Hydroxychloroquine (Plaquenil) and Chloroquine are malaria tablets that have been used for 70 years to treat and prevent malaria. They are also routinely used to treat autoimmune diseases such as rheumatoid arthritis and systemic and discoid lupus erythematosus.
There has been a worldwide surge in demand for these drugs over the past few months. This is a result of mass media attention amidst claims that they can help in the fight against Coronavirus from high profile personalities such as Donald Trump and the Brazilian president Jair Bolsonaro. But can chloroquine and hydroxychloroquine prevent or treat Coronavirus?
What is Hydroxychloroquine and Chloroquine?
Hydroxychloroquine and Chloroquine are two closely related prescription only drugs used to treat autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus. These conditions are caused by an overactive immune system. Hydroxychloroquine and chloroquine work by regulating the activity of the immune system to alleviate pain and swelling and can prevent damage to the joints. The two drugs can also be used in the treatment and prevention of malaria.
How does Hydroxychloroquine and Chloroquine work?
Chloroquine works to prevent and treat malaria by interfering with the replication of the malaria parasite. In recent times, studies have shown that chloroquine has lost effectiveness in treating and preventing malaria. This is because the most common strain of malaria has developed resistance to chloroquine, therefore other anti-malaria tablets are preferred.
Hydroxychloroquine and chloroquine work to control autoimmune diseases by regulating the immune system that is usually overactive in these patients. It can do this without causing risk of infection to the patient, as it does not lower the immune system to a level that is dangerous. The full mechanism of action is not completely understood.
What the science says
There have been numerous reports of studies that have shown chloroquine and hydroxychloroquine to be effective in treating Coronavirus.
In February 2020, a Chinese study reported that chloroquine displayed positive results when tested against COVID-19. This study was conducted in vitro, which means that it was only tested in a laboratory setting and not in a randomised trial with humans. Previous in vitro studies that have shown hydroxychloroquine to be effective against other viruses in a lab setting, have not been proven to be effective when tested on humans in a randomised controlled trial.
A French study published in March 2020 showed promising results and created a media hype. The study was conducted on COVID-19 patients and showed that hydroxychloroquine taken together with azithromycin significantly reduced the viral load. However, reports suggest that the results were not entirely accurate as patients who had died during the trial were not included in the viral shedding analysis. The professional organisation attached to The International Journal of Antimicrobial Agents where this study was published, has claimed that the article does not meet the expected standards.
Another small Chinese study conducted in April 2020 has also shown promising results in patients with mild COVID-19 symptoms. This research was conducted in 62 patients and was randomised unlike the French study. It also compared the treatment and control groups, claiming that patients who were given hydroxychloroquine recovered quicker from cough and fever. The limitation of the study is that it was conducted on a small number of people and it did not include any patients with severe or life-threatening symptoms. The study has not been endorsed by other professionals working in the same field. This is known as a peer-review and is important in verifying and authenticating studies.
In April 2020, a document produced by French scientists concluded that there was no evidence to indicate that hydroxychloroquine was effective in treating Coronavirus. A group of 84 patients receiving hydroxychloroquine were compared with a group of 97 patients who did not. No clear observations were made. However, the limitations to this analysis were that it was not a proper clinical trial and there was no information why certain patients were administered hydroxychloroquine and others not. The paper has not yet been peer-reviewed.
A study was carried out in Brazil with the aim of comparing a high dose of chloroquine against a low dose. The high dose was chosen based upon recommendations from Chinese authorities. This study was drawn to a halt as researchers found increased rates of arrhythmias and a high number of deaths in those taking the higher dose. However, scientists were unable to confirm that the higher dose of chloroquine was the reason for the cardiac side-effects. The efficacy for the lower dose is still being investigated. There was also no control group (a group of patients that receive a placebo).
An observation by US researchers compared the outcomes for 368 COVID-19 patients. One group of patients received hydroxychloroquine, another group received hydroxychloroquine with azithromycin and the third group received neither. The researchers concluded that hydroxychloroquine did not reduce the need for a ventilator, nor did it lower the risk of death. In fact, they found that those taking hydroxychloroquine alone had an increased risk of death. However, this was an analysis and not a randomised controlled trial. It is also important to note that those administered with hydroxychloroquine were in a worse state than the others observed. This study included males only.
Which countries have authorised the use of hydroxychloroquine for COVID-19?
In late March 2020, the US Food and Drugs Administration authorised the ‘emergency use’ of hydroxychloroquine for a limited number of COVID-19 cases. They have not made any categorical claims that it will work but have granted authorisation for hospitals to request the use from government stockpiles. One month later, the FDA issued a warning against the use of hydroxychloroquine and chloroquine outside a clinical trial or hospital setting due to the risk of heart rhythm problems.
France have given approval for doctors to prescribe hydroxychloroquine, however, they have also issued a warning against the side effects.
India recommend that their healthcare workers should use hydroxychloroquine as a preventative treatment and have also authorised doctors to prescribe it to those in close contact with confirmed cases of COVID-19. However, the country’s research body claim that this is ‘experimental’ and should only be used in emergency situations.
The risks of taking Hydroxychloroquine and Chloroquine
Both hydroxychloroquine and chloroquine can cause problems by interfering with the rhythm of the heart. This can be made worse when combined with antibiotics such as azithromycin, which have a similar effect on the heart and can be life threatening. Both drugs are proven to be effective in treating malaria and autoimmune diseases at safe doses, but there has not been any conclusive evidence to prove the safety of hydroxychloroquine or chloroquine in the treatment of Coronavirus. If taken incorrectly, they can cause damage to the liver and kidneys, as well as nerve cells which can cause seizures.
There are many people who rely on hydroxychloroquine to treat autoimmune diseases and research has shown that withdrawal and interruption of treatment can cause a flare up of disease and may be life-threatening. Shortages in the market caused by stock piling and media hype has made it difficult for patients to obtain hydroxychloroquine. Arrangements are in place to allow for an adequate supply for ongoing clinical trials; however, members of the public should refrain from trying to unethically obtain hydroxychloroquine.
So, can Chloroquine and Hydroxychloroquine prevent or treat Coronavirus?
Some studies suggest that chloroquine and hydroxychloroquine have shown promising results, whilst others have not. Currently, there is insufficient evidence to prove that they are effective in preventing or treating COVID-19 and the World Health Organisation has not approved their use. Higher quality and larger randomised controlled trials are required in order to better assess the efficacy of chloroquine and hydroxychloroquine in treating Coronavirus. Those suffering from COVID-19 are likely to be in a vulnerable state and unregulated use of hydroxychloroquine or chloroquine may pose an increased risk to health. These drugs should only be administered under the observation of a qualified healthcare professional.
This article contains advice based on research conducted during the time that this article was written. Advice may have changed, and research may have progressed since this article was published and you should consult a doctor if you are in doubt.