The efficiency and safety of high-dose vitamin C in patients with COVID-19: a retrospective cohort study
Dengfeng Gao, Min Xu, Gang Wang, Jianrui Lv, Xiaorong Ma, Yonghong Guo, Dexin Zhang, Huiyun Yang, Wei Jiang, Fuxue Deng, Guozhi Xia, Ziwei Lu, Lv Lv, Shouping Gong
Background: The inflammatory reaction is the main cause of acute respiratory distress syndrome and multiple organ failure in patients with Coronavirus disease 2019, especially those with severe and critical illness. Several studies suggested that high-dose vitamin C reduced inflammatory reaction associated with sepsis and acute respiratory distress syndrome. This study aimed to determine the efficacy and safety of high-dose vitamin C in Coronavirus disease 2019. Methods: We included 76 patients with Coronavirus disease 2019, classified into the high-dose vitamin C group (loading dose of 6g intravenous infusion per 12 hr on the first day, and 6g once for the following 4 days, n=46) and the standard therapy group (standard therapy alone, n=30). Results: The risk of 28-day mortality was reduced for the high-dose vitamin C versus the standard therapy group (HR=0.14, 95% CI, 0.03-0.72). Oxygen support status was improved more with high-dose vitamin C than standard therapy (63.9% vs 36.1%). No safety events were associated with high-dose vitamin C therapy. Conclusion: High-dose vitamin C may reduce the mortality and improve oxygen support status in patients with Coronavirus disease 2019 without adverse events.
Abbreviations COVID-19: Coronavirus disease 2019; WHO: World Health Organization; ARDS: acute respiratory distress syndrome; IQR: interquartile range; CIs: confidence intervals; hs-CRP: high-sensitivity C-reactive protein; PCT: procalcitonin; IL-1: interleukin-1; IL-2R: interleukin-2 receptor; IL-6: interleukin-6; IL-8: interleukin-8; IL-10: interleukin-10; TNF-α: tumor necrosis factor-α.
AUTHOR CONTRIBUTIONS
CONFLICTS OF INTEREST The authors declare that they have no conflicts of interest.
AGING SUPPLEMENTARY MATERIALS Supplementary Figures Supplementary Figure 1
AGING
Supplementary
References
Ahn, Oh, Huh, Lim, Koh et al., Vitamin C alone does not improve treatment outcomes in mechanically ventilated patients with severe sepsis or septic shock: a retrospective cohort study, J Thorac Dis,
doi:10.21037/jtd.2019.03.03
Armour, Tyml, Lidington, Wilson, Ascorbate prevents microvascular dysfunction in the skeletal muscle of the septic rat, J Appl Physiol,
doi:10.1152/jappl.2001.90.3.795
Beigel, Tebas, Mc, Bajwa, Bell et al., Immune plasma for the treatment of severe influenza: an open-label, multicentre, phase 2 randomised study, Lancet Respir Med,
doi:10.1016/S2213-2600(17)30174-1
Borba, Val, Sampaio, Alexandre, Melo et al., 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, JAMA Netw Open,
doi:10.1001/jamanetworkopen.2020.8857
Borrelli, Roux-Lombard, Grau, Girardin, Ricou et al., Plasma concentrations of cytokines, their soluble receptors, and antioxidant vitamins can predict the development of multiple organ failure in patients at risk, Crit Care Med,
doi:10.1097/00003246-199603000-00006
Boulware, Pullen, Bangdiwala, Pastick, Lofgren et al., A randomized trial of hydroxychloroquine as postexposure prophylaxis for covid-19, N Engl J Med,
doi:10.1056/NEJMoa2016638
Carr, Rosengrave, Bayer, Chambers, Mehrtens et al., Hypovitaminosis C and vitamin C deficiency in critically ill patients despite recommended enteral and parenteral intakes, Crit Care,
doi:10.1186/s13054-017-1891-y
Chakrabarty, Nandi, Mukhopadhyay, Chatterjee, Protective role of ascorbic acid against lipid peroxidation and myocardial injury, Mol Cell Biochem,
doi:10.1007/BF00229572
