those who are the fastest and the most pragmatic, instead of researching a vaccine or a new molecule to cure the coronavirus, did what we call repositioning (aka repurposing), i.e. testing molecules that are old, that are known to be without toxicity issues, against the new virus. They did so, and they found out, as they found out before with SARS, that chloroquine was active In Vitro. »

« I was interviewed by the Chinese TV. They asked me which advice I had for the Chinese, and what I was expecting the Chinese, whom I consider the best virology teams in the world, to do. I told them that I hoped that very rapidly, they would provide the results of a first study about the efficiency of chloroquine for the coronavirus. This study is just out. Yes, it’s efficient for the coronavirus, with 500 mg of chloroquine per day during 10 days. There is a spectacular improvement and it is now recommended in China for all cases of clinically positive coronavirus infections. »

« This is probably the respiratory infection that is the easiest to treat, » concluded the number one communicable diseases expert in the world.

The study referred to by Professor Raoult is:  Gao J, Tian Z, Yang X. Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends. 2020 Mar 16;14(1):72-73

The study summary by Goa, Tian and Yang reads as follows:

« The coronavirus disease 2019 (COVID-19) virus is spreading rapidly, and scientists are endeavoring to discover drugs for its efficacious treatment in China. Chloroquine phosphate, an old drug for treatment of malaria, is shown to have apparent efficacy and acceptable safety against COVID-19 associated pneumonia in multicenter clinical trials conducted in China. »

« The drug is recommended to be included in the next version of the Guidelines for the Prevention, Diagnosis, and Treatment of Pneumonia Caused by COVID-19 issued by the National Health Commission of the People’s Republic of China for treatment of COVID-19 infection in larger populations in the future. »

https://www.jstage.jst.go.jp/article/bst/14/1/14_2020.01047/_pdf/-char/en

Raoult and his team immediately initiated a small clinical trial, to confirm the Chinese results. The study involved 26 patients who received hydroxychloroquine and 16 control patients. 6 patients benefited from a hydroxychloroquine and azithromycin combined treatment.

The study was hastily produced 2 weeks later, and is now available online at: https://www.sciencedirect.com/science/article/pii/S0924857920300996  Gautret et al. (2020) Hydroxychloroquine and azithromycin as a treatment of COVID‐19: results of an open‐label non‐randomized clinical trial. International Journal of Antimicrobial Agents – In Press 17 March 2020 – DOI : 10.1016/j.ijantimicag.2020.105949

Rarely a small study probably has received as much attention as this one. The study shows that the viral load in the patients treated with hydroxychloroquine declines considerably within about a week.

Results showing sharp decline of infection within a week of treatment
using a combination of hydroxychloroquine and an antibiotic.
Source: https://youtu.be/n4J8kydOvbc?t=869 (in French)
The 6 patients treated with the combination of hydroxychloroquine and azithromycin had even a better outcome, with 6 out of the 6 patients testing negative after 6 days.

On the basis of this small study, wider scale trials are now under way in France, and in Europe. There are also trials in the US, Norway and other jurisdictions.

https://presse.inserm.fr/en/launch-of-a-european-clinical-trial-against-covid-19/38737/

At the same time, there is a growing number of medical professionals who, while welcoming additional trials, are recommending the immediate use of this treatment, given the emergency of the situation and the known low risks associated with the treatment.

The reason is simple: there isn’t really an alternative, even if the precise efficacy of this treatment will only be known on the basis of larger trials.

What’s extremely important is to use the treatment at an early stage, if possible before any infections of the lower pulmonary tract. This means that testing must be available and implemented fast on all individuals with symptoms, so that the infection can be treated before it’s too severe.

While we are still at the very beginning with this treatment, it is now used in various medical institutions, yet not a wide scale basis.

In France, the Institut Hospitalo-Universitaire Méditerranée Infection in Marseille announced, in a statement on March 22 signed by Pr Philippe Brouqui, Pr Jean-Christophe Lagier, Pr Matthieu Million, Pr Philippe Parola, Pr Didier Raoult, Dr Marie Hocquart, that it would immediately use the treatment on all diagnosed patients.

They stated that « In accordance with the Hippocratic Oath that we have taken, we obey our duty as a doctor. We provide our patients with the best care for the diagnosis and treatment of a disease. We respect the rules of the art and the most recently acquired data of medical science. »

« We believe it is not moral that this treatment would not be systematically included in therapeutic trials for the treatment of the Covid-19 infection in France. »

https://www.maritima.info/depeches/coronavirus/marseille/66541/coronavirus-le-traitement-a-l-hydroxychloroquine-generalise-a-l-ihu-marseille.html

There are indications that the treatment is growingly used in countries such as Belgium, Norway, USA and Canada.

https://clinicaltrials.gov/ct2/show/NCT04316377?term=chloroquine+and+covid-19&draw=2

In the Province of Québec, the Jewish General Hospital in Montreal is using it in its coronavirus unit.

https://www.journaldemontreal.com/2020/03/19/la-chloroquine-deja-utilisee-a-lhopital-juif-de-montreal-1

While large scale trials are under way, and first results are anticipated within weeks, there is a growing consensus among medical professionals that the treatment should be used, even before the results of those larger scale trials are published, which takes significant time.

