PMID- 34852352
OWN - NLM
STAT- MEDLINE
DCOM- 20220504
LR  - 20221207
IS  - 1662-8128 (Electronic)
IS  - 1662-811X (Print)
IS  - 1662-811X (Linking)
VI  - 14
IP  - 3
DP  - 2022
TI  - ESCAPE: An Open-Label Trial of Personalized Immunotherapy in Critically lll 
      COVID-19 Patients.
PG  - 218-228
LID - 10.1159/000519090 [doi]
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.
CI  - (c) 2021 The Author(s). Published by S. Karger AG, Basel.
FAU - Karakike, Eleni
AU  - Karakike E
AD  - Fourth Department of Internal Medicine, National and Kapodistrian University of 
      Athens, Medical School, Athens, Greece.
FAU - Dalekos, George N
AU  - Dalekos GN
AD  - Department of Medicine and Research Laboratory of Internal Medicine, National 
      Expertise Center of Greece in Autoimmune Liver Diseases, General University 
      Hospital of Larissa, Larissa, Greece.
FAU - Koutsodimitropoulos, Ioannis
AU  - Koutsodimitropoulos I
AD  - Intensive Care Unit of Latseion Burn Center, General Hospital of Eleusis 
      Thriasion, Eleusis, Greece.
FAU - Saridaki, Maria
AU  - Saridaki M
AD  - Fourth Department of Internal Medicine, National and Kapodistrian University of 
      Athens, Medical School, Athens, Greece.
FAU - Pourzitaki, Chryssa
AU  - Pourzitaki C
AD  - Intensive Care Unit, AHEPA Thessaloniki General Hospital, Thessaloniki, Greece.
FAU - Papathanakos, Georgios
AU  - Papathanakos G
AD  - Department of Critical Care Medicine, University of Ioannina, School of Health 
      Sciences, Faculty of Medicine, Ioannina, Greece.
FAU - Kotsaki, Antigone
AU  - Kotsaki A
AD  - Fourth Department of Internal Medicine, National and Kapodistrian University of 
      Athens, Medical School, Athens, Greece.
FAU - Chalvatzis, Stamatios
AU  - Chalvatzis S
AD  - Fourth Department of Internal Medicine, National and Kapodistrian University of 
      Athens, Medical School, Athens, Greece.
FAU - Dimakopoulou, Vasiliki
AU  - Dimakopoulou V
AD  - Department of Internal Medicine, University of Patras, Medical School, Rion, 
      Greece.
FAU - Vechlidis, Nikolaos
AU  - Vechlidis N
AD  - Fourth Department of Internal Medicine, National and Kapodistrian University of 
      Athens, Medical School, Athens, Greece.
FAU - Paramythiotou, Elisabeth
AU  - Paramythiotou E
AD  - Second Department of Critical Care Medicine, National and Kapodistrian University 
      of Athens, Medical School, Athens, Greece.
FAU - Avgoustou, Christina
AU  - Avgoustou C
AD  - Fourth Department of Internal Medicine, National and Kapodistrian University of 
      Athens, Medical School, Athens, Greece.
FAU - Ioakeimidou, Aikaterini
AU  - Ioakeimidou A
AD  - Intensive Care Unit, Asklipeion General Hospital, Voula, Greece.
FAU - Kouriannidi, Elli
AU  - Kouriannidi E
AD  - Fourth Department of Internal Medicine, National and Kapodistrian University of 
      Athens, Medical School, Athens, Greece.
FAU - Komnos, Apostolos
AU  - Komnos A
AD  - Intensive Care Unit, Koutlimpaneion-Triantafylleion Larissa General Hospital, 
      Larissa, Greece.
FAU - Neou, Evangelia
AU  - Neou E
AD  - Intensive Care Unit, Koutlimpaneion-Triantafylleion Larissa General Hospital, 
      Larissa, Greece.
