Hydroxychloroquine: a comprehensive review and its controversial role in coronavirus disease 2019

Abstract

Hydroxychloroquine, initially used as an antimalarial, is used as an immunomodulatory and antiinflammatory agent for the management of autoimmune and rheumatic diseases such as systemic lupus erythematosus. Lately, there has been interest in its potential efficacy against severe acute respiratory syndrome coronavirus 2, with several speculated mechanisms. The purpose of this review is to elaborate on the mechanisms surrounding hydroxychloroquine. The review is an in-depth analysis of the antimalarial, immunomodulatory, and antiviral mechanisms of hydroxychloroquine, with detailed and novel pictorial explanations. The mechanisms of hydroxychloroquine are related to potential cardiotoxic manifestations and demonstrate potential adverse effects when used for coronavirus disease 2019 (COVID-19). Finally, current literature associated with hydroxychloroquine and COVID-19 has been analyzed to interrelate the mechanisms, adverse effects, and use of hydroxychloroquine in the current pandemic. Currently, there is insufficient evidence about the efficacy and safety of hydroxychloroquine in COVID-19. KEY MESSAGES 1. HCQ, initially an antimalarial agent, is used as an immunomodulatory agent for managing several autoimmune diseases, for which its efficacy is linked to inhibiting lysosomal antigen processing, MHC-II antigen presentation, and TLR functions. 2. HCQ is generally well-tolerated although severe life-threatening adverse effects including cardiomyopathy and conduction defects have been reported. 3. HCQ use in COVID-19 should be discouraged outside clinical trials under strict medical supervision.

Large Scale Profiling of SARS-CoV-2-Infected Patients Identified Potential Therapeutic Host Targets and Drug Candidates for COVID-19

“…Multiple TLRs were shown to be upregulated, and many compounds to target these genes were identified by DGIdb. Drugs that bind nonspecifically to TLR proteins have been tested extensively, including such drugs as hydroxychloroquine and ritonavir 16,17,18 . Because this pathway is important for coordinating both adaptive and innate immune responses, there may 10 have been some logic in this strategy, but in practice these drugs did not perform well, as reported by the Recovery trial 19 and the WHO "Solidarity" clinical trial 20 .…”

Hydroxychloroquine, nitazoxanide and ivermectin have similar effects in early COVID-19: a head-to-head comparison of the Pre-AndroCoV Trial.

“…By the time of the submission to the Ethics Committee, safety concerns had been raised for hydroxychloroquine regarding its alleged arrhythmogenic effects (39) and lack of response in previous studies (40,41), although almost none of the studies with hydroxychloroquine was performed in actual early mild COVID-19, before hospitalization. As per its mechanisms of actions, it is expected that hydroxychloroquine become less or not effective when used after seven days or when COVID-19 is severe enough to cause hospitalization, when second and third stages of the disease are undoubtfully installed, and antiviral approaches become less relevant.…”

Science’s Response to COVID-19

“…Assessment of clinical reports on potential CoVID-19-treatment options reveals that most data are often far from clear cut. The importance of side effects of administered drugs can also be subject to debate, 220 and how much drug-drug interactions were considered in planning is not always clear. 221 Dosing, and other simple factors are often not standardized.…”