Hydroxychloroquine with azithromycin in patients hospitalized for mild and moderate COVID-19
Elisa Baranski Lamback, Monica Amorim De Oliveira, Andrea Ferreira Haddad, André Filipe Marcondes Vieira, Armando Leão Ferreira Neto, Taciana Da Silva Maia, Juliana De Rezende Chrisman, Pedro Pimenta De Mello Spineti, Marco Antonio De Mattos, Eduardo Costa
The Brazilian Journal of Infectious Diseases, doi:10.1016/j.bjid.2021.101549
Objectives: To assess the efficacy of hydroxychloroquine in combination with azithromycin in terms of clinical and biochemical outcomes in adult patients with COVID-19 hospitalized for acute respiratory distress syndrome (ARDS), and to describe the occurrence of adverse events. Method: Retrospective comparative study, based in a quaternary private hospital in Rio de Janeiro, Brazil, involving 193 adult patients hospitalized for mild and moderate COVID-19 related ARSD, analyzing treatment efficacy based on clinical and biochemical outcomes.
Results: The active group comprised 101 (52.3%) patients using hydroxychloroquine associated with azithromycin and the control group 92 (47.7%) patients who did not take these medications. Median age was 59 (47-70) in the active group and 65 (47−77) in the control group (p < 0.05). Patients in the control group had greater extent of pulmonary involvement on baseline chest CT scans (p < 0.05). All other baseline variables (BMI, comorbidities, previous use of medications and biochemical assessments) were similar between groups. In the medication group, 25% (25 out of 101) were admitted to the ICU, compared to 21% (19 out of 92) in the control group (p > 0.05). No difference in mortality, duration of non-invasive oxygen use or duration of hospitalization was seen between groups. The therapeutic regimen was well tolerated, with only eight (7.9%) patients presenting gastrointestinal symptoms and eight (7.9%) patients withdrawn treatment due to QTc prolongation. Conclusions: Patients treated with hydroxychloroquine combined with azithromycin and the control group had similar clinical outcomes. This therapeutic regimen was considered
Conflict of interest The authors declare no conflicts of interest.
References
Abubakar, Sani, Godman, Kumar, Islam et al., Systematic review on the therapeutic options for COVID-19: clinical evidence of drug efficacy and implications, Infect Drug Resist
Arshad, Kilgore, Chaudhry, Jacobsen, Wang et al., Treatment with hydroxychloroquine, azithromycin, and combination in patients hospitalized with COVID-19, Int J Infect Dis
Beeching, Fletcher, Fowler, -19
Cavalcanti, Zampieri, Rosa, Azevedo, Veiga et al., Hydroxychloroquine with or without azithromycin in mild-to-moderate Covid-19, N Engl J Med
Colson, Rolain, Lagier, Brouqui, Raoult, Chloroquine and hydroxychloroquine as available weapons to fight COVID-19, Int J Antimicrob Agents
Dagens, Sigfrid, Cai, Lipworth, Cheng et al., Scope, quality, and inclusivity of clinical guidelines produced early in the covid-19 pandemic: rapid review, BMJ
Fauci, Lane, Redfield, Covid-19 -navigating the uncharted, N Engl J Med
Furtado, Berwanger, Fonseca, Corrêa, Ferraz et al., Azithromycin in addition to standard of care versus standard of care alone in the treatment of patients admitted to the hospital with severe COVID-19 in Brazil (COALITION II): a randomised clinical trial, Lancet
Gautret, Lagier, Parola, Hoang, Meddeb et al., 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, Zucker, Baldwin et al., Observational study of hydroxychloroquine in hospitalized patients with Covid-19, N Engl J Med
Ghazy, Almaghraby, Shaaban, Kamal, Beshir et al., A systematic revoew and meta-analysis on chloroquine and hydroxychloroquine as monotherapy or combined with azythromycin in COVID-19 treatment, Sci Rep
Grasselli, Zangrillo, Zanella, Antonelli, Cabrini et al., Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy Region, Italy, JAMA