Chen, Hu, Zhang, Jiang, Han et al., Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial, medRxiv,
doi:10.1101/2020.03.22.20040758
Chen, Liu, Liu, Liu, Liu et al., Analysis of Clinical Features of 29 Patients With 2019 Novel Coronavirus Pneumonia, Zhonghua Jie He He Hu Xi Za Zhi
Chen, Wu, Chen, Yang, Chen et al., Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study, BMJ,
doi:10.1136/bmj.m1091
Chen, Zhou, Dong, Qu, Gong et al., 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
Chorin, Dai, Shulman, Wadhwani, Bar-Cohen et al., The QT interval in patients with COVID-19 treated with hydroxychloroquine and azithromycin, Nat Med,
doi:10.1038/s41591-020-0888-2
Du, Liang, Yang, Wang, Cao et al., Predictors of mortality for patients with COVID-19 pneumonia caused by SARS-CoV-2: a prospective cohort study, Eur Respir J,
doi:10.1183/13993003.00524-2020
Fisher, Seropian, Kraskauskas, Thakkar, Voelkel et al., Ascorbic acid attenuates lipopolysaccharide-induced acute lung injury, Crit Care Med,
doi:10.1097/CCM.0b013e3182120cb8
Fowler Aa 3rd, Syed, Knowlson, Sculthorpe, Farthing et al., Unit Nursing. Phase I safety trial of intravenous ascorbic acid in patients with severe sepsis, J Transl Med,
doi:10.1186/1479-5876-12-32
Fowler Aa 3rd, Truwit, Hite, Morris, Dewilde et al., Effect of vitamin C infusion on organ failure and biomarkers of inflammation and vascular injury in patients with sepsis and severe acute respiratory failure: the CITRIS-ALI randomized clinical trial, JAMA,
doi:10.1001/jama.2019.11825
Goldman, Lye, Hui, Marks, Bruno et al., -540-5773 Investigators. Remdesivir for 5 or 10 days in patients with severe covid-19, N Engl J Med,
doi:10.1056/NEJMoa2015301
Guan, Ni, Hu, Liang, Ou et al., China Medical Treatment Expert Group for Covid-19. Clinical characteristics of coronavirus disease 2019 in China, N Engl J Med,
doi:10.1056/NEJMoa2002032
Holshue, Debolt, Lindquist, Lofy, Wiesman et al., Washington State 2019-nCoV Case Investigation Team. First case of 2019 novel coronavirus in the United States, N Engl J Med,
doi:10.1056/NEJMoa2001191
Hui, Azhar, Madani, Ntoumi, Kock et al., The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health -the latest 2019 novel coronavirus outbreak in Wuhan, China, Int J Infect Dis,
doi:10.1016/j.ijid.2020.01.009
Jensen, Heslet, Jensen, Espersen, Steffensen et al., Procalcitonin increase in early identification of critically ill patients at high risk of mortality, Crit Care Med,
doi:10.1097/01.CCM.0000239116.01855.61
Keshan, Disease Laboratory of Xi'an Medical College. Clinical effect and mechanism of high-dose vitamin C for severe Keshan disease, Zhonghua Nei Ke Za Zhi
Kim, Jo, Eom, Mok, Kim et al., Combined vitamin C, hydrocortisone, and thiamine therapy for patients with severe pneumonia who admitted to the intensive care unit: propensity score-based analysis of a beforeafter cohort study, J Crit Care,
doi:10.1016/j.jcrc.2018.07.004
Li, Xu, Li, Huang, Chen, Dynamics of cytokines and lymphocyte subsets associated with the poor prognosis of severe COVID-19, Eur Rev Med Pharmacol Sci,
doi:10.26355/eurrev_202012_24051
Li, Zhi, Zhi, Mechanism of rescue of Keshan disease with highdose vitamin C. Zhongguo Di Fang Bing
Lobo, Lobo, Bota, Lopes-Ferreira, Soliman et al., C-reactive protein levels correlate with mortality and organ failure in critically ill patients, Chest,
doi:10.1378/chest.123.6.2043
Lu, Stratton, Tang, Outbreak of pneumonia of unknown etiology in Wuhan, China: the mystery and the miracle, J Med Virol,
doi:10.1002/jmv.25678
Marik, Khangoora, Rivera, Hooper, Catravas, Hydrocortisone, vitamin C, and thiamine for the treatment of severe sepsis and septic shock: a retrospective before-after study, Chest,
