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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...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier Inc.
2022
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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. |
format | Online Article Text |
id | pubmed-9014660 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier Inc. |
record_format | MEDLINE/PubMed |
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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