Abstract: P1
BioScience Trends Advance Publication
Original Article
Advance Publication
DOI: 10.5582/bst.2020.03340
Efficacy of early hydroxychloroquine treatment in preventing
COVID-19 pneumonia aggravation, the experience from Shanghai,
China
§
§
§
Yi Su1, , Yun Ling2, , Yuyan Ma1, , Lili Tao3, Qing Miao1, Qingfeng Shi4, Jue Pan1,
Hongzhou Lu2,*, Bijie Hu1,*
1
Department of Infectious Diseases, Zhongshan Hospital Fudan University, Shanghai, China;
Department of Infectious Diseases, Shanghai Public Health Clinical Center, China;
3
UT Southwestern Medical Center, Department of Immunology, Texas, USA;
4
Department of Infectious Control, Zhongshan Hospital Fudan University, Shanghai, China.
2
SUMMARY
The aim of this study is to assess the efficacy of multiple treatments, especially hydroxychloroquine,
used in different disease stages of coronavirus disease 2019 (COVID-19). All consecutive patients with
COVID-19 admitted to Shanghai Public Health Clinical Center (Shanghai, China) between January
20, 2020, and April 30, 2020, were enrolled, and their clinical data were retrospectively collected.
Binary logistic regression was used to screen the factors associated with disease aggravation, and
multivariable analyses with the Cox proportional hazards model were used to estimate the effects
of prognostic factors on the improvement time and PCR conversion days in throat swabs and stool
swabs. A total of 616 patients, including 50 (8.11%) severe and 18 (2.92%) critical patients, were
enrolled in our retrospective cohort study. The early use of hydroxychloroquine was a protective
factor associated with disease aggravation (95% CI: 0.040-0.575, p = 0.006). Clinical improvement
by 20 days was significantly different between patients with hydroxychloroquine used early and those
with hydroxychloroquine not used (p = 0.016, 95% CI: 1.052-1.647). The median time to clinical
improvement was 6 days in the hydroxychloroquine used early group, compared with 9 days in the
without hydroxychloroquine used group and 8 days in the with hydroxychloroquine not used early
group (p < 0.001). Hydroxychloroquine used early was associated with earlier PCR conversion in
both throat swabs (HR = 1.558, p = 0.001) and stool swabs (HR = 1.400, p = 0.028). The use of
hydroxychloroquine at an early stage is a potential therapeutic strategy for treating patients before
irreversible severe respiratory complications occur. The early use of hydroxychloroquine decreased the
improvement time and the duration of COVID-19 detection in throat and stool swabs.
Keywords
clinical management, treatment, hydroxychloroquine, COVID-19, SARS-CoV-2, coronavirus
{ 'indexed': {'date-parts': [[2023, 8, 18]], 'date-time': '2023-08-18T07:05:35Z', 'timestamp': 1692342335429},
'reference-count': 22,
'publisher': 'International Research and Cooperation Association for Bio & Socio-Sciences Advancement '
'(IRCA-BSSA)',
'issue': '6',
'content-domain': {'domain': [], 'crossmark-restriction': False},
'published-print': {'date-parts': [[2020, 12, 31]]},
'DOI': '10.5582/bst.2020.03340',
'type': 'journal-article',
'created': { 'date-parts': [[2020, 12, 17]],
'date-time': '2020-12-17T22:06:44Z',
'timestamp': 1608242804000},
'page': '408-414',
'source': 'Crossref',
'is-referenced-by-count': 4,
