Is Hydroxychloroquine really effective against COVID-19?

Hydroxychloroquine belongs to a class of drugs known as disease-modifying antirheumatic drugs (DMARDs) that are given to patients with rheumatoid arthritis and Systemic lupus erythematosus who could not be treated by any other medication. HCQ is primarily used to treat and prevent malaria.

It is a prescription drug, that means you can’t just buy it over the counter and recently the Government of India has put stricter regulations on the marketing of HCQ. Now a chemist has to keep track of who and when he/she sold this drug to.

The exact action of both HCQ and CQ is unknown. However, both these drugs are said to be immunomodulatory in nature rather than immunosuppressive. This means, these drugs do not suppress the action of your immune system but modify it in a certain way to prevent inflammation and to treat a disease.

They increase the pH inside cells and stop the antigen-presenting cells (APCs) from activating your immune system.

Whenever a harmful organism enters the body, various immune system cells are activated to fight against it. The APCs include cells like macrophages which engulf the harmful pathogen and then process it to present it over their surface for identification by T cells (a kind of white blood cells that kill virus-infected cells). When this stops, it also stops the whole process of cytokine release and inflammation. 

HCQ also suppresses inflammation by inhibiting the binding of toll-like receptors with the microbial markers. These receptors are proteins present on the surface of macrophages and other cells of the innate immune system (the immunity you are born with) and help identify harmful microbes as they enter the body.  

Cytokines and inflammation are among of the major causes of lung damage in COVID-19. So, this action of HCQ gives evidence that it may be effective against SARS-COV-2 too.

Read more: Inflammation and COVID-19

So far, there isn’t much evidence to show that HCQ or CQ is effective against COVID-19. A small non-randomised clinical study done in France showed that HCQ can significantly reduce the viral load (the amount of virus in the patient’s body) in COVID-19 patients and is especially effective when given along with the antibiotic azithromycin. 

A study done in China also indicated that 400g of HCQ can help improve the symptoms of COVID-19 in five days. However, the study concluded that more studies are needed to confirm the evidence.

However, another study done in France showed that the combination of HCQ and azithromycin has no such effects on severe COVID-19.

The National Institute of Health, USA, is set to enrol more than 500 COVID-19 patients to study the efficiency of HCQ. A number of hospitals in the USA are already using HCQ as the first line of treatment for COVID-19.

Read more: Guidelines on the use of hydroxychloroquine for COVID-19

On April 18, Dr Raman Gangakhedkar, the head of the Department of Epidemiology and Communicable Disease at the Indian Council of Medica Research (ICMR) revealed (in a press release) that they are going to do an observational study on the side effects of HCQ by enrolling around 480 people. The study would take more than 8 weeks or 2.5 months. 

He further said that after an earlier announcement about HCQ study, some healthcare workers had already started taking the drug as prophylaxis for COVID-19.

So, ICMR also studied this group of healthcare practitioners to see the effects or side effects of HCQ in them. As per the findings so far, most people in the group had an average age of 35 years. Out of the group, about 6% experienced vomiting, 10% have experienced abdominal pain and about 1.3% noticed hypoglycemia (low blood sugar). About 22% of the healthcare practitioners in the group had some chronic disease, including respiratory illnesses, diabetes, heart disease or high blood pressure. However, around 14% had not even taken ECGs which, as per Dr Gangakhedkar, should have been done before starting the drug as HCQ could increase the risk of conditions like arrhythmia in such patients, especially because the initial dose is very high. 

The All India Institute of Medical Sciences (AIIMS) is also conducting studies to understand the therapeutic and prophylactic impact of HCQ. The results of the study with around 2,000 healthcare workers is expected in July.

On May 22, three scientists from the US and Switzerland published the findings of a multinational registry analysis in The Lancet, a highly regarded peer-reviewed journal. They collated data on COVID-19 patients who were getting HCQ from 671 hospitals across six continents. The data, on 96,032 patients admitted to hospital between December 20, 2019, and April 19, 2020, showed no benefits of HCQ. Instead, there was a higher mortality and more instances of arrhythmia noted in patients who got HCQ—as a standalone or along with another drug.

Hydroxychloroquine can be given to both adults and children and to pregnant women and nursing women, but according to the FDA, it has some safety concerns in both pregnant women and children, and studies show that the medicine is present in the milk of nursing mothers who take it and hence may negatively affect infants. However, according to a study published in the Lancet, it is chloroquine that has harmful effects on fetal development, while HCQ is recommended for women with autoimmune diseases since it prevents congenital heart defects in their babies. Some other risks and safety concerns of hydroxychloroquine include:

• Vomiting, diarrhoea, dizziness, headache, stomach pain and skin rashes are the most common side effects of both hydroxychloroquine and chloroquine.
• This drug may worsen the symptoms of psoriasis and porphyria.
• Those who use this drug for the long term may get eye damage.
• The drug has been associated with fatal cardiomyopathy—a condition of heart muscles in which the heart is not able to pump blood properly.
• Since the drug is excreted through kidneys, those with impaired kidney function may need to be monitored properly for possible side effects.

Studies show that HCQ can be tolerated well up to a dosage of 1200 mg (equal to a 750 mg dose of chloroquine), while chloroquine can only be given up to 500 mg. 

So, there is a possibility that HCQ may be a better candidate for antiviral activity.

As per the ICMR (Indian Council of Medical Research) guidelines, healthcare workers and anybody coming in regular contact with COVID-19 patients should take at least 400 mg of hydroxychloroquine twice a day on the first day and after that, healthcare workers should take the same tablet at least once a week with meals for the next seven weeks while asymptomatic people at home of confirmed COVID-19 patients should take the 400 mg tablet for about three weeks (once a week) with meals. However, the tablet should only be taken on the prescription of a healthcare practitioner.