Outcomes of 2111 COVID-19 Hospitalized Patients Treated with Hydroxychloroquine/Azithromycin and Other Regimens in Marseille, France, 2020: A Monocentric Retrospective Analysis
Jean-Christophe Lagier, Matthieu Million, Sébastien Cortaredona, Léa Delorme, Philippe Colson, Pierre-Edouard Fournier, Philippe Brouqui, Didier Raoult, Philippe Parola
Therapeutics and Clinical Risk Management, doi:10.2147/tcrm.s364022
Objectives: We evaluated the 6-week mortality of SARS-CoV-2 hospitalized patients treated using a standardized protocol in 2020 in Marseille, France. Methods: A retrospective monocentric cohort study was conducted in the standard hospital wards at the Institut Hospitalo-Universitaire Méditerranée Infection, between March and December 2020 in adults with SARS-CoV-2 PCR-proven infection. Results: Of the 2111 hospitalized patients (median age, 67 [IQR 55-79] years; 1154 [54.7%] men), 271 were transferred to the intensive care unit (12.8%) and 239 died (11.3%; the mean age of patients who died was 81.2 (±9.9)). Treatment with hydroxychloroquine plus azithromycin (HCQ-AZ), used in 1270 patients, was an independent protective factor against death (0.68 [0.52 -0.88]). This effect was consistent for all subgroups of age, comorbidities, severity of the disease and comedications with zinc or corticosteroids. Zinc was independently protective against death (0.39 [0.23 -0.67]), in a subgroup analysis of patients treated with HCQ-AZ without dexamethasone. The use of high-flow oxygen therapy in elderly patients who were not eligible for intensive care unit transfer saved 19 patients (33.9%). Conclusions: In our 2020 cohort, treating COVID-19 with HCQ-AZ was associated with lower mortality. These results need to be analyzed in the context of academic discussions about observational studies versus randomized clinical trials. More data will deserve to be analyzed in the SARS-Cov 2 variants, vaccination and post-vaccination era.
Disclosure Prof. Dr Didier Raoult reports personal fees from Scientific board member of Eurofins company, Founder and shareholder of a microbial culture company (Culture Top), received personal fees from Hitachi High-Technologies Corporation, Tokyo, Japan, from 2018 to 2020, Founder and shareholder of Biotechnology "Techno-jouvence", Founder and shareholder of a Biotech company "Gene and Green TK, Founder and shareholder of rapid diagnosis of infectious diseases company "Pocramé", outside the submitted work. The authors declare no other competing interests. Funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.
Therapeutics and Clinical Risk Management
Dovepress
References
Ader, Peiffer-Smadja, Poissy, An open-label randomized controlled trial of the effect of lopinavir/ritonavir, lopinavir/ritonavir plus IFNβ-1a and hydroxychloroquine in hospitalized patients with COVID-19, Clin Microbiol Infect,
doi:10.1016/j.cmi.2021.05.020
Aherfi, Pradines, Devaux, Drug repurposing against SARS-CoV-1, SARS-CoV-2 and MERS-CoV, Future Microbiol,
doi:10.2217/fmb-2021-0019
