{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T15:46:13Z","timestamp":1791387973077,"version":"4.3.3"},"reference-count":32,"publisher":"American Medical Association (AMA)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"DOI":"10.1001\/jamanetworkopen.2020.8857","type":"journal-article","created":{"date-parts":[[2020,4,24]],"date-time":"2020-04-24T12:30:53Z","timestamp":1587731453000},"page":"e208857","source":"Crossref","is-referenced-by-count":778,"title":["Effect of High vs Low Doses of Chloroquine Diphosphate as Adjunctive Therapy for Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection"],"prefix":"10.1001","volume":"3","author":[{"given":"Mayla Gabriela Silva","family":"Borba","sequence":"first","affiliation":[{"name":"Funda\u00e7\u00e3o de Medicina Tropical Dr Heitor Vieira Dourado, Manaus, Brazil"},{"name":"Universidade do Estado do Amazonas, Manaus, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando Fonseca Almeida","family":"Val","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o de Medicina Tropical Dr Heitor Vieira Dourado, Manaus, Brazil"},{"name":"Universidade do Estado do Amazonas, Manaus, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanderson Souza","family":"Sampaio","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o de Medicina Tropical Dr Heitor Vieira Dourado, Manaus, Brazil"},{"name":"Universidade do Estado do Amazonas, Manaus, Brazil"},{"name":"Funda\u00e7\u00e3o de Vigil\u00e2ncia em Sa\u00fade do Amazonas, Manaus, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcia Almeida Ara\u00fajo","family":"Alexandre","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o de Medicina Tropical Dr Heitor Vieira Dourado, Manaus, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gisely Cardoso","family":"Melo","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o de Medicina Tropical Dr Heitor Vieira Dourado, Manaus, Brazil"},{"name":"Universidade do Estado do Amazonas, Manaus, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo","family":"Brito","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o de Medicina Tropical Dr Heitor Vieira Dourado, Manaus, Brazil"},{"name":"Universidade do Estado do Amazonas, Manaus, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Paula Gomes","family":"Mour\u00e3o","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o de Medicina Tropical Dr Heitor Vieira Dourado, Manaus, Brazil"},{"name":"Universidade do Estado do Amazonas, Manaus, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Diego","family":"Brito-Sousa","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o de Medicina Tropical Dr Heitor Vieira Dourado, Manaus, Brazil"},{"name":"Universidade do Estado do Amazonas, Manaus, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Djane","family":"Ba\u00eda-da-Silva","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o de Medicina Tropical Dr Heitor Vieira Dourado, Manaus, Brazil"},{"name":"Universidade do Estado do Amazonas, Manaus, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus Vinitius Farias","family":"Guerra","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o de Medicina Tropical Dr Heitor Vieira Dourado, Manaus, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludhmila Abrah\u00e3o","family":"Hajjar","sequence":"additional","affiliation":[{"name":"Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosemary Costa","family":"Pinto","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o de Vigil\u00e2ncia em Sa\u00fade do Amazonas, Manaus, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio Alcirley Silva","family":"Balieiro","sequence":"additional","affiliation":[{"name":"Instituto Le\u00f4nidas and Maria Deane, Fiocruz Amazonas, Manaus, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ant\u00f4nio Guilherme Fonseca","family":"Pacheco","sequence":"additional","affiliation":[{"name":"Programa de Computa\u00e7\u00e3o Cient\u00edfica, Fiocruz, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"James Dean Oliveira","family":"Santos","sequence":"additional","affiliation":[{"name":"Universidade Federal do Amazonas, Manaus, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe Gomes","family":"Naveca","sequence":"additional","affiliation":[{"name":"Instituto Le\u00f4nidas and Maria Deane, Fiocruz Amazonas, Manaus, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana