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ESCAPE: An Open-Label Trial of Personalized Immunotherapy in Critically lll COVID-19 Patients
BACKGROUND: Macrophage activation-like syndrome (MALS) and complex immune dysregulation (CID) often underlie acute respiratory distress (ARDS) in COVID-19. We aimed to investigate the effect of personalized immunotherapy on clinical improvement of critical COVID-19. METHODS: In this open-label prosp...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
S. Karger AG
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8805059/ https://www.ncbi.nlm.nih.gov/pubmed/34852352 http://dx.doi.org/10.1159/000519090 |
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author | Karakike, Eleni Dalekos, George N. Koutsodimitropoulos, Ioannis Saridaki, Maria Pourzitaki, Chryssa Papathanakos, Georgios Kotsaki, Antigone Chalvatzis, Stamatios Dimakopoulou, Vasiliki Vechlidis, Nikolaos Paramythiotou, Elisabeth Avgoustou, Christina Ioakeimidou, Aikaterini Kouriannidi, Elli Komnos, Apostolos Neou, Evangelia Rovina, Nikoletta Stefanatou, Eleni Milionis, Haralampos Nikolaidis, George Koutsoukou, Antonia Damoraki, Georgia Dimopoulos, George Zoumpos, Vassileios Eugen-Olsen, Jesper Akinosoglou, Karolina Gatselis, Nikolaos K. Koulouras, Vasilios Gkeka, Eleni Markou, Nikolaos Netea, Mihai G. Giamarellos-Bourboulis, Evangelos J. |
author_facet | Karakike, Eleni Dalekos, George N. Koutsodimitropoulos, Ioannis Saridaki, Maria Pourzitaki, Chryssa Papathanakos, Georgios Kotsaki, Antigone Chalvatzis, Stamatios Dimakopoulou, Vasiliki Vechlidis, Nikolaos Paramythiotou, Elisabeth Avgoustou, Christina Ioakeimidou, Aikaterini Kouriannidi, Elli Komnos, Apostolos Neou, Evangelia Rovina, Nikoletta Stefanatou, Eleni Milionis, Haralampos Nikolaidis, George Koutsoukou, Antonia Damoraki, Georgia Dimopoulos, George Zoumpos, Vassileios Eugen-Olsen, Jesper Akinosoglou, Karolina Gatselis, Nikolaos K. Koulouras, Vasilios Gkeka, Eleni Markou, Nikolaos Netea, Mihai G. Giamarellos-Bourboulis, Evangelos J. |
author_sort | Karakike, Eleni |
collection | PubMed |
description | BACKGROUND: Macrophage activation-like syndrome (MALS) and complex immune dysregulation (CID) often underlie acute respiratory distress (ARDS) in COVID-19. We aimed to investigate the effect of personalized immunotherapy on clinical improvement of critical COVID-19. METHODS: In this open-label prospective trial, 102 patients with ARDS by SARS-CoV-2 were screened for MALS (ferritin >4,420 ng/mL) and CID (ferritin ≤4,420 ng/mL and low human leukocyte antigen (HLA)-DR expression on CD14-monocytes). Patients with MALS or CID with increased aminotransferases received intravenous anakinra; those with CID and normal aminotransferases received tocilizumab. The primary outcome was ≥25% decrease in the Sequential Organ Failure Assessment (SOFA) score and/or 50% increase in the respiratory ratio by day 8; 28-day mortality, change of SOFA score by day 28, serum biomarkers, and cytokine production by mononuclear cells were secondary endpoints. RESULTS: The primary study endpoint was met in 58.3% of anakinra-treated patients and in 33.3% of tocilizumab-treated patients (p: 0.01). Most patients in both groups received dexamethasone as standard of care. No differences were found in secondary outcomes, mortality, and SOFA score changes. Ferritin decreased among anakinra-treated patients; interleukin-6, soluble urokinase plasminogen activator receptor, and HLA-DR expression increased among tocilizumab-treated patients. Survivors by day 28 who received anakinra were distributed to lower severity levels of the WHO clinical progression scale. Greater incidence of secondary infections was found with tocilizumab treatment. CONCLUSION: Immune assessment resulted in favorable anakinra responses among critically ill patients with COVID-19 and features of MALS. |
format | Online Article Text |
id | pubmed-8805059 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | S. Karger AG |
record_format | MEDLINE/PubMed |