Amrane, Tissot-Dupont, Doudier, Rapid viral diagnosis and ambulatory management of suspected COVID-19 cases presenting at the infectious diseases referral hospital in Marseille, France, -January 31st to March 1st, 2020: a respiratory virus snapshot, Travel Med Infect Dis,
doi:10.1016/j.tmaid.2020.101632
Andreani, Bideau, Duflot, In vitro testing of combined hydroxychloroquine and azithromycin on SARS-CoV-2 shows synergistic effect, Microb Pathog,
doi:10.1016/j.micpath.2020.104228
Anglemyer, Horvath, Bero, Healthcare outcomes assessed with observational study designs compared with those assessed in randomized trials, Cochrane Database Syst Rev,
doi:10.1002/14651858.MR000034.pub2
Austin, An introduction to propensity score methods for reducing the effects of confounding in observational studies, Multivar Behav Res,
doi:10.1080/00273171.2011.568786
Boulware, Pullen, Bangdiwala, A randomized trial of hydroxychloroquine as postexposure prophylaxis for covid-19, N Engl J Med,
doi:10.1056/NEJMoa2016638
Brouqui, Drancourt, Raoult, On behalf of the ihu task force. COVID-19 management at ihu méditerranée infection: a one-year experience, J Clin Med,
doi:10.3390/jcm10132881
Cao, Wang, Wen, A trial of Lopinavir-Ritonavir in adults hospitalized with severe Covid-19, N Engl J Med,
doi:10.1056/NEJMoa2001282
Carlucci, Ahuja, Petrilli, Rajagopalan, Jones et al., Zinc sulfate in combination with a zinc ionophore may improve outcomes in hospitalized COVID-19 patients, J Med Microbiol,
doi:10.1099/jmm.0.001250
Cavalcanti, Zampieri, Rosa, Hydroxychloroquine with or without azithromycin in mild-to-moderate Covid-19, N Engl J Med,
doi:10.1056/NEJMoa2019014
Colson, Fournier, Chaudet, Analysis of SARS-CoV-2 variants from 24,181 patients exemplifies the role of globalization and zoonosis in pandemics, Front Microbiol,
doi:10.3389/fmicb.2021.786233
De Wilde, Jochmans, Posthuma, Screening of an FDA-approved compound library identifies four small-molecule inhibitors of middle east respiratory syndrome coronavirus replication in cell culture, Antimicrob Agents Chemother,
doi:10.1128/AAC.03011-14
Devaux, Rolain, Colson, Raoult, New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19?, Int J Antimicrob Agents,
doi:10.1016/j.ijantimicag.2020.105938
Edouard, Colson, Melenotte, Evaluating the serological status of COVID-19 patients using an indirect immunofluorescent assay, France, Eur J Clin Microbiol Infect Dis,
doi:10.1007/s10096-020-04104-2
Feikin, Higdon, Abu-Raddad, Duration of effectiveness of vaccines against SARS-CoV-2 infection and COVID-19 disease: results of a systematic review and meta-regression, Lancet,
doi:10.1016/S0140-6736(22)00152-0
Fried, Crawford, Mospan, Patient characteristics and outcomes of 11 721 patients with coronavirus disease 2019 (COVID-19) hospitalized across the United States, Clin Infect Dis,
doi:10.1093/cid/ciaa1268
Gao, Tian, Yang, Breakthrough: chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies, Biosci Trends,
doi:10.5582/bst.2020.01047
Gautret, Lagier, Parola, Clinical and microbiological effect of a combination of hydroxychloroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow up: an observational study, Travel Med Infect Dis,
