Can hydroxychloroquine treat COVID-19?

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Hydroxychloroquine, or hydroxychloroquine sulfate, is an antimalarial medication and a disease-modifying antirheumatic drug (DMARD).

DMARDs are drugs that slow the progression of certain autoimmune diseases, such as:

• rheumatoid arthritis
• juvenile idiopathic arthritis
• lupus

It is not clear why hydroxychloroquine effectively treats autoimmune conditions.

Experts believe that the drug alters cell communication in the immune system. This action inhibits the immune system response that ordinarily triggers inflammation and cell damage.

Again, this may explain why some doctors have tried using hydroxychloroquine to treat severe cases of COVID-19. The theory is that the drug helps stop the immune system from going into overdrive and attacking the body’s organs.

However, it is not clear whether hydroxychloroquine has any effect against COVID-19.

Some doctors and researchers have been using hydroxychloroquine to treat severe cases of COVID-19.

We outline some of the key findings from these trials below.

Studies reporting positive outcomes

Researchers published an initial study in March 2020. It indicated that a combination of hydroxychloroquine and the antibiotic azithromycin might reduce the viral load of SARS-CoV-2, the virus that causes COVID-19.

The viral load is the amount of virus in the body. Doctors usually associate higher viral loads with more severe symptoms.

However, the above study only had a small number of participants, and experts have criticized other aspects of its design.

A Henry Ford Health System study suggests that taking hydroxychloroquine can lower the risk of death from COVID-19.

Among a cohort of more than 2,500 patients hospitalized with the illness, 13% of those who received hydroxychloroquine died, compared with 26% of those who did not receive the drug, the study authors report.

However, the team did not control for some significant confounding variables, such as patient age; 64% of patients who did not receive hydroxychloroquine were over 65, while only 49% of those who received the drug were older than 65.

Other variables, such as the ethnicity, were also notably different among the patient groups.

Studies reporting negative outcomes

A further small study evaluated the effects of hydroxychloroquine and azithromycin on patients hospitalized with COVID-19. The majority of these individuals had co-occurring or “comorbid” conditions, such as obesity, cancer, or HIV.

There was no evidence to suggest that the drug treatment worked for the participants. Notably, one patient had to stop treatment because of a hydroxychloroquine side effect that can lead to fatal heart problems.

Another study investigated the hospital records of 368 patients admitted with COVID-19.

The findings indicate that those taking hydroxychloroquine as a stand-alone drug treatment were at higher risk of death than those who did not take hydroxychloroquine.

This was also the case when the researchers compared them with those who took a combination of hydroxychloroquine and azithromycin.

Importantly, this study has not yet undergone peer review by other scientists.

Studies reporting no benefit

In early June 2020, researchers in the United Kingdom published results from the largest trial to date on hydroxychloroquine.

Of the 4,674 hospitalized patients who took part in the trial, 1,542 received hydroxychloroquine, while 3,132 received standard treatment.

The percentage of people who died after 4 weeks was 25.7% for those receiving the drug and 23.5% for those receiving standard treatment.

These data suggest that there is no meaningful benefit to taking hydroxychloroquine for those with active COVID-19 disease.

Nor does hydroxychloroquine appear to protect healthy people from disease onset after exposure to the virus.

A randomized, double-blind, placebo-controlled trial of 821 participants suggests that the medication does not protect those at high risk of COVID-19 infection.

The NIH were running a clinical trial to evaluate the safety and effectiveness of using hydroxychloroquine to treat adults hospitalized with COVID-19. However, the NIH halted the trial after the initial data suggested that the drug was no more effective than a placebo.

What is the consensus?

Overall, the findings from the above studies suggest that there is limited evidence for the use of hydroxychloroquine for the prevention or treatment of COVID-19.

A meta-analysis of 23 studies investigating the use of hydroxychloroquine for COVID-19 supports this view.

The meta-analysis concludes that the evidence on the benefits and harms of the drug is both weak and conflicting.

Two potential safety concerns about the use of hydroxychloroquine are heart health issues and interactions with other drugs.

Heart health issues

In some studies, people taking hydroxychloroquine have experienced a side effect known as QT prolongation. This is where the heart takes longer than usual to recharge between beats.

QT prolongation may increase the possibility of irregular heartbeat, known as arrhythmia. Certain types of arrhythmia can increase the risk of stroke and sudden cardiac death.

A preprint paper investigated the incidence of QT prolongation among people taking a combination of hydroxychloroquine and azithromycin for COVID-19. Preprints are studies that have not yet undergone peer review.

The study reports that 30% of the 84 participants experienced notable QT prolongation, and an additional 11% were at risk of arrhythmia.

In April 2020, the FDA cautioned against the use of hydroxychloroquine outside of hospitals or clinical trials due to the risk of heart rhythm problems.

Interactions with other drugs

Another recent preprint indicates that hydroxychloroquine can interact with the diabetes medication metformin in mice.

In this animal study, the interaction between the drugs led to a 30–40% mortality rate. However, it is uncertain if this finding also applies to humans.

The NIH have halted a trial examining the safety and efficacy of hydroxychloroquine, and the FDA have withdrawn the drug’s emergency use status.

The World Health Organization (WHO) are currently running an international clinical trial comparing hydroxychloroquine and three other treatments against standard care.

The aim is to provide a strong evidence base of the efficacy — or lack thereof — of each treatment. The WHO have now removed hydroxychloroquine from this trial due to a lack of efficacy.

Remdesivir (Veklury) is a new broad-spectrum antiviral. It was approved by the Food and Drug Administration (FDA) to treat COVID-19 in October 2020.

Veklury was the first drug to have FDA approval to treat COVID-19. It is approved to treat diagnosed or suspected COVID-19 in certain hospitalized people. The drug was previously granted an Emergency Use Authorization (EUA) by the FDA.

Medications and home remedies that help alleviate flu symptoms may also help with mild symptoms of COVID-19.

Another potential treatment is convalescent plasma. Convalescent plasma is blood plasma from people who have recovered from COVID-19 and whose blood contains antibodies to help fight the virus.

A team of researchers from Oxford University in the U.K. has examined the use of a steroid called dexamethasone in the treatment of COVID-19.

In this clinical trial, the researchers found that the drug helped improve survival among patients who required respiratory support within a hospital setting.

Large-scale drug trials are currently underway to identify medications that may help prevent or treat COVID-19. So far, studies investigating the use of hydroxychloroquine as a treatment for COVID-19 have produced weak, limited, or conflicting evidence of its efficacy. Some have also raised concerns about the safety of the drug.

Many trials involving hydroxychloroquine have stopped in recent weeks. This has been due to data suggesting that the drug is no better than standard treatments for COVID-19.

Most people who get COVID-19 will experience mild-to-moderate symptoms. Many will recover with home care and standard treatments for other viral infections. These treatments include rest, hydration, and over-the-counter pain relief.