Sim\u00e3o","family":"Xavier","sequence":"additional","affiliation":[{"name":"Instituto Nacional de Infectologia Carlos Chagas\u2013Fiocruz, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9 Machado","family":"Siqueira","sequence":"additional","affiliation":[{"name":"Instituto Nacional de Infectologia Carlos Chagas\u2013Fiocruz, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Schwarzbold","sequence":"additional","affiliation":[{"name":"Universidade Federal de Santa Maria, Rio Grande do Sul, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00falio","family":"Croda","sequence":"additional","affiliation":[{"name":"Faculdade de Medicina da Universidade Federal do Mato Grosso do Sul, Campo Grande, Brazil"},{"name":"Funda\u00e7\u00e3o Oswaldo Cruz, Mato Grosso do Sul, Campo Grande, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maur\u00edcio Lacerda","family":"Nogueira","sequence":"additional","affiliation":[{"name":"Faculdade de Medicina de S\u00e3o Jos\u00e9 do Rio Preto, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo Adolfo Sierra","family":"Romero","sequence":"additional","affiliation":[{"name":"Universidade de Bras\u00edlia, Bras\u00edlia, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quique","family":"Bassat","sequence":"additional","affiliation":[{"name":"ISGlobal, Hospital Cl\u00ednic\u2013Universitat de Barcelona, Barcelona, Spain"},{"name":"Centro de Investiga\u00e7\u00e3o em Sa\u00fade de Manhi\u00e7a, Maputo, Mozambique"},{"name":"Instituci\u00f3 Catalana de Recerca i Estudis Avan\u00e7ats (ICREA), Barcelona, Spain"},{"name":"Pediatric Infectious Diseases Unit, Pediatrics Department, Hospital Sant Joan de D\u00e9u, University of Barcelona, Barcelona, Spain"},{"name":"Consorcio de Investigaci\u00f3n Biom\u00e9dica en Red de Epidemiolog\u00eda y Salud P\u00fablica, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cor Jesus","family":"Fontes","sequence":"additional","affiliation":[{"name":"Universidade Federal de Mato Grosso, Mato Grosso, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernardino Cl\u00e1udio","family":"Albuquerque","sequence":"additional","affiliation":[{"name":"Faculdade de Medicina da Universidade Federal do Amazonas, Manaus, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cl\u00e1udio-Tadeu","family":"Daniel-Ribeiro","sequence":"additional","affiliation":[{"name":"Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wuelton Marcelo","family":"Monteiro","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o de Medicina Tropical Dr Heitor Vieira Dourado, Manaus, Brazil"},{"name":"Universidade do Estado do Amazonas, Manaus, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus Vin\u00edcius Guimar\u00e3es","family":"Lacerda","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o de Medicina Tropical Dr Heitor Vieira Dourado, Manaus, Brazil"},{"name":"Universidade do Estado do Amazonas, Manaus, Brazil"},{"name":"Instituto Le\u00f4nidas and Maria Deane, Fiocruz Amazonas, Manaus, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the CloroCovid-19 Team","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","published-online":{"date-parts":[[2020,4,24]]},"reference":[{"issue":"10223","key":"zoi200372r1","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1016\/S0140-6736(20)30185-9","article-title":"A novel coronavirus outbreak of global health concern.","volume":"395","author":"Wang","year":"2020","journal-title":"Lancet"},{"issue":"10","key":"zoi200372r2","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1056\/NEJMoa2001191","article-title":"First case of 2019 novel coronavirus in the United States.","volume":"382","author":"Holshue","year":"2020","journal-title":"N Engl J Med"},{"key":"zoi200372r3","doi-asserted-by":"crossref","DOI":"10.1016\/j.tmaid.2020.101613","article-title":"COVID-19 in Latin America: the implications of the first confirmed case in Brazil.","author":"Rodriguez-Morales","year":"2020","journal-title":"Travel Med Infect Dis"},{"key":"zoi200372r4","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejrad.2020.108956","article-title":"Asymptomatic SARS-CoV-2 infected patients with persistent negative CT findings.","volume":"126","author":"Ling","year":"2020","journal-title":"Eur J Radiol"},{"issue":"1","key":"zoi200372r5","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1186\/s13054-020-2833-7","article-title":"Host susceptibility to severe COVID-19 and