doi:10.1016/j.tmaid.2020.101663
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,
doi:10.1056/NEJMoa2012410
Gordon, Hiatt, Bouhaddou, Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms, Science,
doi:10.1126/science.abe9403
Hayashi, Molnupiravir might be dangerous without clarification of its indications, BMJ,
doi:10.1136/bmj.o1030
Keyaerts, Vijgen, Maes, Neyts, Van Ranst, In vitro inhibition of severe acute respiratory syndrome coronavirus by chloroquine, Biochem Biophys Res Commun,
doi:10.1016/j.bbrc.2004.08.085
Lagier, Amrane, Mailhe, High-flow oxygen therapy in elderly patients infected with SARS-CoV2 with a contraindication for transfer to an intensive care unit: a preliminary report, Int J Infect Dis,
doi:10.1016/j.ijid.2021.03.087
Lagier, Million, Gautret, Outcomes of 3737 COVID-19 patients treated with hydroxychloroquine/azithromycin and other regimens in Marseille, France: a retrospective analysis, Travel Med Infect Dis,
doi:10.1016/j.tmaid.2020.101791
Lagier, Raoult, Whipple's disease and Tropheryma whipplei infections: when to suspect them and how to diagnose and treat them, Curr Opin Infect Dis,
doi:10.1097/QCO.0000000000000489
Leger, Jacquier, Barral, Low-dose chest CT for diagnosing and assessing the extent of lung involvement of SARS-CoV-2 pneumonia using a semi quantitative score, PLoS One,
doi:10.1371/journal.pone.0241407
Liao, Wang, Kang, Novel coronavirus infection during the 2019-2020 epidemic: preparing intensive care units-The experience in Sichuan Province, China, Intensive Care Med,
doi:10.1007/s00134-020-05954-2
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
Melenotte, Million, Raoult, New insights in Coxiella burnetii infection: diagnosis and therapeutic update, Expert Rev Anti Infect Ther,
doi:10.1080/14787210.2020.1699055
Million, Dudouet, Chabrière, Predictive factors of clinical assays on hydroxychloroquine for COVID-19 mortality during the first year of the pandemic: a meta-synthesis, Afr J Clin Exp Microbiol,
doi:10.4314/ajcem.v23i1.1
Million, Lagier, Gautret, Early treatment of COVID-19 patients with hydroxychloroquine and azithromycin: a retrospective analysis of 1061 cases in Marseille, France, Travel Med Infect Dis,
doi:10.1016/j.tmaid.2020.101738
Million, Lagier, Tissot-Dupont, Early combination therapy with hydroxychloroquine and azithromycin reduces mortality in 10,429 COVID-19 outpatients, Rev Cardiovasc Med,
doi:10.31083/j.rcm2203116
Mokhtari, Mohraz, Gouya, Clinical outcomes of patients with mild COVID-19 following treatment with hydroxychloroquine in an outpatient setting, Int Immunopharmacol,
doi:10.1016/j.intimp.2021.107636
Ostrov, Bluhm, Li, Highly specific sigma receptor ligands exhibit anti-viral properties in SARS-CoV-2 infected cells, Pathogens,
doi:10.3390/pathogens10111514
Recovery Collaborative Group, Horby, Lim, Emberson, Mafham et al., Dexamethasone in hospitalized patients with Covid-19, N Engl J Med,
doi:10.1056/NEJMoa2021436
Self, Semler, Leither, Effect of hydroxychloroquine on clinical status at 14 days in hospitalized patients with COVID-19: a randomized clinical trial, JAMA,
