ESCAPE: An Open-Label Trial of Personalized Immunotherapy in Critically lll COVID-19 Patients

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

doi:10.1159/000519090

ESCAPE: An Open-Label Trial of Personalized Immunotherapy in Critically lll COVID-19 Patients

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 NikolaidisAntonia 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

Klinisk Forskningsafdeling

9 Citationer (Scopus)

Abstract

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.

Originalsprog	Engelsk
Artikelnummer	000519090
Tidsskrift	Journal of Innate Immunity
Vol/bind	14
Udgave nummer	3
Sider (fra-til)	218-228
Antal sider	11
ISSN	1662-811X
DOI	https://doi.org/10.1159/000519090
Status	Udgivet - 2022

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Karakike, E., Dalekos, G. N., Koutsodimitropoulos, I., Saridaki, M., Pourzitaki, C., Papathanakos, G., Kotsaki, A., Chalvatzis, S., Dimakopoulou, V., Vechlidis, N., Paramythiotou, E., Avgoustou, C., Ioakeimidou, A., Kouriannidi, E., Komnos, A., Neou, E., Rovina, N., Stefanatou, E., Milionis, H., ... Giamarellos-Bourboulis, E. J. (2022). ESCAPE: An Open-Label Trial of Personalized Immunotherapy in Critically lll COVID-19 Patients. Journal of Innate Immunity, 14(3), 218-228. [000519090]. https://doi.org/10.1159/000519090

Karakike, E, Dalekos, GN, Koutsodimitropoulos, I, Saridaki, M, Pourzitaki, C, Papathanakos, G, Kotsaki, A, Chalvatzis, S, Dimakopoulou, V, Vechlidis, N, Paramythiotou, E, Avgoustou, C, Ioakeimidou, A, Kouriannidi, E, Komnos, A, Neou, E, Rovina, N, Stefanatou, E, Milionis, H, Nikolaidis, G, Koutsoukou, A, Damoraki, G, Dimopoulos, G, Zoumpos, V, Eugen-Olsen, J, Akinosoglou, K, Gatselis, NK, Koulouras, V, Gkeka, E, Markou, N, Netea, MG & Giamarellos-Bourboulis, EJ 2022, 'ESCAPE: An Open-Label Trial of Personalized Immunotherapy in Critically lll COVID-19 Patients', Journal of Innate Immunity, bind 14, nr. 3, 000519090, s. 218-228. https://doi.org/10.1159/000519090

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title = "ESCAPE: An Open-Label Trial of Personalized Immunotherapy in Critically lll COVID-19 Patients",

abstract = "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.",

keywords = "COVID-19, Interleukin 1 receptor antagonist protein, Macrophage activation, Monocytes, Respiratory distress syndrome, Tocilizumab",

author = "Eleni Karakike and Dalekos, {George N} and Ioannis Koutsodimitropoulos and Maria Saridaki and Chryssa Pourzitaki and Georgios Papathanakos and Antigone Kotsaki and Stamatios Chalvatzis and Vasiliki Dimakopoulou and Nikolaos Vechlidis and Elisabeth Paramythiotou and Christina Avgoustou and Aikaterini Ioakeimidou and Elli Kouriannidi and Apostolos Komnos and Evangelia Neou and Nikoletta Rovina and Eleni Stefanatou and Haralampos Milionis and George Nikolaidis and Antonia Koutsoukou and Georgia Damoraki and George Dimopoulos and Vassileios Zoumpos and Jesper Eugen-Olsen and Karolina Akinosoglou and Gatselis, {Nikolaos K} and Vasilios Koulouras and Eleni Gkeka and Nikolaos Markou and Netea, {Mihai G} and Giamarellos-Bourboulis, {Evangelos J}",

note = "{\textcopyright} 2021 The Author(s). Published by S. Karger AG, Basel.",

year = "2022",

doi = "10.1159/000519090",

language = "English",

volume = "14",

pages = "218--228",

journal = "Journal of Innate Immunity",

issn = "1662-811X",

publisher = "S.Karger AG",

number = "3",

}

TY - JOUR

T1 - ESCAPE

T2 - An Open-Label Trial of Personalized Immunotherapy in Critically lll COVID-19 Patients

AU - Karakike, Eleni

AU - Dalekos, George N

AU - Koutsodimitropoulos, Ioannis

AU - Saridaki, Maria

AU - Pourzitaki, Chryssa

AU - Papathanakos, Georgios

AU - Kotsaki, Antigone

AU - Chalvatzis, Stamatios

AU - Dimakopoulou, Vasiliki

AU - Vechlidis, Nikolaos

AU - Paramythiotou, Elisabeth

AU - Avgoustou, Christina

AU - Ioakeimidou, Aikaterini

AU - Kouriannidi, Elli

AU - Komnos, Apostolos

AU - Neou, Evangelia

AU - Rovina, Nikoletta

AU - Stefanatou, Eleni

AU - Milionis, Haralampos

AU - Nikolaidis, George

AU - Koutsoukou, Antonia

AU - Damoraki, Georgia

AU - Dimopoulos, George

AU - Zoumpos, Vassileios

AU - Eugen-Olsen, Jesper

AU - Akinosoglou, Karolina

AU - Gatselis, Nikolaos K

AU - Koulouras, Vasilios

AU - Gkeka, Eleni

AU - Markou, Nikolaos

AU - Netea, Mihai G

AU - Giamarellos-Bourboulis, Evangelos J

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

KW - COVID-19

KW - Interleukin 1 receptor antagonist protein

KW - Macrophage activation

KW - Monocytes

KW - Respiratory distress syndrome

KW - Tocilizumab

UR - http://www.scopus.com/inward/record.url?scp=85120621639&partnerID=8YFLogxK

U2 - 10.1159/000519090

DO - 10.1159/000519090

M3 - Journal article

C2 - 34852352

VL - 14

SP - 218

EP - 228

JO - Journal of Innate Immunity

JF - Journal of Innate Immunity

SN - 1662-811X

IS - 3

M1 - 000519090

ER -

ESCAPE: An Open-Label Trial of Personalized Immunotherapy in Critically lll COVID-19 Patients

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