spelling | pubmed-88050592022-02-02 ESCAPE: An Open-Label Trial of Personalized Immunotherapy in Critically lll COVID-19 Patients Karakike, Eleni Dalekos, George N. Koutsodimitropoulos, Ioannis Saridaki, Maria Pourzitaki, Chryssa Papathanakos, Georgios Kotsaki, Antigone Chalvatzis, Stamatios Dimakopoulou, Vasiliki Vechlidis, Nikolaos Paramythiotou, Elisabeth Avgoustou, Christina Ioakeimidou, Aikaterini Kouriannidi, Elli Komnos, Apostolos Neou, Evangelia Rovina, Nikoletta Stefanatou, Eleni Milionis, Haralampos Nikolaidis, George Koutsoukou, Antonia Damoraki, Georgia Dimopoulos, George Zoumpos, Vassileios Eugen-Olsen, Jesper Akinosoglou, Karolina Gatselis, Nikolaos K. Koulouras, Vasilios Gkeka, Eleni Markou, Nikolaos Netea, Mihai G. Giamarellos-Bourboulis, Evangelos J. J Innate Immun Research Article BACKGROUND: Macrophage activation-like syndrome (MALS) and complex immune dysregulation (CID) often underlie acute respiratory distress (ARDS) in COVID-19. We aimed to investigate the effect of personalized immunotherapy on clinical improvement of critical COVID-19. METHODS: In this open-label prospective trial, 102 patients with ARDS by SARS-CoV-2 were screened for MALS (ferritin >4,420 ng/mL) and CID (ferritin ≤4,420 ng/mL and low human leukocyte antigen (HLA)-DR expression on CD14-monocytes). Patients with MALS or CID with increased aminotransferases received intravenous anakinra; those with CID and normal aminotransferases received tocilizumab. The primary outcome was ≥25% decrease in the Sequential Organ Failure Assessment (SOFA) score and/or 50% increase in the respiratory ratio by day 8; 28-day mortality, change of SOFA score by day 28, serum biomarkers, and cytokine production by mononuclear cells were secondary endpoints. RESULTS: The primary study endpoint was met in 58.3% of anakinra-treated patients and in 33.3% of tocilizumab-treated patients (p: 0.01). Most patients in both groups received dexamethasone as standard of care. No differences were found in secondary outcomes, mortality, and SOFA score changes. Ferritin decreased among anakinra-treated patients; interleukin-6, soluble urokinase plasminogen activator receptor, and HLA-DR expression increased among tocilizumab-treated patients. Survivors by day 28 who received anakinra were distributed to lower severity levels of the WHO clinical progression scale. Greater incidence of secondary infections was found with tocilizumab treatment. CONCLUSION: Immune assessment resulted in favorable anakinra responses among critically ill patients with COVID-19 and features of MALS. S. Karger AG 2021-12-01 /pmc/articles/PMC8805059/ /pubmed/34852352 http://dx.doi.org/10.1159/000519090 Text en Copyright © 2021 by S. Karger AG, Basel |
spellingShingle | Research Article Karakike, Eleni Dalekos, George N. Koutsodimitropoulos, Ioannis Saridaki, Maria Pourzitaki, Chryssa Papathanakos, Georgios Kotsaki, Antigone Chalvatzis, Stamatios Dimakopoulou, Vasiliki Vechlidis, Nikolaos Paramythiotou, Elisabeth Avgoustou, Christina Ioakeimidou, Aikaterini Kouriannidi, Elli Komnos, Apostolos Neou, Evangelia Rovina, Nikoletta Stefanatou, Eleni Milionis, Haralampos Nikolaidis, George Koutsoukou, Antonia Damoraki, Georgia Dimopoulos, George Zoumpos, Vassileios Eugen-Olsen, Jesper Akinosoglou, Karolina Gatselis, Nikolaos K. Koulouras, Vasilios Gkeka, Eleni Markou, Nikolaos Netea, Mihai G. Giamarellos-Bourboulis, Evangelos J. ESCAPE: An Open-Label Trial of Personalized Immunotherapy in Critically lll COVID-19 Patients |
title | ESCAPE: An Open-Label Trial of Personalized Immunotherapy in Critically lll COVID-19 Patients |
title_full | ESCAPE: An Open-Label Trial of Personalized Immunotherapy in Critically lll COVID-19 Patients |
title_fullStr | ESCAPE: An Open-Label Trial of Personalized Immunotherapy in Critically lll COVID-19 Patients |
title_full_unstemmed | ESCAPE: An Open-Label Trial of Personalized Immunotherapy in Critically lll COVID-19 Patients |
title_short | ESCAPE: An Open-Label Trial of Personalized Immunotherapy in Critically lll COVID-19 Patients |
title_sort | escape: an open-label trial of personalized immunotherapy in critically lll covid-19 patients |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8805059/ https://www.ncbi.nlm.nih.gov/pubmed/34852352 http://dx.doi.org/10.1159/000519090 |
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