Effect of combination therapy of hydroxychloroquine and azithromycin on mortality in COVID-19 patients

{ 'indexed': {'date-parts': [[2024, 3, 24]], 'date-time': '2024-03-24T02:01:13Z', 'timestamp': 1711245673219}, 'reference-count': 28, 'publisher': 'Wiley', 'issue': '6', 'license': [ { 'start': { 'date-parts': [[2020, 10, 13]], 'date-time': '2020-10-13T00:00:00Z', 'timestamp': 1602547200000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'http://creativecommons.org/licenses/by-nc/4.0/'}], 'content-domain': {'domain': ['ascpt.onlinelibrary.wiley.com'], 'crossmark-restriction': True}, 'published-print': {'date-parts': [[2020, 11]]}, 'abstract': '<jats:p>Conflicting evidence regarding the use of hydroxychloroquine (HCQ) and azithromycin ' 'for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection ' 'do exist. We performed a retrospective single‐center cohort study including 377 consecutive ' 'patients admitted for pneumonia related to coronavirus disease 2019 (COVID‐19). Of these, 297 ' 'were in combination treatment, 17 were on HCQ alone, and 63 did not receive either of these 2 ' 'drugs because of contraindications. The primary end point was in‐hospital death. Mean age was ' '71.8\xa0±\xa013.4\xa0years and 34.2% were women. We recorded 146 deaths: 35 in no treatment, ' '7 in HCQ treatment group, and 102 in HCQ\xa0+\xa0azithromycin treatment group (log rank test ' 'for Kaplan–Meier curve <jats:italic>P</jats:italic>\xa0&lt;\xa00.001). At multivariable Cox ' 'proportional hazard regression analysis, age (hazard ratio (HR) 1.057, 95% confidence ' 'interval (CI) 1.035–1.079, <jats:italic>P</jats:italic>\xa0&lt;\xa00.001), mechanical ' 'ventilation/continuous positive airway pressure (HR 2.726, 95% CI 1.823–4.074, ' '<jats:italic>P</jats:italic>\xa0&lt;\xa00.001), and C reactive protein above the median (HR ' '2.191, 95% CI 1.479–3.246, <jats:italic>P</jats:italic>\xa0&lt;\xa00.001) were directly ' 'associated with death, whereas use of HCQ\xa0+\xa0azithromycin (vs. no treatment; HR 0.265, ' '95% CI 0.171–0.412, <jats:italic>P</jats:italic>\xa0&lt;\xa00.001) was inversely associated. ' 'In this study, we found a reduced in‐hospital mortality in patients treated with a ' 'combination of HCQ and azithromycin after adjustment for comorbidities. A large randomized ' 'trial is necessary to confirm these findings.</jats:p>', 'DOI': '10.1111/cts.12860', 'type': 'journal-article', 'created': {'date-parts': [[2020, 9, 16]], 'date-time': '2020-09-16T07:33:36Z', 'timestamp': 1600241616000}, 'page': '1071-1076', 'update-policy': 'http://dx.doi.org/10.1002/crossmark_policy', 'source': 'Crossref', 'is-referenced-by-count': 34, 'title': 'Effect of Combination Therapy of Hydroxychloroquine and Azithromycin on Mortality in Patients ' 'With COVID‐19', 'prefix': '10.1111', 'volume': '13', 'author': [ { 'given': 'Marinella', 'family': 'Lauriola', 'sequence': 'first', 'affiliation': [{'name': 'Infectious Disease Department Policlinico di Monza Monza Italy'}]}, { 'given': 'Arianna', 'family': 'Pani', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Oncology and Hemato‐Oncology Università degli ' 'Studi di Milano Milan Italy'}]}, { 'given': 'Giovanbattista', 'family': 'Ippoliti', 'sequence': 'additional', 'affiliation': [{'name': 'Internal Medicine Department Policlinico di Monza Monza Italy'}]}, { 'given': 'Andrea', 'family': 'Mortara', 'sequence': 'additional', 'affiliation': [{'name': 'Cardiology Department Policlinico di Monza Monza Italy'}]}, { 'given': 'Stefano', 'family': 'Milighetti', 'sequence': 'additional', 'affiliation': [{'name': 'Internal Medicine Department Policlinico di Monza Monza Italy'}]}, { 'given': 'Marjieh', 'family': 'Mazen', 'sequence': 'additional', 'affiliation': [{'name': 'Internal Medicine Department Policlinico di Monza Monza Italy'}]}, { 'given': 'Gianluca', 'family': 'Perseghin', 'sequence': 'additional', 'affiliation': [ {'name': 'Internal Medicine Department Policlinico di Monza Monza Italy'}, { 'name': 'Department of Medicine and Surgery Università degli Studi di ' 'Milano Bicocca Milan Italy'}]}, { 'given': 'Daniele', 'family': 'Pastori', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Clinical, Internal, Anesthesiologic, and ' 'Cardiovascular Sciences Sapienza University of Rome Rome ' 'Italy'}]}, { 'given': 'Paolo', 'family': 'Grosso', 'sequence': 'additional', 'affiliation': [{'name': 'Intensive Care Unit Policlinico di Monza Monza Italy'}]}, { 'given': 'Francesco', 'family': 'Scaglione', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Oncology and Hemato‐Oncology Università degli ' 'Studi di Milano Milan Italy'}]}], 'member': '311', 'published-online': {'date-parts': [[2020, 10, 13]]}, 'reference': [ {'key': 'e_1_2_8_1_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1056/NEJMoa2001282'}, { 'key': 'e_1_2_8_2_1', 'article-title': 'Remdesivir for the treatment of Covid‐19 ‐ preliminary report', 'author': 'Beigel J.H.', 'journal-title': 'N. 