{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T10:29:21Z","timestamp":1760956161290,"version":"build-2065373602"},"reference-count":37,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,7,30]],"date-time":"2022-07-30T00:00:00Z","timestamp":1659139200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Italian Ministry of Health\u2014Current research IRCCS"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Coagulopathy and immune dysregulation have been identified as important causes of adverse outcomes in coronavirus disease (COVID-19). Mid-region proadrenomedullin (MR-proADM) is associated with endothelial damage and has recently been proposed as a prognostic factor in COVID-19. In non-COVID-19 immunocompromised patients, low in vitro interferon gamma (IFN\u03b3) production correlates with infection risk and mortality. This prospective, monocentric, observational study included adult patients consecutively admitted with radiologic evidence of COVID-19 pneumonia and respiratory failure. MR-proADM and in vitro IFN\u03b3 production were measured at T0 (day 1 from admission) and T1 (day 7 from enrollment). One hundred patients were enrolled. Thirty-six percent were females, median age 65 (Q1\u2013Q3 54.5\u201375) years, and 58% had \u22651 comorbidity. Only 16 patients had received COVID-19 vaccination before hospitalization. At admission, the median PaO2:FiO2 ratio was 241 (157\u2013309) mmHg. In-hospital mortality was 13%. MR-proADM levels differed significantly between deceased and survivors both at T0 (1.41 (1.12\u20131.77) nmol\/L vs. 0.79 (0.63\u20131.03) nmol\/L, p &lt; 0.001) and T1 (1.67 (1.08\u20131.96) nmol\/L vs. 0.66 (0.53\u20130.95) nmol\/L, p &lt; 0.001). In vitro IFN\u03b3 production at T0 and T1 did not vary between groups. When only the subset of non-vaccinated patients was considered, both biomarkers at T1 resulted significantly associated with in-hospital mortality. AUROC for MR-proADM at T0 to predict in-hospital mortality was 0.87 (95%CI 0.79\u20130.94), with the best cut-off point at 1.04 nmol\/L (92% sensitivity, 75% specificity and 98% negative predictive value). In patients with COVID-19 pneumonia and different degrees of respiratory failure, MR-proADM at admission and during hospitalization resulted strongly associated with in-hospital mortality. Low in vitro IFN\u03b3 production after the first week of hospitalization was associated with mortality in non-vaccinated patients possibly identifying the subgroup characterized by a higher degree of immune suppression.<\/jats:p>","DOI":"10.3390\/v14081683","type":"journal-article","created":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T23:49:27Z","timestamp":1659397767000},"page":"1683","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Prognostic Value of Mid-Region Proadrenomedullin and In Vitro Interferon Gamma Production for In-Hospital Mortality in Patients with COVID-19 Pneumonia and Respiratory Failure: An Observational Prospective Study"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7431-5019","authenticated-orcid":false,"given":"Davide","family":"Mangioni","sequence":"first","affiliation":[{"name":"Infectious Diseases Unit, Foundation IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"},{"name":"Department of Pathophysiology and Transplantation, University of Milano, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2709-6965","authenticated-orcid":false,"given":"Massimo","family":"Oggioni","sequence":"additional","affiliation":[{"name":"Clinical Laboratory, Foundation IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liliane","family":"Chatenoud","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Epidemiology, Department of Public Health, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7981-5226","authenticated-orcid":false,"given":"Arianna","family":"Liparoti","sequence":"additional","affiliation":[{"name":"Infectious Diseases Unit, Foundation IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"},{"name":"Department of Pathophysiology and Transplantation, University of Milano, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2027-8478","authenticated-orcid":false,"given":"Sara","family":"Uceda Renteria","sequence":"additional","affiliation":[{"name":"Clinical Laboratory, Foundation IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Alagna","sequence":"additional","affiliation":[{"name":"Infectious Diseases Unit, Foundation IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simona","family":"Biscarini","sequence":"additional","affiliation":[{"name":"Infectious Diseases Unit, Foundation IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matteo","family":"Bolis","sequence":"additional","affiliation":[{"name":"Infectious Diseases Unit, Foundation IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adriana","family":"Di Modugno","sequence":"additional","affiliation":[{"name":"Clinical Laboratory, Foundation IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Mussa","sequence":"additional","affiliation":[{"name":"Infectious Diseases Unit, Foundation IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giulia","family":"Renisi","sequence":"additional","affiliation":[{"name":"Infectious Diseases Unit, Foundation IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riccardo","family":"Ungaro","sequence":"additional","affiliation":[{"name":"Infectious Diseases Unit, Foundation IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Muscatello","sequence":"additional","affiliation":[{"name":"Infectious Diseases Unit, Foundation IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6587-4794","authenticated-orcid":false,"given":"Andrea","family":"Gori","sequence":"additional","affiliation":[{"name":"Infectious Diseases Unit, Foundation IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"},{"name":"Department of Pathophysiology and Transplantation, University of Milano, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0958-5354","authenticated-orcid":false,"given":"Ferruccio","family":"Ceriotti","sequence":"additional","affiliation":[{"name":"Clinical Laboratory, Foundation IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9440-4601","authenticated-orcid":false,"given":"Alessandra","family":"Bandera","sequence":"additional","affiliation":[{"name":"Infectious Diseases Unit, Foundation IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"},{"name":"Department of Pathophysiology and Transplantation, University of Milano, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,30]]},"reference":[{"key":"ref_1","unstructured":"Team E (2020). 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