Chloroquine and Hydroxychloroquine: Efficacy in the Treatment of the COVID-19
Total Page：16
File Type：pdf, Size：1020Kb
pathogens Brief Report Chloroquine and Hydroxychloroquine: Efficacy in the Treatment of the COVID-19 Tzu-Chuan Ho 1,†, Yung-Hsuan Wang 2,†, Yi-Ling Chen 3,†, Wan-Chi Tsai 4 , Che-Hsin Lee 5 , Kuo-Pin Chuang 6, Yi-Ming Arthur Chen 7, Cheng-Hui Yuan 8, Sheng-Yow Ho 9 , Ming-Hui Yang 10,* and Yu-Chang Tyan 1,6,11,* 1 Department of Medical Imaging and Radiological Sciences, Kaohsiung Medical University, Kaohsiung 807, Taiwan; [email protected] 2 St. Dominic Catholic High School, Kaohsiung 802, Taiwan; [email protected] 3 Department of Nuclear Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan; [email protected] 4 Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan; [email protected] 5 Department of Biological Science, National Sun Yat-sen University, Kaohsiung 804, Taiwan; [email protected] 6 Graduate Institute of Animal Vaccine Technology, College of Veterinary Medicine, National Pingtung University of Science and Technology, Pingtung 912, Taiwan; [email protected] 7 Graduate Institute of Biomedical and Pharmaceutical Science, Fu Jen Catholic University, New Taipei City 242, Taiwan; [email protected] 8 Mass Spectrometry Laboratory, Department of Chemistry, National University of Singapore, Singapore 119077, Singapore; [email protected] 9 Department of Radiation Oncology, Chi Mei Medical Center, Graduate Institute of Medical Science, Chang Jung Christian University, Tainan 710, Taiwan; [email protected] 10 Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan Citation: Ho, T.-C.; Wang, Y.-H.; 11 Neuroscience Research Center, Graduate Institute of Medicine, College of Medicine, Chen, Y.-L.; Tsai, W.-C.; Lee, C.-H.; Center for Cancer Research, Research Center for Environmental Medicine, Kaohsiung Medical University, Chuang, K.-P.; Chen, Y.-M.A.; Yuan, Kaohsiung 807, Taiwan C.-H.; Ho, S.-Y.; Yang, M.-H.; et al. * Correspondence: [email protected] (M.-H.Y.); [email protected] (Y.-C.T.) Chloroquine and Hydroxychloroquine: † These authors contributed equally as the first author to this work. Efficacy in the Treatment of the COVID-19. Pathogens 2021, 10, 217. Abstract: Chloroquine (CQ) and its derivative, hydroxychloroquine (HCQ), have attracted wide https://doi.org/10.3390/pathogens attention for treating coronavirus disease 2019 (COVID-19). However, conflicting outcomes have 10020217 been found in COVID-19 clinical trials after treatment with CQ or HCQ. To date, it remains uncertain whether CQ and HCQ are beneficial antiviral drugs for combating COVID-19. We performed a Academic Editor: Alessandra Borsetti systematic review to depict the efficacy of CQ or HCQ for the treatment of COVID-19. The guidelines Received: 14 January 2021 of PRISMA were used to conduct this systematic review. We searched through articles from PubMed, Accepted: 8 February 2021 Web of Science and other sources that were published from 1 January 2020 to 31 October 2020. The Published: 17 February 2021 search terms included combinations of human COVID-19, CQ, and HCQ. Eleven qualitative articles comprising of four clinical trials and seven observation studies were utilized in our systematic Publisher’s Note: MDPI stays neutral review. The analysis shows that CQ and HCQ do not have efficacy in treatment of patients with with regard to jurisdictional claims in published maps and institutional affil- severe COVID-19. In addition, CQ and HCQ have caused life-threatening adverse reactions which iations. included cardiac arrest, electrocardiogram modification, and QTc prolongation, particularly during the treatment of patients with severe COVID-19. Our systematic review suggested that CQ and HCQ are not beneficial antiviral drugs for curing patients with severe COVID-19. The treatment effect of CQ and HCQ is not only null but also causes serious side effects, which may cause potential Copyright: © 2021 by the authors. cardiotoxicity in severe COVID-19 patients. Licensee MDPI, Basel, Switzerland. This article is an open access article Keywords: coronavirus disease; chloroquine; hydroxychloroquine distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). Pathogens 2021, 10, 217. https://doi.org/10.3390/pathogens10020217 https://www.mdpi.com/journal/pathogens PathogensPathogens2021 2021, 10, 10, 217, x FOR PEER REVIEW 2 of 12 9 1. Introduction Coronavirus is a positive-sense, single-stranded RNA virus, including four genera: Coronavirus is a positive-sense, single-stranded RNA virus, including four genera: the alpha, beta, gamma, and delta [1]. It named because of its morphology with the alpha, beta, gamma, and delta [1]. It named because of its morphology with crown- crown-like