A new study has found that hydroxychloroquine does not work against COVID-19. Researchers also highlighted a link between the high mortality rate and intake of the drug.
The ineffectiveness of hydroxychloroquine against COVID-19 was determined by researchers at Brigham and Women's Hospital Heart and Vascular Center, Surgisphere Corporation, the University Hospital Zurich, and the University of Utah. They found no conclusive evidence that the antimalaria medication could improve symptoms of COVID-19. They also detected high mortality rates in patients treated with hydroxychloroquine, compared to patients treated without the drug. Because of their findings, the World Health Organization (WHO) suspended its trial of the drug due to safety reasons. Results were published in the journal The Lancet.
The Mention of Hydroxychloroquine in COVID-19 Treatment
When COVID-19 outbreaks failed to wane quickly, the international medical community investigated existing medications that could be used to treat patients. Since biomedical scientists unlocked the basic details about the pathogen, their findings provided some guidance on what available medicines might work. Some of the findings include the caution on ibuprofen use, the utilization of convalescent plasma therapy from survivors, and the administration of an antimalaria drug called hydroxychloroquine. But none of these medications have been approved as a specific treatment for the novel illness.
Among those three, hydroxychloroquine has been the most controversial due to the lack of concrete evidence to support its efficacy in treating COVID-19. Ibuprofen can aggravate symptoms of the disease while plasma therapy may help critical patients using the antibodies from survivors. The antimalaria medication made headlines because of in vitro results, wherein it featured antiviral properties against SARS-CoV-2, the pathogen of COVID-19. But in vivo or inside a living organism, no solid evidence has been confirmed yet.
So far, in vitro studies indicate that the properties of hydroxychloroquine can interfere with the chemical conditions of human cell membranes. The interference alters the environment needed by the virus to hijack and multiply. This represents that the medication may prevent the virus from attacking human cells and infecting a person. Though, in vitro results are not always the same as in vivo. Since numerous dynamic processes happened inside a living organism, in vivo tests can represent a completely different result, up to the point that in vitro results are contradicted.
Regardless of the insufficient data from the use of hydroxychloroquine for COVID-19, many hospitals around the world decided to use the drug to treat patients. Clinicians probably considered it, despite the lack of solid proof, because there are so many patients to deal with. If a drug can improve symptoms, it will be considered until a specific treatment or vaccine is created against the virus.
WHO-Led Hydroxychloroquine Trial Paused
Recently, the WHO suspended its clinical trial of hydroxychloroquine over safety concerns. The organization paused that trial after a study showed the mortality rate among patients with COVID-19 administered with the drug. There was a statistical difference between the mortality rate of hydroxychloroquine recipients and non-hydroxychloroquine recipients.
"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. Instead, our findings suggest it may be associated with an increased risk of serious heart problems and increased risk of death. Randomized clinical trials are essential to confirm any harms or benefits associated with these agents. In the meantime, we suggest these drugs should not be used as treatments for Covid-19 outside of clinical trials," said Professor Mandeep R. Mehra, lead author of the study and executive director of Brigham and Women's Hospital Heart and Vascular Center, as quoted by The Guardian, a British newspaper.
In the study, researchers conducted a multinational registry analysis on the use of hydroxychloroquine or chloroquine among COVID-19 patients. The scope of their analysis was the use of either medication with or without a macrolide, a class of antibiotics. A total of 671 hospitals in six continents comprised the data, while a total of 96,032 patients hospitalized between December 20, 2019, and April 14, 2020, became the study sample. All patients were confirmed to have COVID-19 through laboratory results.
The patients received treatments 48 hours after diagnosis. As study samples, they were categorized into five groups: the chloroquine only, chloroquine with a macrolide, hydroxychloroquine only, hydroxychloroquine with a macrolide, and non-recipients of hydroxychloroquine or chloroquine, which was assigned as the control group. A total of 14,888 patients were in the subject groups, comprised of 1,868 recipients of chloroquine, 3,783 recipients of chloroquine with a macrolide, 3,016 recipients of hydroxychloroquine, and 6,221 recipients of hydroxychloroquine with a macrolide. A total of 81,144 patients were in the control group.
Researchers examined and controlled confusing factors like preexisting health conditions and lifestyle, and then compared the mortality rate between the subject and control groups. The comparison revealed that 11.1% of patients in the subject groups died, higher than the 9.3% deaths in the control group. Independently, the increased risk of mortality was 16.4% in the chloroquine group, 22.2% in the chloroquine with a macrolide group, 18% in the hydroxychloroquine group, and 23.8% in the hydroxychloroquine with a macrolide group.
Heart arrhythmia was detected as a potential complication from the use of hydroxychloroquine in treating COVID-19. The control group was found with a 0.3% increased risk of heart arrhythmia, substantially smaller compared to the subject groups. The chloroquine group had 4.3%, the chloroquine with a macrolide group had 6.5%, the hydroxychloroquine group had 6.1%, and the hydroxychloroquine with a macrolide group had 8.1% increased risk of heart arrhythmia. The statistical difference urged the WHO to stop its trial as the medication might kill participants.
According to the Mayo Clinic, an American not-for-profit medical center, heart arrhythmia is a condition wherein the heartbeat is irregular. If it is too fast, the condition is called tachycardia while if it too slow, the condition is called bradycardia. Both can lead to serious health complications. Tachycardia can lead to a heart attack or stroke while bradycardia can result in sudden cardiac arrest or sudden death.
Even though the scientific community agrees with the study findings, some expressed support for the use of hydroxychloroquine in carefully controlled clinical trials. Unlike in real clinical settings, clinical trials can monitor and address complications that may arise. So, for scientists, the use of hydroxychloroquine in COVID-19 patients should be prohibited outside clinical trials.