| Literature DB >> 33560382 |
Erica Villa1, Rosina Critelli1, Simone Lasagni1, Alessandra Melegari2, Angela Curatolo1, Ciro Celsa3,4, Dante Romagnoli1, Gabriele Melegari5, Alessandra Pivetti1, Lorenza Di Marco1, Federico Casari6, Dimitriy Arioli7, Fabrizio Turrini8, Valentina Zuccaro9,10, Irene Cassaniti11, Mattia Riefolo12, Elena de Santis2, Veronica Bernabucci1, Marcello Bianchini1, Barbara Lei1, Nicola De Maria1, Lucia Carulli1, Filippo Schepis1, Chiara Gozzi7, Silvio Malaguti5, Mariagrazia Del Buono1, Lucio Brugioni7, Pietro Torricelli6, Tommaso Trenti2, Giovanni Pinelli8, Elisabetta Bertellini5, Raffaele Bruno9,10, Calogero Cammà3, Antonia d'Errico12.
Abstract
This study examined the association between dynamic angiopoietin-2 assessment and COVID-19 short- and long-term clinical course. We included consecutive hospitalized patients from 1 February to 31 May 2020 with laboratory-confirmed COVID-19 from 2 Italian tertiary referral centers (derivation cohort, n = 187 patients; validation cohort, n = 62 patients). Serum biomarker levels were measured by sandwich enzyme-linked immunosorbent assay. Lung tissue from 9 patients was stained for angiopoietin-2, Tie2, CD68, and CD34. Cox model was used to identify risk factors for mortality and nonresolving pulmonary condition. Area under the receiver operating characteristic curve (AUROC) was used to assess the accuracy of 3- and 10-day angiopoietin-2 for in-hospital mortality and nonresolving pulmonary condition, respectively. Three-day angiopoietin-2 increase of at least twofold from baseline was significantly associated with in-hospital mortality by multivariate analysis (hazard ratio [HR], 6.69; 95% confidence interval [CI], 1.85-24.19; P = .004) with AUROC = 0.845 (95% CI, 0.725-0.940). Ten-day angiopoietin-2 of at least twofold from baseline was instead significantly associated with nonresolving pulmonary condition by multivariate analysis (HR, 5.33; 95% CI, 1.34-11.77; P ≤ .0001) with AUROC = 0.969 (95% CI, 0.919-1.000). Patients with persistent elevation of 10-day angiopoietin-2 levels showed severe reticular interstitial thickening and fibrous changes on follow-up computed tomography scans. Angiopoietin-2 and Tie2 were diffusely colocalized in small-vessel endothelia and alveolar new vessels and macrophages. Angiopoietin-2 course is strongly associated with COVID-19 in-hospital mortality and nonresolving pulmonary condition. Angiopoietin-2 may be an early and useful predictor of COVID-19 clinical course, and it could be a relevant part of disease pathogenesis. Angiopoietin-2 blockade may be a COVID-19 treatment option.Entities:
Year: 2021 PMID： 33560382 DOI： 10.1182/bloodadvances.2020003736
Source DB: PubMed Journal: Blood Adv ISSN： 2473-9529