Randomized Prospective Open Label Study Shows No Impact on Clinical Outcome of Adding Losartan to Hospitalized COVID-19 Patients with Mild Hypoxemia
Matthew Geriak, Fadi Haddad, Ravina Kullar, Kristina L Greenwood, Mackenzie Habib, Cole Habib, David Willms, George Sakoulas
Infectious Diseases and Therapy, doi:10.1007/s40121-021-00453-3
Introduction: Despite considerable scientific debate, there have been no prospective clinical studies on the effects of angiotensin II receptor blockers (ARBs) on the course of COVID-19 infection. Losartan is the ARB that was chosen to be tested in this study. Methods: Patients with COVID-19 and mild hypoxia (receipt of B 3 L/min O 2 by nasal cannula) admitted to three hospitals were randomized in a 1:1 ratio within 72 h of SARS-CoV-2 nucleic acid testing confirmation to prospectively receive standard of care (SOC) alone or SOC plus losartan 12.5 mg orally every 12 h for 10 days or until hospital discharge, with the option to titrate upward dependent on blood pressure tolerability. Primary composite endpoint was receipt of mechanical ventilation or death before receiving ventilation. Subjects were followed until discharge to home or until an endpoint was met in the hospital. Results: Sixteen subjects received an ARB plus SOC and 15 subjects received SOC alone. The median age was 53 years for both groups. Median time from hospital admission to study enrollment was 2 days (range 1-6) for the ARB group and 2 days (range 1-4) for the SOC group. Mean Charlson comorbidity index was 2 for both groups. One subject in each group achieved the composite endpoint. Conclusion: This small prospective randomized open-label study showed no clinically significant impacts of ARB therapy in mildly hypoxemic patients hospitalized with COVID-19 early in the pandemic. A larger prospective randomized placebo-controlled trial would be needed to confirm these findings or capture less pronounced effects and probably should focus on outpatients earlier in disease course.
Authorship. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this manuscript, take responsibility for the integrity of the work as a whole and have given their approval for this version to be published. All authors were active participants in at least one category of study design, study execution, data gathering and organization, data analysis and statistics, or manuscript preparation.
Authors
References
Bean, Treatment with ACE-inhibitors is associated with less severe disease with SARS-Covid-19 infection in a multi-site UK acute hospital trust, MedRxiv,
doi:10.1101/2020.04.07.20056788
Beigel, Tomashek, Dodd, Remdesivir for the treatment of Covid-19-preliminary report
Cai, Tay, Kui, Tin, Tan, Impact of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on in-hospital mortality in COVID-19 patients: a systematic review and meta-analysis, Singap Med J,
doi:10.11622/smedj.2020159
Caldeira, Alarca ˜o, Vaz-Carneiro, Costa, Risk of pneumonia associated with use of angiotensin converting enzyme inhibitors and angiotensin receptor blockers: systematic review and metaanalysis, BMJ,
