The efficacy and safety of hydroxychloroquine in COVID19 patients : a multicenter national retrospective cohort

DOI record: { "DOI": "10.1101/2020.11.25.20234914", "URL": "http://dx.doi.org/10.1101/2020.11.25.20234914", "abstract": "<jats:title>ABSTRACT</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Hydroxychloroquine is an antimalarial drug that received worldwide news and media attention in the treatment of COVID-19 patients. This drug was used based on its antimicrobial and antiviral properties despite lack of definite evidence of clinical efficacy. In this study, we aim to assess the efficacy and safety of using Hydroxychloroquine in treatment of COVID-19 patients who are admitted in acute care hospitals in Bahrain.</jats:p></jats:sec><jats:sec><jats:title>Methodology</jats:title><jats:p>We conducted retrospective cohort study on a random sample of admitted COVID19 patients between 24 February and 31 July 2020. The study was conducted in four acute care COVID19 hospitals in Bahrain. Data was extracted from the medical records. The primary endpoint was the requirement of non-invasive ventilation, intubation or death. Secondary endpoint was length of hospitalization for survivors. Three methods of analysis were used to control for confounding factors: logistic multivariate regression, propensity score adjusted regression and matched propensity score analysis.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>A random sample of 1571 patients were included, 440 of which received HCQ (treatment group) and 1131 did not receive it (control group). Our results showed that HCQ did not have a significant effect on primary outcomes due to COVID-19 infection when compared to controls after adjusting for confounders (OR 1.43 95% CI 0.85 to 2.37, P value=0.17). Co-administration of azithromycin had no effect on primary outcomes (OR 2.7 95% CI 0.82 to 8.85 P value =0.10). HCQ was found to be associated with increased risk of hypoglycemia (OR 10.9 95% CI 1.72 - 69.49, P value =0.011) and diarrhea(OR 2.8, 95% CI 1.4-5.5, P value =0.003), but not QT prolongation(OR=1.92, 95% CI 0.95-3.9, P value =0.06) or cardiac arrhythmia.(OR=1.06, 95% CI 0.55-2.05, P value =0.85).</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Our results showed no significant beneficial effect of using hydroxychloroquine on the outcome of COVID-19 patients. Moreover, the risk of hypoglycemia due to hydroxychloroquine would possess a significant risk for out of hospital use.</jats:p></jats:sec>", "accepted": { "date-parts": [ [ 2020, 11, 30 ] ] }, "author": [ { "ORCID": "http://orcid.org/0000-0002-7331-388X", "affiliation": [], "authenticated-orcid": false, "family": "Abdulrahman", "given": "Abdulkarim", "sequence": "first" }, { "affiliation": [], "family": "AlSayed", "given": "Islam", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0002-4363-9846", "affiliation": [], "authenticated-orcid": false, "family": "AlMadhi", "given": "Marwa", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0002-0317-6461", "affiliation": [], "authenticated-orcid": false, "family": "AlArayed", "given": "Jumana", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0002-4849-7939", "affiliation": [], "authenticated-orcid": false, "family": "Mohammed", "given": "Sara Jaafar", "sequence": "additional" }, { "affiliation": [], "family": "Sharif", "given": "Aesha Khalid", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0001-9601-6709", "affiliation": [], "authenticated-orcid": false, "family": "Alansari", "given": "Khadija", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0003-3682-3677", "affiliation": [], "authenticated-orcid": false, "family": "AlAwadhi", "given": "Abdulla I", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0002-1523-0429", "affiliation": [], "authenticated-orcid": false, "family": "AlQahtani", "given": "Manaf", "sequence": "additional" } ], "container-title": [], "content-domain": { "crossmark-restriction": false, "domain": [] }, "created": { "date-parts": [ [ 2020, 11, 30 ] ], "date-time": "2020-11-30T18:02:13Z", "timestamp": 1606759333000 }, "deposited": { "date-parts": [ [ 2020, 12, 2 ] ], "date-time": "2020-12-02T19:13:05Z", "timestamp": 1606936385000 }, "group-title": "Infectious Diseases (except