Chloroquine and hydroxychloroquine as a repurposed agent against COVID-19: a narrative review

Abstract

The predicament arising from the coronavirus disease 2019 (COVID-19) pandemic has become one of the most significant modern public health challenges. Despite uncertainties in the viral determinants and pathogenesis, it is crucial to accurately inspect all available evidence to construct accurate clinical guidelines for optimised patient care. This study aims to discuss the available evidence for the use of chloroquine (CQ) and hydroxychloroquine (HCQ) against COVID-19. Early in vitro studies of CQ/HCQ against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are convincing. But contradictory evidence exists on the clinical use of CQ/HCQ, either alone or in combination with azithromycin. As of now, there is no compelling clinical evidence on CQ, HCQ, and azithromycin in COVID-19 and the available evidence is limited to methodologically inferior non-randomised studies. Studies have also shown detrimental drug reactions to CQ and ‘HCQ plus azithromycin’, mainly cardiac side effects in hospitalised patients with coexisting cardiovascular comorbidities. Therefore, we recommend that physicians avoid high doses and exercise extreme caution in the compassionate use of CQ/HCQ, either alone or in combination with other antiviral drugs.

In Vitro Antiviral Activity of Doxycycline against SARS-CoV-2

“…However, these results must be taken with caution regarding the potential use of antimalarial drugs in SARS-CoV-2-infected patients: it is difficult to translate in vitro study results into actual clinical treatment in patients. For instance, experts agree on the in vitro activity of chloroquine or hydroxychloroquine against SARS-CoV-2 but disagree on the hydroxychloroquine efficacy in COVID-19 treatments, which remains controversial [50,51]. In vivo evaluation in animal experimental models is required to confirm the antiviral effects of doxycycline on SARS-CoV-2.…”

COVID-19, hydroxychloroquine and sudden cardiac death: implications for clinical practice in patients with rheumatic diseases

“…However, it has a narrow therapeutic window, requiring caution in those with presumed altered pharmacodynamics. Furthermore, it can be given safely during pregnancy [ 85 , 86 ]. It has also been shown to be severely toxic in cases of overdose [ 85 ].…”

“…QTc prolongation, arrhythmias particularly torsades de pointes, cardiomyopathy, cardiac arrest and other cardiotoxicities are the most common cardiovascular manifestations [ 67 , 74 , 78 , 85 , 87 ]. The effects on the ocular system are also pronounced, ranging from retinopathy and blurry vision to possible blindness [ 67 , 74 , 78 , 86 ]. HCQ can also lead to gastrointestinal upsets presenting as nausea, vomiting, abdominal cramps, pancreatitis and hepatitis [ 67 , 86 ].…”

“…The effects on the ocular system are also pronounced, ranging from retinopathy and blurry vision to possible blindness [ 67 , 74 , 78 , 86 ]. HCQ can also lead to gastrointestinal upsets presenting as nausea, vomiting, abdominal cramps, pancreatitis and hepatitis [ 67 , 86 ]. At times, neurologic and musculoskeletal manifestations like headache, dizziness, confusion, insomnia, sensorimotor dysfunction, hearing loss and mental disturbances can also be experienced by few patients [ 67 , 85 ].…”

“…Apart from this, HCQ may interfere with metabolic function leading to hypoglycemia and may also cause idiosyncratic reactions, anaphylaxis and skin infections like Pruritis and Stevens-Johnson syndrome in severe cases [ 67 , 74 , 85 ]. Furthermore, the hematologic system might be affected in certain patients presenting as neutropenia, Lymphopenia and eosinophilia [ 85 , 86 ].…”