doi:10.1016/j.chest.2016.11.036
May, Harrison, Role of vitamin C in the function of the vascular endothelium, Antioxid Redox Signal,
doi:10.1089/ars.2013.5205
Mikami, Miyashita, Yamada, Harrington, Steinberg et al., Risk factors for mortality in patients with COVID-19 in New York city, J Gen Intern Med,
doi:10.1007/s11606-020-05983-z
Mukhopadhyay, Ghosh, Chatterjee, Ascorbic acid prevents lipid peroxidation and oxidative damage of proteins in Guinea pig extrahepatic tissue microsomes, Mol Cell Biochem,
doi:10.1007/BF00928915
Richardson, Hirsch, Narasimhan, Crawford, Mcginn et al., and the Northwell COVID-19 Research Consortium. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York city area, JAMA,
doi:10.1001/jama.2020.6775
Wang, Cao, Zhang, Yang, Liu et al., Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro, Cell Res,
doi:10.1038/s41422-020-0282-0
Wang, Changes in thinking and the establishment of high-dose vitamin C therapy-commemorating the 60th anniversary of the discovery of Keshan disease and the AGING 35th anniversary of the high-dose vitamin C therapy, Di Fang Bing Tong Bao
Wang, Fan, Salam, Horby, Hayden et al., Comparative effectiveness of combined favipiravir and oseltamivir therapy versus oseltamivir monotherapy in critically ill patients with influenza virus infection, J Infect Dis,
doi:10.1093/infdis/jiz656
Wang, Hu, Hu, Zhu, Liu et al., Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China, JAMA,
doi:10.1001/jama.2020.1585
Wang, Zhang, Du, Du, Zhao et al., Remdesivir in adults with severe COVID-19: a randomised, doubleblind, placebo-controlled, multicentre trial, Lancet,
doi:10.1016/S0140-6736(20)31022-9
Wilson, Mechanism of action of vitamin C in sepsis: ascorbate modulates redox signaling in endothelium, Biofactors,
doi:10.1002/biof.7
Wu, Wilson, Tyml, Ascorbate protects against impaired arteriolar constriction in sepsis by inhibiting inducible nitric oxide synthase expression, Free Radic Biol Med,
doi:10.1016/j.freeradbiomed.2004.06.025
Xu, Wu, Jiang, Xu, Ying et al., Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series, BMJ,
doi:10.1136/bmj.m606
Yang, Yu, Xu, Shu, Xia et al., 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,
doi:10.1016/S2213-2600(20)30079-5
Zhou, Yu, Du, Fan, Liu et al., 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
Zhu, Zhang, Li, Yang, Song et al., China Novel Coronavirus Investigating and Research Team. A novel coronavirus from patients with pneumonia in China, 2019, N Engl J Med,
doi:10.1056/NEJMoa2001017
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'doi-asserted-by': 'publisher',
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'disease 2019: retrospective study.',
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'year': '2020',
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'doi-asserted-by': 'publisher',
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'doi-asserted-by': 'publisher',
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'novel coronavirus (2019-nCoV)',
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'author': 'Xiao',
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{ 'key': '16',
'doi-asserted-by': 'publisher',
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'doi-asserted-by': 'publisher',
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'volume': '38',
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'year': '2020',
'journal-title': 'N Engl J Med'},
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'doi-asserted-by': 'publisher',
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'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': 'Balieiro',
