1. 2020;23;S351-S366COVID-19 Pandemic - A Narrative Review of the Potential Roles of Chloroquine and Hydroxychloroquine
   Focused Review
   Vanessa B. Boralli, PhD, Sudhir Diwan, MD, Larissa H. Torres, PhD, Cristiano M. Trindade, MD, Raphael C. Tamborelli Garcia, PhD, Flaviane A. Pinheiro, ., Livia Del Bianco Maia, ., Karla C. Mancini Costa, MSc, Carlos M. de Barros, MD, Carolina A. de Faria Almeida, MSc, and Bruna Pereira, PhD.

BACKGROUND: Chloroquine (CQ) and hydroxychloroquine (HCQ) are old drugs used against malaria, rheumatism, inflammation in the joints, lupus, among others. These drugs showed positive results in preliminary scientific research for treatment of the severe acute respiratory syndrome coronavirus (SARS-CoV-2). Since the studies with CQ and HCQ are initial with small patient populations, it is not yet known whether there are adverse effects from the use of CQ and HCQ for patients infected with the coronavirus.

OBJECTIVES: The aim of this study was to evaluate the evidence regarding the efficacy and safety of CQ and HCQ used against viral infection caused by SARS-CoV-2.

STUDY DESIGN: This is a narrative review of the traditional prescriptions of CQ and HCQ efficacy and adverse effects as well as their employment for coronavirus disease 2019 (COVID-19).

SETTING: In vitro and clinical studies comparing the antiviral efficacy and adverse effect profile of CQ and HCQ against COVID-19 in adult patients were evaluated.

METHODS: A systemic search of reviews, including in vitro and clinical trial studies in English focusing on CQ and HCQ effects and adverse effects against COVID-19 in the adult patient population from PubMed was performed. It included studies reporting chloroquine and hydroxychloroquine effects and adverse effects against COVID-19.

RESULTS: A total of 42 articles published between 2004 and April 2020 were reviewed for therapeutic use of CQ and HCQ. Both these drugs showed a significant in vitro potential against coronavirus. Many studies for clinical use of CQ and HCQ showed that patients presented adverse reactions on high doses.

LIMITATIONS: Clinical studies have some methodology shortcomings, such as lack of information about the treatment and small number of experimental patients, leading to a misinterpretation of the data. Besides, there are few clinical studies with a limited sample size. Moreover, most of them did not present control groups, and some patients had died during these protocols.

DISCUSSION: Despite both CQ and HCQ in vitro antiviral evidence, clinically, both drugs, either alone or combined with other medications, may increase the risk of cardiac arrhythmias, leading to cardiac arrest and sudden death. Besides, a lot of uncertainty still remains, such as starting administration period, dose prescribed, length of treatment, patients’ condition, concomitant drug use, among others.

CONCLUSION: From the studies reviewed, it is not possible to state the precise efficacy and safety of CQ and HCQ use in the treatment of COVID-19 at any time in the course of the disease. Future studies are warranted.

KEY WORDS: SARS-CoV-2; COVID-19; chloroquine; hydroxychloroquine; pandemic; coronavirus; adverse effects; side effects; cardiac arrhythmias; ocular toxicity, retinopathy; pharmacokinetic.