spikes under the electron microscope [1]. Only alpha- and beta-coronavirus like spikes under the electron microscope [1]. Only alpha- and beta-coronavirus can can infect humans, and both result in mild or severe respiratory infectious diseases [2–4]. infect humans, and both result in mild or severe respiratory infectious diseases [2–4]. InIn DecemberDecember 2019,2019, thethe novelnovel coronaviruscoronavirus pandemicpandemic beganbegan inin thethe citycity ofof Wuhan,Wuhan, ChinaChina andand triggeredtriggered severesevere acuteacute respiratoryrespiratory syndromesyndrome [[5]5].. AfterAfter thatthat date,date, WHOWHO declareddeclared thisthis diseasedisease toto bebe coronaviruscoronavirus diseasedisease 20192019 (COVID-19)(COVID-19) [[6]6].. TheThe etiologyetiology ofof COVID-19COVID-19 waswas determineddetermined to to be be severe severe acute acute respiratory respiratory syndrome syndrome coronavirus coronavirus 2 (SARS-CoV-2, 2 (SARS-CoV previously-2, pre- knownviously asknown 2019-nCoV) as 2019 by-nCoV) the International by the International Virus Nomenclature Virus Nomenclature Committee Committee [6]. SARS- [6]. CoV-2SARS- isCoV a beta-coronavirus-2 is a beta-coronavirus and shares and similar shares genetic similar backgrounds genetic backgrounds with bothSARS-CoV with both (70%SARS similarity),-CoV (70% andsimilarity), the Middle and Eastthe Middle respiratory East syndromerespiratory MERS-CoV syndrome MERS (40% similarity)-CoV (40% thatsimilarity) previously that led previously to a pandemic led to coronavirus a pandemic disease coronavirus [7]. As ofdi 4sease February [7]. As 2021, of SARS-CoV-4 February 2202 has1, spreadSARS- toCoV 223-2 countries, has spread areas, to or 223 territories, countries and, causedareas, 103,362,039or territories confirmed, and caused cases with103,362 2,244,713,039 confirmed deaths globally cases with [8]. It2,2 urgently44,713 deaths requires globally effective [8]. vaccines It urgently and requires medicines effec- to preventtive vaccines or treat and COVID-19. medicines to prevent or treat COVID-19. ChloroquineChloroquine (CQ)(CQ) andand itsits derivative,derivative, hydroxychloroquinehydroxychloroquine (HCQ),(HCQ), areare medicationsmedications usedused inin treatmenttreatment andand prophylaxisprophylaxis ofof thethe malariamalaria andand autoimmuneautoimmune diseasesdiseases suchsuch asas rheumatoidrheumatoid arthritisarthritis (RA)(RA) andand systemicsystemic lupuslupus erythematosuserythematosus (SLE) (SLE) [[9]9].. TheThe onlyonly chemicalchemical structurestructure differencedifference betweenbetween HCQHCQ andand CQCQ isis thatthat HCQHCQ hashas aa hydroxylhydroxyl substitutionsubstitution atat thethe ethylethyl groupgroup of of amine amine (Figure (Figure1). 1) Evidence. Evidence shows show thats that CQ CQ and and HCQ HCQ inhibit inhibit the infection the infection and replicationand replication of SARS-CoV-2 of SARS-inCoV vitro-2 instudies vitro [10studies–12]. CQ[10 and–12]. HCQ CQ mayand haveHCQ anti-SARS-CoV may have an- activityti-SARS through-CoV activity entry prevention,through entry replication prevention, impairment, replication or immuneimpairment modulation, or immune [13]. CQmodulation and HCQ [13] have. CQ become and HCQ candidates have become for treatment candidate of COVID-19s for treatment due to of their COVID anti-SARS--19 due CoV-2to their properties anti-SARS and-CoV safety-2 properties for treatment and ofsafety malaria for treatment and autoimmune of malaria disease and [autoimmune14]. Clinical findingsdisease [14] from. C Gautretlinical findings [15] and Gaofrom et Gautret al. [16] show[15] and that Gao CQ andet al HCQ. [16] contributeshow that toCQ short- and termHCQ recovery, contribute negative to short virus-term conversion, recovery, negative improvement virus conversion of lung imaging,, improvement and inhibition of lung ofimaging the exacerbation, and inhibition of pneumonia of the exacerbation for hospitalized of pneumonia COVID-19 for patients. hospitalized CQ and COVID HCQ are-19 consideredpatients. CQ as and effective HCQ medicationsare considered to cureas effective COVID-19. medications However, to cure conflicting COVID results-19. How- are foundever, conflict in clinicaling results trials of are COVID-19 found in withclinical CQ trials or HCQ of COVID treatment.-19 with Studies CQ or by HCQ Tang treat- [17], Mahevasment. Studies [18], orby Maganoli Tang [17] et, Mahevas al. [19] show [18], thator Maganoli CQ and HCQ et al. both[19] show have nothat clinical CQ and efficacy HCQ onboth treatment have no ofclinical COVID-19. efficacy To on date, treatment it remains of COVID uncertain-19. To whether date, it CQremains and HCQuncertain are beneficialwhether CQ antiviral and