doi:10.1136/bmj.e4260
Chen, Zhou, Dong, Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study, Lancet,
doi:10.1016/S0140-6736(20)30211-7
Cicco, Cicco, Racanelli, Vacca, Neutrophil extracellular traps (NETs) and damage-associated molecular patterns (DAMPs): two potential targets for COVID-19 treatment, Mediat Inflamm,
doi:10.1155/2020/7527953
De Abajo, Use of renin-angiotensin-aldosterone system inhibitors and risk of COVID-19 requiring admission to hospital: a case-population study, Lancet,
doi:10.1016/S0140-6736(20)31030-8
Geriak, Haddad, Rizvi, Rose, Laplante et al., Clinical data on daptomycin plus ceftaroline versus standard of care monotherapy in the treatment of methicillin-resistant Staphylococcus aureus bacteremia, Antimicrob Agents Chemother,
doi:10.1128/AAC.02483-18
Goldman, Lye, Hui, Remdesivir for 5 or 10 days in patients with severe Covid-19
Gurwitz, Angiotensin receptor blockers as tentative SARS-CoV-2 therapeutics, Drug Dev Res,
doi:10.1002/ddr.21656
Li, Association of renin-angiotensin system inhibitors with severity or risk of death in patients with hypertension hospitalized for coronavirus disease 2019 (COVID-19) infection in Wuhan, China, JAMA Cardiol,
doi:10.1001/jamacardio.2020.1624
Mackey, King, Gurley, Kiefer, Liederbauer et al., Risks and impact of angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers on SARS-CoV-2 infection in adults: a living systematic review, Ann Intern Med,
doi:10.7326/M20-1515
Mahase, Covid-19: FDA authorises neutralising antibody bamlanivimab for non-admitted patients, BMJ,
doi:10.1136/bmj.m4362
Nicolai, Leunig, Brambs, Kaiser, Weinberger et al., Immunothrombotic dysregulation in COVID-19 pneumonia is associated with respiratory failure and coagulopathy, Circulation
Qin, Zhou, Hu, Dysregulation of immune response in patients with COVID-19 in Wuhan, China, Clin Infect Dis,
doi:10.1093/cid/ciaa248
Siddiqu, Mehra, COVID-19 illness in native and immunosuppressed states: a clinical-therapeutic staging proposal, J Heart Lung Transplant,
doi:10.1016/j.healun.2020.03.012
Turgeon, Zieroth, Bewick, Chow, Clarke et al., Use of renin-angiotensin system blockers during the COVID-19 pandemic: early guidance and evolving evidence, Can J Cardiol,
doi:10.1016/j.cjca.2020.05.033
Uozumi, Iguchi, Masuda, Nishibata, Nakazawa et al., Pharmaceutical immunoglobulins reduce neutrophil extracellular trap formation and ameliorate the development of MPO-ANCA-associated vasculitis, Mod Rheumatol,
doi:10.1080/14397595.2019.1602292
Wang, Zhang, Du, Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial, Lancet,
doi:10.1016/S0140-6736(20)31022-9
Who Solidarity, Consortium, Pan, Peto, Henao-Restrepo et al., Repurposed antiviral drugs for Covid-19-interim WHO solidarity trial results, N Engl J Med,
doi:10.1056/NEJMoa2023184
Zhang, Association of inpatient use of angiotensin converting enzyme inhibitors and angiotensin II receptor blockers with mortality among patients with hypertension hospitalized with COVID-19, Circ Res,
doi:10.1161/CIRCRESAHA.120.317134
