Effectiveness of Hydroxychloroquine in COVID-19 disease: A done and dusted situation?

Antonella d’Arminio Monforte; Alessandro Tavelli; Francesca Bai; Giulia Marchetti; Alessandro Cozzi-Lepri

Effectiveness of hydroxychloroquine in COVID-19 disease: A done and dusted deal?

Antonella D’arminio Monforte, Alessandro Tavelli, Francesca Bai, Giulia Marchetti, Alessandro Cozzi-Lepri

International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.07.056

A total of 539 COVID-19 hospitalized patients were included in our cohort in Milan, from February 24 to May 17, 2020, of whom 174 died in hospital (day 14 probability of death: 29.5% -95%CI: 25.5-34.0). We divided a subset of our cohort into three groups who started treatment a median of 1 day after admission: those receiving hydroxychloroquine alone (N = 197), those receiving hydroxycholoroquine + azithromycin (N = 94), and those receiving neither (controls) (N = 92). Of the latter group, ten started HIV antivirals (boosted-lopinavir or -darunavir), one teicoplanin, twelve immunomodulatory drugs, or corticosteroids, 23 heparin and 46 remained untreated. The percent of death in the three groups was 27%, 23%, and 51%. Mechanical ventilation was used in 4.3% of hydroxychloroquine, 14.2% of hydroxychloroquine + azithromycin, and 26.1% of controls. Unweighted and weighted relative hazards of mortality are shown in Table 1 . After adjusting * Adjusted for age, gender, number of comorbidities, CVD (yes/no), duration of symptoms, date of admission, CRP and censoring using IPW. £ The overall estimate was also adjusted for baseline COVID-19 disease severity. # Heparin, immuno-modulatory drugs, HIV antivirals, combinations of these or no drugs at all. & 45 patients missing baseline PO2/FiO2 not included in the stratified analysis.

Declarations of interest None declared. Ethical approval This analysis is part of the study approved by Ethic Committee Area 1, Milan Italy (2020/ST/049 and 2020/ST/049_BIS, 11/03/ 2020).

References

Arshad, Kigore, Chaudhry, Jacobsen, Wang et al., Treatment with hydroxychloroquine, azithromycin, and combination in patients hospitalised with COVID-19, Int J Infect Dis, doi:10.1016/j.ijid.2020.06.09

Devaux, Rolain, Colson, Raoult, New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19?, Int J Antimicrob Agents, doi:10.1016/j.antimicag.2020.105938

Gautret, Lagier, Parola, Hoang, Meddeb et al., Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomised clinical trial, Int J Antimicrob Agents, doi:10.1016/j.antimicag.2020.105949

Geleris, Sun, Platt, Zucker, Baldwin et al., Observational study on hydroxychloroquine in hospitalized patients with COVID-19, N Engl J Med, doi:10.1056/NEJMoa2012410

Horby, Lim, Emberson, Mafham, Bell et al., Effect of desamethasone in hospitalized patients with CVID-19: preliminary report

Lee, Mackenzie, Mcdonald, Tong, An observational cohort study of hydroxychloroquine and azithromycin for COVID-19: (Can't get no) satisfaction, Int J Infect Dis, doi:10.1016/j.ijid.2020.06.095

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

Tang, Cao, Han, Wang, Chen et al., Hydroxychloroquine in patients mainly with mild to moderate COVID-19: an open-label, randomised, controlled trial, BMJ, doi:10.1136/bmj.m1849