FAU - Rovina, Nikoletta
AU  - Rovina N
AD  - First Department of Pulmonary Medicine and Intensive Care Unit, National and 
      Kapodistrian University of Athens, Medical School, Athens, Greece.
FAU - Stefanatou, Eleni
AU  - Stefanatou E
AD  - Intensive Care Unit of Latseion Burn Center, General Hospital of Eleusis 
      Thriasion, Eleusis, Greece.
FAU - Milionis, Haralampos
AU  - Milionis H
AD  - First Department of Internal Medicine, University of Ioannina, School of Health 
      Sciences, Faculty of Medicine, Ioannina, Greece.
FAU - Nikolaidis, George
AU  - Nikolaidis G
AD  - Intensive Care Unit, Asklipeion General Hospital, Voula, Greece.
FAU - Koutsoukou, Antonia
AU  - Koutsoukou A
AD  - First Department of Pulmonary Medicine and Intensive Care Unit, National and 
      Kapodistrian University of Athens, Medical School, Athens, Greece.
FAU - Damoraki, Georgia
AU  - Damoraki G
AD  - Fourth Department of Internal Medicine, National and Kapodistrian University of 
      Athens, Medical School, Athens, Greece.
FAU - Dimopoulos, George
AU  - Dimopoulos G
AD  - Second Department of Critical Care Medicine, National and Kapodistrian University 
      of Athens, Medical School, Athens, Greece.
FAU - Zoumpos, Vassileios
AU  - Zoumpos V
AD  - Fourth Department of Internal Medicine, National and Kapodistrian University of 
      Athens, Medical School, Athens, Greece.
FAU - Eugen-Olsen, Jesper
AU  - Eugen-Olsen J
AD  - Clinical Research Centre, Copenhagen University Hospital Hvidovre, Hvidovre, 
      Denmark.
FAU - Akinosoglou, Karolina
AU  - Akinosoglou K
AD  - Department of Internal Medicine, University of Patras, Medical School, Rion, 
      Greece.
FAU - Gatselis, Nikolaos K
AU  - Gatselis NK
AD  - Department of Medicine and Research Laboratory of Internal Medicine, National 
      Expertise Center of Greece in Autoimmune Liver Diseases, General University 
      Hospital of Larissa, Larissa, Greece.
FAU - Koulouras, Vasilios
AU  - Koulouras V
AD  - Department of Critical Care Medicine, University of Ioannina, School of Health 
      Sciences, Faculty of Medicine, Ioannina, Greece.
FAU - Gkeka, Eleni
AU  - Gkeka E
AD  - Intensive Care Unit, AHEPA Thessaloniki General Hospital, Thessaloniki, Greece.
FAU - Markou, Nikolaos
AU  - Markou N
AD  - Intensive Care Unit of Latseion Burn Center, General Hospital of Eleusis 
      Thriasion, Eleusis, Greece.
FAU - Netea, Mihai G
AU  - Netea MG
AD  - Department of Internal Medicine and Center for Infectious Diseases, Radboud 
      University, Nijmegen, The Netherlands.
AD  - Immunology and Metabolism, Life & Medical Sciences Institute, University of Bonn, 
      Bonn, Germany.