Zhang, Wu, Xu, Du, Effects of renin-angiotensin-aldosterone system (RAAS) inhibitors on disease severity and mortality in patients with COVID-19: a meta-analysis, J Med Virol,
doi:10.1002/jmv.26695
{ 'indexed': {'date-parts': [[2024, 5, 13]], 'date-time': '2024-05-13T12:37:47Z', 'timestamp': 1715603867136},
'reference-count': 30,
'publisher': 'Springer Science and Business Media LLC',
'issue': '3',
'license': [ { 'start': { 'date-parts': [[2021, 5, 11]],
'date-time': '2021-05-11T00:00:00Z',
'timestamp': 1620691200000},
'content-version': 'tdm',
'delay-in-days': 0,
'URL': 'https://creativecommons.org/licenses/by-nc/4.0'},
{ 'start': { 'date-parts': [[2021, 5, 11]],
'date-time': '2021-05-11T00:00:00Z',
'timestamp': 1620691200000},
'content-version': 'vor',
'delay-in-days': 0,
'URL': 'https://creativecommons.org/licenses/by-nc/4.0'}],
'funder': [{'DOI': '10.13039/100011842', 'name': 'Sharp HealthCare', 'doi-asserted-by': 'publisher'}],
'content-domain': {'domain': ['link.springer.com'], 'crossmark-restriction': False},
'published-print': {'date-parts': [[2021, 9]]},
'DOI': '10.1007/s40121-021-00453-3',
'type': 'journal-article',
'created': {'date-parts': [[2021, 5, 11]], 'date-time': '2021-05-11T22:02:50Z', 'timestamp': 1620770570000},
'page': '1323-1330',
'update-policy': 'http://dx.doi.org/10.1007/springer_crossmark_policy',
'source': 'Crossref',
'is-referenced-by-count': 26,
'title': 'Randomized Prospective Open Label Study Shows No Impact on Clinical Outcome of Adding Losartan '
'to Hospitalized COVID-19 Patients with Mild Hypoxemia',
'prefix': '10.1007',
'volume': '10',
'clinical-trial-number': [ { 'clinical-trial-number': 'nct04340557',
'registry': '10.18810/clinical-trials-gov'}],
'author': [ {'given': 'Matthew', 'family': 'Geriak', 'sequence': 'first', 'affiliation': []},
{'given': 'Fadi', 'family': 'Haddad', 'sequence': 'additional', 'affiliation': []},
{'given': 'Ravina', 'family': 'Kullar', 'sequence': 'additional', 'affiliation': []},
{'given': 'Kristina L.', 'family': 'Greenwood', 'sequence': 'additional', 'affiliation': []},
{'given': 'MacKenzie', 'family': 'Habib', 'sequence': 'additional', 'affiliation': []},
{'given': 'Cole', 'family': 'Habib', 'sequence': 'additional', 'affiliation': []},
{'given': 'David', 'family': 'Willms', 'sequence': 'additional', 'affiliation': []},
{'given': 'George', 'family': 'Sakoulas', 'sequence': 'additional', 'affiliation': []}],
'member': '297',
'published-online': {'date-parts': [[2021, 5, 11]]},
'reference': [ { 'key': '453_CR1',
'doi-asserted-by': 'publisher',
'first-page': '5017',
'DOI': '10.1016/S0140-6736(20)30211-7',
'volume': '395',
'author': 'N Chen',
'year': '2020',
'unstructured': 'Chen N, Zhou M, Dong X, et al. Epidemiological and clinical '
'characteristics of 99 cases of 2019 novel coronavirus pneumonia in '
'Wuhan, China: a descriptive study. Lancet. 2020;395:5017–513. '
'https://doi.org/10.1016/S0140-6736(20)30211-7.',
'journal-title': 'Lancet'},
{ 'key': '453_CR2',
'doi-asserted-by': 'publisher',
'DOI': '10.1016/j.healun.2020.03.012',
'author': 'HK Siddiqu',