Guan, Ni, Hu, Liang, Ou et al., Clinical characteristics of coronavirus disease 2019 in China, N Engl J Med
Hernandez, Roman, Pasupuleti, Barboza, White, Update alert 2: hydroxychloroquine or chloroquine for the treatment or prophylaxis of COVID-19, Ann Intern Med
Huang, Zhang, Chen, Zhang, Wei et al., Clinical characteristics of COVID-19 in patients with preexisting ILD: a retrospective study in a single center in Wuhan, China, J Med Virol
Ldh, lactate dehydrogenase
Liu, Cao, Xu, Wang, Zhang et al., Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro, Cell Discov
Maa, Targeting endosomal acidification by chloroquine analogs as a promising strategy for the treatment of emerging viral diseases, Pharmacol Res Perspect
Organization, None
Paccoud, Tubach, Baptiste, Bleibtreu, Hajage et al., Compassionate use of hydroxychloroquine in clinical practice for patients with mild to severe Covid-19 in a French university hospital, Clin Infect Dis
Pathak, Salunke, Thivari, Pandey, Nandy et al., No benefit of hydroxychloroquine in COVID-19: results of systematic review and meta-analysis of randomized controlled trials, Diabetes Metab Syndr
Recovery Collaborative Group, Horby, Mafham, Linsell, Bell et al., Effect of hydroxychloroquine in hospitalized patients with COVID-19: preliminary results from a multi-centre, randomized, controlled trial, N Engl J Med
Sanders, Monogue, Jodlowski, Cutrell, Pharmacologic treatments for coronavirus disease 2019 (COVID-19): a review, JAMA
Savarino, Boelaert, Cassone, Majori, Cauda, Effects of chloroquine on viral infections: an old drug against today's diseases?, Lancet Infect Dis
Schrezenmeier, Dörner, Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology, Nat Rev Rheumatol
Wang, Cao, Zhang, Yang, Liu et al., Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro, Cell Res
Yao, Ye, Zhang, Cui, Huang 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
Zhao, Cytokine storm and immunomodulatory therapy in COVID-19: role of chloroquine and anti-IL-6 monoclonal antibodies, Int J Antimicrob Agents
{ 'indexed': {'date-parts': [[2024, 1, 4]], 'date-time': '2024-01-04T06:41:42Z', 'timestamp': 1704350502611},
'reference-count': 29,
'publisher': 'Elsevier BV',
'issue': '2',
'license': [ { 'start': { 'date-parts': [[2021, 3, 1]],
'date-time': '2021-03-01T00:00:00Z',
'timestamp': 1614556800000},
'content-version': 'tdm',
'delay-in-days': 0,
'URL': 'https://www.elsevier.com/tdm/userlicense/1.0/'},
{ 'start': { 'date-parts': [[2021, 2, 15]],
'date-time': '2021-02-15T00:00:00Z',
'timestamp': 1613347200000},
'content-version': 'vor',
'delay-in-days': 0,
'URL': 'http://creativecommons.org/licenses/by-nc-nd/4.0/'}],
'content-domain': { 'domain': [ 'clinicalkey.jp', 'clinicalkey.com', 'clinicalkey.es', 'clinicalkey.fr',
'clinicalkey.com.au', 'elsevier.com', 'sciencedirect.com'],
'crossmark-restriction': True},
'published-print': {'date-parts': [[2021, 3]]},
'DOI': '10.1016/j.bjid.2021.101549',
'type': 'journal-article',
'created': {'date-parts': [[2021, 2, 21]], 'date-time': '2021-02-21T14:16:12Z', 'timestamp': 1613916972000},
'page': '101549',
'update-policy': 'http://dx.doi.org/10.1016/elsevier_cm_policy',
'source': 'Crossref',
'is-referenced-by-count': 8,
'title': 'Hydroxychloroquine with azithromycin in patients hospitalized for mild and moderate COVID-19',
'prefix': '10.1016',
'volume': '25',
'author': [ { 'ORCID': 'http://orcid.org/0000-0002-6026-4329',
'authenticated-orcid': False,
'given': 'Elisa Baranski',
'family': 'Lamback',
'sequence': 'first',
'affiliation': []},
{ 'given': 'Monica Amorim de',
'family': 'Oliveira',
'sequence': 'additional',
'affiliation': []},
{'given': 'Andrea Ferreira', 'family': 'Haddad', 'sequence': 'additional', 'affiliation': []},
{ 'given': 'André Filipe Marcondes',
'family': 'Vieira',