establishment of a host risk score: findings of 487 cases outside Wuhan.","volume":"24","author":"Shi","year":"2020","journal-title":"Crit Care"},{"key":"zoi200372r6","doi-asserted-by":"crossref","DOI":"10.1016\/S2213-2600(20)30079-5","article-title":"Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study.","author":"Yang","year":"2020","journal-title":"Lancet Respir Med"},{"issue":"10229","key":"zoi200372r7","doi-asserted-by":"publisher","first-page":"1054","DOI":"10.1016\/S0140-6736(20)30566-3","article-title":"Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study.","volume":"395","author":"Zhou","year":"2020","journal-title":"Lancet"},{"key":"zoi200372r8","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1186\/1743-422X-2-69","article-title":"Chloroquine is a potent inhibitor of SARS coronavirus infection and spread.","volume":"2","author":"Vincent","year":"2005","journal-title":"Virol J"},{"issue":"1","key":"zoi200372r9","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1016\/j.bbrc.2004.08.085","article-title":"In vitro inhibition of severe acute respiratory syndrome coronavirus by chloroquine.","volume":"323","author":"Keyaerts","year":"2004","journal-title":"Biochem Biophys Res Commun"},{"issue":"3","key":"zoi200372r10","first-page":"185","article-title":"Expert consensus on chloroquine phosphate for the treatment of novel coronavirus pneumonia.","volume":"43","author":"Multicenter collaboration group of Department of Science and Technology of Guangdong Province and Health Commission of Guangdong Province for chloroquine in the treatment of novel coronavirus pneumonia","year":"2020","journal-title":"Zhonghua Jie He He Hu Xi Za Zhi"},{"issue":"3","key":"zoi200372r11","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1038\/s41422-020-0282-0","article-title":"Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro.","volume":"30","author":"Wang","year":"2020","journal-title":"Cell Res"},{"issue":"1","key":"zoi200372r12","doi-asserted-by":"publisher","first-page":"72","DOI":"10.5582\/bst.2020.01047","article-title":"Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies.","volume":"14","author":"Gao","year":"2020","journal-title":"Biosci Trends"},{"key":"zoi200372r13","doi-asserted-by":"crossref","DOI":"10.1016\/j.ijantimicag.2020.105949","article-title":"Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial.","author":"Gautret","year":"2020","journal-title":"Int J Antimicrob Agents"},{"issue":"4","key":"zoi200372r14","doi-asserted-by":"publisher","first-page":"1468","DOI":"10.1128\/AAC.00339-08","article-title":"Pharmacokinetics of hydroxychloroquine and its clinical implications in chemoprophylaxis against malaria caused by Plasmodium vivax.","volume":"53","author":"Lim","year":"2009","journal-title":"Antimicrob Agents Chemother"},{"issue":"1","key":"zoi200372r16","doi-asserted-by":"publisher","first-page":"89","DOI":"10.4103\/0974-9233.106404","article-title":"Delayed onset chloroquine retinopathy presenting 10 years after long-term usage of chloroquine.","volume":"20","author":"Kazi","year":"2013","journal-title":"Middle East Afr J Ophthalmol"},{"issue":"7","key":"zoi200372r17","doi-asserted-by":"publisher","first-page":"1321","DOI":"10.1016\/S0161-6420(03)00409-3","article-title":"The incidence of irreversible retinal toxicity in patients treated with hydroxychloroquine: a reappraisal.","volume":"110","author":"Mavrikakis","year":"2003","journal-title":"Ophthalmology"},{"issue":"5","key":"zoi200372r18","first-page":"795","article-title":"Chloroquine and QTc interval.","volume":"25","author":"Silva","year":"2007","journal-title":"Clin Exp Rheumatol"},{"issue":"2","key":"zoi200372r19","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1099\/0022-1317-4-2-203","article-title":"Comparison of the antiviral activity in vitro of some non-steroidal anti-inflammatory drugs.","volume":"4","author":"Inglot","year":"1969","journal-title":"J Gen Virol"},{"issue":"6","key":"zoi200372r20","doi-asserted-by":"publisher","first-page":"3605","DOI":"10.1073\/pnas.78.6.3605","article-title":"Antihistaminics, local anesthetics, and other amines as antiviral agents.","volume":"78","author":"Miller","year":"1981","journal-title":"Proc Natl Acad Sci U S A"},{"key":"zoi200372r21","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1186\/1741-7015-8-18","article-title":"CONSORT 2010 Statement: updated guidelines