'year': '2020',
'unstructured': 'Siddiqu HK, Mehra MR. COVID-19 illness in native and immunosuppressed '
'states: a clinical-therapeutic staging proposal. J Heart Lung '
'Transplant. 2020. https://doi.org/10.1016/j.healun.2020.03.012.',
'journal-title': 'J Heart Lung Transplant'},
{ 'key': '453_CR3',
'doi-asserted-by': 'publisher',
'DOI': '10.1093/cid/ciaa248',
'author': 'C Qin',
'year': '2020',
'unstructured': 'Qin C, Zhou L, Hu Z, et al. Dysregulation of immune response in patients '
'with COVID-19 in Wuhan, China. Clin Infect Dis. 2020. '
'https://doi.org/10.1093/cid/ciaa248.',
'journal-title': 'Clin Infect Dis'},
{ 'key': '453_CR4',
'doi-asserted-by': 'publisher',
'first-page': '11727',
'DOI': '10.1073/pnas.2003138117',
'volume': '117',
'author': 'J Shang',
'year': '2020',
'unstructured': 'Shang J, Wan Y, et al. Cell entry mechanisms of SARS-CoV-2. PNAS. '
'2020;117:11727–34. https://doi.org/10.1073/pnas.2003138117.',
'journal-title': 'PNAS'},
{ 'key': '453_CR5',
'doi-asserted-by': 'publisher',
'first-page': '1176',
'DOI': '10.1161/CIRCULATIONAHA.120.048488',
'volume': '142',
'author': 'L Nicolai',
'year': '2020',
'unstructured': 'Nicolai L, Leunig A, Brambs S, Kaiser R, Weinberger T, Weigand M, '
'Muenchhoff M, Hellmuth JC, Ledderose S, Schulz H, Scherer C, Rudelius M, '
'Zoller M, Hochter D, Keppler O, Teupser D, Zwibler B, von '
'Bergwelt-Baildon M, Kaab S, Massberg S, Pekayyvaz K, Stark K. '
'Immunothrombotic dysregulation in COVID-19 pneumonia is associated with '
'respiratory failure and coagulopathy. Circulation. 2020;142:1176–89 '
'(e-pub).',
'journal-title': 'Circulation'},
{ 'key': '453_CR6',
'doi-asserted-by': 'publisher',
'first-page': '7527953',
'DOI': '10.1155/2020/7527953',
'volume': '2020',
'author': 'S Cicco',
'year': '2020',
'unstructured': 'Cicco S, Cicco G, Racanelli V, Vacca A. Neutrophil extracellular traps '
'(NETs) and damage-associated molecular patterns (DAMPs): two potential '
'targets for COVID-19 treatment. Mediat Inflamm. 2020;2020:7527953. '
'https://doi.org/10.1155/2020/7527953.',
'journal-title': 'Mediat Inflamm'},
{ 'issue': '3',
'key': '453_CR7',
'doi-asserted-by': 'publisher',
'first-page': '544',
'DOI': '10.1080/14397595.2019.1602292',
'volume': '30',
'author': 'R Uozumi',
'year': '2020',
'unstructured': 'Uozumi R, Iguchi R, Masuda S, Nishibata Y, Nakazawa D, Tomaru U, Ishizu '
'A. Pharmaceutical immunoglobulins reduce neutrophil extracellular trap '
'formation and ameliorate the development of MPO-ANCA-associated '
'vasculitis. Mod Rheumatol. 2020;30(3):544–50. '
'https://doi.org/10.1080/14397595.2019.1602292.',
'journal-title': 'Mod Rheumatol'},
{ 'key': '453_CR8',
'unstructured': 'https://www.clinicaltrials.gov/ct2/results?cond=Coronavirus&term=losartan&cntry=&state=&city=&dist=.'},
{ 'key': '453_CR9',
'doi-asserted-by': 'publisher',
'first-page': '985',
'DOI': '10.1038/s41440-020-0488-z',
'volume': '43',
'author': 'MM Ciulla',
'year': '2020',
'unstructured': 'Ciulla MM. SARS-CoV-2 downregulation of ACE2 and pleiotropic effects of '
'ACEIs/ARBs. Hypertens Res. 2020;43:985–6. '
