Hydroxychloroquine Controversey for the treatment of COVID-19


May 27, 2020

Post by

Vispi Kanga

The prospect of using hydroxychloroquine to treat persons affected with Covid-19 during this pandemic has sparked rancor and disagreement among politicians and scientists.

What is Hydroxychloroquine?

Hydroxychloroquine (HCQ) and its analog, chloroquine (CQ), are derived from quinine, which French chemists in 1820 isolated from the bark of the cinchona tree. In 1934, German scientists created the synthetic chloroquine an anti-malarial.

Hydroxychloroquine is the less-toxic version of chloroquine.  It is the only known therapy for primary Sjogren’s syndrome and it is used to treat childhood arthritis, some symptoms of lupus erythematosus and other autoimmune diseases. It has value as a “disease-modifying anti-rheumatic drug” that can decrease the pain and swelling of arthritis, according to the American College of Rheumatology. It has a long elimination half-life of 30–45 days, allowing for weekly dosing when used in prevention of malaria, and a short 48-hour treatment course when used to treat malaria. Hydroxychloroquine typically is very well tolerated compared to chloroquine.

Parsi community & Hydroxychloroquine

Chloroquine is contraindicated in people with G6PD (Glucose-6-phosphate dehydrogenase) deficiency causing a condition called hemolytic anemia where red blood cells are prematurely destroyed.  But rarely, hydroxychloroquine can lead to anemia in individuals with G6PD deficiency or porphyria. Therefore, HCQ is preferred over chloroquine in G6PD deficient patients.

PARSI community is believed to have a greater probability to have the gene associated with this condition. Prevalence of G6PD deficiency in India was first reported from the Parsi population of Mumbai in the year 1963 by Baxi et al.  The highest frequency (27.94%) has been reported from Vataliya Prajapati from Surat, Gujarat whereas the Parsi population of Mumbai showed relatively high frequency of 17-19%. (G.J.B.A.H.S., Vol.2(3):10-15, (July – September 2013)

Can Hydroxychloroquine be used to treat Covid-19?

One of the most severe complications from COVID-19 may be related not to the virus itself but to the immune system’s overreaction to the presence of that virus. Increasing evidence suggests that a subgroup of COVID-19 patients experience an immune system reaction known as a cytokine storm. In these cases, the immune system overloads the lungs with inflammation-producing chemicals, causing severe and sometimes fatal damage. Some evidence exists that hydroxychloroquine inhibits the ability of cells to secrete cytokines, blocking this immune-system overreaction.

Antiviral medications, unlike antibiotics, aim to disrupt the ability of a virus to reproduce and proliferate, not to kill the virus directly. Chloroquine & Hydroxychloroquine’s antiviral properties stem from its apparent ability to block some of the cellular processes associated with the ability for some viruses to replicate. Used for this purpose, some evidence suggests, the drug could potentially slow the spread of the novel coronavirus and thus reduce severe complications.

Studies have shown that during COVID illness treatments with Chloroquine and hydroxychloroquine are associated with concerns of cardiovascular toxicity which can trigger ventricular arrhythmias particularly in individuals with cardiovascular disease.

A U.S. Department of Veterans Affairs (VA) study found that severe COVID-19 patients treated with antimalarial hydroxychloroquine alone or in combination with antibiotic azithromycin showed “no evidence” of reduced risk of death or mechanical ventilation over supportive care.

What started the rancor between politicians and scientists and health agencies?

While a theoretical scientific basis exists to the notion that hydroxychloroquine with or without azithromycin can fight coronavirus infections, claims of its potential efficacy against COVID-19 are rooted in a few extremely limited scientific studies whose methods and presentation have been criticized.

All the controversy took momentum after a French study/clinical trial in which the authors published preliminary results “that hydroxychloroquine is efficient in clearing viral nasopharyngeal carriage of [the novel coronavirus] in COVID-19 patients in only three to six days, in most patients.”  This French study on 20 people was not conducted with doctors and patients blind to the treatment, and that only a quarter of the placebo patients had their viral load measured. Even worse, six patients dropped out of the trial from the group receiving the drug, three of them ended up in intensive care and one died. These could be viewed as failures of the drug to work against the virus, according to Alfred Kim of the Washington University Lupus Clinic.

What is the role of antibiotic (azithromycin) in treating a viral infection like COVID-19?

The use of antibiotics in treatment of viral infections is not novel or unusual since it is used to treat co-infections such as bacterial pneumonia which are bacterial in nature.
The combination of hydroxychloroquine with a macrolide, such as azithromycin (or clarithromycin), has also been advocated, despite limited evidence for its effectiveness in treating COVID-19.

Emergency use Authorization by FDA

When COVID-19 cases began to skyrocket in NY, hospital guidance suggested using hydroxychloroquine, which was granted an Emergency Use Authorization for COVID-19 care by the FDA on Mar 29, as a therapeutic option in patients with moderate-to-severe illness. FDA cautions against use of hydroxychloroquine or chloroquine for COVID-19 outside of the hospital setting or a clinical trial due to risk of heart rhythm problems

Clinical Trials

While these drugs are primarily seen as a treatment option, there is also considerable interest in the prophylactic use of hydroxychloroquine.

In the WHO ICTRP-COVID-19 data base Chloroquine and/or hydroxychloroquine were mentioned in 218 studies. As of May 11, globally over 130,000 patients are planned for enrolment in studies assessing CQ/HCQ. WHO May 26th statement: “The Executive Group has implemented a temporary pause of the HCQ arm within the Solidarity Trial while the safety data is reviewed by the Data Safety Monitoring Board. The other arms of the trial are continuing,” Tedros added. In India ICMR recommended that it should be continued for prophylaxis as there no major side effects. Benefit may be there,” ICMR director general Balram Bhargava said.

On April 9th NIH began clinical trial of hydroxychloroquine and azithromycin to treat COVID-19 on 2,000 adults 60 years or older who have confirmed COVID-19 infection and be experiencing fever, cough and/or shortness of breath or have a comorbidity associated with developing serious complications from COVID-19, such as cardiovascular disease or diabetes.

The Lancet” (May 22, 2020) report did not support the benefit of HCQ/HQ in COVID-19

The Lancet” (May 22, 2020) published results of a multinational registry analysis of the use of hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19. The registry comprised data from 671 hospitals in six continents.

“We were unable to confirm a benefit of hydroxychloroquine or chloroquine, when used alone or with a macrolide, on in-hospital outcomes for COVID-19. Each of these drug regimens was associated with decreased in-hospital survival and an increased frequency of ventricular arrhythmias when used for treatment of COVID-19”.

About Vispi Kanga

Vispi Kanga was the principal scientist in global technology at Unilever and has more than 35 years experience in product development in dermatology and skin care formulations, working for multi-national companies in health and personal care industry. He has followed the evolution of the Health & Personal Care industry since the 70’s to it’s current stature as a $146 billion business in the United States.

His expertise has resulted in several patents in the development of new innovative products. He received his BS in Pharmacy from Ahmedabad India and did his postgraduation from Arnold & Marie Schwartz College of Pharmacy & Health Sciences (formerly known as Brooklyn College of Pharmacy).

Vispi has given numerous presentations in the area of skin care delivery systems and use of natural ingredients to the Personal Care Ingredients & Technology division of Health & Beauty America as well as other scientific organizations including Panacea, natural products expo India. He was the contributing editor of HAPPI magazine and also contributed articles and editorials in SpecialChem-The material selection platform. He was also an adjunct professor in the Graduate School of Natural Sciences at Fairleigh Dickinson University.

You can find all articles by Vispi Kanga on Parsi Khabar at this link: Vispi Speaks