for reporting parallel group randomised trials.","volume":"8","author":"Schulz","year":"2010","journal-title":"BMC Med"},{"key":"zoi200372r22","doi-asserted-by":"crossref","DOI":"10.1056\/NEJMc2005073","article-title":"SARS-CoV-2 infection in children.","author":"Lu","year":"2020","journal-title":"N Engl J Med"},{"key":"zoi200372r23","doi-asserted-by":"publisher","first-page":"m1091","DOI":"10.1136\/bmj.m1091","article-title":"Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study.","volume":"368","author":"Chen","year":"2020","journal-title":"BMJ"},{"key":"zoi200372r24","doi-asserted-by":"crossref","DOI":"10.1001\/jama.2020.5394","article-title":"Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy region, Italy.","author":"Grasselli","year":"2020","journal-title":"JAMA"},{"issue":"7","key":"zoi200372r25","doi-asserted-by":"publisher","first-page":"993","DOI":"10.1001\/jamaoncol.2019.0684","article-title":"Effect of gemcitabine and nab-paclitaxel with or without hydroxychloroquine on patients with advanced pancreatic cancer: a phase 2 randomized clinical trial.","volume":"5","author":"Karasic","year":"2019","journal-title":"JAMA Oncol"},{"issue":"8","key":"zoi200372r26","doi-asserted-by":"publisher","first-page":"1369","DOI":"10.4161\/auto.29118","article-title":"Phase I trial of hydroxychloroquine with dose-intense temozolomide in patients with advanced solid tumors and melanoma.","volume":"10","author":"Rangwala","year":"2014","journal-title":"Autophagy"},{"issue":"3","key":"zoi200372r27","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1097\/IAE.0000000000002027","article-title":"Frequent subclinical macular changes in combined BRAF\/MEK inhibition with high-dose hydroxychloroquine as treatment for advanced metastatic BRAF mutant melanoma: preliminary results from a phase i\/ii clinical treatment trial.","volume":"39","author":"Nti","year":"2019","journal-title":"Retina"},{"issue":"1","key":"zoi200372r32","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1016\/j.bbrc.2004.08.085","article-title":"In vitro inhibition of severe acute respiratory syndrome coronavirus by chloroquine.","volume":"323","author":"Keyaerts","year":"2004","journal-title":"Biochem Biophys Res Commun"},{"key":"zoi200372r15","unstructured":"Science Direct. Chloroquine retinopathy. Accessed March 20, 2020. https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/chloroquine-retinopathy"},{"key":"zoi200372r28","unstructured":"US Centers for Disease Control and Prevention. CDC 2019-novel coronavirus (2019-nCoV): real-time RT-PCR diagnostic panel. Updated March 15, 2020. Accessed April 21, 2020. https:\/\/www.fda.gov\/media\/134922\/download"},{"key":"zoi200372r29","unstructured":"ClinicalTrials.gov. Outcomes Related to COVID-19 Treated With Hydroxychloroquine Among In-patients With Symptomatic Disease (ORCHID). Accessed April 21, 2020. https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04332991?term=NCT04332991&draw=2&rank=1"},{"key":"zoi200372r30","unstructured":"ClinicalTrials.gov. Chloroquine Diphosphate in the Prevention of SARS in Covid-19 Infection (CloroCOVID19II). Accessed April 21, 2020. https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04342650?term=NCT04342650&draw=2&rank=1"},{"key":"zoi200372r31","doi-asserted-by":"crossref","unstructured":"Chorin? E, Dai? M, Shulman? E, . The QT interval in patients with SARS-CoV-2 infection treated with hydroxychloroquine\/azithromycin. Published April 3, 2020. Accessed April 20, 2020. https:\/\/www.medrxiv.org\/content\/10.1101\/2020.04.02.20047050v1","DOI":"10.1101\/2020.04.02.20047050"}],"container-title":["JAMA Network Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/articlepdf\/2765499\/borba_2020_oi_200372.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,4,27]],"date-time":"2020-04-27T16:02:40Z","timestamp":1588003360000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/fullarticle\/2765499"}},"subtitle":["A Randomized Clinical Trial"],"short-title":[],"issued":{"date-parts":[[2020,4,24]]},"references-count":32,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2020,4,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamanetworkopen.2020.8857","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.04.07.20056424","asserted-by":"object"}]},"ISSN":["2574-3805"],"issn-type":[{"value":"2574-3805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,24]]}}}