'https://doi.org/10.1038/s41440-020-0488-z.',
'journal-title': 'Hypertens Res'},
{ 'issue': '5',
'key': '453_CR10',
'doi-asserted-by': 'publisher',
'first-page': '537',
'DOI': '10.1002/ddr.21656',
'volume': '81',
'author': 'D Gurwitz',
'year': '2020',
'unstructured': 'Gurwitz D. Angiotensin receptor blockers as tentative SARS-CoV-2 '
'therapeutics. Drug Dev Res. 2020;81(5):537–40. '
'https://doi.org/10.1002/ddr.21656 (Epub 2020 Mar 4).',
'journal-title': 'Drug Dev Res.'},
{ 'issue': '11',
'key': '453_CR11',
'doi-asserted-by': 'publisher',
'first-page': 'e0280',
'DOI': '10.1097/CCE.0000000000000280.PMID:33225306;PMCID:PMC7671875',
'volume': '2',
'author': 'G Sakoulas',
'year': '2020',
'unstructured': 'Sakoulas G, Geriak M, Kullar R, Greenwood KL, Habib M, Vyas A, '
'Ghafourian M, Dintyala VNK, Haddad F. Intravenous immunoglobulin plus '
'methylprednisolone mitigate respiratory morbidity in coronavirus disease '
'2019. Crit Care Explor. 2020;2(11):e0280. '
'https://doi.org/10.1097/CCE.0000000000000280.PMID:33225306;PMCID:PMC7671875.',
'journal-title': 'Crit Care Explor'},
{ 'issue': '5',
'key': '453_CR12',
'doi-asserted-by': 'publisher',
'first-page': 'e02483',
'DOI': '10.1128/AAC.02483-18',
'volume': '63',
'author': 'M Geriak',
'year': '2019',
'unstructured': 'Geriak M, Haddad F, Rizvi K, Rose W, LaPlante K, Yu M, Vasina L, '
'Ouellette K, Zervos M, Nizet V, Sakoulas G. Clinical data on daptomycin '
'plus ceftaroline versus standard of care monotherapy in the treatment of '
'methicillin-resistant Staphylococcus aureus bacteremia. Antimicrob '
'Agents Chemother. 2019;63(5):e02483-e2518. '
'https://doi.org/10.1128/AAC.02483-18.',
'journal-title': 'Antimicrob Agents Chemother'},
{ 'issue': '3',
'key': '453_CR13',
'doi-asserted-by': 'publisher',
'first-page': '195',
'DOI': '10.7326/M20-1515',
'volume': '173',
'author': 'K Mackey',
'year': '2020',
'unstructured': 'Mackey K, King VJ, Gurley S, Kiefer M, Liederbauer E, Vela K, Sonnen P, '
'Kansagara D. Risks and impact of angiotensin-converting enzyme '
'inhibitors or angiotensin-receptor blockers on SARS-CoV-2 infection in '
'adults: a living systematic review. Ann Intern Med. 2020;173(3):195–203. '
'https://doi.org/10.7326/M20-1515 (Epub 2020 May 15).',
'journal-title': 'Ann Intern Med.'},
{ 'key': '453_CR14',
'doi-asserted-by': 'publisher',
'DOI': '10.1056/NEJMoa2008975',
'author': 'HR Reynolds',
'year': '2020',
'unstructured': 'Reynolds HR, et al. Renin–angiotensin–aldosterone system inhibitors and '
'risk of Covid-19. N Engl J Med. 2020. '
'https://doi.org/10.1056/NEJMoa2008975 (e-pub).',
'journal-title': 'N Engl J Med'},
{ 'key': '453_CR15',
'doi-asserted-by': 'publisher',
'DOI': '10.1056/NEJMoa2006923',
'author': 'G Mancia',
'year': '2020',
'unstructured': 'Mancia G, et al. Renin–angiotensin–aldosterone system blockers and the '
'risk of Covid-19. N Engl J Med. 2020. '
'https://doi.org/10.1056/NEJMoa2006923 (e-pub).',
'journal-title': 'N Engl J Med'},
{ 'key': '453_CR16',
'doi-asserted-by': 'publisher',
'DOI': '10.1016/S0140-6736(20)31030-8',
'author': 'FJ de Abajo',
