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 5 187 patients; validation cohort, n 5 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 5 .004) with AUROC 5 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 5 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.

Dynamic angiopoietin-2 assessment predicts survival and chronic course in hospitalized patients with COVID-19 / Villa, E.; Critelli, R.; Lasagni, S.; Melegari, A.; Curatolo, A.; Celsa, C.; Romagnoli, D.; Melegari, G.; Pivetti, A.; Di Marco, L.; Casari, F.; Arioli, D.; Turrini, F.; Zuccaro, V.; Cassaniti, I.; Riefolo, M.; de Santis, E.; Bernabucci, V.; Bianchini, M.; Lei, B.; de Maria, N.; Carulli, L.; Schepis, F.; Gozzi, C.; Malaguti, S.; Del Buono, M.; Brugioni, L.; Torricelli, P.; Trenti, T.; Pinelli, G.; Bertellini, E.; Bruno, R.; Camma, C.; d'Errico, A.. - In: BLOOD ADVANCES. - ISSN 2473-9529. - 5:3(2021), pp. 662-673. [10.1182/bloodadvances.2020003736]

Dynamic angiopoietin-2 assessment predicts survival and chronic course in hospitalized patients with COVID-19

Villa E.;Lasagni S.;Melegari G.;Carulli L.;Schepis F.;Torricelli P.;
2021

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 5 187 patients; validation cohort, n 5 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 5 .004) with AUROC 5 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 5 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.
5
3
662
673
Dynamic angiopoietin-2 assessment predicts survival and chronic course in hospitalized patients with COVID-19 / Villa, E.; Critelli, R.; Lasagni, S.; Melegari, A.; Curatolo, A.; Celsa, C.; Romagnoli, D.; Melegari, G.; Pivetti, A.; Di Marco, L.; Casari, F.; Arioli, D.; Turrini, F.; Zuccaro, V.; Cassaniti, I.; Riefolo, M.; de Santis, E.; Bernabucci, V.; Bianchini, M.; Lei, B.; de Maria, N.; Carulli, L.; Schepis, F.; Gozzi, C.; Malaguti, S.; Del Buono, M.; Brugioni, L.; Torricelli, P.; Trenti, T.; Pinelli, G.; Bertellini, E.; Bruno, R.; Camma, C.; d'Errico, A.. - In: BLOOD ADVANCES. - ISSN 2473-9529. - 5:3(2021), pp. 662-673. [10.1182/bloodadvances.2020003736]
Villa, E.; Critelli, R.; Lasagni, S.; Melegari, A.; Curatolo, A.; Celsa, C.; Romagnoli, D.; Melegari, G.; Pivetti, A.; Di Marco, L.; Casari, F.; Arioli, D.; Turrini, F.; Zuccaro, V.; Cassaniti, I.; Riefolo, M.; de Santis, E.; Bernabucci, V.; Bianchini, M.; Lei, B.; de Maria, N.; Carulli, L.; Schepis, F.; Gozzi, C.; Malaguti, S.; Del Buono, M.; Brugioni, L.; Torricelli, P.; Trenti, T.; Pinelli, G.; Bertellini, E.; Bruno, R.; Camma, C.; D'Errico, A.
File in questo prodotto:
File Dimensione Formato  
advancesadv2020003736.pdf

accesso aperto

Tipologia: Versione dell'editore (versione pubblicata)
Dimensione 3.06 MB
Formato Adobe PDF
3.06 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11380/1249604
Citazioni
  • ???jsp.display-item.citation.pmc??? 12
  • Scopus 16
  • ???jsp.display-item.citation.isi??? 16
social impact