doi:10.1001/jama.2020.22240
Skipper, Pastick, Engen, Hydroxychloroquine in nonhospitalized adults with early COVID-19: a randomized trial, Ann Intern Med,
doi:10.7326/M20-4207
Sulaiman, Mohana, Alawdah, The effect of early hydroxychloroquine-based therapy in COVID-19 patients in ambulatory care settings: a nationwide prospective cohort study, medRxiv,
doi:10.1101/2020.09.09.20184143
Susen, Tacquard, Godon, Mansour, Garrigue et al., Prevention of thromboticrisk in hospitalized patients with COVID-19 and hemostasis monitoring, CritCare,
doi:10.1186/s13054-020-03000-7
Tang, Cao, Han, Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial, BMJ,
doi:10.1136/bmj.m1849
Tesei, Cortesi, Zamagni, Sigma receptors as endoplasmic reticulum stress "Gatekeepers" and their modulators as emerging new weapons in the fight against cancer, Front Pharmacol,
doi:10.3389/fphar.2018.00711
Vincent, Bergeron, Benjannet, Chloroquine is a potent inhibitor of SARS coronavirus infection and spread, Virol J,
doi:10.1186/1743-422X-2-69
Wang, Zhang, Du, Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial, Lancet Infect Dis
Wurtz, Penant, Jardot, Duclos, Scola, Culture of SARS-CoV-2 in a panel of laboratory cell lines, permissivity, and differences in growth profile, Eur J Clin Microbiol Infect Dis,
doi:10.1007/s10096-020-04106-0
{ 'indexed': { 'date-parts': [[2023, 11, 21]],
'date-time': '2023-11-21T08:17:51Z',
'timestamp': 1700554671444},
'reference-count': 54,
'publisher': 'Informa UK Limited',
'license': [ { 'start': { 'date-parts': [[2022, 5, 1]],
'date-time': '2022-05-01T00:00:00Z',
'timestamp': 1651363200000},
'content-version': 'unspecified',
'delay-in-days': 0,
'URL': 'http://creativecommons.org/licenses/by-nc/3.0/'}],
'content-domain': {'domain': [], 'crossmark-restriction': False},
'DOI': '10.2147/tcrm.s364022',
'type': 'journal-article',
'created': {'date-parts': [[2022, 5, 31]], 'date-time': '2022-05-31T09:41:09Z', 'timestamp': 1653990069000},
'page': '603-617',
'source': 'Crossref',
'is-referenced-by-count': 4,
'title': 'Outcomes of 2111 COVID-19 Hospitalized Patients Treated with Hydroxychloroquine/Azithromycin and '
'Other Regimens in Marseille, France, 2020: A Monocentric Retrospective Analysis',
'prefix': '10.2147',
'volume': 'Volume 18',
'author': [ {'given': 'Jean-Christophe', 'family': 'Lagier', 'sequence': 'additional', 'affiliation': []},
{'given': 'Matthieu', 'family': 'Million', 'sequence': 'additional', 'affiliation': []},
{'given': 'Sébastien', 'family': 'Cortaredona', 'sequence': 'additional', 'affiliation': []},
{'given': 'Léa', 'family': 'Delorme', 'sequence': 'additional', 'affiliation': []},
{ 'ORCID': 'http://orcid.org/0000-0001-6285-0308',
'authenticated-orcid': True,
'given': 'Philippe',
'family': 'Colson',
'sequence': 'additional',
'affiliation': []},
{'given': 'Pierre-Edouard', 'family': 'Fournier', 'sequence': 'additional', 'affiliation': []},
{'given': 'Philippe', 'family': 'Brouqui', 'sequence': 'additional', 'affiliation': []},
{'given': 'Didier', 'family': 'Raoult', 'sequence': 'additional', 'affiliation': []},