'year': '2020',
'unstructured': 'de Abajo FJ, et al. Use of renin–angiotensin–aldosterone system '
'inhibitors and risk of COVID-19 requiring admission to hospital: a '
'case-population study. Lancet. 2020. '
'https://doi.org/10.1016/S0140-6736(20)31030-8 (e-pub).',
'journal-title': 'Lancet'},
{ 'key': '453_CR17',
'doi-asserted-by': 'publisher',
'DOI': '10.1001/jamacardio.2020.1624',
'author': 'J Li',
'year': '2020',
'unstructured': 'Li J, et al. Association of renin-angiotensin system inhibitors with '
'severity or risk of death in patients with hypertension hospitalized for '
'coronavirus disease 2019 (COVID-19) infection in Wuhan, China. JAMA '
'Cardiol. 2020. https://doi.org/10.1001/jamacardio.2020.1624 (e-pub).',
'journal-title': 'JAMA Cardiol'},
{ 'key': '453_CR18',
'doi-asserted-by': 'publisher',
'DOI': '10.1161/CIRCRESAHA.120.317134',
'author': 'P Zhang',
'year': '2020',
'unstructured': 'Zhang P, et al. Association of inpatient use of angiotensin converting '
'enzyme inhibitors and angiotensin II receptor blockers with mortality '
'among patients with hypertension hospitalized with COVID-19. Circ Res. '
'2020. https://doi.org/10.1161/CIRCRESAHA.120.317134 (e-pub).',
'journal-title': 'Circ Res'},
{ 'key': '453_CR19',
'doi-asserted-by': 'publisher',
'DOI': '10.1101/2020.04.07.20056788',
'author': 'DM Bean',
'year': '2020',
'unstructured': 'Bean DM, et al. Treatment with ACE-inhibitors is associated with less '
'severe disease with SARS-Covid-19 infection in a multi-site UK acute '
'hospital trust. MedRxiv. 2020. '
'https://doi.org/10.1101/2020.04.07.20056788 (Preprint).',
'journal-title': 'MedRxiv'},
{ 'issue': '8',
'key': '453_CR20',
'doi-asserted-by': 'publisher',
'first-page': '1180',
'DOI': '10.1016/j.cjca.2020.05.033',
'volume': '36',
'author': 'RD Turgeon',
'year': '2020',
'unstructured': 'Turgeon RD, Zieroth S, Bewick D, Chow CM, Clarke B, Cowan S, Fordyce CB, '
'Fournier A, Gin K, Gupta A, Hardiman S, Jackson S, Lau B, Leong-Poi H, '
'Mansour S, Marelli A, Quraishi AR, Roifman I, Ruel M, Sapp J, Singh G, '
'Small G, Virani S, Wood DA, Krahn A. Use of renin–angiotensin system '
'blockers during the COVID-19 pandemic: early guidance and evolving '
'evidence. Can J Cardiol. 2020;36(8):1180–2. '
'https://doi.org/10.1016/j.cjca.2020.05.033 (Epub 2020 Jun 2).',
'journal-title': 'Can J Cardiol.'},
{ 'issue': '25',
'key': '453_CR21',
'doi-asserted-by': 'publisher',
'first-page': '2042',
'DOI': '10.1161/CIRCULATIONAHA.120.047022',
'volume': '141',
'author': 'FH Messerli',
'year': '2020',
'unstructured': 'Messerli FH, Siontis GCM, Rexhaj E. COVID-19 and renin angiotensin '
'blockers: current evidence and recommendations. Circulation. '
'2020;141(25):2042–4. https://doi.org/10.1161/CIRCULATIONAHA.120.047022 '
'(Epub 2020 Apr 13).',
'journal-title': 'Circulation'},
{ 'key': '453_CR22',
'doi-asserted-by': 'publisher',
'DOI': '10.1002/jmv.26695',
'author': 'G Zhang',
'year': '2020',
'unstructured': 'Zhang G, Wu Y, Xu R, Du X. Effects of renin–angiotensin–aldosterone '
'system (RAAS) inhibitors on disease severity and mortality in patients '
