Association of Treatment With Hydroxychloroquine or Azithromycin With In-Hospital Mortality in Patients With COVID-19 in New York State
PhD Eli S Rosenberg, MD Elizabeth M Dufort, PhD Tomoko Udo, MS Larissa A Wilberschied, DO; Jessica Kumar, PhD James Tesoriero, PA Patti Weinberg, MPH James Kirkwood, MPH Alison Muse, MD Jack Dehovitz, MD Debra S Blog, MPH Brad Hutton, PhD David R Holtgrave, MD Howard A Zucker
JAMA, doi:10.1001/jama.2020.8630
IMPORTANCE Hydroxychloroquine, with or without azithromycin, has been considered as a possible therapeutic agent for patients with coronavirus disease 2019 (COVID-19). However, there are limited data on efficacy and associated adverse events. OBJECTIVE To describe the association between use of hydroxychloroquine, with or without azithromycin, and clinical outcomes among hospital inpatients diagnosed with COVID-19.
DESIGN, SETTING, AND PARTICIPANTS Retrospective multicenter cohort study of patients from a random sample of all admitted patients with laboratory-confirmed COVID-19 in 25 hospitals, representing 88.2% of patients with COVID-19 in the New York metropolitan region. Eligible patients were admitted for at least 24 hours between March 15 and 28, 2020. Medications, preexisting conditions, clinical measures on admission, outcomes, and adverse events were abstracted from medical records. The date of final follow-up was April 24, 2020.
Abbreviations: COVID-19, coronavirus disease 2019; ICU, intensive care unit; IQR, interquartile range. a Receipt of intensive care may not have been in a traditional critical care unit. b Based on open-text and ICD-10 fields for cause of death. Causes are not mutually exclusive. c Denominator is the total patient-days in the hospital experienced by the group. d Not applicable (NA) because there was only 1 patient in this group still admitted at analysis.
ARTICLE INFORMATION
References
Cdc Covid-, Preliminary estimates of the prevalence of selected underlying health conditions among patients with coronavirus disease 2019 -United States, February 12, MMWR Morb Mortal Wkly Rep,
doi:10.15585/mmwr.mm6913e2
Chen, Hu, Zhang, Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial. medRxiv,
doi:10.1101/2020.03.22.20040758
Chorin, Dai, Shulman, The QT interval in patients with COVID-19 treated with hydroxychloroquine and azithromycin, Nat Med. Published online,
doi:10.1038/s41591-020-0888-2
Davis, Hyde, Bangdiwala, Nelson, An example of dependencies among variables in a conditional logistic regression
Fda, Fact sheet for health care providers: emergency use authorization (EUA) of hydroxychloroquine sulfate supplied from the strategic national stockpile for treatment of COVID-19 in certain hospitalized patients, Posted
Garg, Kim, Whitaker, Hospitalization rates and characteristics of patients hospitalized with laboratory-confirmed coronavirus disease 2019 -COVID-NET, 14 States, MMWR Morb Mortal Wkly Rep,
doi:10.15585/mmwr.mm6915e3
Gautret, Lagier, Parola, Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial, Int J Antimicrob Agents,
doi:10.1016/j.ijantimicag.2020.105949
Geleris, Sun, Platt, Observational study of hydroxychloroquine in hospitalized patients with Covid-19, N Engl J Med. Published online,
doi:10.1056/NEJMoa2012410
Gorgels, Gijsbers, De Vreede-Swagemakers, Lousberg, Wellens, Out-of-hospital cardiac arrest: the relevance of heart failure, Eur Heart J,
doi:10.1016/S0195-668X(03)00191-X
Goyal, Choi, Pinheiro, Clinical characteristics of Covid-19 in New York City, N Engl J Med. Published online,
doi:10.1056/NEJMc2010419
Hung, Wang, Lin, Wang, Chiou et al., Hydroxychloroquine may be associated with reduced risk of coronary artery diseases in patients with rheumatoid arthritis: A nationwide population-based cohort study, Int J Clin Pract,
doi:10.1111/ijcp.13095
Liu, Cao, Xu, Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro, Cell Discov,
doi:10.1038/s41421-020-0156-0
Magagnoli, Narendran, Pereira, Outcomes of hydroxychloroquine usage in United States veterans hospitalized with Covid-19. medRxiv,
doi:10.1101/2020.04.16.20065920
