{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:31:01Z","timestamp":1760236261528,"version":"build-2065373602"},"reference-count":23,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2021,11,10]],"date-time":"2021-11-10T00:00:00Z","timestamp":1636502400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010067","name":"Government of Aragon","doi-asserted-by":"publisher","award":["Recognized Groups Grant reference B01_20R and Decree-Law 3\/2020, published on 3 June"],"award-info":[{"award-number":["Recognized Groups Grant reference B01_20R and Decree-Law 3\/2020, published on 3 June"]}],"id":[{"id":"10.13039\/501100010067","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>This study aims to identify baseline medications that, as a proxy for the diseases they are dispensed for, are associated with increased risk of mortality in COVID-19 patients from two regions in Spain and Italy using real-world data. We conducted a cross-country, retrospective, observational study including 8570 individuals from both regions with confirmed SARS-CoV-2 infection between 4 March and 17 April 2020, and followed them for a minimum of 30 days to allow sufficient time for the studied event, in this case death, to occur. Baseline demographic variables and all drugs dispensed in community pharmacies three months prior to infection were extracted from the PRECOVID Study cohort (Aragon, Spain) and the Campania Region Database (Campania, Italy) and analyzed using logistic regression models. Results show that the presence at baseline of potassium-sparing agents, antipsychotics, vasodilators, high-ceiling diuretics, antithrombotic agents, vitamin B12, folic acid, and antiepileptics were systematically associated with mortality in COVID-19 patients from both countries. Treatments for chronic cardiovascular and metabolic diseases, systemic inflammation, and processes with increased risk of thrombosis as proxies for the conditions they are intended for can serve as timely indicators of an increased likelihood of mortality after the infection, and the assessment of pharmacological profiles can be an additional approach to the identification of at-risk individuals in clinical practice.<\/jats:p>","DOI":"10.3390\/ijerph182211786","type":"journal-article","created":{"date-parts":[[2021,11,10]],"date-time":"2021-11-10T09:19:21Z","timestamp":1636535961000},"page":"11786","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Baseline Drug Treatments as Indicators of Increased Risk of COVID-19 Mortality in Spain and Italy"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4812-4657","authenticated-orcid":false,"given":"Kevin","family":"Bliek-Bueno","sequence":"first","affiliation":[{"name":"EpiChron Research Group, Aragon Health Sciences Institute (IACS), IIS Arag\u00f3n, Miguel Servet University Hospital, 50009 Zaragoza, Spain"},{"name":"Teaching Unit of Preventive Medicine and Public Health, Miguel Servet University Hospital, 50009 Zaragoza, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3357-5655","authenticated-orcid":false,"given":"Sara","family":"Mucherino","sequence":"additional","affiliation":[{"name":"Centro Interdipartimentale di Ricerca in Farmacoeconomia e Farmacoutilizzazione (CIRFF), Center of Drug Utilization and Pharmacoeconomics, Department of Pharmacy, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5119-5093","authenticated-orcid":false,"given":"Beatriz","family":"Poblador-Plou","sequence":"additional","affiliation":[{"name":"EpiChron Research Group, Aragon Health Sciences Institute (IACS), IIS Arag\u00f3n, Miguel Servet University Hospital, 50009 Zaragoza, Spain"},{"name":"Health Services Research on Chronic Patients Network (REDISSEC), Institute of Health Carlos III (ISCIII), 28222 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisca","family":"Gonz\u00e1lez-Rubio","sequence":"additional","affiliation":[{"name":"EpiChron Research Group, Aragon Health Sciences Institute (IACS), IIS Arag\u00f3n, Miguel Servet University Hospital, 50009 Zaragoza, Spain"},{"name":"Health Services Research on Chronic Patients Network (REDISSEC), Institute of Health Carlos III (ISCIII), 28222 Madrid, Spain"},{"name":"Delicias-Sur Primary Care Health Centre, Aragon Health Service (SALUD), 50009 Zaragoza, Spain"},{"name":"Drug Utilization Work Group, Spanish Society of Family and Community Medicine (semFYC), 08009 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mercedes","family":"Aza-Pascual-Salcedo","sequence":"additional","affiliation":[{"name":"EpiChron Research Group, Aragon Health Sciences Institute (IACS), IIS Arag\u00f3n, Miguel Servet University Hospital, 50009 Zaragoza, Spain"},{"name":"Health Services Research on Chronic Patients Network (REDISSEC), Institute of Health Carlos III (ISCIII), 28222 Madrid, Spain"},{"name":"Primary Care Pharmacy Service Zaragoza III, Aragon Health Service (SALUD), 50017 Zaragoza, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8209-8878","authenticated-orcid":false,"given":"Valentina","family":"Orlando","sequence":"additional","affiliation":[{"name":"Centro Interdipartimentale di Ricerca in Farmacoeconomia e Farmacoutilizzazione (CIRFF), Center of Drug Utilization and Pharmacoeconomics, Department of Pharmacy, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mercedes","family":"Clerencia-Sierra","sequence":"additional","affiliation":[{"name":"EpiChron Research Group, Aragon