Observational Study of the Efficiency of Treatments in Patients Hospitalized with Covid-19 in Madrid
Nikolas Bernaola, Raquel Mena, Ander Bernaola, Cesar Carballo, Antonio Lara, Concha Bielza, Pedro Larrañaga
doi:10.1101/2020.07.17.20155960
Background Many different treatments were heavily administered to patients with COVID-19 during the peak of the pandemic in Madrid without robust evidence supporting them.
Methods We examined the association between sixteen treatments in four groups (steroids, antivirals, antibiotics and immunomodulators) and intubation or death. Data were obtained from patients that were admitted to an HM hospital with suspicion of COVID-19 until 24/04/2020, excluding unconfirmed diagnosis, those who were admitted before the epidemic started in Madrid, had an outcome that was not discharge or death or died within 24 hours of presentation. We compared outcomes between treated and untreated patients using propensity-score caliper matching.
Results Of 2,307 patients in the dataset, 679 were excluded. Of the remaining 1,645 patients, 263 (16%) died and 311 (18.9%) died or were intubated. Except for hydroxychloroquine and prednisone, patients that were treated with any of the medications were more likely to go through an outcome of death or intubation at baseline. After propensity matching we found an association between treatment with hydroxychloroquine and prednisone and better outcomes (hazard ratios with 95% CI of 0.83 ± 0.06 and 0.85 ± 0.03). Results were similar in multiple sensitivity analyses.
Conclusions In this multicenter study of patients admitted with COVID-19 hydroxychloroquine and prednisone administration was found to be associated with improved outcomes. Other treatments were associated with no effect or worse outcomes. Randomized, controlled trials of these medications in patients with COVID-19 are needed to avoid heavy administration of treatments with no strong evidence to support them. .
Appendix 1: HM dataset description The following text has been copied from a document released by the HM hospital network along with its database explaining its project and the structure of the dataset. The information is organized in tables according to their content, all of them linked by a unique admission identifier. This identifier is the de-anonymization key, explicitly created for this purpose, and has nothing to do with the actual identifier of each admission.
References
Alzghari, Acuña, Chan, Jfw, Yao et al., Treatment with lopinavir/ritonavir or interferon-β1b improves outcome of MERSCoV infection in a nonhuman primate model of common marmoset, J Clin Virol
Banjanac, Kos, Nujić, Anti-inflammatory mechanism of action of azithromycin in LPS-stimulated J774A.1 cells, Pharmacol Res
Berkley, COVID-19 needs a Manhattan Project, Science
Caliendo, Kopeinig, Some practical guidance for the implementation of propensity score matching, J Econ Surv
Cao, Wang, Wen, A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19, N Engl J Med,
doi:10.1056/NEJMoa2001282Cochran, Db, Controlling bias in observational studies: a review
Das, Bhowmick, Tiwari, Sen, An Updated systematic review of the therapeutic role of hydroxychloroquine in coronavirus disease-19
Dastan, Nadji, Saffaei, Subcutaneous administration of Interferon beta-1a for COVID-19: A non-controlled prospective trial, Int Immunopharmacol
Du, Tu, Zhu, Clinical features of 85 fatal cases of COVID-19 from Wuhan: A retrospective observational study, Am J Respir Crit Care Med
Ellis, None, Ser. A
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
Geleris, Sun, Platt, Observational study of hydroxychloroquine in hospitalized patients with Covid-19, N Engl J Med
