The Hydroxychloroquine Conundrum

The world has been gripped in the throes of a terrible pandemic for months now, and one thing that has made the pandemic even more terrible is the unavailability of definite cure for it. Just when scientists, researchers, and other health experts think they may have found a possible cure, results from other studies come up to debunk their claims. Perhaps, one of the most controversial drugs that has attracted attention worldwide is chloroquine and its close derivative, hydroxychloroquine. While some studies have lauded the effectiveness of hydroxychloroquine in treating COVID-19, some others seem to be hell-bent on rejecting the efficacy of the drug. Where does truth begin and where does fantasy end for hydroxychloroquine.

The first case of the Coronavirus disease 2019 (COVID-19) caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Cov-2) was identified in Wuhan, China, in December 2019. 118,000 cases in 114 countries later, the World Health Organisation (WHO) declared the disease a pandemic on March 11, 2020. At about the same time a heated search for a cure was on, and a number of drugs were being recommended for managing identified COVID-19 cases. The recommended drugs include Remdesivir, Lopinavir/ritonavir, and Hydroxychloroquine.

Having identified these drugs, the next step for most researchers and the WHO was to determine if any, of the drugs would work to cure people of or prevent people from contracting COVID-19. WHO launched the ‘Solidarity Trial’ on March 18, 2020, an international clinical trial taking place in more than 60 countries. The information on WHO’s website noted,  ‘The Solidarity Trial compares options against standard of care, to assess their relative effectiveness against COVID-19. By enrolling patients in multiple countries, the Solidarity Trial aims to rapidly discover whether any of the drugs slow disease progression or improve survival.’  

A similar trial touted as the  ‘largest randomised controlled trial of potential COVID-19 treatments in the world’  was rolled out in the United Kingdom on the 3rd of April 2020. The trial code-named RECOVERY, short for Randomised Evaluation of Covid-19  therapy , consisted of about 11,000 patients from 175 NHS hospitals in the UK. These two trials notwithstanding, there were other independent trials being conducted in different hospitals/clinics/laboratories across the world.

We’ll come back to the WHO, RECOVERY, and other trials later. First, a quick detour that will explain how hydroxychloroquine came to be included in the discussion for a COVID-19 cure.

Chloroquine and its less toxic metabolite, hydroxychloroquine, have been historically used in the treatment of malaria, rheumatoid arthritis, and lupus erythematosus among other diseases. In 2005, a study by Vincent et al. found Chloroquine to be effective in the treatment of SARS-CoV, also a coronavirus (SARS was discovered in Guangdong, China, in 2002). So when COVID-19 was discovered, it was easy for researchers to consider the possibility of hydroxychloroquine being effective against the virus. This assumption was further strengthened by American President Donald Trump’s statement in March, backing the use of hydroxychloroquine for COVID-19 treatment. Trump’s action was based on a study carried out by French researcher, Professor Didier Raoult, who claimed a 100% recovery rate for patients treated with a combination of hydroxychloroquine and azithromycin. This contributed to the US’s Food and Drug Administration’s decision to issue an Emergency Use Authorisation (EUA) for hydroxychloroquine and chloroquine in the management of COVID-19 in March.

The above set the stage for an all-out barrage of discoveries and retractions, accusations and counter-accusations, studies and counter-studies that have divided key players into two teams: Pro-hydroxychloroquine and anti-hydroxychloroquine, with little room for being on the fence.

One of the first study results about the use of hydroxychloroquine in treating COVID-19 was the one by Wei Tang et al., who concluded that hydroxychloroquine was ineffective and even harmful in the management of COVID-19.

Perhaps one of the most popular results was the one published on May 22nd by the British Medical Journal, The Lancet, which claimed hydroxychloroquine was ineffective against COVID-19 and caused a higher mortality rate among administered patients. According to the researchers,  ‘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.’  The study was later retracted after severe backlash from peer reviewers, but this was after it influenced the WHO to temporarily suspend the hydroxychloroquine arm of its ‘Solidarity Trial’ on May 25th. The trial resumed on the 3rd of June.

Two days after the WHO resumed the hydroxychloroquine arm of its ‘Solidarity Trial’, the UK’s RECOVERY Trial team published the results of their findings on hydroxychloroquine. Alas, it was another death knell for the drug and its possible efficacy against COVID-19. According to Martin Landray, Professor of Medicine and Epidemiology at the Nuffield Department of Population Health, University of Oxford, and Deputy Chief Investigator, “There has been huge speculation and uncertainty about the role of hydroxychloroquine as a treatment for COVID-19, but an absence of reliable information from large randomised trials. Today’s preliminary results from the RECOVERY trial are quite clear – hydroxychloroquine does not reduce the risk of death among hospitalised patients with this new disease. This result should change medical practice worldwide and demonstrates the importance of large, randomised trials to inform decisions about both the efficacy and the safety of treatments.”

