Jean-Pierre Kiekens is an independent policy analyst. He is a former lecturer at the University of Brussels and a graduate of the universities of Oxford and Brussels.
This article is about the Canadian situation, where the epidemic is still active, especially in Québec and Ontario, and where there may be thousands of fatalities from COVID-19 in the coming months.
The article maintains that many lives could still be saved with a simple change in policy by the federal and provincial governments. The policy change requires to focus on early treatment of the disease, with the best available therapies.
The article is largely applicable to other countries such as the UK, Australia, and others, which are also “waiting for the research” before taking real therapeutic action and are in the mean time, like Canada, only offering high-mortality hospital treatments to those suffering from COVID-19.
In an American Journal of Epidemiology article published on May 27, medical doctor and Yale epidemiology professor Harvey Risch argues that:
“It is our obligation not to stand by … as the old and infirm and inner city of us are killed by this disease and our economy is destroyed by it and we have nothing to offer except high-mortality hospital treatment.”
Professor Risch recommends using Hydroxychloroquine + Azithromycin (or Doxycycline), preferably with Zinc, as an outpatient treatment, “at least until we find or add something better.”
“Available evidence of efficacy of HCQ+AZ has been repeatedly described in the media as “anecdotal,” but most certainly is not,” writes Professor Risch.
What Professor Risch recommends is essentially the early treatment that has been implemented with success by Professor Raoult and his team since March at the IHU-Marseille, which is France’s specialized institute in infectious diseases, with some 700 employees and several of the best experts in the world.
What was the therapeutic system implemented at IHU Marseille? It involves mass screening and early treatment under medical supervision, either at the hospital or as outpatient. It also involves isolation of those infected, to avoid further spreading the disease.
On May 27, the IHU-Marseille published the summary of their latest findings in treating patients for COVID-19. The study covers 3,737 patients and confirms the hydroxychloroquine and azithromycin treatment reduces the risk of hospitalization, the risk of transfer to the ICU and the risk of death.
This study is just the latest of a sequence of studies carried out at the IHU-Marseille and published since March. The Marseille team actually relied on early therapeutic results in China, and improved the treatment protocols.
Using Hydroxychloroquine for viral infections is not a new concept. In a November 2003 article in The Lancet, Dr Savarino and collaborators already argued about the benefits of the drug:
“Due to its broad spectrum of antiviral activity … hydroxychloroquine may also find a place in the treatment of other viral infections characterized by symptoms associated with inflammatory processes and/or immune-hyperactivation.”
The 2003 study Lancet study also argued that the treatment is safe:
“Chloroquine/hydroxychloroquine has a well-studied toxicity profile. The half-century-long use of this drug in the therapy of malaria demonstrates the safety of acute administration of chloroquine to human beings.”
While there has been abundant controversy in the past months about alleged safety risks with hydroxychloroquine, and even a politicization of the medication, the IHU-Marseille data released on May 27 confirmed a low toxicity, even when hydroxychloroquine is taken in conjunction with azithromycin, as long as it’s done under medical supervision.
Among the 3,737 patients covered in the study, cardiac monitoring led to a cessation of the treatment in just 3 cases. “No cases of torsade de pointe or sudden death were observed,” notes the summary of the study.
This extremely low risk associated with early hydroxychloroquine-based treatment needs to be contrasted with a high risk of death, that can exceed 10%, when COVID-19 is not treated early and one relies instead on what professor Risch calls “high-mortality hospital treatment.”
Sometimes not stressed enough is the fact that, if not treated early, many patients who overcome COVID-19 will still suffer considerable organ damage, including to the lungs, with possible life-long sequels. This is an additional reason why early testing and treatment are so critical.
Thousands Can Still be Saved
Today, the death toll from COVID-19 in Canada exceeds 7000 deaths, and the number of new daily cases still exceeds 700. Those are mostly located in Québec and Ontario, and there is no clear trend in those two provinces towards a rapid end of the epidemic, as community transmission remains active.
The average case fatality rate in Canada – the number of deaths divided by the number of cases – is 8%. Let’s contrast this with Marseille, where many, but not all, patients were treated at Professor Raoult’s university hospital, the IHU-Marseille.
For those patients treated at the IHU, the case fatality rate was less than 1%, while it was about 8% elsewhere in Marseille, according to an analysis in the France-Soir newspaper.
Suggesting that the fatality resulting from the disease can be about 8 times less, thanks to hydroxychloroquine-based early treatments, is not unreasonable. It’s actually consistent with what’s observed in placebo arms of clinical trials, where fatality rates of around 12% are not uncommon.
Such a reduction in case fatality rate is considerable, as it amounts to over 80% reduction in mortality among those infected, while the risk is about nil, as long as the treatment is medically supervised.