Geleris, Sun, Platt, Observational study of hydroxychloroquine in hospitalized patients with Covid-19, N Engl J Med,
doi:10.1056/NEJMoa2012410Hung, Lung, Tso, Triple combination of interferon beta-1b, lopinavir-ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: An open-label, randomised, phase 2 trial, Lancet
Hung, Lung, Tso, Triple combination of interferon beta-1b, lopinavir-ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: An open-label, randomised, phase 2 trial, Lancet
Kelley, Preacher, On effect size, Association
Mehta, Mcauley, Brown, Sanchez, Tattersall et al., COVID-19: consider cytokine storm syndromes and immunosuppression
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
Organ, None
Robins, Hernán, Brumback, Marginal structural models and causal inference in epidemiology, Epidemiology
Rosenberg, Dufort, Udo, Association of treatment with hydroxychloroquine or azithromycin with in-hospital mortality in patients with COVID-19 in New York State, JAMA -J Am Med Assoc
Rubin, Multiple imputation for nonresponse in surveys
Sankhyā Indian, Stat, None
Shang, Zhao, Hu, Du, Cao, On the use of corticosteroids for 2019-nCoV pneumonia
Shang, Zhao, Hu, Du, Cao, On the use of corticosteroids for 2019-nCoV pneumonia
Srinivas, Sacha, Koval, Antivirals for COVID-19, Cleve Clin J Med
Srinivas, Sacha, Koval, Antivirals for COVID-19, Cleve Clin J Med
Toniati, Piva, Cattalini, Tocilizumab for the treatment of severe COVID-19 pneumonia with hyperinflammatory syndrome and acute respiratory failure: A single center study of 100 patients in Brescia, Italy, Autoimmun. Rev
Wang, Hu, Hu, Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China, JAMA -J Am Med Assoc
Who B, Naming the coronavirus disease (COVID-19) and the virus that causes it, World Heal
Yang, Yu, Xu, Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: A single-centered, retrospective, observational study, Lancet Respir Med
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)
{ 'institution': [{'name': 'medRxiv'}],
'indexed': {'date-parts': [[2023, 8, 28]], 'date-time': '2023-08-28T12:51:10Z', 'timestamp': 1693227070871},
'posted': {'date-parts': [[2020, 7, 21]]},
'group-title': 'Public and Global Health',
'reference-count': 39,
'publisher': 'Cold Spring Harbor Laboratory',
'content-domain': {'domain': [], 'crossmark-restriction': False},
'accepted': {'date-parts': [[2020, 7, 21]]},
'abstract': '<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Many '
'different treatments were heavily administered to patients with COVID-19 during the peak of '
'the pandemic in Madrid without robust evidence supporting '
'them.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We examined the '
'association between sixteen treatments in four groups (steroids, antivirals, antibiotics and '
'immunomodulators) and intubation or death. Data were obtained from patients that were '
'admitted to an HM hospital with suspicion of COVID-19 until 24/04/2020, excluding unconfirmed '
'diagnosis, those who were admitted before the epidemic started in Madrid, had an outcome that '
'was not discharge or death or died within 24 hours of presentation. We compared outcomes '
'between treated and untreated patients using propensity-score caliper '
'matching.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Of 2,307 '
'patients in the dataset, 679 were excluded. Of the remaining 1,645 patients, 263 (16%) died '
'and 311 (18.9%) died or were intubated. Except for hydroxychloroquine and prednisone, '
'patients that were treated with any of the medications were more likely to go through an '