Not long after the RECOVERY result was published, the WHO discontinued the hydroxychloroquine arm of its ‘Solidarity Trial’. The WHO based their decision to discontinue the study on the recommendations from the International Steering Committee formulated of the Solidarity Trial. According to them,  ‘These interim trial results show that hydroxychloroquine and lopinavir/ritonavir produce little or no reduction in the mortality of hospitalised COVID-19 patients when compared to standard of care. Solidarity trial investigators will interrupt the trials with immediate effect.’

The results above and from other studies not quoted here led to a massive boycott of hydroxychloroquine in some countries and quarters. The American Food and Drug Administration in June revoked the Emergency Use Authorisation for hydroxychloroquine they had previously issued. France was not left behind, as they also ordered a stoppage in the use of hydroxychloroquine to treat COVID-19.

The evidence-based verdicts above notwithstanding, there is still massive support for the use of hydroxychloroquine from the pro-hydroxychloroquine team and also evidence-based fact for the purported effectiveness of the drug in treating COVID-19.

A very vocal member of team hydroxychloroquine is none other than President Donald Trump. President Trump’s initial support for the drug was established earlier in this piece, and his stand has made him the subject of several criticisms and backlash from the media. In May, Trump informed the American Press that he was taking hydroxychloroquine, perhaps to put his money where his mouth is. There have been insinuations that Trump’s support for the drug is not all altruistic, and that he probably stands to be financially compensated if the drug is accepted.

Another popular pro-hydroxychloroquiner is Brazilian President Jair Bolsonaro. Bolsonaro has for months eulogised the efficacy of hydroxychloroquine and also used the drug when he contracted COVID-19 in July.  Bolsonaro has faced his own share of criticisms and accusations over his unpopular stand, but like his American counterpart he remains unwavering in his belief.

Asides anecdotal support for the use of hydroxychloroquine in treating COVID-19, there is research and other practical evidence to back this claim.

An analysis published in July by the Henry Ford Health System, an American non-profit organisation, showed that hydroxychloroquine helped reduce the death rate in hospitalised COVID-19 patients. Dr Steven Kalkanis, CEO, Henry Ford Medical Group and Senior Vice President and Chief Academic Officer of Henry Ford Health System said, “Our analysis shows that using hydroxychloroquine helped save lives. As doctors and scientists, we look to the data for insight. And the data here is clear that there was benefit to using the drug as a treatment for sick, hospitalized patients.”

Another research showing the usefulness of hydroxychloroquine as a cure for COVID-19 is the one by French Professor Didier Raoult et al. cited earlier in this piece. It must be mentioned that Raoult has faced stiff backlash over his findings, with people questioning its accuracy or otherwise.

Some other countries like Cuba, India, Senegal, have claimed hydroxychloroquine works as cure and preventative measures against COVID-19.

But is hydroxychloroquine truly ineffective or is there is more to the stiff opposition? Hydroxychloroquine is a relatively cheap drug, and accessing it is quite easy.  Could it be that in a race for who will earn more if an expensive drug is touted as being effective in the treatment for COVID-19, researchers, doctors and other stakeholders are playing poker with the truth? This may have remained largely in the realm of conjecture, but a recent video by Cameroonian-American doctor, Dr Stella Immanuel, seems to lend credence to this assertion.

In the video which has since been taken down, Dr Immauel claimed to have cured over 350 COVID-19 patients using a combination of hydroxychloroquine, zithromax and zinc. Dr Immanuel went further to cast aspersions on the researchers who say hydroxychloroquine is not effective in treating COVID-19. Many individuals and bodies have of course come out to debunk Dr Immanuel’s claims, but it is still not clear who exactly to believe at this point?

The giant of Africa is still running clinical trials on hydroxychloroquine. Preliminary trials in Lagos State have found a promising drug that will serve as a preventive measure.  The Nigerian Centre for Disease Control has cautioned against the use of hydroxychloroquine in the management of COVID-19, pending definitive results from these studies,. Mr Doyin Okupe, a former presidential aide, shared his experience with hydroxychloroquine in May. Mr Okupe contracted COVID-19 in April and said he used a combination of hydroxychloroquine, azithromycin and vitamin C.

While scientists, researchers, and other health professionals worldwide continue in their quest to find a cure for COVID-19, it is recommended that they all give room for every country to try out what works best for them.

Oriyomi Adebare

Writer and editor

Categories: Health

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