In an excellent Forbes March 22 article, the perspectives of several scientists are reported on.

« Despite the limitations of this study, in the absence of any effective treatment, in this urgent situation, this Plaquenil and Azithromycin combination therapy should be given to patients with COVID-19 as a treatment option, » Ying Zhang, a professor of microbiology at Johns Hopkins Bloomberg School of Public Health, wrote in an email. « For now, there is no time to wait. »

“I would recommend real-time online posting of treatment evaluation results of the Plaquenil+Azithromycin at multi-center sites across the US and the Globe,” Zhang wrote. “Someone has to coordinate this online registry and resources.” Other treatments should be included, added Professor Ying Zhang.

Brian Fallon, a research scientist and clinical trials investigator at the Columbia University Irving Medical Center, wrote the journalist by email: « Given the life and death situation of hospitalized patients with COVID-19 and the possibility that hydroxychloroquine plus azithromycin may be helpful, it was valuable and ethical for the authors to report these promising, preliminary results. »

The Forbes article is really worth reading, as it also relates the personal story of a patient who was administered the treatment.

https://www.forbes.com/sites/marybethpfeiffer/2020/03/22/one-patient-dodges-a-covid-bullet-is-she-a-harbinger-or-outlier

Today, in a commentary in the Wall Street Journal titled « These Drugs Are Helping Our Coronavirus Patients, »  Daniel Hinthorn, a Professor at Kansas University Hopital, and Dr. Colyer, a practicing physician and chairman of the National Advisory Commission on Rural Health, strongly argue in favor of the treatment.

« We don’t want to peddle false hope; we have seen promising drugs turn out to be duds. But
the public expects an answer, and we don’t have the luxury of time. We have a drug with an excellent safety profile but limited clinical outcomes—and no better alternatives until long after this disaster peaks. We can use this treatment to help save lives and prevent others from becoming infected. »

https://www.wsj.com/articles/these-drugs-are-helping-our-coronavirus-patients-11584899438

Things are developping fast now. During a Sunday press briefing, the Governor of the State of New York Andrew Cuomo said 750,000 doses of chloroquine, 70,000 doses of hydroxychloroquine and 10,000 doses of Zithromax were acquired by New York state for a large scale trial.

https://www.forbes.com/sites/lisettevoytko/2020/03/22/new-york-to-begin-clinical-trials-for-coronavirus-treatment-tuesday-cuomo-says

Massive Production Under Way – Yet Widespread Shortages

In his February 25 announcement, Professor Raoult commented that soon, there would be shortages of chloroquine. And he was right.

Both individuals and health institutions have procured the medicine in anticipation of a surge in its use. Today, there are widespread shortages, reported in countries such as France and the US. Medical professionals are prevented from using this therapeutic tool.

Yet, major pharmaceutical companies have already boosted the production of hydroxychloroquine. On March 18, Bayer announced it was donating donating 3 million tablets of malaria medicine chloroquine to the US government.

https://www.fiercepharma.com/pharma/bayer-preps-u-s-donation-malaria-med-chloroquine-to-help-covid-19-fight-report

Novartis has pledged a global donation of up to 130 million hydroxychloroquine tablets, pending regulatory approvals for COVID-19. Mylan is ramping up production at its West Virginia Facility with enough supplies to make 50 million tablets. Teva is donating 16 million tablets to hospitals around the U.S.

https://www.fiercepharma.com/pharma/new-commitments-mylan-and-teva-move-to-supply-tens-millions-hydroxychloroquine-tablets-to

These production surges came at the same time as President Trump informed the world, on March 19, about the potential for hydroxychloroquine to be a game changer in the fight against the pandemic.

There is less information at this stage about the supply of azithromycin, yet it appears is is produced by numerous manufacturers, and like with hydroxychloroquine, supply should not be an issue, except maybe in the very short term.

http://www.antimicrobe.org/drugpopup/Azithromycin%20-%20Brand%20names.htm

While these massive boosts in supply are under way, there are, in the short term, shortages for the drugs.

In France, Dr Christian Perrone, head of the infectiology department at the Raymond-Poincaré Hospital, stressed millions of doses are needed immediately. He stressed the medicines should be available everywhere in hospitals in France, and that the 300,000 doses foreseen by the government were totally insufficient.