Health Sciences Institute (IACS), IIS Arag\u00f3n, Miguel Servet University Hospital, 50009 Zaragoza, Spain"},{"name":"Health Services Research on Chronic Patients Network (REDISSEC), Institute of Health Carlos III (ISCIII), 28222 Madrid, Spain"},{"name":"Aragon Health Service (SALUD), Miguel Servet University Hospital, 50009 Zaragoza, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6518-749X","authenticated-orcid":false,"given":"Ignatios","family":"Ioakeim-Skoufa","sequence":"additional","affiliation":[{"name":"EpiChron Research Group, Aragon Health Sciences Institute (IACS), IIS Arag\u00f3n, Miguel Servet University Hospital, 50009 Zaragoza, Spain"},{"name":"Drug Utilization Work Group, Spanish Society of Family and Community Medicine (semFYC), 08009 Barcelona, Spain"},{"name":"WHO Collaborating Centre for Drug Statistics Methodology, Norwegian Institute of Public Health, 0213 Oslo, Norway"},{"name":"Department of Drug Statistics, Division of Health Data and Digitalisation, Norwegian Institute of Public Health, 0213 Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enrico","family":"Coscioni","sequence":"additional","affiliation":[{"name":"Division of Cardiac Surgery, AOU San Giovanni di Dio e Ruggi d\u2019Aragona, 84131 Salerno, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jon\u00e1s","family":"Carmona-P\u00edrez","sequence":"additional","affiliation":[{"name":"EpiChron Research Group, Aragon Health Sciences Institute (IACS), IIS Arag\u00f3n, Miguel Servet University Hospital, 50009 Zaragoza, Spain"},{"name":"Health Services Research on Chronic Patients Network (REDISSEC), Institute of Health Carlos III (ISCIII), 28222 Madrid, Spain"},{"name":"Delicias-Sur Primary Care Health Centre, Aragon Health Service (SALUD), 50009 Zaragoza, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2812-8500","authenticated-orcid":false,"given":"Alessandro","family":"Perrella","sequence":"additional","affiliation":[{"name":"Infectious Disease of Healthcare Direction, AORN Antonio Cardarelli, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ugo","family":"Trama","sequence":"additional","affiliation":[{"name":"Regional Pharmaceutical Unit, Campania Region, 80143 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5704-6056","authenticated-orcid":false,"given":"Alexandra","family":"Prados-Torres","sequence":"additional","affiliation":[{"name":"EpiChron Research Group, Aragon Health Sciences Institute (IACS), IIS Arag\u00f3n, Miguel Servet University Hospital, 50009 Zaragoza, Spain"},{"name":"Health Services Research on Chronic Patients Network (REDISSEC), Institute of Health Carlos III (ISCIII), 28222 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enrica","family":"Menditto","sequence":"additional","affiliation":[{"name":"Centro Interdipartimentale di Ricerca in Farmacoeconomia e Farmacoutilizzazione (CIRFF), Center of Drug Utilization and Pharmacoeconomics, Department of Pharmacy, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5440-1710","authenticated-orcid":false,"given":"Antonio","family":"Gimeno-Miguel","sequence":"additional","affiliation":[{"name":"EpiChron Research Group, Aragon Health Sciences Institute (IACS), IIS Arag\u00f3n, Miguel Servet University Hospital, 50009 Zaragoza, Spain"},{"name":"Health Services Research on Chronic Patients Network (REDISSEC), Institute of Health Carlos III (ISCIII), 28222 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,10]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2021, July 15). Coronavirus Disease (COVID-19) Weekly Epidemiological Update and Weekly Operational Update. Available online: https:\/\/www.who.int\/emergencies\/diseases\/novel-coronavirus-2019\/situation-reports."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Poblador-Plou, B., Carmona-P\u00edrez, J., Ioakeim-Skoufa, I., Poncel-Falc\u00f3, A., Bliek-Bueno, K., Pozo, M.C.-D., Gimeno-Feli\u00fa, L.A., Gonz\u00e1lez-Rubio, F., Aza-Pascual-Salcedo, M., and Bandr\u00e9s-Liso, A.C. (2020). Baseline Chronic Comorbidity and Mortality in Laboratory-Confirmed COVID-19 Cases: Results from the PRECOVID Study in Spain. Int. J. Environ. Res. Public Health, 17.","DOI":"10.3390\/ijerph17145171"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Li, X., Zhong, X., Wang, Y., Zeng, X., Luo, T., and Liu, Q. (2021). Clinical determinants of the severity of COVID-19: A systematic review and meta-analysis. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0250602"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"6660930","DOI":"10.1155\/2021\/6660930","article-title":"A Systematic Review and Meta-Analysis of Risk Factors Associated with Severity and Death in COVID-19 Patients","volume":"2021","author":"Du","year":"2021","journal-title":"Can. J. Infect. Dis. Med Microbiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"104673","DOI":"10.1016\/j.micpath.2020.104673","article-title":"The interplay between inflammatory pathways and COVID-19: A critical review on pathogenesis and therapeutic options","volume":"150","author":"Choudhary","year":"2021","journal-title":"Microb. Pathog."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e14","DOI":"10.1016\/j.japh.2021.05.006","article-title":"Polypharmacy among COVID-19 patients: A systematic review","volume":"61","author":"Iloanusi","year":"2021","journal-title":"J. Am. Pharm. Assoc."