Observational Study of the Efficiency of Treatments in Patients Hospitalized with Covid-19 in Madrid

DOI record: { "DOI": "10.1101/2020.07.17.20155960", "URL": "http://dx.doi.org/10.1101/2020.07.17.20155960", "abstract": "<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Many different treatments were heavily administered to patients with COVID-19 during the peak of the pandemic in Madrid without robust evidence supporting them.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We examined the association between sixteen treatments in four groups (steroids, antivirals, antibiotics and immunomodulators) and intubation or death. Data were obtained from patients that were admitted to an HM hospital with suspicion of COVID-19 until 24/04/2020, excluding unconfirmed diagnosis, those who were admitted before the epidemic started in Madrid, had an outcome that was not discharge or death or died within 24 hours of presentation. We compared outcomes between treated and untreated patients using propensity-score caliper matching.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Of 2,307 patients in the dataset, 679 were excluded. Of the remaining 1,645 patients, 263 (16%) died and 311 (18.9%) died or were intubated. Except for hydroxychloroquine and prednisone, patients that were treated with any of the medications were more likely to go through an outcome of death or intubation at baseline. After propensity matching we found an association between treatment with hydroxychloroquine and prednisone and better outcomes (hazard ratios with 95% CI of 0.83 ± 0.06 and 0.85 ± 0.03). Results were similar in multiple sensitivity analyses.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>In this multicenter study of patients admitted with COVID-19 hydroxychloroquine and prednisone administration was found to be associated with improved outcomes. Other treatments were associated with no effect or worse outcomes. Randomized, controlled trials of these medications in patients with COVID-19 are needed to avoid heavy administration of treatments with no strong evidence to support them.</jats:p></jats:sec>", "accepted": { "date-parts": [ [ 2020, 7, 21 ] ] }, "author": [ { "ORCID": "http://orcid.org/0000-0002-8780-6837", "affiliation": [], "authenticated-orcid": false, "family": "Bernaola", "given": "Nikolas", "sequence": "first" }, { "affiliation": [], "family": "Mena", "given": "Raquel", "sequence": "additional" }, { "affiliation": [], "family": "Bernaola", "given": "Ander", "sequence": "additional" }, { "affiliation": [], "family": "Carballo", "given": "Cesar", "sequence": "additional" }, { "affiliation": [], "family": "Lara", "given": "Antonio", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0001-7109-2668", "affiliation": [], "authenticated-orcid": false, "family": "Bielza", "given": "Concha", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0002-1885-4501", "affiliation": [], "authenticated-orcid": false, "family": "Larrañaga", "given": "Pedro", "sequence": "additional" } ], "container-title": [], "content-domain": { "crossmark-restriction": false, "domain": [] }, "created": { "date-parts": [ [ 2020, 7, 21 ] ], "date-time": "2020-07-21T19:22:48Z", "timestamp": 1595359368000 }, "deposited": { "date-parts": [ [ 2021, 1, 17 ] ], "date-time": "2021-01-17T11:40:47Z", "timestamp": 1610883647000 }, "group-title": "Public and Global Health", "indexed": { "date-parts": [ [ 2023, 8, 28 ] ], "date-time": "2023-08-28T12:51:10Z", "timestamp": 1693227070871 }, "institution": [ { "name": "medRxiv" } ], "is-referenced-by-count": 7, "issued": { "date-parts": [ [ 2020, 7, 21 ] ] }, "link": [ { "URL": "https://syndication.highwire.org/content/doi/10.1101/2020.07.17.20155960", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "246", "original-title": [], "posted": { "date-parts": [ [ 2020, 7, 21 ] ] }, "prefix": "10.1101", "published": { "date-parts": [ [ 2020, 7, 21 ] ] }, "publisher": "Cold Spring Harbor Laboratory", "reference": [ { "key": "2021011703400606000_2020.07.17.20155960v1.1", "unstructured": "WHO b. Naming the coronavirus disease (COVID-19) and the virus that causes it [Internet]. World Heal. Organ. 