Short-term Hydroxychloroquine in COVID-19 Infection in People With or Without Metabolic Syndrome - Clearing Safety Issues and Good Clinical Practice

Hydroxychloroquine has been used in rheumatology for decades. This review highlights the mechanistic, clinical and safety data with regards to hydroxychloroquine use in novel coronavirus disease (COVID-19) in people with or without metabolic syndrome. PubMed and Medline were searched for articles published from January 1970 to March 2020 using the terms 'COVID-19', 'corona-virus 2019', 'hydroxychloroquine', 'hypertension', 'diabetes', 'cardiac disease', 'retina' and 'kidney disease'. Hypertension, diabetes and cardiovascular disease are the three most common comorbidities in people with COVID-19, meaning that such people have greater morbidity and mortality. Mechanistically, hydroxychloroquine inhibits SARS-CoV-2 virus uptake into cells by inhibiting angiotensin-converting enzyme 2 glycosylation. This inhibits lysosome activation and the associated cytokine storm, thus reducing the risk of acute respiratory distress syndrome and multiple organ dysfunction syndrome, which is the primary cause of death. Small, in-human studies have shown hydroxychloroquine to improve outcomes in COVID-19, either alone or in combination with azathioprine and other antiviral medications. Retina safety is not an issue with short term use of hydroxychloroquine in COVID-19. Dose reduction is warranted when glomerular filtration rate is <50 mL/min. Cardiac monitoring is warranted in people with established cardiac disease, and cardiac rhythm should be closely monitored when hydroxychloroquine is used with azithromycin, lopinavir, ritonavir or remdesivir. Anti-diabetes medication doses may need to be reduced during treatment with hydroxychloroquine. While we await data from large, in-human trials, short-term use of hydroxychloroquine in COVID-19 is justified, as this molecule has stood the test of time with regards to use in humans for other indications.