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"8913","DOI":"10.1038\/s41598-021-88398-y","article-title":"Drug-utilisation profiles and COVID-19","volume":"11","author":"Orlando","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Orlando, V., Rea, F., Savar\u00e9, L., Guarino, I., Mucherino, S., Perrella, A., Trama, U., Coscioni, E., Menditto, E., and Corrao, G. (2021). Development and validation of a clinical risk score to predict the risk of SARS-CoV-2 infection from administrative data: A population-based cohort study from Italy. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0237202"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"586187","DOI":"10.3389\/fphar.2020.586187","article-title":"Comorbidity in an Older Population with Type-2 Diabetes Mellitus: Identification of the Characteristics and Healthcare Utilization of High-Cost Patients","volume":"11","author":"Orlando","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e021122","DOI":"10.1136\/bmjopen-2017-021122","article-title":"The validity of the Rx-Risk Comorbidity Index using medicines mapped to the Anatomical Therapeutic Chemical (ATC) Classification System","volume":"8","author":"Pratt","year":"2018","journal-title":"BMJ Open"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"870","DOI":"10.3389\/fphar.2019.00870","article-title":"Treatment Patterns of Diabetes in Italy: A Population-Based Study","volume":"10","author":"Juste","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Orlando, V., Mucherino, S., Guarino, I., Guerriero, F., Trama, U., and Menditto, E. (2020). Gender Differences in Medication Use: A Drug Utilization Study Based on Real World Data. Int. J. Environ. Res. Public Health, 17.","DOI":"10.3390\/ijerph17113926"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"63","DOI":"10.2147\/RMHP.S223042","article-title":"Drug utilization pattern of antibiotics: The role of age, sex and municipalities in determining variation","volume":"13","author":"Orlando","year":"2020","journal-title":"Risk Manag. Healthc. Policy"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2000045","DOI":"10.2807\/1560-7917.ES.2020.25.3.2000045","article-title":"Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR","volume":"25","author":"Corman","year":"2020","journal-title":"Eurosurveillance"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e044640","DOI":"10.1136\/bmjopen-2020-044640","article-title":"Demographic risk factors for COVID-19 infection, severity, ICU admission and death: A meta-analysis of 59 studies","volume":"11","author":"Pijls","year":"2021","journal-title":"BMJ Open"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"101205","DOI":"10.1016\/j.arr.2020.101205","article-title":"Aging in COVID-19: Vulnerability, immunity and intervention","volume":"65","author":"Chen","year":"2020","journal-title":"Ageing Res. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1111\/all.14657","article-title":"Risk factors for severe and critically ill COVID-19 patients: A review","volume":"76","author":"Gao","year":"2021","journal-title":"Allergy"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.jjcc.2020.10.015","article-title":"Lack of association of antihypertensive drugs with the risk and severity of COVID-19: A meta-analysis","volume":"77","author":"Ren","year":"2021","journal-title":"J. Cardiol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"G\u00fclc\u00fc, O., Aksakal, E., Aydemir, S., Do\u011fan, R., Sara\u00e7, \u0130., Ayd\u0131n, S.\u015e., \u00d6zt\u00fcrk, M., Aksu, U., Kalkan, K., and Tanbo\u011fa, \u0130.H. (2021). Association between previous anticoagulant use and mortality among hospitalized patients with COVID-19. J. Thromb. Thrombolysis, 1\u20138.","DOI":"10.1007\/s11239-021-02489-1"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1111\/jcmm.16198","article-title":"Mortality and pre-hospitalization use of low-dose aspirin in COVID-19 patients with coronary artery disease","volume":"25","author":"Yuan","year":"2021","journal-title":"J. Cell. Mol. Med."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"McQueenie, R., Foster, H.M.E., Jani, B.D., Katikireddi, S.V., Sattar, N., Pell, J.P., Ho, F.K., Niedzwiedz, C.L., Hastie, C.E., and Anderson, J. (2021). Correction: Multimorbidity, polypharmacy, and COVID-19 infection within the UK Biobank cohort. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0251613"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.jchf.2020.11.003","article-title":"Clinical Outcomes in Patients with Heart Failure Hospitalized with COVID-19","volume":"9","author":"Bhatt","year":"2021","journal-title":"JACC Hear. Fail."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/1475-2891-14-6","article-title":"Role of homocysteine in the development of cardiovascular disease","volume":"14","author":"Ganguly","year":"2015","journal-title":"Nutr. J."}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/18\/22\/11786\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:28:01Z","timestamp":1760167681000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/18\/22\/11786"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,10]]},"references-count":23,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["ijerph182211786"],"URL":"https:\/\/doi.org\/10.3390\/ijerph182211786","relation":{},"ISSN":["1660-4601"],"issn-type":[{"type":"electronic","value":"1660-4601"}],"subject":[],"published":{"date-parts":[[2021,11,10]]}}}