2020 [cited 2020 Jun 4];Available from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/technical-guidance/naming-the-coronavirus-disease-(covid-2019)-and-the-virus-that-causes-it" }, { "key": "2021011703400606000_2020.07.17.20155960v1.2", "unstructured": "COVID-19 situation update worldwide, as of 22 June 2020 [Internet]. European Centre for Disease Prevention and Control. 2020 [cited 2020 June 22] Available from: https://www.ecdc.europa.eu/en/geographical-distribution-2019-ncov-cases" }, { "key": "2021011703400606000_2020.07.17.20155960v1.3", "unstructured": "Flawed data casts cloud over Spain’s lockdown strategy | Financial Times [Internet]. [cited 2020 Jun 6];Available from: https://www.ft.com/content/77eb7a13-cd26-41dd-9642-616708b43673" }, { "DOI": "10.2139/ssrn.3546088", "doi-asserted-by": "crossref", "key": "2021011703400606000_2020.07.17.20155960v1.4", "unstructured": "Du Y , Tu L , Zhu P , et al. Clinical features of 85 fatal cases of COVID-19 from Wuhan: A retrospective observational study. Am J Respir Crit Care Med 2020;" }, { "DOI": "10.1126/science.abb8654", "doi-asserted-by": "publisher", "key": "2021011703400606000_2020.07.17.20155960v1.5" }, { "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", "doi-asserted-by": "crossref", "first-page": "475", "issue": "5", "journal-title": "Lancet Respir Med", "key": "2021011703400606000_2020.07.17.20155960v1.6", "volume": "8", "year": "2020" }, { "key": "2021011703400606000_2020.07.17.20155960v1.7", "unstructured": "Covid Data Save Lives [Internet]. [cited 2020 Jun 13];Available from: https://www.hmhospitales.com/coronavirus/covid-data-save-lives" }, { "DOI": "10.1097/00001648-200009000-00011", "doi-asserted-by": "publisher", "key": "2021011703400606000_2020.07.17.20155960v1.8" }, { "DOI": "10.1111/j.1467-6419.2007.00527.x", "doi-asserted-by": "publisher", "key": "2021011703400606000_2020.07.17.20155960v1.9" }, { "DOI": "10.1371/journal.pone.0081045", "article-title": "Optimal caliper width for propensity score matching of three treatment groups: A Monte Carlo study", "doi-asserted-by": "crossref", "first-page": "e81045", "issue": "12", "journal-title": "PLoS One [Internet]", "key": "2021011703400606000_2020.07.17.20155960v1.10", "volume": "8", "year": "2013" }, { "article-title": "Controlling bias in observational studies: a review [Internet]", "first-page": "417", "journal-title": "Sankhya Indian J. Stat. Ser. A", "key": "2021011703400606000_2020.07.17.20155960v1.11", "volume": "35", "year": "2020" }, { "key": "2021011703400606000_2020.07.17.20155960v1.12", "unstructured": "Ellis PD . The Essential Guide to Effect Sizes [Internet]. Cambridge University Press; 2010 [cited 2020 Jun 20]. Available from: /core/books/essential-guide-to-effect-sizes/72C26CA99366A19CAC4EF5B16AE3297F" }, { "key": "2021011703400606000_2020.07.17.20155960v1.13", "unstructured": "Rubin DB . Multiple imputation for nonresponse in surveys. Wiley-Interscience; 2004." }, { "article-title": "On effect size", "first-page": "137", "issue": "2", "journal-title": "Association", "key": "2021011703400606000_2020.07.17.20155960v1.14", "volume": "17", "year": "2012" }, { "DOI": "10.1056/NEJMoa2012410", "doi-asserted-by": "crossref", "key": "2021011703400606000_2020.07.17.20155960v1.15", "unstructured": "Geleris J , Sun Y , Platt J , et al. Observational study of hydroxychloroquine in hospitalized patients with Covid-19. N Engl J Med 2020." }, { "DOI": "10.1007/s40261-020-00927-1", "doi-asserted-by": "crossref", "key": "2021011703400606000_2020.07.17.20155960v1.16", "unstructured": "Das S , Bhowmick S , Tiwari S , Sen S. An Updated systematic review of the therapeutic role of hydroxychloroquine in coronavirus disease-19 (COVID-19) [Internet]. Clin. Drug Investig. 