'sequence': 'additional',
'affiliation': []},
{ 'given': 'Armando Leão Ferreira',
'family': 'Neto',
'sequence': 'additional',
'affiliation': []},
{'given': 'Taciana da Silva', 'family': 'Maia', 'sequence': 'additional', 'affiliation': []},
{ 'given': 'Juliana de Rezende',
'family': 'Chrisman',
'sequence': 'additional',
'affiliation': []},
{ 'given': 'Pedro Pimenta de Mello',
'family': 'Spineti',
'sequence': 'additional',
'affiliation': []},
{'given': 'Marco Antonio de', 'family': 'Mattos', 'sequence': 'additional', 'affiliation': []},
{'given': 'Eduardo', 'family': 'Costa', 'sequence': 'additional', 'affiliation': []}],
'member': '78',
'reference': [ { 'key': '10.1016/j.bjid.2021.101549_bib0005',
'doi-asserted-by': 'crossref',
'first-page': '1574',
'DOI': '10.1001/jama.2020.5394',
'article-title': 'Baseline characteristics and outcomes of 1591 patients infected with '
'SARS-CoV-2 admitted to ICUs of the Lombardy Region, Italy',
'volume': '323',
'author': 'Grasselli',
'year': '2020',
'journal-title': 'JAMA'},
{'key': '10.1016/j.bjid.2021.101549_bib0010', 'author': 'Organization WH'},
{ 'key': '10.1016/j.bjid.2021.101549_bib0015',
'doi-asserted-by': 'crossref',
'first-page': '1268',
'DOI': '10.1056/NEJMe2002387',
'article-title': 'Covid-19 — navigating the uncharted',
'volume': '382',
'author': 'Fauci',
'year': '2020',
'journal-title': 'N Engl J Med'},
{ 'key': '10.1016/j.bjid.2021.101549_bib0020',
'doi-asserted-by': 'crossref',
'first-page': '1708',
'DOI': '10.1056/NEJMoa2002032',
'article-title': 'Clinical characteristics of coronavirus disease 2019 in China',
'volume': '382',
'author': 'Guan',
'year': '2020',
'journal-title': 'N Engl J Med'},
{ 'key': '10.1016/j.bjid.2021.101549_bib0025',
'series-title': 'BMJ best practice coronavirus disease (COVID-19)',
'author': 'Beeching',
'year': '2020'},
{ 'key': '10.1016/j.bjid.2021.101549_bib0030',
'doi-asserted-by': 'crossref',
'first-page': '269',
'DOI': '10.1038/s41422-020-0282-0',
'article-title': 'Remdesivir and chloroquine effectively inhibit the recently emerged '
'novel coronavirus (2019-nCoV) in vitro',
'volume': '30',
'author': 'Wang',
'year': '2020',
'journal-title': 'Cell Res'},
{ 'key': '10.1016/j.bjid.2021.101549_bib0035',
'doi-asserted-by': 'crossref',
'first-page': '732',
'DOI': '10.1093/cid/ciaa237',
'article-title': '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)',
'volume': '71',
'author': 'Yao',
'year': '2020',
'journal-title': 'Clin Infect Dis'},
{ 'key': '10.1016/j.bjid.2021.101549_bib0040',
'first-page': '1824',
'article-title': 'Pharmacologic treatments for coronavirus disease 2019 (COVID-19): a '
'review',
'volume': '323',
'author': 'Sanders',
'year': '2020',
'journal-title': 'JAMA'},
{ 'key': '10.1016/j.bjid.2021.101549_bib0045',
'doi-asserted-by': 'crossref',
'DOI': '10.1002/prp2.293',
'article-title': 'Targeting endosomal acidification by chloroquine analogs as a promising '
'strategy for the treatment of emerging viral diseases',
'volume': '5',
'author': 'Al-Bari',
'year': '2017',
'journal-title': 'Pharmacol Res Perspect'},
{ 'key': '10.1016/j.bjid.2021.101549_bib0050',
'doi-asserted-by': 'crossref',
'first-page': '722',
'DOI': '10.1016/S1473-3099(03)00806-5',
'article-title': 'Effects of chloroquine on viral infections: an old drug against today’s '
'diseases?',
'volume': '3',
'author': 'Savarino',
'year': '2003',
'journal-title': 'Lancet Infect Dis'},
{ 'key': '10.1016/j.bjid.2021.101549_bib0055',
'doi-asserted-by': 'crossref',
'first-page': '16',
'DOI': '10.1038/s41421-020-0156-0',
'article-title': 'Hydroxychloroquine, a less toxic derivative of chloroquine, is '
'effective in inhibiting SARS-CoV-2 infection in vitro',
'volume': '6',
'author': 'Liu',
'year': '2020',
'journal-title': 'Cell Discov'},
{ 'key': '10.1016/j.bjid.2021.101549_bib0060',
'doi-asserted-by': 'crossref',
'DOI': '10.1016/j.ijantimicag.2020.105982',