« We are in a war medicine today, and one needs to make war to the virus to save our patients » he declared Dr Perrone.

« The French State must ask industry to massively produce the medicines, he added. If there is a better treatment later on, ok, we will take it later. But right now, there is nothing else. »

« From an ethical viewpoint, we cannot wait for additional research, » he stressed in this interview.

He said he thought he would be able to give the treatment to his patients, but was told by email, by the central pharmacy for hospitals in France, that the medicine was unavailable, that the stocks were already empty.

https://youtu.be/-acK_ClEvjE

The short term challenge is to make those medicines available to medical institutions and to address any regulatory, bureaucratic hurdle that may be in the way.

Fortunately, in terms administrating the treatment, this is a very simple and safe. Doctors can right away administer the treatment and take the required precautionary measures that are needed.

Implications for Containing the Pandemic

Here are my thoughts about the implications for containing the pandemic.

In the short and medium term, all the measures aimed controlling the spread of the virus should be strictly abided to. Actually, in many countries, stricter measures are needed, so as to avoid overburdening health facilities, which is expected about everywhere, as just a handful of countries has so far controlled the spread of the virus.

And countries that are late in the game, such as Sweden and the Netherlands, should speedily implement draconian measures to reduce the spread of the disease. The Italian and Spanish experiences have demonstrated how essential this is to avoid massive casualties.

“Flatten the Curve” – Source: Wired
In other words, yes the curve must be flattened.

At the same time, the hydroxychloroquine / azithromycin treatment should be made as rapidly as possible available to hospitals and other health institutions in all countries, including those where the situation is not yet severe. This is critical, as the pandemic is growing exponentially.

Testing needs to be boosted, as early detection of infected patients is absolutely critical. South Korea like drive through testing facilities and other systems need to be multiplied. 

At this point, some countries, such as the US and France, are very late in the game in terms of testing. Others, such as South Korea and Germany, are much more in advance.

With early detection, the treatment can be administered before the patient is in a critical conditions, which will ensure maximum efficacy.

For hospitals and other health facilities, this is critical, as with this approach, emergency rooms will not be needed to treat most patients.

This will alleviate one of the most important hurdles in dealing with the pandemic: the insufficient number of emergency rooms, respirators, and associated equipments.

And most importantly, it will require much less medical staff for each treated patient. And this approach will much less expose the medical staff to infections, in addition to providing a treatment to those medical staff that have unfortunately been infected.

At the individual level, i.e. when it comes to things that are in your direct control, the strategy is to avoid infection as much as possible, especially in the coming weeks when health facilities will be overburdened and when treatment will not be available yet in many locations.

But if you get infected and develop symptoms at some stage, seek testing and rapidly seek treatment before the infection is too advanced. And of course, take all the precautions to avoid infecting others.

Even if the health, medical, logistical and other challenges are considerable, the formula to address this pandemic becomes straightforward: Testing – Quantifying – Treating – Following Up – as explained by Professor Didier Raoult.

https://youtu.be/SfiUlVpqHfE
https://youtu.be/ydcrROJFEU0

Bye bye the hypothetical and extremely deadly herd immunity approach initially adopted by the British government, that was not relying on a treatment but rather a massive infection of the population.

Unfortunately, Sweden and the Netherlands seem to have adopted the UK’s initial herd immunity approach, and voluntarily let the virus spread instead of doing everything to contain it.

This approach is particularly deadly in the short and medium term, as the hypothetical herd immunity that is sought requires over 90% of the population to be infected.

You can do the maths in terms of how many deaths this means, if no effective treatment is made widely available to the population.

The country where the spread of the virus first exploded was China. Today, the spread of the virus in China is largely contained.

The challenge ahead for authorities in all the countries where the virus is not in control, and is on the verge to explode – because of its exponential growth – is to combine the strict policies to slow down the spread of the virus, with dramatically increasing testing and treatment at an early stage.

We will soon know more precisely how effective the hydroxychloroquine / azithromycin treatment is, and there are other treatments being tested, that may also be effective.

What seems clear is that treatment may play a much more important role in dealing with the pandemic than initially thought.

And this may allow humanity to overcome this pandemic faster than anticipated.

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Thanks for your reading! Please share with anyone you think might benefit from this information. And take care of yourself, your relatives and all those in need in these difficult times!

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Other contributions by the author

Opinion: Postpone the Tokyo Olympics to 2022 – March 19

Coronavirus: Time to be Proactive – March 4

Sailing and the Coronavirus – February 26

Coronavirus: What is at Stake & How to Deal with It – Feb 20.

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