Mahevas, Tran, Roumier, No evidence of clinical efficacy of hydroxychloroquine in patients hospitalized for COVID-19 infection with oxygen requirement: results of a study using routinely collected data to emulate a target trial. medRxiv,
doi:10.1101/2020.04.10.20060699
Mcghie, Harvey, Su, Anderson, Tomlinson et al., Electrocardiogram abnormalities related to anti-malarials in systemic lupus erythematosus, Clin Exp Rheumatol
Petrilli, Jones, Yang, Factors associated with hospitalization and critical illness among 4,103 patients with COVID-19 disease in New York City. medRxiv,
doi:10.1101/2020.04.08.20057794
Rosenberg, Dufort, Blog, COVID-19 testing, epidemic features, hospital outcomes, and household prevalence, New York State, Clin Infect Dis. Published online,
doi:10.1093/cid/ciaa549
Tracker, None
Vanderweele, Ding, Sensitivity analysis in observational research: introducing the E-value, Ann Intern Med,
doi:10.7326/M16-2607
Yao, Ye, Zhang, In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Clin Infect Dis,
doi:10.1093/cid/ciaa237
Zhou, Yu, Du, Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study, Lancet,
doi:10.1016/S0140-6736(20)30566-3
{ 'indexed': {'date-parts': [[2024, 4, 5]], 'date-time': '2024-04-05T00:16:51Z', 'timestamp': 1712276211182},
'reference-count': 32,
'publisher': 'American Medical Association (AMA)',
'issue': '24',
'content-domain': {'domain': [], 'crossmark-restriction': False},
'published-print': {'date-parts': [[2020, 6, 23]]},
'DOI': '10.1001/jama.2020.8630',
'type': 'journal-article',
'created': {'date-parts': [[2020, 5, 12]], 'date-time': '2020-05-12T04:18:58Z', 'timestamp': 1589257138000},
'page': '2493',
'source': 'Crossref',
'is-referenced-by-count': 857,
'title': 'Association of Treatment With Hydroxychloroquine or Azithromycin With In-Hospital Mortality in '
'Patients With COVID-19 in New York State',
'prefix': '10.1001',
'volume': '323',
'author': [ { 'given': 'Eli S.',
'family': 'Rosenberg',
'sequence': 'first',
'affiliation': [ { 'name': 'University at Albany School of Public Health, State University '
'of New York, Rensselaer'}]},
{ 'given': 'Elizabeth M.',
'family': 'Dufort',
'sequence': 'additional',
'affiliation': [{'name': 'New York State Department of Health, Albany'}]},
{ 'given': 'Tomoko',
'family': 'Udo',
'sequence': 'additional',
'affiliation': [ { 'name': 'University at Albany School of Public Health, State University '
'of New York, Rensselaer'}]},
{ 'given': 'Larissa A.',
'family': 'Wilberschied',
'sequence': 'additional',
'affiliation': [{'name': 'New York State Department of Health, Albany'}]},
{ 'given': 'Jessica',
'family': 'Kumar',
'sequence': 'additional',
'affiliation': [{'name': 'New York State Department of Health, Albany'}]},
{ 'given': 'James',
'family': 'Tesoriero',
'sequence': 'additional',
'affiliation': [{'name': 'New York State Department of Health, Albany'}]},
{ 'given': 'Patti',
'family': 'Weinberg',
'sequence': 'additional',
'affiliation': [{'name': 'IPRO, Lake Success, New York'}]},
{ 'given': 'James',
'family': 'Kirkwood',
'sequence': 'additional',
'affiliation': [{'name': 'New York State Department of Health, Albany'}]},
{ 'given': 'Alison',
'family': 'Muse',
'sequence': 'additional',
'affiliation': [{'name': 'New York State Department of Health, Albany'}]},
{ 'given': 'Jack',
'family': 'DeHovitz',
'sequence': 'additional',
'affiliation': [ {'name': 'IPRO, Lake Success, New York'},
{ 'name': 'Downstate Health Sciences University, State University of New '
'York, Brooklyn'}]},
{ 'given': 'Debra S.',
'family': 'Blog',
'sequence': 'additional',
'affiliation': [{'name': 'New York State Department of Health, Albany'}]},
{ 'given': 'Brad',
'family': 'Hutton',
'sequence': 'additional',
'affiliation': [{'name': 'New York State Department of Health, Albany'}]},
{ 'given': 'David R.',
'family': 'Holtgrave',
'sequence': 'additional',
'affiliation': [ { 'name': 'University at Albany School of Public Health, State University '
'of New York, Rensselaer'}]},
{ 'given': 'Howard A.',
'family': 'Zucker',
'sequence': 'additional',
'affiliation': [{'name': 'New York State Department of Health, Albany'}]}],
'member': '10',
'reference': [ { 'issue': '10223',
'key': 'joi200055r1',