When one talks to medical doctors who treat COVID-19 patients, the message tends to be always the same. At the first symptoms, you need to seek medical help. In a recent interview, Dr J. Varon, who is Professor of Acute and Continuing Care at the University of Texas Health and Chief of Critical Care at United Memorial Medical Center in Houston, insists on early treatment.
Professor Varon stresses that the earlier patients are treated, the better the chances of a prompt recovery and avoidance of long term lung and other organ damage. Professor Varon, like Professor Paul Marik from the Eastern Virginia Medical Group, is part of a network of excellence in the treatment of COVID-19 which relies on hydroxychloroquine as part of their treatment protocols.
Excellence in hospital treatment improves the odds of recovery and reduces the likelihood of death. Yet, these front-line medical experts, who also are esteemed academics, all agree that even better is to avoid hospitalization and receive early treatment, which can usually take place on an outpatient basis.
Now, what’s the situation with early treatment in Canada? The official position of the federal government is to wait for clinical trials. Professor Risch, in the context of the US, analyzes the implication of such position of waiting for the outcomes of domestically run clinical trials testing hydroxychloroquine / azithromycin.
“For the earliest trial, between now and September, assuming a flat epidemic curve of 10,000 deaths per week, I estimate that approximately 180,000 more deaths will occur in the US before the trial results are known.”
In Canada, there are 38 authorized clinical trials for COVID-19, yet none of them is testing the best available therapy comprising hydroxychloroquine, azithromycin and zinc. Most therapeutic trials test hydroxychloroquine alone, which is already known to be much less effective.
Only one Canadian trial tests hydroxychloroquine combined with azithromycin, but it also uses the more toxic chloroquine, and fails to control for zinc. In short, the ongoing clinical trials in Canada can’t unfortunately be expected to be of much help to guide best therapeutic practices for COVID-19.
Therapeutic knowledge has evolved considerably since clinical trial protocols were designed in Canada. Conventional research is simply too slow and not agile enough to provide a proper response to the COVID-19 crisis. Canada needs to rely instead on international knowledge, on the best available therapeutic protocols, which happen to be those involving early treatment of the disease.
Like in the US, thousands of deaths may occur before the results of the Canadian trials are published. Too many lives are at stake. There is no such time to waste.
The Way Forward for Canada
What needs to be done in the Canadian context? We can again follow the recommendations of Professor Harvey Risch, who actually worked for a period of time as a faculty member in epidemiology and biostatistics at the University of Toronto.
“We cannot afford the luxury of perfect knowledge and must evaluate, now and on an ongoing basis, the evidence for benefit and risk of these medications.”
“for the great majority … Hydroxychloroquine+Azithromycin or HCQ+Doxycycline, preferably with Zinc, can be this outpatient treatment”
“we have a solution, imperfect, to attempt to deal with the disease. We have to let physicians employing good clinical judgement use it and informed patients choose it.”
“There is a small chance that it may not work. But the urgency demands that we at least start to take that risk and evaluate what happens, and if our situation does not improve we can stop it …”
“… but we will know that we did everything that we could instead of sitting by and letting … thousands die because we did not have the courage to act according to our rational calculations.”
Note for UK Readers
The main clinical trials in the UK do not test the hydroxychloroquine / azithromycin bi-therapy, and don’t control for Zinc either. First results are not anticipated before July. Like in Canada, there is therefore not much to expect from these clinical trials, except maybe providing a pretext for inaction to the government … See this March 28 article where I already highlighted those flaws of the RECOVERY research program.
Harvey A Risch, Early Outpatient Treatment of Symptomatic, High-Risk Covid-19 Patients that Should be Ramped-Up Immediately as Key to the Pandemic Crisis, American Journal of Epidemiology. https://doi.org/10.1093/aje/kwaa093
Interview with Doctor Joseph Varon, Professor of Acute and Continuing Care at the University of Texas Health Science Center and Chief of Staff/Chief of Critical Care at United Memorial Medical Center in Houston, Texas.
Early Diagnosis and Management of COVID-19 Patients: a Real-Life Cohort Study of 3,737 Patients, Marseille, France. May 27 2020 version. https://www.mediterranee-infection.com/early-diagnosis-and-management-of-covid-19-patients-a-real-life-cohort-study-of-3737-patients-marseille-france/
COVID-19 : Marseille 5 – Paris 1 juste les chiffres. France-Soir. http://www.francesoir.fr/societe-sante/marseille-5-paris-1-juste-les-chiffres
Coronavirus disease (COVID-19): Outbreak update (in Canada) — https://www.canada.ca/en/public-health/services/diseases/2019-novel-coronavirus-infection.html
Drugs and vaccines for COVID-19: List of authorized clinical trials (in Canada) —