'with COVID-19: a meta-analysis. J Med Virol. 2020. '
'https://doi.org/10.1002/jmv.26695 (Epub ahead of print).',
'journal-title': 'J Med Virol.'},
{ 'key': '453_CR23',
'doi-asserted-by': 'publisher',
'DOI': '10.11622/smedj.2020159',
'author': 'XJ Cai',
'year': '2020',
'unstructured': 'Cai XJ, Tay JCK, Kui SL, Tin AS, Tan VH. Impact of '
'angiotensin-converting enzyme inhibitors and angiotensin receptor '
'blockers on in-hospital mortality in COVID-19 patients: a systematic '
'review and meta-analysis. Singap Med J. 2020. '
'https://doi.org/10.11622/smedj.2020159 (Epub ahead of print).',
'journal-title': 'Singap Med J.'},
{ 'key': '453_CR24',
'doi-asserted-by': 'publisher',
'first-page': 'e4260',
'DOI': '10.1136/bmj.e4260',
'volume': '345',
'author': 'D Caldeira',
'year': '2012',
'unstructured': 'Caldeira D, Alarcão J, Vaz-Carneiro A, Costa J. Risk of pneumonia '
'associated with use of angiotensin converting enzyme inhibitors and '
'angiotensin receptor blockers: systematic review and meta-analysis. BMJ. '
'2012;345:e4260. https://doi.org/10.1136/bmj.e4260.',
'journal-title': 'BMJ'},
{ 'key': '453_CR25',
'doi-asserted-by': 'publisher',
'DOI': '10.1056/NEJMoa2007764',
'author': 'JH Beigel',
'year': '2020',
'unstructured': 'Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the treatment of '
'Covid-19—preliminary report [published online ahead of print, 2020 May '
'22]. N Engl J Med. 2020. https://doi.org/10.1056/NEJMoa2007764.',
'journal-title': 'N Engl J Med.'},
{ 'issue': '10236',
'key': '453_CR26',
'doi-asserted-by': 'publisher',
'first-page': '1569',
'DOI': '10.1016/S0140-6736(20)31022-9',
'volume': '395',
'author': 'Y Wang',
'year': '2020',
'unstructured': 'Wang Y, Zhang D, Du G, et al. Remdesivir in adults with severe COVID-19: '
'a randomised, double-blind, placebo-controlled, multicentre trial '
'[published correction appears in Lancet. 2020 May 30;395(10238):1694]. '
'Lancet. 2020;395(10236):1569–78. '
'https://doi.org/10.1016/S0140-6736(20)31022-9.',
'journal-title': 'Lancet'},
{ 'key': '453_CR27',
'doi-asserted-by': 'publisher',
'DOI': '10.1056/NEJMoa2015301',
'author': 'JD Goldman',
'year': '2020',
'unstructured': 'Goldman JD, Lye DCB, Hui DS, et al. Remdesivir for 5 or 10 days in '
'patients with severe Covid-19 [published online ahead of print, 2020 May '
'27]. N Engl J Med. 2020. https://doi.org/10.1056/NEJMoa2015301.',
'journal-title': 'N Engl J Med.'},
{ 'key': '453_CR28',
'doi-asserted-by': 'publisher',
'DOI': '10.1056/NEJMoa2021436',
'author': 'P Horby',
'year': '2020',
'unstructured': 'RECOVERY Collaborative Group, Horby P, Lim WS, et al. Dexamethasone in '
'hospitalized patients with Covid-19—preliminary report [published online '
'ahead of print, 2020 Jul 17]. N Engl J Med. 2020. '
'https://doi.org/10.1056/NEJMoa2021436.',
'journal-title': 'N Engl J Med.'},
{ 'issue': '371',
'key': '453_CR29',
'doi-asserted-by': 'publisher',
'first-page': 'm4362',
'DOI': '10.1136/bmj.m4362',
'volume': '11',
'author': 'E Mahase',
'year': '2020',
