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...
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Karger Publishers
2021
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oai:doaj.org-article:1a1b1ce9f0cc42099e276c4bad6ad8ae2021-12-02T12:40:22ZESCAPE: An Open-Label Trial of Personalized Immunotherapy in Critically lll COVID-19 Patients1662-811X1662-812810.1159/000519090https://doaj.org/article/1a1b1ce9f0cc42099e276c4bad6ad8ae2021-12-01T00:00:00Zhttps://www.karger.com/Article/FullText/519090https://doaj.org/toc/1662-811Xhttps://doaj.org/toc/1662-8128Background: 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.Eleni KarakikeGeorge N. DalekosIoannis KoutsodimitropoulosMaria SaridakiChryssa PourzitakiGeorgios PapathanakosAntigone KotsakiStamatios ChalvatzisVasiliki DimakopoulouNikolaos VechlidisElisabeth ParamythiotouChristina AvgoustouAikaterini IoakeimidouElli KouriannidiApostolos KomnosEvangelia NeouNikoletta RovinaEleni StefanatouHaralampos MilionisGeorge NikolaidisAntonia KoutsoukouGeorgia DamorakiGeorge DimopoulosVassileios ZoumposJesper Eugen-OlsenKarolina AkinosoglouNikolaos K. GatselisVasilios KoulourasEleni GkekaNikolaos MarkouMihai G. NeteaEvangelos J. Giamarellos-BourboulisKarger Publishersarticleinterleukin 1 receptor antagonist proteintocilizumabrespiratory distress syndromecovid-19macrophage activationmonocytesMedicineRInternal medicineRC31-1245ENJournal of Innate Immunity, Pp 1-11 (2021) |
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DOAJ |
| language |
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| topic |
interleukin 1 receptor antagonist protein tocilizumab respiratory distress syndrome covid-19 macrophage activation monocytes Medicine R Internal medicine RC31-1245 |
| spellingShingle |
interleukin 1 receptor antagonist protein tocilizumab respiratory distress syndrome covid-19 macrophage activation monocytes Medicine R Internal medicine RC31-1245 Eleni Karakike George N. Dalekos Ioannis Koutsodimitropoulos Maria Saridaki Chryssa Pourzitaki Georgios Papathanakos Antigone Kotsaki Stamatios Chalvatzis Vasiliki Dimakopoulou Nikolaos Vechlidis Elisabeth Paramythiotou Christina Avgoustou Aikaterini Ioakeimidou Elli Kouriannidi Apostolos Komnos Evangelia Neou Nikoletta Rovina Eleni Stefanatou Haralampos Milionis George Nikolaidis Antonia Koutsoukou Georgia Damoraki George Dimopoulos Vassileios Zoumpos Jesper Eugen-Olsen Karolina Akinosoglou Nikolaos K. Gatselis Vasilios Koulouras Eleni Gkeka Nikolaos Markou Mihai G. Netea Evangelos J. Giamarellos-Bourboulis ESCAPE: An Open-Label Trial of Personalized Immunotherapy in Critically lll COVID-19 Patients |
| 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 |
article |
| author |
Eleni Karakike George N. Dalekos Ioannis Koutsodimitropoulos Maria Saridaki Chryssa Pourzitaki Georgios Papathanakos Antigone Kotsaki Stamatios Chalvatzis Vasiliki Dimakopoulou Nikolaos Vechlidis Elisabeth Paramythiotou Christina Avgoustou Aikaterini Ioakeimidou Elli Kouriannidi Apostolos Komnos Evangelia Neou Nikoletta Rovina Eleni Stefanatou Haralampos Milionis George Nikolaidis Antonia Koutsoukou Georgia Damoraki George Dimopoulos Vassileios Zoumpos Jesper Eugen-Olsen Karolina Akinosoglou Nikolaos K. Gatselis Vasilios Koulouras Eleni Gkeka Nikolaos Markou Mihai G. Netea Evangelos J. Giamarellos-Bourboulis |
| author_facet |
Eleni Karakike George N. Dalekos Ioannis Koutsodimitropoulos Maria Saridaki Chryssa Pourzitaki Georgios Papathanakos Antigone Kotsaki Stamatios Chalvatzis Vasiliki Dimakopoulou Nikolaos Vechlidis Elisabeth Paramythiotou Christina Avgoustou Aikaterini Ioakeimidou Elli Kouriannidi Apostolos Komnos Evangelia Neou Nikoletta Rovina Eleni Stefanatou Haralampos Milionis George Nikolaidis Antonia Koutsoukou Georgia Damoraki George Dimopoulos Vassileios Zoumpos Jesper Eugen-Olsen Karolina Akinosoglou Nikolaos K. Gatselis Vasilios Koulouras Eleni Gkeka Nikolaos Markou Mihai G. Netea Evangelos J. Giamarellos-Bourboulis |
| author_sort |
Eleni Karakike |
| title |
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_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_sort |
escape: an open-label trial of personalized immunotherapy in critically lll covid-19 patients |
| publisher |
Karger Publishers |
| publishDate |
2021 |
| url |
https://doaj.org/article/1a1b1ce9f0cc42099e276c4bad6ad8ae |
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