Hydroxychloroquine May Cause More Harm Than Benefit To COVID-19 Patients, Says New Lancet Study
Colorized scanning electron micrograph of a dying cell (blue) heavily infected with SARS-COV-2 (yellow), the virus that causes COVID-19

New research published in The Lancet on Friday found that hydroxychloroquine and chloroquine has ‘no benefit’ for coronavirus patients, and could even increase the risk of heart arrhythmias and mortality. 

“This is the first large scale study to find statistically robust evidence that treatment with chloroquine or hydroxychloroquine does not benefit patients with COVID-19,” said lead author of the study and Executive Director of the Brigham and Women’s Hospital Center in Boston Mandeep R. Mehra. “Instead, our findings suggest it may be associated with an increased risk of serious heart problems and increased risk of death.”

In the worst-case scenario, some 8% of patients in The Lancet study who were given hydroxychloroquine combined with azithromycin developed a heart arrhythmia (502/6,221), compared with 0.3% patients in the control group (226/81144).

Hydroxychloroquine and chloroquine use predicts in-hospital mortality

Treatment with hydroxychloroquine, chloroquine, or either drug in combination with azithromycin was also associated with higher odds of death, even after accounting for age, race, body mass index, and preexisting conditions.

While not a randomized control study, The Lancet article is the largest study to date on the hyped drugs, analyzing data from nearly 15,000 COVID-19 patients who received hydroxychloroquine, chloroquine, or a combination of either drug with a macrolide antibiotic such as azithromycin, and 81,000 COVID-19 patients who did not receive any of those treatments. The data came from 671 hospitals across 6 continents.

In light of mounting evidence that hydroxychloroquine provides little benefit to coronavirus patients, health experts are again repeating calls to take caution in rolling out emergency approval for unproven treatments, even as countries all over the map cautiously begin to authorize the use of hydroxychloroquine for COVID-19. India even issued a revised advisory on Friday expanding the use of hydroxychloroquine as a prophylactic treatment in healthcare workers and contacts of lab-confirmed coronavirus patients.

Experts from the World Health Organization have also been cautioning against widespread, unmonitored use of the drug. 

“We do point to the fact that… the current clinical evidence does not support the widespread use of hydroxychloroquine for the treatment of COVID-19, not until the trials are completed and we have clear results,” said WHO’s Executive Director of Emergencies Programme Mike Ryan, at WHO’s press conference on Friday, referring to evidence from clinical and systematic reviews carried out by the WHO Pan American Health Organization (PAHO).

Hydroxychloroquine, and hydroxychloroquine plus azithromycin are two of the drug regimens being tested for COVID-19 patients in WHO’s giant, multicountry Solidarity Trial.

The Lancet results support previous findings from a widely disseminated Brazilian study that found an increased risk of heart arrhythmias in COVID-19 patients receiving high doses of the drug. The study was discontinued shortly after, as subjecting patients to increased risk of death in the trial was deemed unethical by study coordinators.

The Lancet study however, does not explore another use for hydroxychloroquine – taking the drug to prevent onset of COVID-19.

India Revises Hydroxychloroquine Recommendations To Promote Prophylactic Use
Indian Ministry of Health recommends prophylactic use of hydroxychloroquine in revised advisory

On Friday, India’s National Task force (NTF) for COVID-19 issued a revised advisory on prophylactic use of hydroxychloroquine – expanding the recommendation to include all asymptomatic healthcare workers in COVID-19 positive and non-COVID-19 settings, all asymptomatic frontline workers in the COVID-19 response including contact tracers, and all asymptomatic household contacts of laboratory confirmed cases. 

The previous advisory, issued on 23 March, restricted the recommendation to healthcare workers who worked directly with confirmed and suspected COVID-19 patients, and asymptomatic household contacts of laboratory confirmed cases. 

The revised recommendation was based on a small prospective observational study of 334 healthcare workers. According to the advisory, the incidence of COVID-19 infection in the 248 healthcare workers who took HCQ prophylaxis in New Delhi was lower than the incidence of infection in those who did not take it after following up with the study subjects for a median of 6 weeks, however the exact reduction was not listed.

Still, the revised advisory recommends that the drug has to be given under ‘strict medical supervision with informed consent’ and ‘only on the prescription of a registered medical practitioner’ – noting a number of preexisting conditions that make taking the drug risky. 

The advisory also notes that only under ‘rare’ circumstances does hydroxychloroquine lead to the dangerous cardiovascular side effects. Among 1323 healthcare workers who took HCQ prophylaxis, serious side effects were reported in 7. Among those 7, three healthcare workers had a serious cardiac side effect – prolongation of QT interval on ECG.

“Rarely the drug causes cardiovascular side effects such as cardiomyopathy and rhythm (heart rate) disorders. In that situation the drug needs to be discontinued,” said the advisory. 

ChinaSpain, Brazil, and the United States have also issued recommendations for use of hydroxychloroquine in limited populations, largely restricting them to use in clinical trial settings in light of the new reports of serious cardiac side effects.

But the authors of The Lancet study still warn that the overall likelihood that these drugs improve clinical outcomes in COVID-19 patients is quite low, and underline that the medicines should not be recommended by countries for widespread treatment of COVID-19.

 “Several countries have advocated use of chloroquine and hydroxychloroquine, either alone or in combination, as potential treatments for COVID-19. Justification for repurposing these medicines in this way is based on a small number of anecdotal experiences that suggest they may have beneficial effects for people infected with the SARS-CoV-2 virus,”  said Director of the Heart Center at University Hospital Zurich Frank Ruschitzka, who also co-authored The Lancet study.

Image Credits: NIAID, The Lancet, India Ministry of Health.