'outcome of death or intubation at baseline. After propensity matching we found an association '
'between treatment with hydroxychloroquine and prednisone and better outcomes (hazard ratios '
'with 95% CI of 0.83 ± 0.06 and 0.85 ± 0.03). Results were similar in multiple sensitivity '
'analyses.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>In this '
'multicenter study of patients admitted with COVID-19 hydroxychloroquine and prednisone '
'administration was found to be associated with improved outcomes. Other treatments were '
'associated with no effect or worse outcomes. Randomized, controlled trials of these '
'medications in patients with COVID-19 are needed to avoid heavy administration of treatments '
'with no strong evidence to support them.</jats:p></jats:sec>',
'DOI': '10.1101/2020.07.17.20155960',
'type': 'posted-content',
'created': {'date-parts': [[2020, 7, 21]], 'date-time': '2020-07-21T19:22:48Z', 'timestamp': 1595359368000},
'source': 'Crossref',
'is-referenced-by-count': 7,
'title': 'Observational Study of the Efficiency of Treatments in Patients Hospitalized with Covid-19 in '
'Madrid',
'prefix': '10.1101',
'author': [ { 'ORCID': 'http://orcid.org/0000-0002-8780-6837',
'authenticated-orcid': False,
'given': 'Nikolas',
'family': 'Bernaola',
'sequence': 'first',
'affiliation': []},
{'given': 'Raquel', 'family': 'Mena', 'sequence': 'additional', 'affiliation': []},
{'given': 'Ander', 'family': 'Bernaola', 'sequence': 'additional', 'affiliation': []},
{'given': 'Cesar', 'family': 'Carballo', 'sequence': 'additional', 'affiliation': []},
{'given': 'Antonio', 'family': 'Lara', 'sequence': 'additional', 'affiliation': []},
{ 'ORCID': 'http://orcid.org/0000-0001-7109-2668',
'authenticated-orcid': False,
'given': 'Concha',
'family': 'Bielza',
'sequence': 'additional',
'affiliation': []},
{ 'ORCID': 'http://orcid.org/0000-0002-1885-4501',
'authenticated-orcid': False,
'given': 'Pedro',
'family': 'Larrañaga',
'sequence': 'additional',
'affiliation': []}],
'member': '246',
'reference': [ { 'key': '2021011703400606000_2020.07.17.20155960v1.1',
'unstructured': 'WHO b. Naming the coronavirus disease (COVID-19) and the virus that '
'causes it [Internet]. World Heal. Organ. 2020 [cited 2020 Jun '
'4];Available from: '
'https://www.who.int/emergencies/diseases/novel-coronavirus-2019/technical-guidance/naming-the-coronavirus-disease-(covid-2019)-and-the-virus-that-causes-it'},
{ 'key': '2021011703400606000_2020.07.17.20155960v1.2',
'unstructured': 'COVID-19 situation update worldwide, as of 22 June 2020 [Internet]. '
'European Centre for Disease Prevention and Control. 2020 [cited 2020 '
'June 22] Available from: '
'https://www.ecdc.europa.eu/en/geographical-distribution-2019-ncov-cases'},
{ 'key': '2021011703400606000_2020.07.17.20155960v1.3',
'unstructured': 'Flawed data casts cloud over Spain’s lockdown strategy | Financial Times '
'[Internet]. [cited 2020 Jun 6];Available from: '
'https://www.ft.com/content/77eb7a13-cd26-41dd-9642-616708b43673'},
{ 'key': '2021011703400606000_2020.07.17.20155960v1.4',
'doi-asserted-by': 'crossref',
'unstructured': 'Du Y , Tu L , Zhu P , et al. Clinical features of 85 fatal cases of '
'COVID-19 from Wuhan: A retrospective observational study. Am J Respir '
'Crit Care Med 2020;',
'DOI': '10.2139/ssrn.3546088'},
{ 'key': '2021011703400606000_2020.07.17.20155960v1.5',
'doi-asserted-by': 'publisher',
'DOI': '10.1126/science.abb8654'},
{ 'issue': '5',
'key': '2021011703400606000_2020.07.17.20155960v1.6',
'doi-asserted-by': 'crossref',
'first-page': '475',
'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',
'volume': '8',
'year': '2020',
'journal-title': 'Lancet Respir Med'},