'year': '2020',
'journal-title': 'JAMA Netw Open'},
{ 'key': '19',
'doi-asserted-by': 'publisher',
'first-page': '808',
'DOI': '10.1038/s41591-020-0888-2',
'article-title': 'The QT interval in patients with COVID-19 treated with '
'hydroxychloroquine and azithromycin.',
'volume': '2',
'author': 'Jankelson',
'year': '2020',
'journal-title': 'Nat Med'},
{ 'key': '20',
'doi-asserted-by': 'publisher',
'first-page': '795',
'DOI': '10.1152/jappl.2001.90.3.795',
'article-title': 'Ascorbate prevents microvascular dysfunction in the skeletal muscle of '
'the septic rat.',
'volume': '9',
'author': 'Wilson',
'year': '2001',
'journal-title': 'J Appl Physiol (1985)'},
{ 'key': '21',
'doi-asserted-by': 'publisher',
'first-page': '1282',
'DOI': '10.1016/j.freeradbiomed.2004.06.025',
'article-title': 'Ascorbate protects against impaired arteriolar constriction in sepsis '
'by inhibiting inducible nitric oxide synthase expression.',
'volume': '3',
'author': 'Tyml',
'year': '2004',
'journal-title': 'Free Radic Biol Med'},
{ 'key': '22',
'doi-asserted-by': 'publisher',
'first-page': '41',
'DOI': '10.1007/BF00229572',
'article-title': 'Protective role of ascorbic acid against lipid peroxidation and '
'myocardial injury.',
'volume': '11',
'author': 'Chatterjee',
'year': '1992',
'journal-title': 'Mol Cell Biochem'},
{ 'key': '23',
'doi-asserted-by': 'publisher',
'first-page': '71',
'DOI': '10.1007/BF00928915',
'article-title': 'Ascorbic acid prevents lipid peroxidation and oxidative damage of '
'proteins in Guinea pig extrahepatic tissue microsomes.',
'volume': '14',
'author': 'Chatterjee',
'year': '1995',
'journal-title': 'Mol Cell Biochem'},
{ 'key': '24',
'first-page': '33',
'article-title': 'Mechanism of rescue of Keshan disease with high-dose vitamin C.',
'volume': '1',
'author': 'Li',
'year': '1996',
'journal-title': 'Zhongguo Di Fang Bing Fang Zhi Za Zhi'},
{ 'key': '25',
'unstructured': "Keshan Disease Laboratory of Xi'an Medical College. Clinical effect and "
'mechanism of high-dose vitamin C for severe Keshan disease. Zhonghua Nei '
'Ke Za Zhi. 1961; 9:436.'},
{ 'key': '26',
'first-page': '7',
'article-title': 'Changes in thinking and the establishment of high-dose vitamin C '
'therapy-commemorating the 60th anniversary of the discovery of Keshan '
'disease and the 35th anniversary of the high-dose vitamin C therapy.',
'volume': '1',
'author': 'Wang',
'year': '1996',
'journal-title': 'Di Fang Bing Tong Bao'},
{ 'key': '27',
'doi-asserted-by': 'publisher',
'first-page': '1229',
'DOI': '10.1016/j.chest.2016.11.036',
'article-title': 'Hydrocortisone, vitamin C, and thiamine for the treatment of severe '
'sepsis and septic shock: a retrospective before-after study.',
'volume': '15',
'author': 'Catravas',
'year': '2017',
'journal-title': 'Chest'},
{ 'key': '28',
'doi-asserted-by': 'publisher',
'first-page': '1261',
'DOI': '10.1001/jama.2019.11825',
'article-title': 'Effect of vitamin C infusion on organ failure and biomarkers of '
'inflammation and vascular injury in patients with sepsis and severe '
'acute respiratory failure: the CITRIS-ALI randomized clinical trial.',
'volume': '32',
'author': 'Syed',
'year': '2019',
'journal-title': 'JAMA'},
{ 'key': '29',
'doi-asserted-by': 'publisher',
'first-page': '32',
'DOI': '10.1186/1479-5876-12-32',
'article-title': 'Phase I safety trial of intravenous ascorbic acid in patients with '
'severe sepsis.',
'volume': '1',
'author': 'Natarajan',
'year': '2014',
'journal-title': 'J Transl Med'},
{ 'key': '30',
'doi-asserted-by': 'publisher',
'first-page': '211',
'DOI': '10.1016/j.jcrc.2018.07.004',
