Systematic Review and Pharmacological Considerations for Chloroquine and Its Analogs in the Treatment for COVID-19.

Hongwei Peng,Zhangren Chen,Xin Lai,Chuanfei Zeng,Jinfang Hu,Yanmei Zhang,Jinhua Wen,Xiaohua Wei,Lijuan Du,Yunyun Wang,Li Cao,Mengjun Zhao,Tiantian Xu,Tao Hong,Simei Ren

doi:10.3389/fphar.2020.554172

Abstract

COVID-19 has been announced pandemic by WHO and over 17,000,000 people infected (Till April 21st 2020). The disease is currently under control in China, with a curative rate of 86.8%. Chloroquine (CQ) is an old anti-malarial drug with good tolerability, which had proved to be effective in previous SARS-coronavirus, which spread and disappeared between 2002-2003. In vitro studies demonstrated the efficacy of CQ in curing COVID-19. Consequently, via analytical PBPK modeling, a further preliminary clinical trial has proved the efficacy and safety of CQ in China., and multiple clinical trials were registered and approved to investigate the activity of other analogs of CQ against COVID-19. We have listed all the clinical trials and made a meta-analysis of published data of hydroxychloroquine (HCQ). HCQ could increase the CT improvement and adverse reactions (ADRs) significantly though there was considerable heterogeneity among current researches. Actually, CQ and its analogs have unique pharmacokinetic characteristics, which would induce severe side effects in some circumstances. We have then summarized pharmacological considerations for these drugs so as to provide to the busy clinicians to avoid potential side effects when administered CQ or its analogs to COVID-19 patients, especially in the elderly, pediatrics, and pregnancies.

Highlights

COVID-19 has been pandemic around the world by WHO, with millions of people infected currently and causes 5–10% of patients’ deaths
HCQ group had a higher risk ratio in inducing adverse reaction, which may due to the pharmacokinetic characteristics of HCQ (P = 0.002) (Figure 6)
Piperaquine is bound to human plasma proteins more than 99%, and dihydroartemisinin is 44 to

Summary

Introduction

COVID-19 (coronavirus disease 2019) has been pandemic around the world by WHO, with millions of people infected currently and causes 5–10% of patients’ deaths. COVID-19 was first reported in December 2019, and the pathogen was firstly isolated on January 7th, 2020 and named SARS-CoV-2 by International Committee on Taxonomy of Viruses (ICTV), as it shares. Pharmacological Considerations for Chloroquine in the Treatment for COVID-19 great similarity in genomics with the previous emerged SARSCoV. Chloroquine (CQ) was firstly found to be effective in vitro and showed promising activity against SARS-CoV-2 infection (2019). Due to the long halflife, it is more prone to be accumulated in vivo and cause various side effects, which may hinder the treatment of COVID-19. We aim to provide rational suggestions to busy clinicians to avoid potential side effects that CQ or its analogs if prescribed to treat COVID-19

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