{ 'key': '2021011703400606000_2020.07.17.20155960v1.7',
'unstructured': 'Covid Data Save Lives [Internet]. [cited 2020 Jun 13];Available from: '
'https://www.hmhospitales.com/coronavirus/covid-data-save-lives'},
{ 'key': '2021011703400606000_2020.07.17.20155960v1.8',
'doi-asserted-by': 'publisher',
'DOI': '10.1097/00001648-200009000-00011'},
{ 'key': '2021011703400606000_2020.07.17.20155960v1.9',
'doi-asserted-by': 'publisher',
'DOI': '10.1111/j.1467-6419.2007.00527.x'},
{ 'issue': '12',
'key': '2021011703400606000_2020.07.17.20155960v1.10',
'doi-asserted-by': 'crossref',
'first-page': 'e81045',
'DOI': '10.1371/journal.pone.0081045',
'article-title': 'Optimal caliper width for propensity score matching of three treatment '
'groups: A Monte Carlo study',
'volume': '8',
'year': '2013',
'journal-title': 'PLoS One [Internet]'},
{ 'key': '2021011703400606000_2020.07.17.20155960v1.11',
'first-page': '417',
'article-title': 'Controlling bias in observational studies: a review [Internet]',
'volume': '35',
'year': '2020',
'journal-title': 'Sankhya Indian J. Stat. Ser. A'},
{ 'key': '2021011703400606000_2020.07.17.20155960v1.12',
'unstructured': 'Ellis PD . The Essential Guide to Effect Sizes [Internet]. Cambridge '
'University Press; 2010 [cited 2020 Jun 20]. Available from: '
'/core/books/essential-guide-to-effect-sizes/72C26CA99366A19CAC4EF5B16AE3297F'},
{ 'key': '2021011703400606000_2020.07.17.20155960v1.13',
'unstructured': 'Rubin DB . Multiple imputation for nonresponse in surveys. '
'Wiley-Interscience; 2004.'},
{ 'issue': '2',
'key': '2021011703400606000_2020.07.17.20155960v1.14',
'first-page': '137',
'article-title': 'On effect size',
'volume': '17',
'year': '2012',
'journal-title': 'Association'},
{ 'key': '2021011703400606000_2020.07.17.20155960v1.15',
'doi-asserted-by': 'crossref',
'unstructured': 'Geleris J , Sun Y , Platt J , et al. Observational study of '
'hydroxychloroquine in hospitalized patients with Covid-19. N Engl J Med '
'2020.',
'DOI': '10.1056/NEJMoa2012410'},
{ 'key': '2021011703400606000_2020.07.17.20155960v1.16',
'doi-asserted-by': 'crossref',
'unstructured': 'Das S , Bhowmick S , Tiwari S , Sen S. An Updated systematic review of '
'the therapeutic role of hydroxychloroquine in coronavirus disease-19 '
'(COVID-19) [Internet]. Clin. Drug Investig. 2020 [cited 2020 Jun '
'21];1–11. Available from: '
'https://link.springer.com/article/10.1007/s40261-020-00927-1',
'DOI': '10.1007/s40261-020-00927-1'},
{ 'key': '2021011703400606000_2020.07.17.20155960v1.17',
'doi-asserted-by': 'crossref',
'unstructured': 'Srinivas P , Sacha G , Koval C. Antivirals for COVID-19. Cleve Clin J '
'Med [Internet] 2020 [cited 2020 Jun 21];Available from: '
'https://www.ccjm.org/content/early/2020/05/27/ccjm.87a.ccc030',
'DOI': '10.3949/ccjm.87a.ccc030'},
{ 'key': '2021011703400606000_2020.07.17.20155960v1.18',
'doi-asserted-by': 'publisher',
'DOI': '10.1016/j.autrev.2020.102568'},
{ 'issue': '10238',
'key': '2021011703400606000_2020.07.17.20155960v1.19',
'doi-asserted-by': 'crossref',
'first-page': '1695',
'DOI': '10.1016/S0140-6736(20)31042-4',
'article-title': 'Triple combination of interferon beta-1b, lopinavir–ritonavir, and '
'ribavirin in the treatment of patients admitted to hospital with '
'COVID-19: An open-label, randomised, phase 2 trial',
'volume': '395',
'year': '2020',
'journal-title': 'Lancet [Internet]'},
{ 'key': '2021011703400606000_2020.07.17.20155960v1.20',
'doi-asserted-by': 'publisher',
'DOI': '10.1016/S0140-6736(20)30361-5'},
{ 'key': '2021011703400606000_2020.07.17.20155960v1.21',
'unstructured': 'Dexamethasone reduces death in hospitalised patients with severe '