{ 'ORCID': 'http://orcid.org/0000-0002-1061-1927',
'authenticated-orcid': True,
'given': 'Philippe',
'family': 'Parola',
'sequence': 'additional',
'affiliation': []}],
'member': '301',
'published-online': {'date-parts': [[2022, 5]]},
'reference': [ { 'key': 'ref1',
'unstructured': 'Johns Hopkins University. Coronavirus Resource Center. COVID-19 '
'dashboard by the Center for Systems Science and Engineering (CSSE) at '
'Johns Hopkins University (JHU). Available from: '
'https://coronavirus.jhu.edu/map.html. Accessed January 17, 2022.'},
{ 'key': 'ref2',
'doi-asserted-by': 'publisher',
'first-page': '72',
'DOI': '10.5582/bst.2020.01047',
'volume': '14',
'author': 'Gao',
'year': '2020',
'journal-title': 'Biosci Trends'},
{ 'key': 'ref3',
'doi-asserted-by': 'publisher',
'first-page': '16',
'DOI': '10.1038/s41421-020-0156-0',
'volume': '6',
'author': 'Liu',
'year': '2020',
'journal-title': 'Cell Discov'},
{ 'key': 'ref4',
'doi-asserted-by': 'publisher',
'first-page': '104228',
'DOI': '10.1016/j.micpath.2020.104228',
'volume': '145',
'author': 'Andreani',
'year': '2020',
'journal-title': 'Microb Pathog'},
{ 'key': 'ref5',
'doi-asserted-by': 'publisher',
'first-page': '105949',
'DOI': '10.1016/j.ijantimicag.2020.105949',
'volume': '56',
'author': 'Gautret',
'year': '2020',
'journal-title': 'Int J Antimicrob Agents'},
{ 'key': 'ref6',
'doi-asserted-by': 'publisher',
'first-page': '101663',
'DOI': '10.1016/j.tmaid.2020.101663',
'volume': '34',
'author': 'Gautret',
'year': '2020',
'journal-title': 'Travel Med Infect Dis'},
{ 'key': 'ref7',
'doi-asserted-by': 'publisher',
'first-page': '101738',
'DOI': '10.1016/j.tmaid.2020.101738',
'volume': '35',
'author': 'Million',
'year': '2020',
'journal-title': 'Travel Med Infect Dis'},
{ 'key': 'ref8',
'doi-asserted-by': 'publisher',
'first-page': '1787',
'DOI': '10.1056/NEJMoa2001282',
'volume': '382',
'author': 'Cao',
'year': '2020',
'journal-title': 'N Engl J Med'},
{ 'key': 'ref9',
'first-page': '1569',
'volume': '395',
'author': 'Wang',
'year': '2020',
'journal-title': 'Lancet Infect Dis'},
{ 'key': 'ref10',
'doi-asserted-by': 'crossref',
'unstructured': 'RECOVERY Collaborative Group, Horby P, Lim WS, Emberson JR, Mafham M, '
'Bell JL et al. Dexamethasone in hospitalized patients with Covid-19. N '
'Engl J Med. 2021;384(8):693–704. doi:10.1056/NEJMoa2021436',
'DOI': '10.1056/NEJMoa2021436'},
{ 'key': 'ref11',
'doi-asserted-by': 'publisher',
'first-page': '264',
'DOI': '10.1016/j.bbrc.2004.08.085',
'volume': '323',
'author': 'Keyaerts',
'year': '2004',
'journal-title': 'Biochem Biophys Res Commun'},
{ 'key': 'ref12',
'doi-asserted-by': 'publisher',
'first-page': '69',
'DOI': '10.1186/1743-422X-2-69',
'volume': '2',
'author': 'Vincent',
'year': '2005',
'journal-title': 'Virol J'},
{ 'key': 'ref13',
'doi-asserted-by': 'publisher',
'first-page': '4875',
'DOI': '10.1128/AAC.03011-14',
'volume': '58',
'author': 'de Wilde',
'year': '2014',
'journal-title': 'Antimicrob Agents Chemother'},
{ 'key': 'ref14',
'doi-asserted-by': 'publisher',
'first-page': '459',
'DOI': '10.1038/s41586-020-2286-9',
'volume': '583',
'author': 'Gordon',
'year': '2020',