'article-title': 'Cytokine storm and immunomodulatory therapy in COVID-19: role of '
'chloroquine and anti-IL-6 monoclonal antibodies',
'volume': '55',
'author': 'Zhao',
'year': '2020',
'journal-title': 'Int J Antimicrob Agents'},
{ 'key': '10.1016/j.bjid.2021.101549_bib0065',
'doi-asserted-by': 'crossref',
'first-page': '2742',
'DOI': '10.1002/jmv.26174',
'article-title': 'Clinical characteristics of COVID-19 in patients with preexisting ILD: '
'a retrospective study in a single center in Wuhan, China',
'volume': '92',
'author': 'Huang',
'year': '2020',
'journal-title': 'J Med Virol'},
{ 'key': '10.1016/j.bjid.2021.101549_bib0070',
'doi-asserted-by': 'crossref',
'first-page': '155',
'DOI': '10.1038/s41584-020-0372-x',
'article-title': 'Mechanisms of action of hydroxychloroquine and chloroquine: '
'implications for rheumatology',
'volume': '16',
'author': 'Schrezenmeier',
'year': '2020',
'journal-title': 'Nat Rev Rheumatol'},
{ 'key': '10.1016/j.bjid.2021.101549_bib0075',
'doi-asserted-by': 'crossref',
'DOI': '10.1016/j.ijantimicag.2020.105949',
'article-title': 'Hydroxychloroquine and azithromycin as a treatment of COVID-19: results '
'of an open-label non-randomized clinical trial',
'volume': '56',
'author': 'Gautret',
'year': '2020',
'journal-title': 'Int J Antimicrob Agents'},
{ 'key': '10.1016/j.bjid.2021.101549_bib0080',
'doi-asserted-by': 'crossref',
'DOI': '10.1016/j.ijantimicag.2020.105932',
'article-title': 'Chloroquine and hydroxychloroquine as available weapons to fight '
'COVID-19',
'volume': '55',
'author': 'Colson',
'year': '2020',
'journal-title': 'Int J Antimicrob Agents'},
{ 'key': '10.1016/j.bjid.2021.101549_bib0085',
'article-title': 'Scope, quality, and inclusivity of clinical guidelines produced early '
'in the covid-19 pandemic: rapid review',
'volume': '369',
'author': 'Dagens',
'year': '2020',
'journal-title': 'BMJ'},
{ 'key': '10.1016/j.bjid.2021.101549_bib0090',
'series-title': 'Cloroquina poderá ser usada em casos graves do coronavírus',
'year': '2020'},
{ 'key': '10.1016/j.bjid.2021.101549_bib0095',
'series-title': 'Ministério da Saúde divulga diretrizes para tratamento medicamentoso de '
'pacientes',
'year': '2020'},
{ 'key': '10.1016/j.bjid.2021.101549_bib0100',
'doi-asserted-by': 'crossref',
'first-page': '2411',
'DOI': '10.1056/NEJMoa2012410',
'article-title': 'Observational study of hydroxychloroquine in hospitalized patients with '
'Covid-19',
'volume': '382',
'author': 'Geleris',
'year': '2020',
'journal-title': 'N Engl J Med'},
{ 'key': '10.1016/j.bjid.2021.101549_bib0105',
'doi-asserted-by': 'crossref',
'DOI': '10.1093/cid/ciaa791',
'article-title': 'Compassionate use of hydroxychloroquine in clinical practice for '
'patients with mild to severe Covid-19 in a French university hospital',
'author': 'Paccoud',
'year': '2020',
'journal-title': 'Clin Infect Dis'},
{ 'key': '10.1016/j.bjid.2021.101549_bib0110',
'doi-asserted-by': 'crossref',
'first-page': '396',
'DOI': '10.1016/j.ijid.2020.06.099',
'article-title': 'Treatment with hydroxychloroquine, azithromycin, and combination in '
'patients hospitalized with COVID-19',
'volume': '97',
'author': 'Arshad',
'year': '2020',
'journal-title': 'Int J Infect Dis'},
{ 'key': '10.1016/j.bjid.2021.101549_bib0115',
'doi-asserted-by': 'crossref',
'first-page': '959',
'DOI': '10.1016/S0140-6736(20)31862-6',
'article-title': 'Azithromycin in addition to standard of care versus standard of care '
'alone in the treatment of patients admitted to the hospital with severe '
'COVID-19 in Brazil (COALITION II): a randomised clinical trial',
'volume': '396',
'author': 'Furtado',
'year': '2020',
'journal-title': 'Lancet'},
{ 'key': '10.1016/j.bjid.2021.101549_bib0120',
'doi-asserted-by': 'crossref',
'first-page': '2030',
'DOI': '10.1056/NEJMoa2022926',
'article-title': 'Effect of hydroxychloroquine in hospitalized patients with COVID-19: '