'respiratory complications of COVID-19 | University of Oxford [Internet]. '
'[cited 2020 Jun 21];Available from: '
'http://www.ox.ac.uk/news/2020-06-16-dexamethasone-reduces-death-hospitalised-patients-severe-respiratory-complications'},
{ 'key': '2021011703400606000_2020.07.17.20155960v1.22',
'unstructured': 'Coronavirus disease 2019 (COVID-19): Management in hospitalized adults - '
'UpToDate [Internet]. [cited 2020 Jun 21];Available from: '
'https://www.uptodate.com/contents/coronavirus-disease-2019-covid-19-management-in-hospitalized-adults'},
{ 'key': '2021011703400606000_2020.07.17.20155960v1.23',
'doi-asserted-by': 'publisher',
'DOI': '10.1016/S0140-6736(20)30361-5'},
{ 'key': '2021011703400606000_2020.07.17.20155960v1.24',
'unstructured': 'Dexamethasone reduces death in hospitalised patients with severe '
'respiratory complications of COVID-19 | University of Oxford [Internet]. '
'[cited 2020 Jun 21];Available from: '
'http://www.ox.ac.uk/news/2020-06-16-dexamethasone-reduces-death-hospitalised-patients-severe-respiratory-complications'},
{ 'issue': '19',
'key': '2021011703400606000_2020.07.17.20155960v1.25',
'doi-asserted-by': 'crossref',
'first-page': '1787',
'DOI': '10.1056/NEJMoa2001282',
'article-title': 'A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe '
'Covid-19',
'volume': '382',
'year': '2020',
'journal-title': 'N Engl J Med [Internet]'},
{ 'key': '2021011703400606000_2020.07.17.20155960v1.26',
'doi-asserted-by': 'crossref',
'unstructured': 'Srinivas P , Sacha G , Koval C. Antivirals for COVID-19. Cleve Clin J '
'Med [Internet] 2020 [cited 2020 Jun 21];Available from: '
'https://www.ccjm.org/content/early/2020/05/27/ccjm.87a.ccc030',
'DOI': '10.3949/ccjm.87a.ccc030'},
{ 'issue': '11',
'key': '2021011703400606000_2020.07.17.20155960v1.27',
'doi-asserted-by': 'crossref',
'first-page': '1061',
'DOI': '10.1001/jama.2020.1585',
'article-title': 'Clinical characteristics of 138 hospitalized patients with 2019 novel '
'coronavirus-infected pneumonia in Wuhan, China',
'volume': '323',
'year': '2020',
'journal-title': 'JAMA - J Am Med Assoc [Internet]'},
{ 'issue': '4',
'key': '2021011703400606000_2020.07.17.20155960v1.28',
'doi-asserted-by': 'crossref',
'first-page': '357',
'DOI': '10.1016/j.phrs.2012.06.011',
'article-title': 'Anti-inflammatory mechanism of action of azithromycin in LPS-stimulated '
'J774A.1 cells',
'volume': '66',
'year': '2012',
'journal-title': 'Pharmacol Res [Internet]'},
{ 'key': '2021011703400606000_2020.07.17.20155960v1.29',
'doi-asserted-by': 'crossref',
'unstructured': 'Gautret P , Lagier J-C , Parola P , et al. Hydroxychloroquine and '
'azithromycin as a treatment of COVID-19: results of an open-label '
'non-randomized clinical trial. Int J Antimicrob Agents [Internet] 2020 '
'[cited 2020 Jun 21];105949. Available from: '
'https://pubmed.ncbi.nlm.nih.gov/32205204/',
'DOI': '10.1016/j.ijantimicag.2020.105949'},
{ 'key': '2021011703400606000_2020.07.17.20155960v1.30',
'doi-asserted-by': 'crossref',
'unstructured': 'Yao X , Ye F , Zhang M , et al. 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 [Internet] 2020 [cited 2020 Jun '
'21];Available from: '
'https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7108130/',
'DOI': '10.1093/cid/ciaa237'},
{ 'key': '2021011703400606000_2020.07.17.20155960v1.31',
'doi-asserted-by': 'crossref',
'unstructured': 'Das S , Bhowmick S , Tiwari S , Sen S. An Updated systematic review of '
'the therapeutic role of hydroxychloroquine in Coronavirus Disease-19 '
'(COVID-19) [Internet]. Clin. Drug Investig. 2020 [cited 2020 Jun '
'21];1–11. Available from: '
'https://link.springer.com/article/10.1007/s40261-020-00927-1',