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Agents'}, {'key': 'e_1_2_8_16_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1177/2048872620922784'}, { 'key': 'e_1_2_8_17_1', 'article-title': 'Finding the dose for hydroxychloroquine prophylaxis for COVID‐19: the ' 'desperate search for effectiveness', 'author': 'Al‐Kofahi M.', 'journal-title': 'Clin. Pharmacol. Ther.'}, {'key': 'e_1_2_8_18_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1038/s41421-020-0156-0'}, { 'key': 'e_1_2_8_19_1', '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)', 'author': 'Yao X.', 'journal-title': 'Clin. Infect. Dis.'}, { 'key': 'e_1_2_8_20_1', 'article-title': 'Towards optimization of hydroxychloroquine dosing in intensive care ' 'unit COVID‐19 patients', 'author': 'Perinel S.', 'journal-title': 'Clin. Infect. Dis'}, {'key': 'e_1_2_8_21_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1111/cts.12797'}, { 'key': 'e_1_2_8_22_1', 'article-title': 'Impact of disease on plasma and lung exposure of chloroquine, ' 'hydroxy‐chloroquine and azithromycin: application of PBPK modelling', 'author': 'Rowland Yeo K.', 'journal-title': 'Clin. Pharmacol. Ther.'}, { 'key': 'e_1_2_8_23_1', 'article-title': 'Synergistic antiviral effect of hydroxychloroquine and azithromycin in ' 'combination against SARS‐CoV‐2: what molecular dynamics studies of ' 'virus‐host interactions reveal', 'author': 'Fantini J.', 'journal-title': 'Int. J. Antimicrob. Agents'}, { 'key': 'e_1_2_8_24_1', 'article-title': 'Hydroxychloroquine, coronavirus disease 2019, and QT prolongation', 'author': 'Bonow R.O.', 'journal-title': 'JAMA Cardiol.'}, { 'key': 'e_1_2_8_25_1', 'article-title': 'Risk of QT interval prolongation associated with use of ' 'hydroxychloroquine with or without concomitant azithromycin among ' 'hospitalized patients testing positive for coronavirus disease 2019 ' '(COVID‐19)', 'author': 'Mercuro N.J.', 'journal-title': 'JAMA Cardiol.'}, { 'key': 'e_1_2_8_26_1', 'article-title': 'Assessment of QT intervals in a case series of patients with ' 'coronavirus disease 2019 (COVID‐19) infection treated with ' 'hydroxychloroquine alone or in combination with azithromycin in an ' 'intensive care unit', 'author': 'Bessiere F.', 'journal-title': 'JAMA Cardiol.'}, {'key': 'e_1_2_8_27_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.jacc.2020.04.032'}, {'key': 'e_1_2_8_28_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1177/0004563220922255'}], 'container-title': 'Clinical and Translational Science', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fcts.12860', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://onlinelibrary.wiley.com/doi/pdf/10.1111/cts.12860', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://onlinelibrary.wiley.com/doi/full-xml/10.1111/cts.12860', 'content-type': 'application/xml', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://ascpt.onlinelibrary.wiley.com/doi/pdf/10.1111/cts.12860', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2023, 9, 4]], 'date-time': '2023-09-04T09:28:23Z', 'timestamp': 1693819703000}, 'score': 1, 'resource': {'primary': {'URL': 'https://ascpt.onlinelibrary.wiley.com/doi/10.1111/cts.12860'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2020, 10, 13]]}, 'references-count': 28, 'journal-issue': {'issue': '6', 'published-print': {'date-parts': [[2020, 11]]}}, 'alternative-id': ['10.1111/cts.12860'], 'URL': 'http://dx.doi.org/10.1111/cts.12860', 'relation': {}, 'ISSN': ['1752-8054', '1752-8062'], 'subject': [ 'General Pharmacology, Toxicology and Pharmaceutics', 'General Biochemistry, Genetics and Molecular Biology', 'General Medicine', 'General Neuroscience'], 'container-title-short': 'Clinical Translational Sci', 'published': {'date-parts': [[2020, 10, 13]]}, 'assertion': [ { 'value': '2020-06-23', 'order': 0, 'name': 'received', 'label': 'Received', 'group': {'name': 'publication_history', 'label': 'Publication History'}}, { 'value': '2020-07-13', 'order': 1, 'name': 'accepted', 'label': 'Accepted', 'group': {'name': 'publication_history', 'label': 'Publication History'}}, { 'value': '2020-10-13', 'order': 2, 'name': 'published', 'label': 'Published', 'group': {'name': 'publication_history', 'label': 'Publication History'}}]}