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Combined administration of inhaled DNase, baricitinib and tocilizumab as rescue treatment in COVID-19 patients with severe respiratory failure

Aiming to reduce mortality in COVID-19 with severe respiratory failure we administered a combined rescue treatment (COMBI) on top of standard-of-care (SOC: dexamethasone/heparin) consisted of inhaled DNase to dissolve thrombogenic neutrophil extracellular traps, plus agents against cytokine-mediated...

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Autores principales: Gavriilidis, Efstratios, Antoniadou, Christina, Chrysanthopoulou, Akrivi, Ntinopoulou, Maria, Smyrlis, Andreas, Fotiadou, Iliana, Zioga, Nikoleta, Kogias, Dionysios, Natsi, Anastasia-Maria, Pelekoudas, Christos, Satiridou, Evangelia, Bakola, Stefania-Aspasia, Papagoras, Charalampos, Mitroulis, Ioannis, Peichamperis, Paschalis, Mikroulis, Dimitrios, Papadopoulos, Vasileios, Skendros, Panagiotis, Ritis, Konstantinos
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9014660/
https://www.ncbi.nlm.nih.gov/pubmed/35447311
http://dx.doi.org/10.1016/j.clim.2022.109016
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author Gavriilidis, Efstratios
Antoniadou, Christina
Chrysanthopoulou, Akrivi
Ntinopoulou, Maria
Smyrlis, Andreas
Fotiadou, Iliana
Zioga, Nikoleta
Kogias, Dionysios
Natsi, Anastasia-Maria
Pelekoudas, Christos
Satiridou, Evangelia
Bakola, Stefania-Aspasia
Papagoras, Charalampos
Mitroulis, Ioannis
Peichamperis, Paschalis
Mikroulis, Dimitrios
Papadopoulos, Vasileios
Skendros, Panagiotis
Ritis, Konstantinos
author_facet Gavriilidis, Efstratios
Antoniadou, Christina
Chrysanthopoulou, Akrivi
Ntinopoulou, Maria
Smyrlis, Andreas
Fotiadou, Iliana
Zioga, Nikoleta
Kogias, Dionysios
Natsi, Anastasia-Maria
Pelekoudas, Christos
Satiridou, Evangelia
Bakola, Stefania-Aspasia
Papagoras, Charalampos
Mitroulis, Ioannis
Peichamperis, Paschalis
Mikroulis, Dimitrios
Papadopoulos, Vasileios
Skendros, Panagiotis
Ritis, Konstantinos
author_sort Gavriilidis, Efstratios
collection PubMed
description Aiming to reduce mortality in COVID-19 with severe respiratory failure we administered a combined rescue treatment (COMBI) on top of standard-of-care (SOC: dexamethasone/heparin) consisted of inhaled DNase to dissolve thrombogenic neutrophil extracellular traps, plus agents against cytokine-mediated hyperinflammation, namely anti-IL-6-receptor tocilizumab and JAK1/2 inhibitor baricitinib. Patients with PaO2/FiO2 < 100 mmHg were analysed. COMBI group (n = 22) was compared with similar groups that had received SOC alone (n = 26) or SOC plus monotherapy with either IL-1-receptor antagonist anakinra (n = 19) or tocilizumab (n = 11). COMBI was significantly associated with lower in-hospital mortality and intubation rate, shorter duration of hospitalization, and prolonged overall survival after a median follow-up of 110 days. In vitro, COVID-19 plasma induced tissue factor/thrombin pathway in primary lung fibroblasts. This effect was inhibited by the immunomodulatory agents of COMBI providing a mechanistic explanation for the clinical observations. These results support the conduct of randomized trials using combined immunomodulation in COVID-19 to target multiple interconnected pathways of immunothrombosis.
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spelling pubmed-90146602022-04-18 Combined administration of inhaled DNase, baricitinib and tocilizumab as rescue treatment in COVID-19 patients with severe respiratory failure Gavriilidis, Efstratios Antoniadou, Christina Chrysanthopoulou, Akrivi Ntinopoulou, Maria Smyrlis, Andreas Fotiadou, Iliana Zioga, Nikoleta Kogias, Dionysios Natsi, Anastasia-Maria Pelekoudas, Christos Satiridou, Evangelia Bakola, Stefania-Aspasia Papagoras, Charalampos Mitroulis, Ioannis Peichamperis, Paschalis Mikroulis, Dimitrios Papadopoulos, Vasileios Skendros, Panagiotis Ritis, Konstantinos Clin Immunol Article Aiming to reduce mortality in COVID-19 with severe respiratory failure we administered a combined rescue treatment (COMBI) on top of standard-of-care (SOC: dexamethasone/heparin) consisted of inhaled DNase to dissolve thrombogenic neutrophil extracellular traps, plus agents against cytokine-mediated hyperinflammation, namely anti-IL-6-receptor tocilizumab and JAK1/2 inhibitor baricitinib. Patients with PaO2/FiO2 < 100 mmHg were analysed. COMBI group (n = 22) was compared with similar groups that had received SOC alone (n = 26) or SOC plus monotherapy with either IL-1-receptor antagonist anakinra (n = 19) or tocilizumab (n = 11). COMBI was significantly associated with lower in-hospital mortality and intubation rate, shorter duration of hospitalization, and prolonged overall survival after a median follow-up of 110 days. In vitro, COVID-19 plasma induced tissue factor/thrombin pathway in primary lung fibroblasts. This effect was inhibited by the immunomodulatory agents of COMBI providing a mechanistic explanation for the clinical observations. These results support the conduct of randomized trials using combined immunomodulation in COVID-19 to target multiple interconnected pathways of immunothrombosis. Elsevier Inc. 2022-05 2022-04-18 /pmc/articles/PMC9014660/ /pubmed/35447311 http://dx.doi.org/10.1016/j.clim.2022.109016 Text en © 2022 Elsevier Inc. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Article
Gavriilidis, Efstratios
Antoniadou, Christina
Chrysanthopoulou, Akrivi
Ntinopoulou, Maria
Smyrlis, Andreas
Fotiadou, Iliana
Zioga, Nikoleta
Kogias, Dionysios
Natsi, Anastasia-Maria
Pelekoudas, Christos
Satiridou, Evangelia
Bakola, Stefania-Aspasia
Papagoras, Charalampos
Mitroulis, Ioannis
Peichamperis, Paschalis
Mikroulis, Dimitrios
Papadopoulos, Vasileios
Skendros, Panagiotis
Ritis, Konstantinos
Combined administration of inhaled DNase, baricitinib and tocilizumab as rescue treatment in COVID-19 patients with severe respiratory failure
title Combined administration of inhaled DNase, baricitinib and tocilizumab as rescue treatment in COVID-19 patients with severe respiratory failure
title_full Combined administration of inhaled DNase, baricitinib and tocilizumab as rescue treatment in COVID-19 patients with severe respiratory failure
title_fullStr Combined administration of inhaled DNase, baricitinib and tocilizumab as rescue treatment in COVID-19 patients with severe respiratory failure
title_full_unstemmed Combined administration of inhaled DNase, baricitinib and tocilizumab as rescue treatment in COVID-19 patients with severe respiratory failure
title_short Combined administration of inhaled DNase, baricitinib and tocilizumab as rescue treatment in COVID-19 patients with severe respiratory failure
title_sort combined administration of inhaled dnase, baricitinib and tocilizumab as rescue treatment in covid-19 patients with severe respiratory failure
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9014660/
https://www.ncbi.nlm.nih.gov/pubmed/35447311
http://dx.doi.org/10.1016/j.clim.2022.109016
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