'unstructured': 'Mahase E. Covid-19: FDA authorises neutralising antibody bamlanivimab '
'for non-admitted patients. BMJ. 2020;11(371):m4362. '
'https://doi.org/10.1136/bmj.m4362.',
'journal-title': 'BMJ'},
{ 'key': '453_CR30',
'doi-asserted-by': 'publisher',
'DOI': '10.1056/NEJMoa2023184',
'author': 'H Pan',
'year': '2020',
'unstructured': 'WHO Solidarity Trial Consortium, Pan H, Peto R, Henao-Restrepo AM, '
'Preziosi MP, Sathiyamoorthy V, Abdool Karim Q, Alejandria MM, Hernández '
'García C, Kieny MP, Malekzadeh R, Murthy S, Reddy KS, Roses Periago M, '
'Abi Hanna P, Ader F, Al-Bader AM, Alhasawi A, Allum E, Alotaibi A, '
'Alvarez-Moreno CA, Appadoo S, Asiri A, Aukrust P, Barratt-Due A, Bellani '
'S, Branca M, Cappel-Porter HBC, Cerrato N, Chow TS, Como N, Eustace J, '
'García PJ, Godbole S, Gotuzzo E, Griskevicius L, Hamra R, Hassan M, '
'Hassany M, Hutton D, Irmansyah I, Jancoriene L, Kirwan J, Kumar S, '
'Lennon P, Lopardo G, Lydon P, Magrini N, Maguire T, Manevska S, Manuel '
'O, McGinty S, Medina MT, Mesa Rubio ML, Miranda-Montoya MC, Nel J, Nunes '
'EP, Perola M, Portolés A, Rasmin MR, Raza A, Rees H, Reges PPS, Rogers '
'CA, Salami K, Salvadori MI, Sinani N, Sterne JAC, Stevanovikj M, '
'Tacconelli E, Tikkinen KAO, Trelle S, Zaid H, Røttingen JA, Swaminathan '
'S. Repurposed antiviral drugs for Covid-19—interim WHO solidarity trial '
'results. N Engl J Med. 2020. https://doi.org/10.1056/NEJMoa2023184 (Epub '
'ahead of print).',
'journal-title': 'N Engl J Med.'}],
'container-title': 'Infectious Diseases and Therapy',
'original-title': [],
'language': 'en',
'link': [ { 'URL': 'https://link.springer.com/content/pdf/10.1007/s40121-021-00453-3.pdf',
'content-type': 'application/pdf',
'content-version': 'vor',
'intended-application': 'text-mining'},
{ 'URL': 'https://link.springer.com/article/10.1007/s40121-021-00453-3/fulltext.html',
'content-type': 'text/html',
'content-version': 'vor',
'intended-application': 'text-mining'},
{ 'URL': 'https://link.springer.com/content/pdf/10.1007/s40121-021-00453-3.pdf',
'content-type': 'application/pdf',
'content-version': 'vor',
'intended-application': 'similarity-checking'}],
'deposited': { 'date-parts': [[2021, 8, 10]],
'date-time': '2021-08-10T17:20:07Z',
'timestamp': 1628616007000},
'score': 1,
'resource': {'primary': {'URL': 'https://link.springer.com/10.1007/s40121-021-00453-3'}},
'subtitle': [],
'short-title': [],
'issued': {'date-parts': [[2021, 5, 11]]},
'references-count': 30,
'journal-issue': {'issue': '3', 'published-print': {'date-parts': [[2021, 9]]}},
'alternative-id': ['453'],
'URL': 'http://dx.doi.org/10.1007/s40121-021-00453-3',
'relation': {},
'ISSN': ['2193-8229', '2193-6382'],
'subject': [],
'container-title-short': 'Infect Dis Ther',
'published': {'date-parts': [[2021, 5, 11]]},
'assertion': [ { 'value': '28 April 2021',
'order': 1,
'name': 'accepted',
'label': 'Accepted',
'group': {'name': 'ArticleHistory', 'label': 'Article History'}},
{ 'value': '11 May 2021',
'order': 2,
'name': 'first_online',
'label': 'First Online',
'group': {'name': 'ArticleHistory', 'label': 'Article History'}}]}