2020 [cited 2020 Jun 21];1–11. Available from: https://link.springer.com/article/10.1007/s40261-020-00927-1" }, { "DOI": "10.3949/ccjm.87a.ccc030", "doi-asserted-by": "crossref", "key": "2021011703400606000_2020.07.17.20155960v1.17", "unstructured": "Srinivas P , Sacha G , Koval C. Antivirals for COVID-19. Cleve Clin J Med [Internet] 2020 [cited 2020 Jun 21];Available from: https://www.ccjm.org/content/early/2020/05/27/ccjm.87a.ccc030" }, { "DOI": "10.1016/j.autrev.2020.102568", "doi-asserted-by": "publisher", "key": "2021011703400606000_2020.07.17.20155960v1.18" }, { "DOI": "10.1016/S0140-6736(20)31042-4", "article-title": "Triple combination of interferon beta-1b, lopinavir–ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: An open-label, randomised, phase 2 trial", "doi-asserted-by": "crossref", "first-page": "1695", "issue": "10238", "journal-title": "Lancet [Internet]", "key": "2021011703400606000_2020.07.17.20155960v1.19", "volume": "395", "year": "2020" }, { "DOI": "10.1016/S0140-6736(20)30361-5", "doi-asserted-by": "publisher", "key": "2021011703400606000_2020.07.17.20155960v1.20" }, { "key": "2021011703400606000_2020.07.17.20155960v1.21", "unstructured": "Dexamethasone reduces death in hospitalised patients with severe respiratory complications of COVID-19 | University of Oxford [Internet]. [cited 2020 Jun 21];Available from: http://www.ox.ac.uk/news/2020-06-16-dexamethasone-reduces-death-hospitalised-patients-severe-respiratory-complications" }, { "key": "2021011703400606000_2020.07.17.20155960v1.22", "unstructured": "Coronavirus disease 2019 (COVID-19): Management in hospitalized adults - UpToDate [Internet]. [cited 2020 Jun 21];Available from: https://www.uptodate.com/contents/coronavirus-disease-2019-covid-19-management-in-hospitalized-adults" }, { "DOI": "10.1016/S0140-6736(20)30361-5", "doi-asserted-by": "publisher", "key": "2021011703400606000_2020.07.17.20155960v1.23" }, { "key": "2021011703400606000_2020.07.17.20155960v1.24", "unstructured": "Dexamethasone reduces death in hospitalised patients with severe respiratory complications of COVID-19 | University of Oxford [Internet]. [cited 2020 Jun 21];Available from: http://www.ox.ac.uk/news/2020-06-16-dexamethasone-reduces-death-hospitalised-patients-severe-respiratory-complications" }, { "DOI": "10.1056/NEJMoa2001282", "article-title": "A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19", "doi-asserted-by": "crossref", "first-page": "1787", "issue": "19", "journal-title": "N Engl J Med [Internet]", "key": "2021011703400606000_2020.07.17.20155960v1.25", "volume": "382", "year": "2020" }, { "DOI": "10.3949/ccjm.87a.ccc030", "doi-asserted-by": "crossref", "key": "2021011703400606000_2020.07.17.20155960v1.26", "unstructured": "Srinivas P , Sacha G , Koval C. Antivirals for COVID-19. Cleve Clin J Med [Internet] 2020 [cited 2020 Jun 21];Available from: https://www.ccjm.org/content/early/2020/05/27/ccjm.87a.ccc030" }, { "DOI": "10.1001/jama.2020.1585", "article-title": "Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China", "doi-asserted-by": "crossref", "first-page": "1061", "issue": "11", "journal-title": "JAMA - J Am Med Assoc [Internet]", "key": "2021011703400606000_2020.07.17.20155960v1.27", "volume": "323", "year": "2020" }, { "DOI": "10.1016/j.phrs.2012.06.011", "article-title": "Anti-inflammatory mechanism of action of azithromycin in LPS-stimulated J774A.1 cells", "doi-asserted-by": "crossref", "first-page": "357", "issue": "4", "journal-title": "Pharmacol Res [Internet]", "key": "2021011703400606000_2020.07.17.20155960v1.28", "volume": "66", "year": "2012" }, { "DOI": "10.1016/j.ijantimicag.2020.105949", "doi-asserted-by": "crossref", "key": "2021011703400606000_2020.07.17.20155960v1.29", "unstructured": "Gautret P , Lagier J-C , Parola P , et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents [Internet] 2020 [cited 2020 Jun 21];105949. Available from: https://pubmed.ncbi.nlm.nih.gov/32205204/" }, { "DOI": "10.1093/cid/ciaa237", "doi-asserted-by": "crossref", "key": "2021011703400606000_2020.07.17.20155960v1.30", "unstructured": "Yao X , Ye F , Zhang M , 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 [Internet] 2020 [cited 2020 Jun 21];Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7108130/" }, { "DOI": "10.1007/s40261-020-00927-1", "doi-asserted-by": "crossref", "key": "2021011703400606000_2020.07.17.20155960v1.31", "unstructured": "Das S , Bhowmick S , Tiwari S , Sen S. An Updated systematic review of the therapeutic role of hydroxychloroquine in Coronavirus Disease-19 (COVID-19) [Internet]. Clin. Drug Investig. 2020 [cited 2020 Jun 21];1–11. Available from: https://link.springer.com/article/10.1007/s40261-020-00927-1" }, { "DOI": "10.1016/j.tmaid.2020.101738", "article-title": "Early treatment of COVID-19 patients with hydroxychloroquine and azithromycin: A retrospective analysis of 1061 cases in Marseille, France", "doi-asserted-by": "crossref", "first-page": "101738", "journal-title": "Travel Med Infect Dis", "key": "2021011703400606000_2020.07.17.20155960v1.32", "volume": "35", "year": "2020" }, { "DOI": "10.1056/NEJMoa2012410", "doi-asserted-by": "crossref", "key": "2021011703400606000_2020.07.17.20155960v1.33", "unstructured": "Geleris J , Sun Y , Platt J , et al. Observational study of hydroxychloroquine in hospitalized patients with Covid-19. N Engl J Med [Internet] 2020 [cited 2020 Jun 21];Available from: https://www.nejm.org/doi/full/10.1056/NEJMoa2012410" }, { "DOI": "10.1001/jama.2020.8630", "doi-asserted-by": "crossref", "key": "2021011703400606000_2020.07.17.20155960v1.34", "unstructured": "Rosenberg ES , Dufort EM , Udo T , et al. Association of treatment with hydroxychloroquine or azithromycin with in-hospital mortality in patients with COVID-19 in New York State. JAMA - J Am Med Assoc [Internet] 2020 [cited 2020 Jun 21];Available from: https://jamanetwork.com/journals/jama/fullarticle/2766117" }, { "DOI": "10.1016/S0140-6736(20)30628-0", "doi-asserted-by": "publisher", "key": "2021011703400606000_2020.07.17.20155960v1.35" }, { "DOI": "10.1016/j.jcv.2020.104380", "doi-asserted-by": "crossref", "key": "2021011703400606000_2020.07.17.20155960v1.36", "unstructured": "Alzghari SK , Acuña VS. Supportive treatment with tocilizumab for COVID-19: A systematic review. J Clin Virol [Internet] 2020 [cited 2020 Jun 21];127. Available from: https://pubmed.ncbi.nlm.nih.gov/32353761/" }, { "DOI": "10.1093/infdis/jiv392", "article-title": "Treatment with lopinavir/ritonavir or interferon-β1b improves outcome of MERSCoV infection in a nonhuman primate model of common marmoset", "doi-asserted-by": "crossref", "first-page": "1904", "issue": "12", "journal-title": "J Infect Dis [Internet]", "key": "2021011703400606000_2020.07.17.20155960v1.37", "volume": "212", "year": "2015" }, { "DOI": "10.1016/j.intimp.2020.106688", "doi-asserted-by": "crossref", "key": "2021011703400606000_2020.07.17.20155960v1.38", "unstructured": "Dastan F , Alireza Nadji S , Saffaei A , et al. Subcutaneous administration of Interferon beta-1a for COVID-19: A non-controlled prospective trial. Int Immunopharmacol 2020;106688." }, { "DOI": "10.1016/S0140-6736(20)31042-4", "article-title": "Triple combination of interferon beta-1b, lopinavir-ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: An open-label, randomised, phase 2 trial", "doi-asserted-by": "crossref", "first-page": "1695", "issue": "10238", "journal-title": "Lancet [Internet]", "key": "2021011703400606000_2020.07.17.20155960v1.39", "volume": "395", "year": "2020" } ], "reference-count": 39, "references-count": 39, "relation": {}, "resource": { "primary": { "URL": "http://medrxiv.org/lookup/doi/10.1101/2020.07.17.20155960" } }, "score": 1, "short-title": [], "source": "Crossref", "subtitle": [], "subtype": "preprint", "title": "Observational Study of the Efficiency of Treatments in Patients Hospitalized with Covid-19 in Madrid", "type": "posted-content" }