HIV/AIDS)", "indexed": { "date-parts": [ [ 2022, 4, 4 ] ], "date-time": "2022-04-04T10:09:40Z", "timestamp": 1649066980306 }, "institution": [ { "name": "medRxiv" } ], "is-referenced-by-count": 0, "issued": { "date-parts": [ [ 2020, 11, 30 ] ] }, "link": [ { "URL": "https://syndication.highwire.org/content/doi/10.1101/2020.11.25.20234914", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "246", "original-title": [], "posted": { "date-parts": [ [ 2020, 11, 30 ] ] }, "prefix": "10.1101", "published": { "date-parts": [ [ 2020, 11, 30 ] ] }, "publisher": "Cold Spring Harbor Laboratory", "reference": [ { "DOI": "10.23750/abm.v91i1.9397", "doi-asserted-by": "publisher", "key": "2020120211101020000_2020.11.25.20234914v1.1" }, { "key": "2020120211101020000_2020.11.25.20234914v1.2", "unstructured": "WHO. WHO Coronavirus Disease (COVID-19) Dashboard 2020 [7 October 2020]. Available from: https://covid19.who.int." }, { "DOI": "10.6061/clinics/2013(06)07", "article-title": "Hydroxychloroquine decreases Th17-related cytokines in systemic lupus erythematosus and rheumatoid arthritis patients", "doi-asserted-by": "crossref", "first-page": "766", "issue": "6", "journal-title": "Clinics (Sao Paulo)", "key": "2020120211101020000_2020.11.25.20234914v1.3", "volume": "68", "year": "2013" }, { "DOI": "10.1038/s41421-020-0156-0", "article-title": "Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro", "doi-asserted-by": "crossref", "first-page": "16", "journal-title": "Cell Discov", "key": "2020120211101020000_2020.11.25.20234914v1.4", "volume": "6", "year": "2020" }, { "DOI": "10.1128/JVI.03398-14", "doi-asserted-by": "publisher", "key": "2020120211101020000_2020.11.25.20234914v1.5" }, { "DOI": "10.1093/jac/dkaa114", "article-title": "COVID-19: a recommendation to examine the effect of hydroxychloroquine in preventing infection and progression", "doi-asserted-by": "crossref", "first-page": "1667", "issue": "7", "journal-title": "J Antimicrob Chemother", "key": "2020120211101020000_2020.11.25.20234914v1.6", "volume": "75", "year": "2020" }, { "DOI": "10.1016/S0140-6736(20)30183-5", "doi-asserted-by": "publisher", "key": "2020120211101020000_2020.11.25.20234914v1.7" }, { "DOI": "10.1038/s41584-020-0372-x", "doi-asserted-by": "publisher", "key": "2020120211101020000_2020.11.25.20234914v1.8" }, { "DOI": "10.1136/bmj.m1335", "doi-asserted-by": "publisher", "key": "2020120211101020000_2020.11.25.20234914v1.9" }, { "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", "doi-asserted-by": "crossref", "first-page": "105949", "issue": "1", "journal-title": "Int J Antimicrob Agents", "key": "2020120211101020000_2020.11.25.20234914v1.10", "volume": "56", "year": "2020" }, { "DOI": "10.1001/jama.2020.8630", "article-title": "Association of Treatment With Hydroxychloroquine or Azithromycin With In-Hospital Mortality in Patients With COVID-19 in New York State", "doi-asserted-by": "crossref", "first-page": "2493", "issue": "24", "journal-title": "JAMA", "key": "2020120211101020000_2020.11.25.20234914v1.11", "volume": "323", "year": "2020" }, { "DOI": "10.1056/NEJMoa2012410", "article-title": "Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid-19", "doi-asserted-by": "crossref", "first-page": "2411", "issue": "25", "journal-title": "N Engl J Med", "key": "2020120211101020000_2020.11.25.20234914v1.12", "volume": "382", "year": "2020" }, { "DOI": "10.1016/S0140-6736(20)31180-6", "doi-asserted-by": "crossref", "key": "2020120211101020000_2020.11.25.20234914v1.13", "unstructured": "Mehra MR , Desai SS , Ruschitzka F , Patel AN . RETRACTED: Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis. Lancet. 2020." }, { "key": "2020120211101020000_2020.11.25.20234914v1.14", "unstructured": "WHO. “Solidarity” clinical trial for COVID-19 treatments [9 November 2020]. Available from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/global-research-on-novel-coronavirus-2019-ncov/solidarity-clinical-trial-for-covid-19-treatments." }, { "DOI": "10.1101/2020.06.22.20137273", "doi-asserted-by": "crossref", "key": "2020120211101020000_2020.11.25.20234914v1.15", "unstructured": "Horby P , Mafham M , Linsell L , Bell JL , Staplin N , Emberson JR , et al. Effect of Hydroxychloroquine in Hospitalized Patients with Covid-19. N Engl J Med. 