'title': 'Efficacy of early hydroxychloroquine treatment in preventing COVID-19 pneumonia aggravation, the '
'experience from Shanghai, China',
'prefix': '10.5582',
'volume': '14',
'author': [ { 'given': 'Yi',
'family': 'Su',
'sequence': 'first',
'affiliation': [ { 'name': 'Department of Infectious Diseases, Zhongshan Hospital Fudan '
'University, Shanghai, China.'}]},
{ 'given': 'Yun',
'family': 'Ling',
'sequence': 'additional',
'affiliation': [ { 'name': 'Department of Infectious Diseases, Shanghai Public Health '
'Clinical Center, China.'}]},
{ 'given': 'Yuyan',
'family': 'Ma',
'sequence': 'additional',
'affiliation': [ { 'name': 'Department of Infectious Diseases, Zhongshan Hospital Fudan '
'University, Shanghai, China.'}]},
{ 'given': 'Lili',
'family': 'Tao',
'sequence': 'additional',
'affiliation': [ { 'name': 'UT Southwestern Medical Center, Department of Immunology, Texas, '
'USA.'}]},
{ 'given': 'Qing',
'family': 'Miao',
'sequence': 'additional',
'affiliation': [ { 'name': 'Department of Infectious Diseases, Zhongshan Hospital Fudan '
'University, Shanghai, China.'}]},
{ 'given': 'Qingfeng',
'family': 'Shi',
'sequence': 'additional',
'affiliation': [ { 'name': 'Department of Infectious Control, Zhongshan Hospital Fudan '
'University, Shanghai, China.'}]},
{ 'given': 'Jue',
'family': 'Pan',
'sequence': 'additional',
'affiliation': [ { 'name': 'Department of Infectious Diseases, Zhongshan Hospital Fudan '
'University, Shanghai, China.'}]},
{ 'given': 'Hongzhou',
'family': 'Lu',
'sequence': 'additional',
'affiliation': [ { 'name': 'Department of Infectious Diseases, Shanghai Public Health '
'Clinical Center, China.'}]},
{ 'given': 'Bijie',
'family': 'Hu',
'sequence': 'additional',
'affiliation': [ { 'name': 'Department of Infectious Diseases, Zhongshan Hospital Fudan '
'University, Shanghai, China.'}]}],
'member': '3542',
'reference': [ { 'key': '1',
'doi-asserted-by': 'crossref',
'unstructured': '1. Philippe G, Jean-Christophe L, Philippe P, <i>et al. '
'</i>Hydroxychloroquine and azithromycin as a treatment of COVID-19: '
'results of an open-label non-randomized clinical trial. Int J Antimicrob '
'Agents. 2020; 56:105949.',
'DOI': '10.1016/j.ijantimicag.2020.105949'},
{ 'key': '2',
'doi-asserted-by': 'crossref',
'unstructured': '2. Fei Z, Ting Y, Ronghui D, <i>et al.</i> Clinical course and risk '
'factors for mortality of adult inpatients with COVID-19 in Wuhan, China: '
'a retrospective cohort study. Lancet. 2020; 395:1054-1062.',
'DOI': '10.1016/S0140-6736(20)30566-3'},
{ 'key': '3',
'doi-asserted-by': 'crossref',
'unstructured': '3. Jiao G, Jingyi O, Xueping Q, Yusheng J, Yaqiong C, Lianxiong Y, Jing '
'C, Mingkai T, Wengxiong X, Fang Z, Yaling S, Bo H. A tool to early '
'predict severe corona virus disease 2019 (COVID-19): A multicenter study '
'using the risk Nomogram in Wuhan and Guangdong, China. Clin Infect Dis. '
'2020; 71:833-840.',
'DOI': '10.1093/cid/ciaa443'},
{ 'key': '4',
'doi-asserted-by': 'crossref',
'unstructured': '4. Zheng Z, Peng F, Xu B, Zhao J, Liu H, Peng J, Li Q, Jiang C, Zhou Y, '
'Liu S, Ye C, Zhang P, Xing Y, Guo H, Tang W. Risk factors of critical '
'& mortal COVID-19 cases: A systematic literature review and '
'meta-analysis. J Infect. 2020; 81:e16-e25.',
'DOI': '10.1016/j.jinf.2020.04.021'},
{ 'key': '5',