'journal-title': 'Nature'},
{ 'key': 'ref15',
'doi-asserted-by': 'publisher',
'first-page': 'eabe9403',
'DOI': '10.1126/science.abe9403',
'volume': '370',
'author': 'Gordon',
'year': '2020',
'journal-title': 'Science'},
{ 'key': 'ref16',
'doi-asserted-by': 'publisher',
'first-page': '1159',
'DOI': '10.1080/1744666X.2021.1847640',
'volume': '16',
'author': 'Gautret',
'year': '2020',
'journal-title': 'Expert Rev Clin Immunol'},
{ 'key': 'ref17',
'doi-asserted-by': 'publisher',
'first-page': '105938',
'DOI': '10.1016/j.ijantimicag.2020.105938',
'volume': '55',
'author': 'Devaux',
'year': '2020',
'journal-title': 'Int J Antimicrob Agents'},
{ 'key': 'ref18',
'doi-asserted-by': 'publisher',
'first-page': '1514',
'DOI': '10.3390/pathogens10111514',
'volume': '10',
'author': 'Ostrov',
'year': '2021',
'journal-title': 'Pathogens'},
{ 'key': 'ref19',
'doi-asserted-by': 'publisher',
'first-page': '711',
'DOI': '10.3389/fphar.2018.00711',
'volume': '9',
'author': 'Tesei',
'year': '2018',
'journal-title': 'Front Pharmacol'},
{ 'key': 'ref20',
'doi-asserted-by': 'crossref',
'unstructured': 'RECOVERY Collaborative Group, Horby P, Mafham M, et al. Effect of '
'hydroxychloroquine in hospitalized patients with Covid-19. N Engl J Med. '
'2020;383:2030. doi:10.1056/NEJMoa2022926',
'DOI': '10.1056/NEJMoa2022926'},
{ 'key': 'ref21',
'doi-asserted-by': 'publisher',
'first-page': 'm1849',
'DOI': '10.1136/bmj.m1849',
'volume': '369',
'author': 'Tang',
'year': '2020',
'journal-title': 'BMJ'},
{ 'key': 'ref22',
'doi-asserted-by': 'publisher',
'first-page': '2041',
'DOI': '10.1056/NEJMoa2019014',
'volume': '383',
'author': 'Cavalcanti',
'year': '2020',
'journal-title': 'N Engl J Med'},
{ 'key': 'ref23',
'doi-asserted-by': 'publisher',
'first-page': '2165',
'DOI': '10.1001/jama.2020.22240',
'volume': '324',
'author': 'Self',
'year': '2020',
'journal-title': 'JAMA'},
{ 'key': 'ref24',
'doi-asserted-by': 'publisher',
'first-page': '2411',
'DOI': '10.1056/NEJMoa2012410',
'volume': '382',
'author': 'Geleris',
'year': '2020',
'journal-title': 'N Engl J Med'},
{ 'key': 'ref25',
'doi-asserted-by': 'publisher',
'first-page': '463',
'DOI': '10.1097/QCO.0000000000000489',
'volume': '31',
'author': 'Lagier',
'year': '2018',
'journal-title': 'Curr Opin Infect Dis'},
{ 'key': 'ref26',
'doi-asserted-by': 'publisher',
'first-page': '75',
'DOI': '10.1080/14787210.2020.1699055',
'volume': '18',
'author': 'Melenotte',
'year': '2020',
'journal-title': 'Expert Rev Anti Infect Ther'},
{ 'key': 'ref27',
'doi-asserted-by': 'publisher',
'first-page': 'e558',
'DOI': '10.1093/cid/ciaa1268',
'volume': '72',
'author': 'Fried',
'year': '2021',
'journal-title': 'Clin Infect Dis'},
{ 'key': 'ref28',
'doi-asserted-by': 'publisher',
'first-page': '623e31',
'DOI': '10.7326/M20-4207',
'volume': '173',
'author': 'Skipper',
'year': '2020',
'journal-title': 'Ann Intern Med'},
{ 'key': 'ref29',
'doi-asserted-by': 'publisher',
'first-page': '517e25',
'DOI': '10.1056/NEJMoa2016638',
'volume': '383',
'author': 'Boulware',
'year': '2020',
'journal-title': 'N Engl J Med'},
{ 'key': 'ref30',
'doi-asserted-by': 'publisher',