2020." }, { "DOI": "10.1001/jama.2015.13896", "doi-asserted-by": "publisher", "key": "2020120211101020000_2020.11.25.20234914v1.16" }, { "DOI": "10.1016/j.micpath.2020.104228", "doi-asserted-by": "publisher", "key": "2020120211101020000_2020.11.25.20234914v1.17" }, { "DOI": "10.1016/j.ophtha.2016.01.058", "doi-asserted-by": "publisher", "key": "2020120211101020000_2020.11.25.20234914v1.18" }, { "DOI": "10.1093/rheumatology/kel402", "doi-asserted-by": "publisher", "key": "2020120211101020000_2020.11.25.20234914v1.19" }, { "DOI": "10.1016/j.hrthm.2020.05.030", "article-title": "Fatal arrhythmias: Another reason why doctors remain cautious about chloroquine/hydroxychloroquine for treating COVID-19", "doi-asserted-by": "crossref", "first-page": "1445", "issue": "9", "journal-title": "Heart Rhythm", "key": "2020120211101020000_2020.11.25.20234914v1.20", "volume": "17", "year": "2020" }, { "DOI": "10.1016/j.hrthm.2015.05.027", "article-title": "Hydroxychloroquine reduces heart rate by modulating the hyperpolarization-activated current If: Novel electrophysiological insights and therapeutic potential", "doi-asserted-by": "crossref", "first-page": "2186", "issue": "10", "journal-title": "Heart Rhythm", "key": "2020120211101020000_2020.11.25.20234914v1.21", "volume": "12", "year": "2015" }, { "DOI": "10.1001/jamanetworkopen.2020.8857", "article-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: A Randomized Clinical Trial", "doi-asserted-by": "crossref", "first-page": "e208857", "issue": "4", "journal-title": "JAMA Netw Open", "key": "2020120211101020000_2020.11.25.20234914v1.22", "volume": "3", "year": "2020" }, { "article-title": "Liver and Kidney Injuries in COVID-19 and Their Effects on Drug Therapy; a Letter to Editor", "first-page": "e17", "issue": "1", "journal-title": "Arch Acad Emerg Med", "key": "2020120211101020000_2020.11.25.20234914v1.23", "volume": "8", "year": "2020" }, { "DOI": "10.1016/s2468-1253(20)30057-1", "doi-asserted-by": "publisher", "key": "2020120211101020000_2020.11.25.20234914v1.24" }, { "DOI": "10.1183/13993003.01112-2020", "doi-asserted-by": "crossref", "key": "2020120211101020000_2020.11.25.20234914v1.25", "unstructured": "Liu Y , Mao B , Liang S , Yang JW , Lu HW , Chai YH , et al. Association between age and clinical characteristics and outcomes of COVID-19. Eur Respir J. 2020;55(5)." }, { "DOI": "10.1093/gerona/glaa089", "article-title": "Clinical Characteristics and Outcomes of Older Patients with Coronavirus Disease 2019 (COVID-19) in Wuhan, China: A Single-Centered, Retrospective Study", "doi-asserted-by": "crossref", "first-page": "1788", "issue": "9", "journal-title": "J Gerontol A Biol Sci Med Sci", "key": "2020120211101020000_2020.11.25.20234914v1.26", "volume": "75", "year": "2020" }, { "DOI": "10.1136/bmj.m1091", "doi-asserted-by": "publisher", "key": "2020120211101020000_2020.11.25.20234914v1.27" }, { "DOI": "10.1038/s41467-020-18786-x", "article-title": "Early prediction of disease progression in COVID-19 pneumonia patients with chest CT and clinical characteristics", "doi-asserted-by": "crossref", "first-page": "4968", "issue": "1", "journal-title": "Nat Commun", "key": "2020120211101020000_2020.11.25.20234914v1.28", "volume": "11", "year": "2020" }, { "DOI": "10.3390/ijerph17165974", "doi-asserted-by": "crossref", "key": "2020120211101020000_2020.11.25.20234914v1.29", "unstructured": "Romero Starke K , Petereit-Haack G , Schubert M , Kämpf D , Schliebner A , Hegewald J , et al. The Age-Related Risk of Severe Outcomes Due to COVID-19 Infection: A Rapid Review, Meta-Analysis, and Meta-Regression. Int J Environ Res Public Health. 2020;17(16)." }, { "DOI": "10.1016/j.ijid.2020.07.029", "article-title": "Comorbidities and the risk of severe or fatal outcomes associated with coronavirus disease 2019: A systematic review and meta-analysis", "doi-asserted-by": "crossref", "first-page": "47", "journal-title": "Int J Infect Dis", "key": "2020120211101020000_2020.11.25.20234914v1.30", "volume": "99", "year": "2020" }, { "key": "2020120211101020000_2020.11.25.20234914v1.31", "unstructured": "WHO. Noncommunicable diseases country profiles 2018 [2 November 2020]. Available from: https://www.who.int/nmh/countries/2018/bhr_en.pdf?ua=1." }, { "DOI": "10.1111/ejh.13432", "article-title": "COVID-19 