'doi-asserted-by': 'crossref',
'unstructured': '5. Triggle CR, Bansal D, Farag EABA, Ding H, Sultan AA. COVID-19: '
'Learning from lessons to guide treatment and prevention interventions. '
'mSphere. 2020; 5:e00317-20.',
'DOI': '10.1128/mSphere.00317-20'},
{ 'key': '6',
'doi-asserted-by': 'crossref',
'unstructured': '6. Pastick KA, Okafor EC, Wang F, <i>et al.</i> Review: '
'Hydroxychloroquine and chloroquine for treatment of SARS-CoV-2 '
'(COVID-19). Open Forum Infect Dis. 2020; 7:ofaa130.',
'DOI': '10.1093/ofid/ofaa130'},
{ 'key': '7',
'unstructured': '7. National Health Commission. Interpretation of the Seventh Edition of '
'the Guidance for COVID-19: Prevention, Control, Diagnosis, and '
'Management. Guideline for COVID-19 (version 7.0). '
'<i>http://www.nhc.gov.cn/yzygj/s7653p/202003/46c9294a7dfe4cef80dc7f5912eb1989/files/ce3e6945832a438eaae415350a8ce964.pdf</i> '
'(accessed Mar 3, 2020). (in Chinese)'},
{ 'key': '8',
'doi-asserted-by': 'crossref',
'unstructured': '8. Dong L, Hu S, Gao J. Discovering drugs to treat coronavirus disease '
'2019 (COVID-19). Drug Discov Ther. 2020; 14:58-60.',
'DOI': '10.5582/ddt.2020.01012'},
{ 'key': '9',
'doi-asserted-by': 'crossref',
'unstructured': '9. Arabi YM, Asseri A, Webb S, Marshall J, Al Moamary MS. Clinical '
'trials for coronavirus disease 2019: what is being evaluated and what is '
'not. Ann Thorac Med. 2020; 15:49-51.',
'DOI': '10.4103/atm.ATM_99_20'},
{ 'key': '10',
'doi-asserted-by': 'crossref',
'unstructured': '10. Fantini J, Scala CD, Chahinian H, Yahi N. Structural and molecular '
'modeling studies reveal a new mechanism of action of chloroquine and '
'hydroxychloroquine against SARS-CoV-2 infection. Int J Antimicrob '
'Agents. 2020; 55:105960.',
'DOI': '10.1016/j.ijantimicag.2020.105960'},
{ 'key': '11',
'doi-asserted-by': 'crossref',
'unstructured': '11. Yao X, Ye F, Zhang M, Cui C, Huang BY, Niu PH, Liu X, Zhao L, Dong '
'E, Song CL, Zhan SY, Lu RJ, Li HY, Tan WJ, Liu DY. <i>In vitro</i> '
'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. 2020; 71:732-739.',
'DOI': '10.1093/cid/ciaa237'},
{ 'key': '12',
'doi-asserted-by': 'crossref',
'unstructured': '12. Liu J, Cao RY, Xu MY, Wang X, Zhang HY, Hu HR, Li YF, Hu ZH, Zhong '
'W, Wang ML. Hydroxychloroquine, a less toxic derivative of chloroquine, '
'is effective in inhibiting SARS-CoV-2 infection <i>in vitro</i>. Cell '
'Discov. 2020; 6:16.',
'DOI': '10.1038/s41421-020-0156-0'},
{ 'key': '13',
'doi-asserted-by': 'crossref',
'unstructured': '13. Yu B, Li C, Chen P, Zhou N, Wang L, Li J, Jiang H, Wang DW. Low dose '
'of hydroxychloroquine reduces fatality of critically ill patients with '
'COVID-19. Sci China Life Sci. 2020; 63:1515-1521.',
'DOI': '10.1007/s11427-020-1732-2'},
{ 'key': '14',
'doi-asserted-by': 'crossref',
'unstructured': '14. Sarma P, Kaur H, Kumar H, Mahendru D, Avti P, Bhattacharyya A, '
'Prajapat M, Shekhar N, Kumar S, Singh R, Singh A, Dhibar DP, Prakash A, '
'Medhi B. Virological and clinical cure in COVID-19 patients treated with '
'hydroxychloroquine: A systematic review and meta-analysis. J Med Virol. '
'2020; 92:776-785.',
'DOI': '10.1002/jmv.25898'},
{ 'key': '15',
'unstructured': '15. Xing Li, Ying Wang, Patrizia Agostinis, Arnold Rabson, Gerry Melino, '
'Ernesto Carafoli, Yufang Shi, Erwei Sun. Is hydroxychloroquine '
