What do we know about Hydroxychloroquine? | Euronews answers

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Virus Outbreak India Malaria Drug Copyright Rafiq Maqbool/Copyright 2020 The Associated Press. All rights reserved.
Copyright Rafiq Maqbool/Copyright 2020 The Associated Press. All rights reserved.
By Seana Davis
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The US president has yet again touted the drug. But what does the science say about Hydroxychloroquine?


Hydroxychloroquine has been touted numerous times by the President of the United States as a potential 'cure' for the coronavirus. On Monday, Trump went further by claiming that he had been taking the drug as a preventative measure against SARS-CoV-2.

It's a drug that has caused significant debate beyond the scientific sphere and on the political stage, with French President Emmanuel Macron calling for clinical trials in mid-April. Behind the headlines and within the pharmaceutical realm, the consensus is anything but clear.

What is Hydroxychloroquine?

Hydroxychloroquine has been used for decades as an antimalarial drug and as a treatment for other so-called protozoal infections. Since then, its use has been broadened to treat rheumatic diseases such as lupus. The drug acts as an "immunomodulatory agent," Dr Petr Horák, President of the European Association of Hospital Pharmacists (EAHP), told Euronews. Such drugs can modify an immune response and can act, in some cases, as an antiviral or anti-inflammatory drug for rare diseases.

Why is Hydroxychloroquine being trialled to fight COVID-19?

The drug was used, experimentally, to treat SARS in 2003, and with SARS-CoV-2, being another coronavirus, clinicians have been trialing Hydroxychloroquine yet again. "There is some merit in the concept, in the science behind Hydroxychloroquine," Dr Hamid A Merchant, Subject Leader in Pharmacy at the University of Huddersfield told Euronews. Much of the basis lies on the anti-inflammatory effect Hydroxychloroquine can have and whether it could be used to treat serious cases of pneumonia on the cellular level, or at least dull the inflammation caused in the lungs by SARS-CoV-2.

What side effects can the drug cause?

Hydroxychloroquine is medically prescribed and can have serious side effects, especially for those with cardiovascular diseases, pacemakers, or diabetes. It can cause a prolongation of the QT interval of the cardiac rhythm. "This is something we see on the electrocardiogram," Dr Horák explained. "It is one of the most important ones and it can be made more important when people take certain classes of drugs like some antibiotics or antidepressants and altogether, it can be very severe, even life-threatening".

"But there are more side effects," Dr Horák cautioned, adding that it can cause damage to the skin and eyes such as retinopathy. Administering such drugs at a time such as a pandemic throws forward ethical considerations, whether it could cause more harm than good, with the need for a medical assessment prior to administering the drug.

"This is what people need to understand," Dr Syed Shahzad Hasan, Senior Research Fellow at the Department of Pharmacy at the University of Huddersfield told Euronews. "Hydroxychloroquine is not paracetamol - it is a prescription-only drug. Therefore, a consultation with a healthcare professional is required". Beyond a consultation, monitoring is also needed in some cases, Dr Hasan added. "It should be done in a setting where somebody can look after the patient and see their history".

"I would tell European citizens not to take Hydroxychloroquine unless it is medically prescribed by a doctor," Dr Horák urged.

What do the results from the clinical trials show?

Dr Merchant and his colleague Dr Hasan wrote a paper along with Dr Chia Siang Kow on the quality of the clinical trials which are administering Hydroxychloroquine. To date, they noted that there has been some evidence to suggest that the drug could be of use in serious cases of the virus.

However, there has been no evidence that it should be used as a preventative measure against the virus and the drug has the potential of causing serious harm. Results from early trials have also been polarised into two distinct groups.

"Now, if you look at the literature, you can see two groups. One group is supporting the use of Hydroxychloroquine and the other group is opposing the use of Hydroxychloroquine. If you look at the results of the trials, you will see some very good results supporting the use of Hydroxychloroquine and this is coming out from a particular group," Dr Hasan said.

Has the wave of preprint studies caused misinterpretations?

Science has moved at breakneck speed, with a wave of preprints published. The aim of this is to disseminate information amongst the scientific community in the hope that the vast sharing of data could lead to a breakthrough. However, there are caveats to loosening some scientific norms, such as a dip in quality control.

Both Dr Merchant and Dr Hasan have analysed the quality of reporting within these trials and found that many are not reporting to the standard guideline, with bias creeping into results. "I can't believe any good journal would accept a clinical trial that would publish a study without that quality criteria met. But with this condition, this pandemic, everything is so important that these quality benchmarks are not being met," Dr Merchant said.

Researchers can provide a percentage mark representing the quality of a clinical trial. If the mark reaches 100%, the trial doesn't have any loopholes. However, Dr Merchant and Dr Hasan have found that the majority of trials had a score of below 50% with some dipping as low as 10%.

What have the stumbling blocks been with regard to clinical trials?

In an ideal scenario, a clinical trial would involve a randomised control group in an effort to limit bias in the study. One group would be administered the drug whilst another could be given a placebo. This, however, can be difficult to do - with lives on the line. "There are some compromises that are done to the trials and we can understand why. The utmost responsibility of clinicians is not to have top quality science data now, their priority is to save lives," Dr Hasan said.

The studies can, however, outline the disease status at the start of the trail, whether the patients have underlying health issues such as asthma or diabetes, or whether patients have mild or moderate strains of the virus. Should a trial fail to stratify data, and subgroup the severity of the disease, the recovery rate is difficult to assess. If both mild and severe patients take Hydroxychloroquine as part of a trial, researchers may not be able to assess how strong of an effect the drug itself has had on the patient. Instead, it may reflect the strength of the virus on an individual.

Most studies, outside of the pandemic, have a clearly defined peer-reviewed system where the research is assessed and often bounced back to the researcher should the piece have pitfalls. This, however, may take months. If such studies are printed without peer review and make strong conclusions, some warn this may lead to misinterpretation at a time when strong science is needed most. Without adjusting for confounders, a study can't conclude, strongly, that the drug had a clear effect.

Is it justified to test Hydroxychloroquine?

"What we have seen is either there are people who are supporting Hydroxychloroquine or there are people against it. The balanced approach is missing out," Dr Hasan said. "In our paper, we didn't want to take any sides".


The issue is that the science is just coming to the fore. Fully-fledged studies with strong results have yet to catch up with the debate. "We don't want to discredit any beneficial effect of this drug. We don't want to take this away from humanity in this particular time of emergency when people most need it," Dr Hasan noted.

What would happen if, years down the line with high-quality control trials, the drug came back as effective? Toeing this line, the FDA and other groups have authorised the emergency use of the drug when medically prescribed in certain settings.

"I think we should be very careful about what we are doing," Dr Hasan said. "There is no hiding place. If anything bad happens, who is answerable for all of those decisions? It's very easy to come up on television and say 'I used it and nothing happened', but how could you guarantee that not everybody would benefit or not everybody could be harmed with the approach you have taken?"

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