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Favorable Anakinra Responses in COVID-19 Patients with Severe Respiratory Failure

17 Pages Posted: 29 Apr 2020 Publication Status: Published

See all articles by George Dimopoulos

George Dimopoulos

National and Kapodistrian University of Athens - 2nd Department of Critical Care Medicine

Quirijn de Mast

Radboud University Nijmegen - Nijmegen Institute of International Health

Nikolaos Markou

Latsion Hospital - Intensive Care Unit

Maria Theodorakopoulou

National and Kapodistrian University of Athens - 2nd Department of Critical Care Medicine

Apostolos Komnos

Koutlibaneion-Triantafyllion Hospital - Intensive Care Unit

Maria Mouktaroudi

National and Kapodistrian University of Athens - 4th Department of Internal Medicine

Mihai G. Netea

Radboud University Nijmegen - Radboud Institute for Molecular Life Sciences (RIMLS)

Rebecca J. Verheggen

Radboud University Nijmegen - Radboud Center for Infectious Diseases (RCI)

Jacobien Hoogerwerf

Radboud University Nijmegen - Radboud Center for Infectious Diseases (RCI)

Alexandra Lachana

National and Kapodistrian University of Athens - 2nd Department of Critical Care Medicine

Frank L. van de Veerdonk

Radboud University Nijmegen - Radboud Center for Infectious Diseases (RCI)

Evangelos Giamarellos-Bourboulis

National and Kapodistrian University of Athens - 4th Department of Internal Medicine

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Abstract

Dysregulation of inflammation is hypothesized to play a crucial role for inducing the severe complications of Covid-19, with IL-1/IL-6 pathway being central in these events. Eight patients with severe Covid-19 pneumonia treated with the interleukin-1 receptor antagonist anakinra are reported; seven patients hospitalized in intensive care units (ICUs) in Greece and one non-ICU patient in the Netherlands. Patients scored positive for the hemophagocytosis score and they were diagnosed with secondary hemophagocytic lymphohistocytosis (sHLH). At the end-of-treatment with anakinra, ICU patients had less demands on vasopressors; they also had lower C-reactive protein, procalcitonin, troponin I, D-dimers, and ferritin - the hallmark marker of sHLH. All patients improved their respiratory function. Only two patients died. These data argue that the administration of anakinra may be a viable treatment in severe Covid-19 with sHLH, supporting for larger clinical studies to validate this concept.

Note: Funding: The study was funded in part by the Horizon 2020 grant ImmunoSep (#847422) and in part by the Hellenic Institute for the Study of Sepsis. MGN was supported by an ERC Advanced grant (#833247) and a Spinoza grant of the Netherlands Organization for Scientific Research.

Conflict of Interest: E.J. Giamarellos-Bourboulis has received honoraria from AbbVie USA, Abbott CH, InflaRx GmbH, MSD Greece, XBiotech Inc. and Angelini Italy; independent educational grants from AbbVie, Abbott, Astellas Pharma Europe, AxisShield, bioMérieux Inc, InflaRx GmbH, and XBiotech Inc; and funding from the FrameWork 7 program HemoSpec (granted to the National and Kapodistrian University of Athens), the Horizon2020 Marie-Curie Project European Sepsis Academy (granted to the National and Kapodistrian University of Athens), and the Horizon 2020 European Grant ImmunoSep (granted to the Hellenic Institute for the Study of Sepsis). Mihai G. Netea is supported by an ERC Advanced Grant (#833247) and a Spinoza grant of the Netherlands Organization for Scientific Research. Frank L van de Veerdonk was supported by a Vidi grant of the Netherlands Association for Scientific Research.

Keywords: hemophagocytic lymphohistocytosis, COVID-19, anakinra, ferritin, respiratory function

Suggested Citation

Dimopoulos, George and de Mast, Quirijn and Markou, Nikolaos and Theodorakopoulou, Maria and Komnos, Apostolos and Mouktaroudi, Maria and Netea, Mihai G. and Verheggen, Rebecca J. and Hoogerwerf, Jacobien and Lachana, Alexandra and van de Veerdonk, Frank L. and Giamarellos-Bourboulis, Evangelos, Favorable Anakinra Responses in COVID-19 Patients with Severe Respiratory Failure. Available at SSRN: https://ssrn.com/abstract=3578042 or http://dx.doi.org/10.2139/ssrn.3578042
This version of the paper has not been formally peer reviewed.

George Dimopoulos

National and Kapodistrian University of Athens - 2nd Department of Critical Care Medicine

Greece

Quirijn De Mast

Radboud University Nijmegen - Nijmegen Institute of International Health ( email )

Netherlands

Nikolaos Markou

Latsion Hospital - Intensive Care Unit

Greece

Maria Theodorakopoulou

National and Kapodistrian University of Athens - 2nd Department of Critical Care Medicine

Greece

Apostolos Komnos

Koutlibaneion-Triantafyllion Hospital - Intensive Care Unit

Greece

Maria Mouktaroudi

National and Kapodistrian University of Athens - 4th Department of Internal Medicine

Greece

Mihai G. Netea

Radboud University Nijmegen - Radboud Institute for Molecular Life Sciences (RIMLS)

6525 GA Nijmegen
Netherlands

Rebecca J. Verheggen

Radboud University Nijmegen - Radboud Center for Infectious Diseases (RCI)

Nijmegen
Netherlands

Jacobien Hoogerwerf

Radboud University Nijmegen - Radboud Center for Infectious Diseases (RCI)

Nijmegen
Netherlands

Alexandra Lachana

National and Kapodistrian University of Athens - 2nd Department of Critical Care Medicine

Greece

Frank L. Van de Veerdonk

Radboud University Nijmegen - Radboud Center for Infectious Diseases (RCI)

Nijmegen
Netherlands

Evangelos Giamarellos-Bourboulis (Contact Author)

National and Kapodistrian University of Athens - 4th Department of Internal Medicine

Greece

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