FAU - Giamarellos-Bourboulis, Evangelos J
AU  - Giamarellos-Bourboulis EJ
AD  - Fourth Department of Internal Medicine, National and Kapodistrian University of 
      Athens, Medical School, Athens, Greece.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20211201
PL  - Switzerland
TA  - J Innate Immun
JT  - Journal of innate immunity
JID - 101469471
RN  - 0 (Interleukin 1 Receptor Antagonist Protein)
RN  - 9007-73-2 (Ferritins)
RN  - EC 2.6.1.- (Transaminases)
SB  - IM
MH  - Ferritins
MH  - Humans
MH  - Immunotherapy
MH  - Interleukin 1 Receptor Antagonist Protein/therapeutic use
MH  - Prospective Studies
MH  - *Respiratory Distress Syndrome/drug therapy
MH  - SARS-CoV-2
MH  - Transaminases
MH  - *COVID-19 Drug Treatment
PMC - PMC8805059
OTO - NOTNLM
OT  - COVID-19
OT  - Interleukin 1 receptor antagonist protein
OT  - Macrophage activation
OT  - Monocytes
OT  - Respiratory distress syndrome
OT  - Tocilizumab
COIS- George N. Dalekos has acted as advisor/lecturer for Abbvie, Bristol-Myers Squibb, 
      Gilead, Novartis, Roche, Amgen, MSD, Janssen, Ipsen, Genkyotex, Sobi, and Pfizer; 
      has received grant support from Bristol-Myers Squib, Gilead, Roche, Janssen, 
      Abbvie, and Bayer; and was or is currently PI in national and international 
      protocols sponsored by Abbvie, Bristol-Myers Squibb, Novartis, Gilead, Novo 
      Nordisk, Genkyotex, Regulus Therapeutics Inc., Tiziana Life Sciences, Bayer, 
      Astellas, Ipsen, Pfizer, Amyndas Pharamaceuticals, CymaBay Therapeutics Inc., and 
      Roche. E. Karakike has received funding from Horizon 2020 Marie Sklodowska-Curie 
      Grant European Sepsis Academy (Grant No. 676129), outside of the submitted work. 
      Haralampos Milionis reports receiving honoraria, consulting fees, and 
      nonfinancial support from health-care companies, including Amgen, Angelini, 
      Bayer, Mylan, MSD, Pfizer, and Servier. J. Eugen-Olsen is a cofounder, 
      shareholder, and CSO of ViroGates A7S, Denmark, and is named inventor on patents 
      on suPAR owned by Copenhagen University Hospital Hvidovre, Denmark. He is granted 
      by the Horizon 2020 European Grant RISKinCOVID. M.G. Netea is a scientific 
      founder of TTxD and received research grants from GSK and ViiV Healthcare. E.J. 
      Giamarellos-Bourboulis has received honoraria from Abbott CH, Angelini Italy, 
      InflaRx GmbH, MSD Greece, XBiotech Inc., Sobi AB, and B.R.A.H.M.S GmbH (Thermo 
      Fisher Scientific); independent educational grants from AbbVie Inc., Abbott CH, 
      Astellas Pharma Europe, AxisShield, bioMerieux Inc, Johnson & Johnson, Novartis, 
      InflaRx GmbH, Sobi AB, XBiotech Inc (granted to the Hellenic Institute for the 
      Study of Sepsis); and funding from the FrameWork 7 program HemoSpec (granted to 
      the National and Kapodistrian University of Athens), the Horizon 2020 Marie-Curie 
      Project European Sepsis Academy (granted to the National and Kapodistrian 
      University of Athens), the Horizon 2020 European Grant ImmunoSep (granted to the 
      Hellenic Institute for the Study of Sepsis), and the Horizon 2020 RISKinCOVID 
      (granted to the Hellenic Institute for the Study of Sepsis). The other authors do 
      not report any conflict of interest.
EDAT- 2021/12/02 06:00
MHDA- 2022/05/06 06:00
PMCR- 2021/12/01
CRDT- 2021/12/01 20:10
PHST- 2021/04/09 00:00 [received]
PHST- 2021/08/04 00:00 [accepted]
PHST- 2021/12/02 06:00 [pubmed]
PHST- 2022/05/06 06:00 [medline]
PHST- 2021/12/01 20:10 [entrez]
PHST- 2021/12/01 00:00 [pmc-release]
AID - 000519090 [pii]
AID - jin-0014-0218 [pii]
AID - 10.1159/000519090 [doi]
PST - ppublish
SO  - J Innate Immun. 2022;14(3):218-228. doi: 10.1159/000519090. Epub 2021 Dec 1.