Evidence still lacking for prophylactic chloroquine, hydroxychloroquine in COVID-19
A review of the available literature suggested that although preclinical results are promising, there remains little evidence supporting the use of hydroxychloroquine or chloroquine to prevent COVID-19, according to findings published in the International Journal of Rheumatic Diseases.
“The potential drug targets depend on the natural cycle of this virus,” Sanket Shah, MD, of the Jawaharlal Institute of Postgraduate Medical Education and Research, in Pondicherry, India, and colleagues wrote. “The virus depends on pH-dependent internalization and fusion with lysosomes. HCQ and CQ target this pathway by increasing the pH as they get concentrated into the lysosome and endosomes. This, in turn, affects viral replication and also helps in immune regulation and prevention of cytokine storm as the antigen presentation is affected. But the challenge is the translational impact of in vitro models to in vivo ones.”
“There are studies from China and other countries highlighting the use of anti-malarial anthraquinones including mention of the same in the latest guidelines,” they added. “A recent advisory issued by a national body from a South Asian country suggested the use of prophylactic hydroxychloroquine at a dose of 400 mg twice daily, followed by once weekly, for health care workers managing patients with COVID-19 and close contacts of proven COVID-19 cases. However, these studies and guidelines differ on the prophylactic use of these drugs causing further dilemma amongst the health care professionals.”
To review available data on the role of hydroxychloroquine and chloroquine in curbing the spread of COVID-19, Shah and colleagues performed a systematic literature review of all relevant, completed and published preclinical and clinical studies. The researchers also searched for commentaries, reviews, viewpoints or opinions if original clinical studies were not available.
After searching the PubMed, EMBASE, ClinicalTrials.gov, ICTRP and Cochrane Library databases, Shah and colleagues screened a total of 45 articles. They included five — three in vitro preclinical studies and two clinical opinions —in the final analysis. All included studies had been published on or before March 30, 2020.
According to the researchers, preclinical studies demonstrated the prophylactic effects of hydroxychloroquine and chloroquine against COVID-19. Further, the included clinical opinions advocated the prophylactic use of the drugs against COVID19. However, there were no original clinical studies on their prophylactic use in COVID19 available.
“The pandemic Coronavirus Disease-19 (COVID-19) has pushed the global health care system to a crisis and amounted to a huge economic and societal burden,” Shah and colleagues wrote. “Prevention of transmission of the disease in the population, particularly among high-risk individuals, is the urgent need of the hour. Different drugs for prophylaxis against COVID-19 including CQ or HCQ have been tried. Although pre-clinical results are promising, till date, there is dearth of good quality evidence to support the clinical efficacy of CQ or HCQ in preventing COVID-19.”
They added, “Because of the lack of robust clinical evidence till date, and duly considering the questionable efficacy, safety concerns, danger of deprivation of these essential drugs to legitimate patients, due to panic stocking and instilling a false sense of protection among the common mass, the prophylactic use of CQ or HCQ against COVID-19 needs to be further reviewed as more data pour in.”