'beneficial for COVID-19 patients? Cell Death Dis. 2020; 11:512'},
{ 'key': '16',
'unstructured': '16. Multicenter Collaboration Group of Department of Science and '
'Technology of Guangdong Province and Health Commission of Guangdong '
'Province for chloroquine in the treatment of novel coronavirus '
'pneumonia. Expert consensus on chloroquine phosphate for the treatment '
'of novel coronavirus pneumonia. Zhonghua Jie He He Hu Xi Za Zhi. 2020; '
'43:185-188. (in Chinese)'},
{ 'key': '17',
'doi-asserted-by': 'crossref',
'unstructured': '17. Tang W, Cao Z, Han M, <i>et al.</i> Hydroxychloroquine in patients '
'with mainly mild to moderate Coronavirus Disease 2019: Open label, '
'randomised controlled trial. BMJ. 2020; 369:m1849.',
'DOI': '10.1136/bmj.m1849'},
{ 'key': '18',
'doi-asserted-by': 'crossref',
'unstructured': '18. Rosenberg ES, Dufort EM, Udo T, <i>et al.</i> Association of '
'treatment with hydroxychloroquine or azithromycin with in-hospital '
'mortality in patients with COVID-19 in New York State. JAMA. 2020; '
'323:2493-502.',
'DOI': '10.1001/jama.2020.8630'},
{ 'key': '19',
'doi-asserted-by': 'crossref',
'unstructured': '19. Million M, Lagier JC, Gautret P, <i>et al.</i> Early treatment of '
'COVID-19 patients with hydroxychloroquine and azithromycin: A '
'retrospective analysis of 1061 cases in Marseille, France. Travel Med '
'Infect Dis. 2020; 35:101738.',
'DOI': '10.1016/j.tmaid.2020.101738'},
{ 'key': '20',
'doi-asserted-by': 'crossref',
'unstructured': '20. Liu YP, Pang Y, Hu ZH, <i>et al.</i> Thymosin alpha 1 (Tα1) reduces '
'the mortality of severe COVID-19 by restoration of lymphocytopenia and '
'reversion of exhausted T cells. Clin Infect Dis. 2020; 71:2150-2157.',
'DOI': '10.1093/cid/ciaa630'},
{ 'key': '21',
'doi-asserted-by': 'crossref',
'unstructured': '21. Hemilä H, Chalker E. Vitamin C can shorten the length of stay in the '
'ICU: a meta- analysis. Nutrients. 2019; 11:708.',
'DOI': '10.3390/nu11040708'},
{ 'key': '22',
'doi-asserted-by': 'crossref',
'unstructured': '22. Cao B, Wang Y, Wen D, <i>et al.</i> A trial of lopinavir-ritonavir '
'in adults hospitalized with severe Covid-19. A trial of '
'lopinavir-ritonavir in adults hospitalized with severe Covid-19. N Engl '
'J Med. 2020; 382:1787-1799.',
'DOI': '10.1056/NEJMoa2001282'}],
'container-title': 'BioScience Trends',
'original-title': [],
'language': 'en',
'link': [ { 'URL': 'https://www.jstage.jst.go.jp/article/bst/14/6/14_2020.03340/_pdf',
'content-type': 'unspecified',
'content-version': 'vor',
'intended-application': 'similarity-checking'}],
'deposited': { 'date-parts': [[2021, 1, 23]],
'date-time': '2021-01-23T03:48:08Z',
'timestamp': 1611373688000},
'score': 1,
'resource': {'primary': {'URL': 'https://www.jstage.jst.go.jp/article/bst/14/6/14_2020.03340/_article'}},
'subtitle': [],
'short-title': [],
'issued': {'date-parts': [[2020, 12, 31]]},
'references-count': 22,
'journal-issue': {'issue': '6', 'published-print': {'date-parts': [[2020]]}},
'URL': 'http://dx.doi.org/10.5582/bst.2020.03340',
'relation': {},
'ISSN': ['1881-7815', '1881-7823'],
'subject': [ 'General Biochemistry, Genetics and Molecular Biology', 'General Medicine',
'Health (social science)'],
'container-title-short': 'BST',
'published': {'date-parts': [[2020, 12, 31]]}}
