Pharmacological and cardiovascular perspectives on the treatment of COVID-19 with chloroquine derivatives

Abstract

The novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) and an ongoing severe pandemic. Curative drugs specific for COVID-19 are currently lacking. Chloroquine phosphate and its derivative hydroxychloroquine, which have been used in the treatment and prevention of malaria and autoimmune diseases for decades, were found to inhibit SARS-CoV-2 infection with high potency in vitro and have shown clinical and virologic benefits in COVID-19 patients. Therefore, chloroquine phosphate was first used in the treatment of COVID-19 in China. Later, under a limited emergency-use authorization from the FDA, hydroxychloroquine in combination with azithromycin was used to treat COVID-19 patients in the USA, although the mechanisms of the anti-COVID-19 effects remain unclear. Preliminary outcomes from clinical trials in several countries have generated controversial results. The desperation to control the pandemic overrode the concerns regarding the serious adverse effects of chloroquine derivatives and combination drugs, including lethal arrhythmias and cardiomyopathy. The risks of these treatments have become more complex as a result of findings that COVID-19 is actually a multisystem disease. While respiratory symptoms are the major clinical manifestations, cardiovascular abnormalities, including arrhythmias, myocarditis, heart failure, and ischemic stroke, have been reported in a significant number of COVID-19 patients. Patients with preexisting cardiovascular conditions (hypertension, arrhythmias, etc.) are at increased risk of severe COVID-19 and death. From pharmacological and cardiovascular perspectives, therefore, the treatment of COVID-19 with chloroquine and its derivatives should be systematically evaluated, and patients should be routinely monitored for cardiovascular conditions to prevent lethal adverse events.

Inhibition of drug-metabolizing enzymes by Jingyin granules: implications of herb–drug interactions in antiviral therapy

“…Considering that lopinavir is frequently used for antiviral therapy in combination with other antiviral drugs or herbal medicines, the daily dose of lopinavir can be partially reduced to avoid potential DDIs/HDIs when it is co-administered with other antiviral drugs or herbal medicines in consecutive dosages. Notably, COVID-19 is a complex systemic disease, and severe COVID-19 patients often have excessive inflammation and abnormal coagulation [ 51 – 56 ]. To successfully treat severe COVID-19, the combination of antiviral agents, anti-inflammatory drugs and anti-coagulant agents (such as warfarin, a common anti-coagulant agent but with a very narrow therapeutic window) is frequently used.…”

Comparison of the antiviral effect of Arbidol and Chloroquine in treating COVID-19

“…The main concern about antiviral treatment with Arbidol and Chloroquine is their adverse effects (12)(13)(14). Chloroquine has been used to treat malaria and autoimmune diseases, and has adverse effects that are well known and can be severe, including psychiatric effects, cardiac toxicity, arrhythmia, and sudden death (15).…”

Reviews on Biological Activity, Clinical Trial and Synthesis Progress of Small Molecules for the Treatment of COVID-19

“…Zhang et al [ 87 ] systematically evaluated the treatment of COVID-19 with CLQ and CLQ-OH for efficacy and safety, and asserted a potential mechanism involving COVID-19-induced injury of multiple organs as well as the pharmacological effects of CLQ-OH on COVID-19 (Fig. 19 ); the authors concluded that COVID-19 is actually a multisystem disease, with respiratory symptoms as the major clinical manifestation.…”