'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'},
{ 'key': 'joi200055r3',
'article-title': 'COVID-19 testing, epidemic features, hospital outcomes, and household '
'prevalence, New York State—March 2020.',
'author': 'Rosenberg',
'journal-title': 'Clin Infect Dis'},
{ 'issue': '1',
'key': 'joi200055r5',
'doi-asserted-by': 'publisher',
'first-page': '16',
'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.',
'volume': '6',
'author': 'Liu',
'year': '2020',
'journal-title': 'Cell Discov'},
{ 'key': 'joi200055r6',
'doi-asserted-by': 'crossref',
'DOI': '10.1093/cid/ciaa237',
'article-title': 'In vitro antiviral activity and projection of optimized dosing design '
'of hydroxychloroquine for the treatment of severe acute respiratory '
'syndrome coronavirus 2 (SARS-CoV-2).',
'author': 'Yao',
'year': '2020',
'journal-title': 'Clin Infect Dis'},
{ 'issue': '4',
'key': 'joi200055r7',
'doi-asserted-by': 'crossref',
'DOI': '10.1016/j.ijantimicag.2020.105932',
'article-title': 'Chloroquine and hydroxychloroquine as available weapons to fight '
'COVID-19.',
'volume': '55',
'author': 'Colson',
'year': '2020',
'journal-title': 'Int J Antimicrob Agents'},
{ 'key': 'joi200055r8',
'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': 'joi200055r10',
'first-page': '545',
'article-title': 'Electrocardiogram abnormalities related to anti-malarials in systemic '
'lupus erythematosus.',
'volume': '36',
'author': 'McGhie',
'year': '2018',
'journal-title': 'Clin Exp Rheumatol'},
{ 'issue': '5',
'key': 'joi200055r11',
'doi-asserted-by': 'crossref',
'DOI': '10.1111/ijcp.13095',
'article-title': 'Hydroxychloroquine may be associated with reduced risk of coronary '
'artery diseases in patients with rheumatoid arthritis: A nationwide '
'population-based cohort study.',
'volume': '72',
'author': 'Hung',
'year': '2018',
'journal-title': 'Int J Clin Pract'},
{ 'key': 'joi200055r12',
'doi-asserted-by': 'crossref',
'DOI': '10.1038/s41591-020-0888-2',
'article-title': 'The QT interval in patients with COVID-19 treated with '
'hydroxychloroquine and azithromycin.',
'author': 'Chorin',
'year': '2020',
'journal-title': 'Nat Med'},
{ 'issue': '4',
'key': 'joi200055r13',
'doi-asserted-by': 'crossref',
'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.',
'volume': '3',
'author': 'Borba',
'year': '2020',
'journal-title': 'JAMA Netw Open'},
{ 'issue': '15',
'key': 'joi200055r15',
'doi-asserted-by': 'publisher',
'first-page': '458',
'DOI': '10.15585/mmwr.mm6915e3',
'article-title': 'Hospitalization rates and characteristics of patients hospitalized with '
'laboratory-confirmed coronavirus disease 2019 - COVID-NET, 14 States, '
'March 1-30, 2020.',
'volume': '69',
'author': 'Garg',
'year': '2020',
'journal-title': 'MMWR Morb Mortal Wkly Rep'},
{ 'issue': '13',
'key': 'joi200055r16',
'doi-asserted-by': 'publisher',
'first-page': '382',
'DOI': '10.15585/mmwr.mm6913e2',
'article-title': 'Preliminary estimates of the prevalence of selected underlying health '
'conditions among patients with coronavirus disease 2019 - United '
'States, February 12-March 28, 2020.',
'volume': '69',
'author': 'CDC COVID-19 Response Team',
'year': '2020',
'journal-title': 'MMWR Morb Mortal Wkly Rep'},
{ 'key': 'joi200055r18',
'doi-asserted-by': 'crossref',
'DOI': '10.1056/NEJMc2010419',
'article-title': 'Clinical characteristics of Covid-19 in New York City.',
'author': 'Goyal',
'year': '2020',
'journal-title': 'N Engl J Med'},
{ 'issue': '408',
'key': 'joi200055r21',
'doi-asserted-by': 'publisher',
'first-page': '1074',
'DOI': '10.1080/01621459.1989.10478874',
'article-title': 'The Robust inference for the Cox proportional hazards model.',
'volume': '84',
'author': 'Lin',
'year': '1989',
'journal-title': 'J Am Stat Assoc'},
{ 'issue': '4',
'key': 'joi200055r22',
'doi-asserted-by': 'publisher',
'first-page': '268',
'DOI': '10.7326/M16-2607',
'article-title': 'Sensitivity analysis in observational research: introducing the '
'E-value.',
'volume': '167',
'author': 'VanderWeele',
'year': '2017',
'journal-title': 'Ann Intern Med'},
{ 'key': 'joi200055r24',
'article-title': 'Observational study of hydroxychloroquine in hospitalized patients with '
