Hydroxychloroquine received considerable public attention during the COVID-19 pandemic as researchers and medical professionals explored various avenues for treating the novel coronavirus. Its sudden prominence stemmed from early hypotheses about its potential to combat the virus, leading to its rapid investigation in numerous studies globally.
Understanding Hydroxychloroquine
Hydroxychloroquine is classified as an antimalarial and immunomodulatory drug. It is a derivative of chloroquine, developed to have a more tolerable safety profile. The U.S. Food and Drug Administration (FDA) approved its use in 1955.
Historically, hydroxychloroquine has been used to treat and prevent malaria. Beyond malaria, it is widely prescribed for autoimmune diseases such as lupus and rheumatoid arthritis. In these conditions, it works by decreasing the activity of the immune system.
Why it was Considered for COVID-19
Initial interest in hydroxychloroquine as a potential COVID-19 treatment arose from its theoretical antiviral properties. Early in-vitro laboratory studies suggested that the drug could inhibit SARS-CoV-2, the virus causing COVID-19. These studies proposed that hydroxychloroquine might interfere with the virus’s ability to enter human cells.
The drug was thought to disrupt specific lipid rafts on cell membranes, structures the virus uses to attach and gain entry. It was also hypothesized that hydroxychloroquine could modulate the immune response, potentially preventing the excessive inflammation, often referred to as a “cytokine storm,” observed in severely ill COVID-19 patients. These preliminary findings and anecdotal observations fueled the hope for a rapid solution during the early stages of the pandemic.
What Clinical Studies Revealed
Despite initial promise, extensive clinical trials worldwide consistently demonstrated that hydroxychloroquine was not effective against COVID-19. Large-scale, well-designed randomized controlled trials provided robust evidence that the drug did not reduce the risk of hospitalization or mortality in patients with COVID-19.
The World Health Organization (WHO)’s Solidarity Trial, a major international clinical trial, discontinued its hydroxychloroquine arm in June 2020. This decision, along with findings from the UK’s Recovery trial, indicated that hydroxychloroquine did not improve outcomes for hospitalized COVID-19 patients compared to standard care. Trials sponsored by the National Institutes of Health (NIH) reached comparable conclusions.
For instance, the NIH-funded ORCHID study, a blinded, placebo-controlled randomized clinical trial, was halted early in June 2020 because a data and safety monitoring board determined the drug was unlikely to provide any benefit. Final analyses from this trial, published in November 2020, formally concluded that hydroxychloroquine offered no clinical benefit. Over 200 randomized controlled trials investigating hydroxychloroquine for SARS-CoV-2 were launched, and many were slow to terminate despite conclusive evidence of its ineffectiveness.
Associated Risks and Safety Concerns
While hydroxychloroquine has an established safety profile for its approved uses, its consideration for COVID-19 brought increased scrutiny to its potential risks, especially when used inappropriately or in high doses. A significant concern is its effect on the heart, specifically the risk of QT prolongation. This condition, an abnormality in the heart’s electrical activity, can lead to serious arrhythmias and, in rare cases, sudden cardiac arrest.
The risk of cardiac issues is heightened when hydroxychloroquine is combined with other medications known to prolong the QT interval, such as the antibiotic azithromycin. Patients with pre-existing heart conditions, heart failure, or imbalances in electrolytes like potassium and magnesium are at an increased risk. Long-term or high-dose use of hydroxychloroquine can also lead to retinopathy, a dose-related and irreversible eye damage. Other less common but serious side effects include seizures, nerve damage affecting muscles, and bone marrow suppression. These safety concerns were particularly relevant when considering the drug for a broad population of COVID-19 patients, many of whom had underlying health issues.
Current Medical Guidance
Major health organizations do not recommend hydroxychloroquine for the treatment or prevention of COVID-19. The U.S. Food and Drug Administration (FDA) revoked its Emergency Use Authorization (EUA) for COVID-19 in June 2020. This decision was based on scientific data from large, randomized clinical trials showing no benefit for hospitalized patients.
The Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) align with this stance, emphasizing there is no scientific evidence to support its use for COVID-19 outside of specific research settings. While hydroxychloroquine remains an approved and effective treatment for malaria and autoimmune conditions like lupus and rheumatoid arthritis, its use for COVID-19 is not supported by current medical evidence due to its ineffectiveness and potential for serious adverse effects.