'first-page': '1826',
'DOI': '10.1016/j.cmi.2021.05.020',
'volume': '27',
'author': 'Ader',
'year': '2021',
'journal-title': 'Clin Microbiol Infect'},
{ 'key': 'ref31',
'doi-asserted-by': 'publisher',
'author': 'Sulaiman',
'year': '2020',
'journal-title': 'medRxiv',
'DOI': '10.1101/2020.09.09.20184143'},
{ 'key': 'ref32',
'doi-asserted-by': 'publisher',
'first-page': '107636',
'DOI': '10.1016/j.intimp.2021.107636',
'volume': '96',
'author': 'Mokhtari',
'year': '2021',
'journal-title': 'Int Immunopharmacol'},
{ 'key': 'ref33',
'unstructured': 'Global HCQ/CQ studies. Available from: https://c19study.com. Accessed '
'May 24, 2022.'},
{ 'key': 'ref34',
'doi-asserted-by': 'publisher',
'first-page': '101791',
'DOI': '10.1016/j.tmaid.2020.101791',
'volume': '36',
'author': 'Lagier',
'year': '2020',
'journal-title': 'Travel Med Infect Dis'},
{ 'key': 'ref35',
'doi-asserted-by': 'publisher',
'first-page': '1063',
'DOI': '10.31083/j.rcm2203116',
'volume': '22',
'author': 'Million',
'year': '2021',
'journal-title': 'Rev Cardiovasc Med'},
{ 'key': 'ref36',
'doi-asserted-by': 'publisher',
'first-page': '1228',
'DOI': '10.1099/jmm.0.001250',
'volume': '69',
'author': 'Carlucci',
'year': '2020',
'journal-title': 'J Med Microbiol'},
{ 'key': 'ref37',
'doi-asserted-by': 'publisher',
'first-page': '101632',
'DOI': '10.1016/j.tmaid.2020.101632',
'volume': '36',
'author': 'Amrane',
'year': '2020',
'journal-title': 'Travel Med Infect Dis'},
{ 'key': 'ref38',
'doi-asserted-by': 'publisher',
'first-page': '2881',
'DOI': '10.3390/jcm10132881',
'volume': '10',
'author': 'Brouqui',
'year': '2021',
'journal-title': 'J Clin Med'},
{ 'key': 'ref39',
'doi-asserted-by': 'publisher',
'first-page': '1245',
'DOI': '10.1016/0895-4356(94)90129-5',
'volume': '47',
'author': 'Charlson',
'year': '1994',
'journal-title': 'J Clin Epidemiol'},
{ 'key': 'ref40',
'doi-asserted-by': 'publisher',
'first-page': '357',
'DOI': '10.1007/s00134-020-05954-2',
'volume': '46',
'author': 'Liao',
'year': '2020',
'journal-title': 'Intensive Care Med'},
{ 'key': 'ref41',
'doi-asserted-by': 'publisher',
'first-page': '361',
'DOI': '10.1007/s10096-020-04104-2',
'volume': '40',
'author': 'Edouard',
'year': '2021',
'journal-title': 'Eur J Clin Microbiol Infect Dis'},
{ 'key': 'ref42',
'doi-asserted-by': 'publisher',
'first-page': '477',
'DOI': '10.1007/s10096-020-04106-0',
'volume': '40',
'author': 'Wurtz',
'year': '2021',
'journal-title': 'Eur J Clin Microbiol Infect Dis'},
{ 'key': 'ref43',
'doi-asserted-by': 'publisher',
'first-page': 'e0241407',
'DOI': '10.1371/journal.pone.0241407',
'volume': '15',
'author': 'Leger',
'year': '2020',
'journal-title': 'PLoS One'},
{ 'key': 'ref44',
'doi-asserted-by': 'crossref',
'unstructured': 'Susen S, Tacquard CA, Godon A, Mansour A, Garrigue D, Nguyen P, Godier '
'A,Testa S, Levy JH, Albaladejo P, Gruel Y; GIHP and GFHT. Prevention of '
'thromboticrisk in hospitalized patients with COVID-19 and hemostasis '
'monitoring. CritCare. 2020 Jun 19;24(1):364. '
'doi:10.1186/s13054-020-03000-7. PMID: 32560658;PMCID: PMC7303590.',
'DOI': '10.1186/s13054-020-03000-7'},
