Savino Spadaro1, Alberto Fogagnolo2, Carlo Alberto Volta2, Marco Contoli3, Gianluca Campo4,5, Ottavio Zucchetti4,5, Marco Verri2, Irene Ottaviani2, Tanushree Tunstall6, Salvatore Grasso7, Valentina Scaramuzzo2, Francesco Murgolo7, Elisabetta Marangoni2, Francesco Vieceli Dalla Sega7, Francesca Fortini7, Rita Pavasini4, Paola Rizzo5,8, Roberto Ferrari4,5, Alberto Papi3. 1. Intensive Care Unit, Department of Translational medicine and for Romagna, University of Ferrara, Azienda Ospedaliera Universitaria di Ferrara, Via Aldo Moro 8, 44124, Ferrara, Italy. savinospadaro@gmail.com. 2. Intensive Care Unit, Department of Translational medicine and for Romagna, University of Ferrara, Azienda Ospedaliera Universitaria di Ferrara, Via Aldo Moro 8, 44124, Ferrara, Italy. 3. Respiratory Section, Department of Morphology, Surgery, and Experimental Medicine, University of Ferrara, Ferrara, Italy. 4. Cardiovascular Institute, Azienda Ospedaliero-Universitaria di Ferrara, Cona, FE, Italy. 5. Maria Cecilia Hospital, GVM Care and Research, Cotignola, RA, Italy. 6. Department of Infection Biology, School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK. 7. Dipartimento dell'Emergenza e Trapianti d'Organo (DETO), Sezione di Anestesiologia e Rianimazione, Università degli Studi di Bari "Aldo Moro", Bari, Italy. 8. Department of Morphology, Surgery, and Experimental Medicine, Laboratory for Technologies of Advanced Therapies, University of Ferrara, Ferrara, Italy.
Abstract
BACKGROUND: Biomarkers can be used to detect the presence of endothelial and/or alveolar epithelial injuries in case of ARDS. Angiopoietin-2 (Ang-2), soluble intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion protein-1 (VCAM-1), P-selectin and E-selectin are biomarkers of endothelial injury, whereas the receptor for advanced glycation end-products (RAGE) reflects alveolar epithelial injury. The aims of this study were to evaluate whether the plasma concentration of the above-mentioned biomarkers was different 1) in survivors and non-survivors of COVID-19-related ARDS and 2) in COVID-19-related and classical ARDS. METHODS: This prospective study was performed in two COVID-19-dedicated Intensive Care Units (ICU) and one non-COVID-19 ICU at Ferrara University Hospital. A cohort of 31 mechanically ventilated patients with COVID-19 ARDS and a cohort of 11 patients with classical ARDS were enrolled. Ang-2, ICAM-1, VCAM-1, P-selectin, E-selectin and RAGE were determined with a bead-based multiplex immunoassay at three time points: inclusion in the study (T1), after 7 ± 2 days (T2) and 14 ± 2 days (T3). The primary outcome was to evaluate the plasma trend of the biomarker levels in survivors and non-survivors. The secondary outcome was to evaluate the differences in respiratory mechanics variables and gas exchanges between survivors and non-survivors. Furthermore, we compared the plasma levels of the biomarkers at T1 in patients with COVID-19-related ARDS and classical ARDS. RESULTS: In COVID-19-related ARDS, the plasma levels of Ang-2 and ICAM-1 at T1 were statistically higher in non-survivors than survivors, (p = 0.04 and p = 0.03, respectively), whereas those of P-selectin, E-selectin and RAGE did not differ. Ang-2 and ICAM-1 at T1 were predictors of mortality (AUROC 0.650 and 0.717, respectively). At T1, RAGE and P-selectin levels were higher in classical ARDS than in COVID-19-related ARDS. Ang-2, ICAM-1 and E-selectin were lower in classical ARDS than in COVID-19-related ARDS (all p < 0.001). CONCLUSIONS: COVID-19 ARDS is characterized by an early pulmonary endothelial injury, as detected by Ang-2 and ICAM-1. COVID-19 ARDS and classical ARDS exhibited a different expression of biomarkers, suggesting different pathological pathways. Trial registration NCT04343053 , Date of registration: April 13, 2020.
BACKGROUND: Biomarkers can be used to detect the presence of endothelial and/or alveolar epithelial injuries in case of ARDS. Angiopoietin-2 (Ang-2), soluble intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion protein-1 (VCAM-1), P-selectin and E-selectin are biomarkers of endothelial injury, whereas the receptor for advanced glycation end-products (RAGE) reflects alveolar epithelial injury. The aims of this study were to evaluate whether the plasma concentration of the above-mentioned biomarkers was different 1) in survivors and non-survivors of COVID-19-related ARDS and 2) in COVID-19-related and classical ARDS. METHODS: This prospective study was performed in two COVID-19-dedicated Intensive Care Units (ICU) and one non-COVID-19 ICU at Ferrara University Hospital. A cohort of 31 mechanically ventilated patients with COVID-19ARDS and a cohort of 11 patients with classical ARDS were enrolled. Ang-2, ICAM-1, VCAM-1, P-selectin, E-selectin and RAGE were determined with a bead-based multiplex immunoassay at three time points: inclusion in the study (T1), after 7 ± 2 days (T2) and 14 ± 2 days (T3). The primary outcome was to evaluate the plasma trend of the biomarker levels in survivors and non-survivors. The secondary outcome was to evaluate the differences in respiratory mechanics variables and gas exchanges between survivors and non-survivors. Furthermore, we compared the plasma levels of the biomarkers at T1 in patients with COVID-19-related ARDS and classical ARDS. RESULTS: In COVID-19-related ARDS, the plasma levels of Ang-2 and ICAM-1 at T1 were statistically higher in non-survivors than survivors, (p = 0.04 and p = 0.03, respectively), whereas those of P-selectin, E-selectin and RAGE did not differ. Ang-2 and ICAM-1 at T1 were predictors of mortality (AUROC 0.650 and 0.717, respectively). At T1, RAGE and P-selectin levels were higher in classical ARDS than in COVID-19-related ARDS. Ang-2, ICAM-1 and E-selectin were lower in classical ARDS than in COVID-19-related ARDS (all p < 0.001). CONCLUSIONS:COVID-19ARDS is characterized by an early pulmonary endothelial injury, as detected by Ang-2 and ICAM-1. COVID-19ARDS and classical ARDS exhibited a different expression of biomarkers, suggesting different pathological pathways. Trial registration NCT04343053 , Date of registration: April 13, 2020.
Authors: Michael Hultström; Karin Fromell; Anders Larsson; Barbro Persson; Bo Nilsson; Susan E Quaggin; Christer Betsholtz; Robert Frithiof; Miklos Lipcsey; Marie Jeansson Journal: Biomedicines Date: 2022-06-06
Authors: Valle Coronado-Vázquez; Maria Del Valle Ramírez-Durán; Juan Gómez-Salgado; María Silvia Dorado-Rabaneda; Elena Benito-Alonso; Marina Holgado-Juan; Cristina Bronchalo-González Journal: J Pers Med Date: 2021-05-24