infection and treatment with hydroxychloroquine cause severe haemolysis crisis in a patient with glucose-6-phosphate dehydrogenase deficiency", "doi-asserted-by": "crossref", "first-page": "357", "issue": "3", "journal-title": "Eur J Haematol", "key": "2020120211101020000_2020.11.25.20234914v1.32", "volume": "105", "year": "2020" }, { "article-title": "Current coronavirus (SARS-CoV-2) epidemiological, diagnostic and therapeutic approaches: An updated review until June 2020", "first-page": "992", "journal-title": "EXCLI J", "key": "2020120211101020000_2020.11.25.20234914v1.33", "volume": "19", "year": "2020" }, { "DOI": "10.1016/j.kint.2020.03.005", "doi-asserted-by": "publisher", "key": "2020120211101020000_2020.11.25.20234914v1.34" }, { "DOI": "10.2196/19636", "article-title": "Identification of Symptoms Prognostic of COVID-19 Severity: Multivariate Data Analysis of a Case Series in Henan Province", "doi-asserted-by": "crossref", "first-page": "e19636", "issue": "6", "journal-title": "J Med Internet Res", "key": "2020120211101020000_2020.11.25.20234914v1.35", "volume": "22", "year": "2020" }, { "DOI": "10.1093/cid/ciaa674", "doi-asserted-by": "crossref", "key": "2020120211101020000_2020.11.25.20234914v1.36", "unstructured": "Bhargava A , Fukushima EA , Levine M , Zhao W , Tanveer F , Szpunar SM , et al. Predictors for Severe COVID-19 Infection. Clin Infect Dis. 2020." }, { "DOI": "10.1159/000083340", "doi-asserted-by": "publisher", "key": "2020120211101020000_2020.11.25.20234914v1.37" }, { "key": "2020120211101020000_2020.11.25.20234914v1.38", "unstructured": "Cavalcanti AB , Zampieri FG , Rosa RG , Azevedo LCP , Veiga VC , Avezum A , et al. Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19. N Engl J Med. 2020." }, { "DOI": "10.1136/bmj.m1849", "doi-asserted-by": "publisher", "key": "2020120211101020000_2020.11.25.20234914v1.39" }, { "DOI": "10.1016/j.jsps.2020.09.019", "doi-asserted-by": "crossref", "key": "2020120211101020000_2020.11.25.20234914v1.40", "unstructured": "Almazrou SH , Almalki ZS , Alanazi AS , Alqahtani AM , AlGhamd SM . Comparing the impact of Hydroxychloroquine based regimens and standard treatment on COVID-19 patient outcomes: A retrospective cohort study. Saudi Pharm J. 2020." }, { "DOI": "10.1016/j.jgar.2020.07.018", "article-title": "Hydroxychloroquine use in hospitalised patients with COVID-19: An observational matched cohort study", "doi-asserted-by": "crossref", "first-page": "842", "journal-title": "J Glob Antimicrob Resist", "key": "2020120211101020000_2020.11.25.20234914v1.41", "volume": "22", "year": "2020" }, { "DOI": "10.1136/bmj.294.6576.900", "doi-asserted-by": "publisher", "key": "2020120211101020000_2020.11.25.20234914v1.42" }, { "DOI": "10.2337/diab.33.12.1133", "doi-asserted-by": "publisher", "key": "2020120211101020000_2020.11.25.20234914v1.43" }, { "DOI": "10.1093/ofid/ofaa500", "doi-asserted-by": "crossref", "key": "2020120211101020000_2020.11.25.20234914v1.44", "unstructured": "Lofgren SMM , Nicol MR , Bangdiwala AS , Pastick KA , Okafor EC , Skipper CP , et al. Safety of Hydroxychloroquine among Outpatient Clinical Trial Participants for COVID-19. medRxiv. 2020." }, { "DOI": "10.1016/j.ipej.2020.10.002", "doi-asserted-by": "crossref", "key": "2020120211101020000_2020.11.25.20234914v1.45", "unstructured": "Agstam S , Yadav A , Praveen Kumar M , Gupta A. Hydroxychloroquine and QTc prolongation in patients with COVID-19: A systematic review and meta-analysis. Indian Pacing Electrophysiol J. 2020." }, { "DOI": "10.1001/jama.2020.22240", "doi-asserted-by": "crossref", "key": "2020120211101020000_2020.11.25.20234914v1.46", "unstructured": "Self WH , Semler MW , Leither LM , Casey JD , Angus DC , Brower RG , et al. Effect of Hydroxychloroquine on Clinical Status at 14 Days in Hospitalized Patients With COVID-19: A Randomized Clinical Trial. JAMA. 2020." } ], "reference-count": 46, "references-count": 46, "relation": {}, "resource": { "primary": { "URL": "http://medrxiv.org/lookup/doi/10.1101/2020.11.25.20234914" } }, "score": 1, "short-title": [], "source": "Crossref", "subtitle": [], "subtype": "preprint", "title": "The efficacy and safety of hydroxychloroquine in COVID19 patients : a multicenter national retrospective cohort", "type": "posted-content" }