'Covid-19.',
'author': 'Geleris',
'journal-title': 'N Engl J Med'},
{ 'issue': '13',
'key': 'joi200055r25',
'doi-asserted-by': 'publisher',
'first-page': '1204',
'DOI': '10.1016/S0195-668X(03)00191-X',
'article-title': 'Out-of-hospital cardiac arrest: the relevance of heart failure.',
'volume': '24',
'author': 'Gorgels',
'year': '2003',
'journal-title': 'Eur Heart J'},
{ 'issue': '5',
'key': 'joi200055r26',
'doi-asserted-by': 'crossref',
'DOI': '10.1161/JAHA.114.001339',
'article-title': 'Importance of coronary artery disease in sudden cardiac death.',
'volume': '3',
'author': 'Low',
'year': '2014',
'journal-title': 'J Am Heart Assoc'},
{ 'key': 'joi200055r27',
'doi-asserted-by': 'crossref',
'DOI': '10.1001/jama.2020.6775',
'article-title': 'Presenting characteristics, comorbidities, and outcomes among 5700 '
'patients hospitalized with COVID-19 in the New York City area.',
'author': 'Richardson',
'year': '2020',
'journal-title': 'JAMA'},
{ 'issue': '10229',
'key': 'joi200055r28',
'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': 'joi200055r29',
'doi-asserted-by': 'crossref',
'DOI': '10.1001/jama.2020.6548',
'article-title': 'COVID-19 and African Americans.',
'author': 'Yancy',
'year': '2020',
'journal-title': 'JAMA'},
{'key': 'joi200055r9', 'author': 'Chen', 'year': '2020'},
{'key': 'joi200055r17', 'author': 'Magagnoli', 'year': '2020'},
{'key': 'joi200055r19', 'author': 'Petrilli', 'year': '2020'},
{'key': 'joi200055r20', 'author': 'Davis', 'year': '1986'},
{'key': 'joi200055r23', 'author': 'Mahevas', 'year': '2020'},
{ 'key': 'joi200055r2',
'unstructured': 'The Center for Systems Science and Engineering at Johns Hopkins '
'University. COVID-19 dashboard. 2020. Accessed March 24, 2020. '
'https://gisanddata.maps.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299423467b48e9ecf6'},
{ 'key': 'joi200055r4',
'unstructured': 'New York State Department of Health. COVID-19 Tracker. 2020. Accessed '
'May 7, 2020. '
'https://covid19tracker.health.ny.gov/views/NYS-COVID19-Tracker/NYSDOHCOVID-19Tracker-Map?%3Aembed=yes&%3Atoolbar=no&%3Atabs=n'},
{ 'key': 'joi200055r14',
'unstructured': 'FDA. Fact sheet for health care providers: emergency use authorization '
'(EUA) of hydroxychloroquine sulfate supplied from the strategic national '
'stockpile for treatment of COVID-19 in certain hospitalized patients. '
'Posted April 27, 2020. Accessed May 7, 2020. '
'https://www.fda.gov/media/136537/download'},
{ 'key': 'joi200055r30',
'unstructured': 'NIH. COVID-19 treatment guidelines. Accessed April 24, 2020. '
'https://covid19treatmentguidelines.nih.gov/introduction/'},
{ 'key': 'joi200055r31',
'unstructured': 'Infectious Diseases Society of America Guidelines on the Treatment and '
'Management of Patients with COVID-19. Posted April 11, 2020. Accessed '
'April 24, 2020. '
'https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/'},
{ 'key': 'joi200055r32',
'unstructured': 'FDA Drug Safety Communication. FDA cautions against use of '
'hydroxychloroquine or chloroquine for COVID-19 outside of the hospital '
'setting or a clinical trial due to risk of heart rhythm problems. Posted '
'April 24, 2020. Accessed May 8, 2020. '
'https://www.fda.gov/media/137250/download'}],
'container-title': 'JAMA',
'original-title': [],
'language': 'en',
'link': [ { 'URL': 'https://jamanetwork.com/journals/jama/articlepdf/2766117/jama_rosenberg_2020_oi_200055.pdf',
'content-type': 'unspecified',
'content-version': 'vor',
'intended-application': 'similarity-checking'}],
'deposited': { 'date-parts': [[2020, 6, 23]],
'date-time': '2020-06-23T15:02:11Z',
'timestamp': 1592924531000},
'score': 1,
'resource': {'primary': {'URL': 'https://jamanetwork.com/journals/jama/fullarticle/2766117'}},
'subtitle': [],
'short-title': [],
'issued': {'date-parts': [[2020, 6, 23]]},
'references-count': 32,
'journal-issue': {'issue': '24', 'published-print': {'date-parts': [[2020, 6, 23]]}},
'URL': 'http://dx.doi.org/10.1001/jama.2020.8630',
'relation': {},
'ISSN': ['0098-7484'],
'subject': ['General Medicine'],
'container-title-short': 'JAMA',
'published': {'date-parts': [[2020, 6, 23]]}}