Sydney Morning Herald, March 3, 2022. A grateful nation rewards Clive Palmer with the Prime Ministership for using his personal fortune to save Australia from a Covid catastrophe. President Trump tweets his congratulations noting that the two men are “kindred spirits”.
Three page advertisements in newspapers across the country in recent days are informing Australians that Mr. Clive Palmer, with, he insists, the blessing of health minister Hunt, has used his personal fortune to buy 32,900,000 doses of Hydroxychloroquine (HC) to provide one million of us with a course of the drug to prevent or treat COVID-19 infections. Given that the USA has a stockpile of just 29 million doses of the drug for 363 million people and is having trouble sourcing more, how Palmer sourced such a huge quantity of Hydroxychloroquine is an important question.While Hunt has approved the use of the drug by doctors if they think it might help patients I can’t find any public statement of thanks to Palmer from the minister but he has thanked billionaire Andrew Forrest for buying ten million COVID-19 tests for the virus from China. All very peculiar!
To quickly ‘cut to the chase’ the unjustified enthusiasm for the use of this drug represents a distressing reality. At a time when a very serious problem should be addressed by disciplined, evidence based science, ill-informed ‘hearsay’ can actually compromise the search for all important data needed to manage that problem. We saw that during the early years of the HIV epidemic when patients were lured to Mexico to have their blood heated, the Philippines to be treated by a ‘faith-healer’ or to Melbourne where massive doses of Vitamin C were being hailed as curative.
Before a little more dissection of the controversy surrounding the use of anti-malarial drugs to treat COVID-19 infections here is a summary of the situation dated May 2, 2020 in the New England Journal of Medicine, one of the most respected of medical journals:
“Although new treatment approaches to the management of COVID-19 are needed desperately, we are troubled that most of the available information in relation to the use of Chloroquine/Hydroxychloroquine for COVID-19 comes from studies that were either poorly designed or available in only non–peer-reviewed preprints. Placebo-controlled studies evaluating the role of CQ/HCQ as post-exposure prophylaxis, in outpatient clinics (mild disease), and in hospitalized patients have now been started. Given the currently available limited efficacy of the data and the concerns regarding toxicity, we believe that CQ/HCQ should not be used for COVID-19 until controlled clinical trials demonstrate that benefits outweigh potential harms.”
HC can kill corona viruses in laboratory testing, it interferes with the little hook the virus must use to bind to human cells. In February scientists demonstrated that this was true with COVID-19. The finding was important but, as most must know by know, was seized upon by Dr Trump to tell the world that a “game changer” had been found. Just two very small studies in humans were available at the time to assess efficacy, one from China and one from France. Both claimed positive responses to the drug. Both had serious methodological problems and were reasonably criticised by experienced investigators. Two large studies, one from Brazil and one from the Veterans Administration Hospitals in the USA reported no benefit and raised concerns about side effects. Both of these studies also had some features that made any definitive conclusions difficult.
Serious side effects, though uncommon, include potentially fatal problems with the rhythm of the hearts beating, damage to one’s eyes, muscle weakness, dizziness and liver problems. Deaths occurring from the use of the drug have been noted in COVID trials.
Ideally we would like in any epidemic of an infectious disease to have a drug(s) that would prevent infection, stop mild disease from deteriorating into severe life threatening disease and those life threatening complications that might require treatment in an Intensive Care Unit. Given the potential side effects of HC it is not ethical to use the drug in the hope that it will prevent infection in the current state of our knowledge. Yet we had so many doctors in Australia providing prescriptions to family and friends for the prophylactic use of HC that the Medical Board of Australia was forced to order doctors to stop such prescribing.
What is ethical and important are properly conducted trials of HC in patients with mild disease and serious disease. Internationally more than 100 such trials are in various stages of implementation including some here. Such is the effect of the injudicious publicity given to unfounded expectations of benefit from HC that investigators are finding it difficult to get patients to enter a placebo controlled trial. Many investigators wishing to try other drugs that might be beneficial are struggling to recruit subjects who are willing to not try HC. ‘Cocktails’ containing HC and other agents are popular and even less scientific. One GP in the USA has launched a series of Videos claiming a 99% cure rate for a combination of HC, an antibiotic called Azithromycin and Zinc supplements. No control group of course and since most people recover spontaneously and completely from a COVID-19 infection in about two weeks, such reports have little scientific merit but have huge impact on public enthusiasm for the therapy.
While it is strange, to say the least, to have private citizens actually buying (as opposed to donating) complex medical testing kits that require expert validation, we do need more testing capacity. We are doing well in minimising the spread of COVID-19 in Australia as a result of social distancing. Now to lessen restrictions safely we need far more testing to find our ‘silent spreaders’ and the Contact Tracing units of excellence that will limit cross infection from such individuals. We don’t need millions of doses of HC. HC tablets cost about 30 cents each so the ten million dollars Palmer has spent could be so much better used.
In summary there is no definitive evidence that HC can treat COVID infections and there is no definitive evidence that it cannot. It is not a benign drug so any generalised use should await results from quality scientific evaluations.
To end on a positive note there is reason to think that the drug Remdesivir, originally created to tackle the Ebola virus, may have real potential for minimising the severity of COVID-19 infections. More than 1000 patients in 68 US hospitals had 4 days less in ICU than did patients not on the drug. Given that the need for extended treatment in an ICU and the need for a ventilator is associated with an 80% mortality rate, this is impressive. Remdesivir must be given by an intravenous infusion and is hard to make but it’s the first drug about which legitimate if cautious scientific enthusiasm is warranted.
Professor John Dwyer. Immunologist and Emeritus Professor of Medicine UNSW