'article-title': 'Combined vitamin C, hydrocortisone, and thiamine therapy for patients '
'with severe pneumonia who were admitted to the intensive care unit: '
'propensity score-based analysis of a before-after cohort study.',
'volume': '4',
'author': 'Lee',
'year': '2018',
'journal-title': 'J Crit Care'},
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'doi-asserted-by': 'publisher',
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'DOI': '10.1186/s13054-017-1891-y',
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'despite recommended enteral and parenteral intakes.',
'volume': '2',
'author': 'Shaw',
'year': '2017',
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'doi-asserted-by': 'publisher',
'first-page': '392',
'DOI': '10.1097/00003246-199603000-00006',
'article-title': 'Plasma concentrations of cytokines, their soluble receptors, and '
'antioxidant vitamins can predict the development of multiple organ '
'failure in patients at risk.',
'volume': '2',
'author': 'Suter',
'year': '1996',
'journal-title': 'Crit Care Med'},
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'doi-asserted-by': 'publisher',
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'DOI': '10.1002/14651858.CD005532.pub3',
'article-title': 'Vitamin C for preventing and treating pneumonia.',
'volume': '8',
'author': 'Louhiala',
'year': '2013',
'journal-title': 'Cochrane Database Syst Rev'},
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'doi-asserted-by': 'publisher',
'first-page': '1454',
'DOI': '10.1097/CCM.0b013e3182120cb8',
'article-title': 'Ascorbic acid attenuates lipopolysaccharide-induced acute lung injury.',
'volume': '3',
'author': 'Natarajan',
'year': '2011',
'journal-title': 'Crit Care Med'},
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'doi-asserted-by': 'publisher',
'first-page': '2596',
'DOI': '10.1097/01.CCM.0000239116.01855.61',
'article-title': 'Procalcitonin increase in early identification of critically ill '
'patients at high risk of mortality.',
'volume': '3',
'author': 'Tvede',
'year': '2006',
'journal-title': 'Crit Care Med'},
{ 'key': '36',
'first-page': '203',
'article-title': '[Analysis of Clinical Features of 29 Patients With 2019 Novel '
'Coronavirus Pneumonia].',
'volume': '4',
'author': 'Wei',
'year': '2020',
'journal-title': 'Zhonghua Jie He He Hu Xi Za Zhi'},
{ 'key': '37',
'doi-asserted-by': 'publisher',
'first-page': '2043',
'DOI': '10.1378/chest.123.6.2043',
'article-title': 'C-reactive protein levels correlate with mortality and organ failure in '
'critically ill patients.',
'volume': '12',
'author': 'Vincent',
'year': '2003',
'journal-title': 'Chest'},
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'doi-asserted-by': 'publisher',
'first-page': '241',
'DOI': '10.1016/j.ccc.2010.12.010',
'article-title': 'Biomarkers in the critically ill patient: C-reactive protein.',
'volume': '2',
'author': 'Schmit',
'year': '2011',
'journal-title': 'Crit Care Clin'},
{ 'key': '39',
'doi-asserted-by': 'publisher',
'first-page': '5',
'DOI': '10.1002/biof.7',
'article-title': 'Mechanism of action of vitamin C in sepsis: ascorbate modulates redox '
'signaling in endothelium.',
'volume': '3',
'author': 'Wilson',
'year': '2009',
'journal-title': 'Biofactors'},
{ 'key': '40',
'doi-asserted-by': 'publisher',
'first-page': '2068',
'DOI': '10.1089/ars.2013.5205',
'article-title': 'Role of vitamin C in the function of the vascular endothelium.',
'volume': '1',
'author': 'Harrison',
'year': '2013',
'journal-title': 'Antioxid Redox Signal'},
{ 'key': '41',
'doi-asserted-by': 'publisher',
'first-page': '12536',
'DOI': '10.26355/eurrev_202012_24051',
'article-title': 'Dynamics of cytokines and lymphocyte subsets associated with the poor '