DOI record: { "DOI": "10.1016/j.ijid.2020.07.056", "ISSN": [ "1201-9712" ], "URL": "http://dx.doi.org/10.1016/j.ijid.2020.07.056", "alternative-id": [ "S1201971220306007" ], "assertion": [ { "label": "This article is maintained by", "name": "publisher", "value": "Elsevier" }, { "label": "Article Title", "name": "articletitle", "value": "Effectiveness of hydroxychloroquine in COVID-19 disease: A done and dusted deal?" }, { "label": "Journal Title", "name": "journaltitle", "value": "International Journal of Infectious Diseases" }, { "label": "CrossRef DOI link to publisher maintained version", "name": "articlelink", "value": "https://doi.org/10.1016/j.ijid.2020.07.056" }, { "label": "CrossRef DOI link to the associated document", "name": "associatedlink", "value": "https://doi.org/10.1016/j.ijid.2020.06.099" }, { "label": "Content Type", "name": "content_type", "value": "simple-article" }, { "label": "Copyright", "name": "copyright", "value": "© 2020 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases." } ], "author": [ { "affiliation": [], "family": "d’Arminio Monforte", "given": "Antonella", "sequence": "first" }, { "affiliation": [], "family": "Tavelli", "given": "Alessandro", "sequence": "additional" }, { "affiliation": [], "family": "Bai", "given": "Francesca", "sequence": "additional" }, { "affiliation": [], "family": "Marchetti", "given": "Giulia", "sequence": "additional" }, { "affiliation": [], "family": "Cozzi-Lepri", "given": "Alessandro", "sequence": "additional" } ], "container-title": "International Journal of Infectious Diseases", "container-title-short": "International Journal of Infectious Diseases", "content-domain": { "crossmark-restriction": true, "domain": [ "ijidonline.com", "clinicalkey.jp", "clinicalkey.com", "clinicalkey.es", "clinicalkey.fr", "clinicalkey.com.au", "elsevier.com", "sciencedirect.com" ] }, "created": { "date-parts": [ [ 2020, 7, 29 ] ], "date-time": "2020-07-29T16:31:01Z", "timestamp": 1596040261000 }, "deposited": { "date-parts": [ [ 2020, 10, 24 ] ], "date-time": "2020-10-24T00:43:40Z", "timestamp": 1603500220000 }, "indexed": { "date-parts": [ [ 2022, 4, 27 ] ], "date-time": "2022-04-27T06:48:55Z", "timestamp": 1651042135584 }, "is-referenced-by-count": 7, "issued": { "date-parts": [ [ 2020, 10 ] ] }, "language": "en", "license": [ { "URL": "https://www.elsevier.com/tdm/userlicense/1.0/", "content-version": "tdm", "delay-in-days": 0, "start": { "date-parts": [ [ 2020, 10, 1 ] ], "date-time": "2020-10-01T00:00:00Z", "timestamp": 1601510400000 } }, { "URL": "http://creativecommons.org/licenses/by-nc-nd/4.0/", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2020, 7, 27 ] ], "date-time": "2020-07-27T00:00:00Z", "timestamp": 1595808000000 } } ], "link": [ { "URL": "https://api.elsevier.com/content/article/PII:S1201971220306007?httpAccept=text/xml", "content-type": "text/xml", "content-version": "vor", "intended-application": "text-mining" }, { "URL": "https://api.elsevier.com/content/article/PII:S1201971220306007?httpAccept=text/plain", "content-type": "text/plain", "content-version": "vor", "intended-application": "text-mining" } ], "member": "78", "original-title": [], "page": "75-76", "prefix": "10.1016", "published": { "date-parts": [ [ 2020, 10 ] ] }, "published-print": { "date-parts": [ [ 2020, 10 ] ] }, "publisher": "Elsevier BV", "reference": [ { "DOI": "10.1016/j.ijid.2020.06.099", "article-title": "Treatment with hydroxychloroquine, azithromycin, and combination in patients hospitalised with COVID-19", "author": "Arshad", "doi-asserted-by": "crossref", "journal-title": "Int J Infect Dis", "key": "10.1016/j.ijid.2020.07.056_bib0005", "year": "2020" }, { "DOI": "10.1016/j.ijantimicag.2020.105938", "article-title": "New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19?", "author": "Devaux", "doi-asserted-by": "crossref", "journal-title": "Int J Antimicrob Agents", "key": "10.1016/j.ijid.2020.07.056_bib0010", "year": "2020" }, { "DOI": "10.1016/j.ijantimicag.2020.105949", "article-title": "Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomised clinical trial", "author": "Gautret", "doi-asserted-by": "crossref", "journal-title": "Int J Antimicrob Agents", "key": "10.1016/j.ijid.2020.07.056_bib0015", "year": "2020" }, { "DOI": "10.1056/NEJMoa2012410", "article-title": "Observational study on hydroxychloroquine in hospitalized patients with COVID-19", "author": "Geleris", "doi-asserted-by": "crossref", "first-page": "2411", "journal-title": "N Engl J Med", "key": "10.1016/j.ijid.2020.07.056_bib0020", "volume": "382", "year": "2020" }, { "author": "Horby", "key": "10.1016/j.ijid.2020.07.056_bib0025", "series-title": "Effect of desamethasone in hospitalized patients with CVID-19: preliminary report. COVID-19 SARS-CoV-2 preprints from medRxiv and bioRxiv", "year": "2020" }, { "DOI": "10.1016/j.ijid.2020.06.095", "article-title": "An observational cohort study of hydroxychloroquine and azithromycin for COVID-19: (Can’t get no) satisfaction", "author": "Lee", "doi-asserted-by": "crossref", "journal-title": "Int J Infect Dis", "key": "10.1016/j.ijid.2020.07.056_bib0030", "year": "2020" }, { "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", "author": "Liu", "doi-asserted-by": "crossref", "first-page": "16", "journal-title": "Cell Discov", "key": "10.1016/j.ijid.2020.07.056_bib0035", "volume": "6", "year": "2020" }, { "DOI": "10.1136/bmj.m1849", "article-title": "Hydroxychloroquine in patients mainly with mild to moderate COVID-19: an open-label, randomised, controlled trial", "author": "Tang", "doi-asserted-by": "crossref", "first-page": "m1849", "journal-title": "BMJ", "key": "10.1016/j.ijid.2020.07.056_bib0040", "volume": "369", "year": "2020" }, { "author": "World Health Organization", "key": "10.1016/j.ijid.2020.07.056_bib0045", "series-title": "“Solidarity” clinical trial for COVID-19 treatments – update on hydroxychloroquine", "year": "2020" } ], "reference-count": 9, "references-count": 9, "relation": {}, "resource": { "primary": { "URL": "https://linkinghub.elsevier.com/retrieve/pii/S1201971220306007" } }, "score": 1, "short-title": [], "source": "Crossref", "subject": [ "Infectious Diseases", "Microbiology (medical)", "General Medicine" ], "subtitle": [], "title": "Effectiveness of hydroxychloroquine in COVID-19 disease: A done and dusted deal?", "type": "journal-article", "update-policy": "http://dx.doi.org/10.1016/elsevier_cm_policy", "volume": "99" }