'preliminary results from a multi-centre, randomized, controlled trial',
'volume': '383',
'author': 'RECOVERY Collaborative Group',
'year': '2020',
'journal-title': 'N Engl J Med'},
{ 'key': '10.1016/j.bjid.2021.101549_bib0125',
'doi-asserted-by': 'crossref',
'first-page': 'W128',
'DOI': '10.7326/L20-1054',
'article-title': 'Update alert 2: hydroxychloroquine or chloroquine for the treatment or '
'prophylaxis of COVID-19',
'volume': '173',
'author': 'Hernandez',
'year': '2020',
'journal-title': 'Ann Intern Med'},
{ 'key': '10.1016/j.bjid.2021.101549_bib0130',
'doi-asserted-by': 'crossref',
'first-page': '2041',
'DOI': '10.1056/NEJMoa2019014',
'article-title': 'Hydroxychloroquine with or without azithromycin in mild-to-moderate '
'Covid-19',
'volume': '383',
'author': 'Cavalcanti',
'year': '2020',
'journal-title': 'N Engl J Med'},
{ 'key': '10.1016/j.bjid.2021.101549_bib0135',
'doi-asserted-by': 'crossref',
'first-page': '1673',
'DOI': '10.1016/j.dsx.2020.08.033',
'article-title': 'No benefit of hydroxychloroquine in COVID-19: results of systematic '
'review and meta-analysis of randomized controlled trials',
'volume': '14',
'author': 'Pathak',
'year': '2020',
'journal-title': 'Diabetes Metab Syndr'},
{ 'key': '10.1016/j.bjid.2021.101549_bib0140',
'article-title': 'A systematic revoew and meta-analysis on chloroquine and '
'hydroxychloroquine as monotherapy or combined with azythromycin in '
'COVID-19 treatment',
'volume': '17',
'author': 'Ghazy',
'year': '2020',
'journal-title': 'Sci Rep'},
{ 'key': '10.1016/j.bjid.2021.101549_bib0145',
'doi-asserted-by': 'crossref',
'first-page': '4673',
'DOI': '10.2147/IDR.S289037',
'article-title': 'Systematic review on the therapeutic options for COVID-19: clinical '
'evidence of drug efficacy and implications',
'volume': '13',
'author': 'Abubakar',
'year': '2020',
'journal-title': 'Infect Drug Resist'}],
'container-title': 'The Brazilian Journal of Infectious Diseases',
'original-title': [],
'language': 'en',
'link': [ { 'URL': 'https://api.elsevier.com/content/article/PII:S141386702100012X?httpAccept=text/xml',
'content-type': 'text/xml',
'content-version': 'vor',
'intended-application': 'text-mining'},
{ 'URL': 'https://api.elsevier.com/content/article/PII:S141386702100012X?httpAccept=text/plain',
'content-type': 'text/plain',
'content-version': 'vor',
'intended-application': 'text-mining'}],
'deposited': { 'date-parts': [[2021, 5, 11]],
'date-time': '2021-05-11T12:17:53Z',
'timestamp': 1620735473000},
'score': 1,
'resource': {'primary': {'URL': 'https://linkinghub.elsevier.com/retrieve/pii/S141386702100012X'}},
'subtitle': [],
'short-title': [],
'issued': {'date-parts': [[2021, 3]]},
'references-count': 29,
'journal-issue': {'issue': '2', 'published-print': {'date-parts': [[2021, 3]]}},
'alternative-id': ['S141386702100012X'],
'URL': 'http://dx.doi.org/10.1016/j.bjid.2021.101549',
'relation': {},
'ISSN': ['1413-8670'],
'subject': ['Infectious Diseases', 'Microbiology (medical)'],
'container-title-short': 'The Brazilian Journal of Infectious Diseases',
'published': {'date-parts': [[2021, 3]]},
'assertion': [ {'value': 'Elsevier', 'name': 'publisher', 'label': 'This article is maintained by'},
{ 'value': 'Hydroxychloroquine with azithromycin in patients hospitalized for mild and '
'moderate COVID-19',
'name': 'articletitle',
'label': 'Article Title'},
{ 'value': 'The Brazilian Journal of Infectious Diseases',
'name': 'journaltitle',
'label': 'Journal Title'},
{ 'value': 'https://doi.org/10.1016/j.bjid.2021.101549',
'name': 'articlelink',
'label': 'CrossRef DOI link to publisher maintained version'},
{'value': 'article', 'name': 'content_type', 'label': 'Content Type'},
{ 'value': '© 2021 Sociedade Brasileira de Infectologia. Published by Elsevier España, '
'S.L.U.',
'name': 'copyright',
'label': 'Copyright'}],
'article-number': '101549'}