'prognosis of severe COVID-19.',
'volume': '2',
'author': 'Chen',
'year': '2020',
'journal-title': 'Eur Rev Med Pharmacol Sci'},
{ 'key': '42',
'doi-asserted-by': 'publisher',
'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',
'author': 'Pan',
'year': '2020',
'journal-title': 'Lancet Respir Med'},
{ 'key': '43',
'doi-asserted-by': 'publisher',
'first-page': '1708',
'DOI': '10.1056/NEJMoa2002032',
'article-title': 'Clinical characteristics of coronavirus disease 2019 in China.',
'volume': '38',
'author': 'Zeng',
'year': '2020',
'journal-title': 'N Engl J Med'},
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'doi-asserted-by': 'publisher',
'first-page': '17',
'DOI': '10.1007/s11606-020-05983-z',
'article-title': 'Risk factors for mortality in patients with COVID-19 in New York city.',
'volume': '13',
'author': 'Siau',
'year': '2020',
'journal-title': 'J Gen Intern Med'},
{ 'key': '45',
'doi-asserted-by': 'publisher',
'first-page': '2000524',
'DOI': '10.1183/13993003.00524-2020',
'article-title': 'Predictors of mortality for patients with COVID-19 pneumonia caused by '
'SARS-CoV-2: a prospective cohort study.',
'volume': '5',
'author': 'Shi',
'year': '2020',
'journal-title': 'Eur Respir J'},
{ 'key': '46',
'doi-asserted-by': 'publisher',
'first-page': '1562',
'DOI': '10.21037/jtd.2019.03.03',
'article-title': 'Vitamin C alone does not improve treatment outcomes in mechanically '
'ventilated patients with severe sepsis or septic shock: a retrospective '
'cohort study.',
'volume': '1',
'author': 'Hong',
'year': '2019',
'journal-title': 'J Thorac Dis'},
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'doi-asserted-by': 'publisher',
'first-page': 'm606',
'DOI': '10.1136/bmj.m606',
'article-title': 'Clinical findings in a group of patients infected with the 2019 novel '
'coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case '
'series.',
'volume': '36',
'author': 'Li',
'year': '2020',
'journal-title': 'BMJ'},
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'doi-asserted-by': 'publisher',
'first-page': '929',
'DOI': '10.1056/NEJMoa2001191',
'article-title': 'First case of 2019 novel coronavirus in the United States.',
'volume': '38',
'author': 'Fox',
'year': '2020',
'journal-title': 'N Engl J Med'},
{ 'key': '49',
'doi-asserted-by': 'publisher',
'first-page': '473',
'DOI': '10.1016/S0140-6736(20)30317-2',
'article-title': 'Clinical evidence does not support corticosteroid treatment for '
'2019-nCoV lung injury.',
'volume': '39',
'author': 'Baillie',
'year': '2020',
'journal-title': 'Lancet'},
{ 'key': '50',
'unstructured': 'Comprehensive treatment and management of corona virus disease 2019: '
'expert consensus statement from Shanghai City. Zhonghua Chuan Ran Bing '
'Za Zhi. 2020; 38:134-38.'},
{ 'key': '51',
'unstructured': 'Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (Trial '
'Version 7). 2020. '
'http://www.gov.cn/zhengce/zhengceku/2020-03/04/content_5486705.htm.'},
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'doi-asserted-by': 'publisher',
'first-page': '1688',
'DOI': '10.1093/infdis/jiz656',
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'therapy versus oseltamivir monotherapy in critically ill patients with '
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'volume': '22',
'author': 'Cao',
'year': '2020',
'journal-title': 'J Infect Dis'},
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'doi-asserted-by': 'publisher',
'first-page': '500',
'DOI': '10.1016/S2213-2600(17)30174-1',
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'volume': '5',
'author': 'Danko',
'year': '2017',
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