{ 'key': 'ref45',
'doi-asserted-by': 'publisher',
'first-page': '1',
'DOI': '10.1016/j.ijid.2021.03.087',
'volume': '108',
'author': 'Lagier',
'year': '2021',
'journal-title': 'Int J Infect Dis'},
{ 'key': 'ref46',
'doi-asserted-by': 'publisher',
'DOI': '10.1080/00273171.2011.568786',
'volume': '46',
'author': 'Austin',
'year': '2011',
'journal-title': 'Multivar Behav Res'},
{ 'key': 'ref47',
'doi-asserted-by': 'publisher',
'first-page': '100714',
'DOI': '10.1016/j.nmni.2020.100714',
'volume': '37',
'author': 'Gautret',
'year': '2020',
'journal-title': 'New Microbes New Infect'},
{ 'key': 'ref48',
'doi-asserted-by': 'publisher',
'first-page': 'MR000034',
'DOI': '10.1002/14651858.MR000034.pub2',
'author': 'Anglemyer',
'year': '2014',
'journal-title': 'Cochrane Database Syst Rev'},
{ 'key': 'ref49',
'doi-asserted-by': 'publisher',
'first-page': '1640',
'DOI': '10.1038/s41591-019-0624-y',
'volume': '25',
'author': 'Janket',
'year': '2019',
'journal-title': 'Nat Med'},
{ 'key': 'ref50',
'doi-asserted-by': 'publisher',
'first-page': '1',
'DOI': '10.4314/ajcem.v23i1.1',
'volume': '23',
'author': 'Million',
'year': '2022',
'journal-title': 'Afr J Clin Exp Microbiol'},
{ 'key': 'ref51',
'doi-asserted-by': 'publisher',
'first-page': '1341',
'DOI': '10.2217/fmb-2021-0019',
'volume': '16',
'author': 'Aherfi',
'year': '2021',
'journal-title': 'Future Microbiol'},
{ 'key': 'ref52',
'doi-asserted-by': 'publisher',
'first-page': 'o1030',
'DOI': '10.1136/bmj.o1030',
'volume': '377',
'author': 'Hayashi',
'year': '2022',
'journal-title': 'BMJ'},
{ 'key': 'ref53',
'doi-asserted-by': 'publisher',
'first-page': '786233',
'DOI': '10.3389/fmicb.2021.786233',
'volume': '12',
'author': 'Colson',
'year': '2022',
'journal-title': 'Front Microbiol'},
{ 'key': 'ref54',
'doi-asserted-by': 'publisher',
'first-page': '924',
'DOI': '10.1016/S0140-6736(22)00152-0',
'volume': '399',
'author': 'Feikin',
'year': '2022',
'journal-title': 'Lancet'}],
'container-title': 'Therapeutics and Clinical Risk Management',
'original-title': [],
'language': 'en',
'link': [ { 'URL': 'https://www.dovepress.com/getfile.php?fileID=81167',
'content-type': 'application/pdf',
'content-version': 'vor',
'intended-application': 'text-mining'},
{ 'URL': 'https://www.dovepress.com/getfile.php?fileID=81167',
'content-type': 'application/pdf',
'content-version': 'vor',
'intended-application': 'similarity-checking'}],
'deposited': { 'date-parts': [[2022, 5, 31]],
'date-time': '2022-05-31T09:41:16Z',
'timestamp': 1653990076000},
'score': 1,
'resource': { 'primary': { 'URL': 'https://www.dovepress.com/outcomes-of-2111-covid-19-hospitalized-patients-treated-with-hydroxych-peer-reviewed-fulltext-article-TCRM'}},
'subtitle': [],
'short-title': [],
'issued': {'date-parts': [[2022, 5]]},
'references-count': 54,
'URL': 'http://dx.doi.org/10.2147/TCRM.S364022',
'relation': {},
'ISSN': ['1178-203X'],
'subject': [ 'Chemical Health and Safety', 'Pharmacology (medical)',
'General Pharmacology, Toxicology and Pharmaceutics', 'Safety Research', 'General Medicine'],
'container-title-short': 'TCRM',
'published': {'date-parts': [[2022, 5]]}}