'DOI': '10.1007/s40261-020-00927-1'},
{ 'key': '2021011703400606000_2020.07.17.20155960v1.32',
'doi-asserted-by': 'crossref',
'first-page': '101738',
'DOI': '10.1016/j.tmaid.2020.101738',
'article-title': 'Early treatment of COVID-19 patients with hydroxychloroquine and '
'azithromycin: A retrospective analysis of 1061 cases in Marseille, '
'France',
'volume': '35',
'year': '2020',
'journal-title': 'Travel Med Infect Dis'},
{ 'key': '2021011703400606000_2020.07.17.20155960v1.33',
'doi-asserted-by': 'crossref',
'unstructured': 'Geleris J , Sun Y , Platt J , et al. Observational study of '
'hydroxychloroquine in hospitalized patients with Covid-19. N Engl J Med '
'[Internet] 2020 [cited 2020 Jun 21];Available from: '
'https://www.nejm.org/doi/full/10.1056/NEJMoa2012410',
'DOI': '10.1056/NEJMoa2012410'},
{ 'key': '2021011703400606000_2020.07.17.20155960v1.34',
'doi-asserted-by': 'crossref',
'unstructured': 'Rosenberg ES , Dufort EM , Udo T , et al. Association of treatment with '
'hydroxychloroquine or azithromycin with in-hospital mortality in '
'patients with COVID-19 in New York State. JAMA - J Am Med Assoc '
'[Internet] 2020 [cited 2020 Jun 21];Available from: '
'https://jamanetwork.com/journals/jama/fullarticle/2766117',
'DOI': '10.1001/jama.2020.8630'},
{ 'key': '2021011703400606000_2020.07.17.20155960v1.35',
'doi-asserted-by': 'publisher',
'DOI': '10.1016/S0140-6736(20)30628-0'},
{ 'key': '2021011703400606000_2020.07.17.20155960v1.36',
'doi-asserted-by': 'crossref',
'unstructured': 'Alzghari SK , Acuña VS. Supportive treatment with tocilizumab for '
'COVID-19: A systematic review. J Clin Virol [Internet] 2020 [cited 2020 '
'Jun 21];127. Available from: https://pubmed.ncbi.nlm.nih.gov/32353761/',
'DOI': '10.1016/j.jcv.2020.104380'},
{ 'issue': '12',
'key': '2021011703400606000_2020.07.17.20155960v1.37',
'doi-asserted-by': 'crossref',
'first-page': '1904',
'DOI': '10.1093/infdis/jiv392',
'article-title': 'Treatment with lopinavir/ritonavir or interferon-β1b improves outcome '
'of MERSCoV infection in a nonhuman primate model of common marmoset',
'volume': '212',
'year': '2015',
'journal-title': 'J Infect Dis [Internet]'},
{ 'key': '2021011703400606000_2020.07.17.20155960v1.38',
'doi-asserted-by': 'crossref',
'unstructured': 'Dastan F , Alireza Nadji S , Saffaei A , et al. Subcutaneous '
'administration of Interferon beta-1a for COVID-19: A non-controlled '
'prospective trial. Int Immunopharmacol 2020;106688.',
'DOI': '10.1016/j.intimp.2020.106688'},
{ 'issue': '10238',
'key': '2021011703400606000_2020.07.17.20155960v1.39',
'doi-asserted-by': 'crossref',
'first-page': '1695',
'DOI': '10.1016/S0140-6736(20)31042-4',
'article-title': 'Triple combination of interferon beta-1b, lopinavir-ritonavir, and '
'ribavirin in the treatment of patients admitted to hospital with '
'COVID-19: An open-label, randomised, phase 2 trial',
'volume': '395',
'year': '2020',
'journal-title': 'Lancet [Internet]'}],
'container-title': [],
'original-title': [],
'link': [ { 'URL': 'https://syndication.highwire.org/content/doi/10.1101/2020.07.17.20155960',
'content-type': 'unspecified',
'content-version': 'vor',
'intended-application': 'similarity-checking'}],
'deposited': { 'date-parts': [[2021, 1, 17]],
'date-time': '2021-01-17T11:40:47Z',
'timestamp': 1610883647000},
'score': 1,
'resource': {'primary': {'URL': 'http://medrxiv.org/lookup/doi/10.1101/2020.07.17.20155960'}},
'subtitle': [],
'short-title': [],
'issued': {'date-parts': [[2020, 7, 21]]},
'references-count': 39,
'URL': 'http://dx.doi.org/10.1101/2020.07.17.20155960',
'relation': {},
'published': {'date-parts': [[2020, 7, 21]]},
'subtype': 'preprint'}
