eLife (Mar 2021)
An open label trial of anakinra to prevent respiratory failure in COVID-19
- Evdoxia Kyriazopoulou,
- Periklis Panagopoulos,
- Symeon Metallidis,
- George N Dalekos,
- Garyphallia Poulakou,
- Nikolaos Gatselis,
- Eleni Karakike,
- Maria Saridaki,
- Georgia Loli,
- Aggelos Stefos,
- Danai Prasianaki,
- Sarah Georgiadou,
- Olga Tsachouridou,
- Vasileios Petrakis,
- Konstantinos Tsiakos,
- Maria Kosmidou,
- Vassiliki Lygoura,
- Maria Dareioti,
- Haralampos Milionis,
- Ilias C Papanikolaou,
- Karolina Akinosoglou,
- Dimitra-Melia Myrodia,
- Areti Gravvani,
- Aliki Stamou,
- Theologia Gkavogianni,
- Konstantina Katrini,
- Theodoros Marantos,
- Ioannis P Trontzas,
- Konstantinos Syrigos,
- Loukas Chatzis,
- Stamatios Chatzis,
- Nikolaos Vechlidis,
- Christina Avgoustou,
- Stamatios Chalvatzis,
- Miltiades Kyprianou,
- Jos WM van der Meer,
- Jesper Eugen-Olsen,
- Mihai G Netea,
- Evangelos J Giamarellos-Bourboulis
Affiliations
- Evdoxia Kyriazopoulou
- ORCiD
- 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece
- Periklis Panagopoulos
- 2nd Department of Internal Medicine, Democritus University of Thrace, Medical School, Alexandroupolis, Greece
- Symeon Metallidis
- 1st Department of Internal Medicine, Aristotle University ofThessaloniki, Thessaloniki, Greece
- George N Dalekos
- 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
- Garyphallia Poulakou
- 3rd Department of Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece
- Nikolaos Gatselis
- 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
- Eleni Karakike
- 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece
- Maria Saridaki
- 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece
- Georgia Loli
- 1st Department of Internal Medicine, Aristotle University ofThessaloniki, Thessaloniki, Greece
- Aggelos Stefos
- 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
- Danai Prasianaki
- 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece
- Sarah Georgiadou
- 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
- Olga Tsachouridou
- 1st Department of Internal Medicine, Aristotle University ofThessaloniki, Thessaloniki, Greece
- Vasileios Petrakis
- 2nd Department of Internal Medicine, Democritus University of Thrace, Medical School, Alexandroupolis, Greece
- Konstantinos Tsiakos
- 3rd Department of Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece
- Maria Kosmidou
- ORCiD
- 1st Department of Internal Medicine,University of Ioannina, School of HealthSciences, Faculty of Medicine, Ioannina, Greece
- Vassiliki Lygoura
- 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
- Maria Dareioti
- 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece
- Haralampos Milionis
- 1st Department of Internal Medicine,University of Ioannina, School of HealthSciences, Faculty of Medicine, Ioannina, Greece
- Ilias C Papanikolaou
- Department of Pulmonary Medicine, General Hospital of Kerkyra, Kerkyra, Greece
- Karolina Akinosoglou
- Department of Internal Medicine, University of Patras, Medical School, Rion, Greece
- Dimitra-Melia Myrodia
- 3rd Department of Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece
- Areti Gravvani
- 3rd Department of Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece
- Aliki Stamou
- 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece
- Theologia Gkavogianni
- 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece
- Konstantina Katrini
- 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece
- Theodoros Marantos
- 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece
- Ioannis P Trontzas
- 3rd Department of Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece
- Konstantinos Syrigos
- 3rd Department of Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece
- Loukas Chatzis
- ORCiD
- 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece
- Stamatios Chatzis
- 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece
- Nikolaos Vechlidis
- 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece
- Christina Avgoustou
- 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece
- Stamatios Chalvatzis
- 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece
- Miltiades Kyprianou
- 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece
- Jos WM van der Meer
- Department of Internal Medicine and Center for Infectious Diseases, Radboud University, Nijmegen, Netherlands
- Jesper Eugen-Olsen
- Clinical Research Centre, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
- Mihai G Netea
- Department of Internal Medicine and Center for Infectious Diseases, Radboud University, Nijmegen, Netherlands; Immunology and Metabolism, Life & Medical Sciences Institute, University of Bonn, Bonn, Germany
- Evangelos J Giamarellos-Bourboulis
- ORCiD
- 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece
- DOI
- https://doi.org/10.7554/eLife.66125
- Journal volume & issue
-
Vol. 10
Abstract
Background: It was studied if early suPAR-guided anakinra treatment can prevent severe respiratory failure (SRF) of COVID-19. Methods: A total of 130 patients with suPAR ≥6 ng/ml were assigned to subcutaneous anakinra 100 mg once daily for 10 days. Primary outcome was SRF incidence by day 14 defined as any respiratory ratio below 150 mmHg necessitating mechanical or non-invasive ventilation. Main secondary outcomes were 30-day mortality and inflammatory mediators; 28-day WHO-CPS was explored. Propensity-matched standard-of care comparators were studied. Results: 22.3% with anakinra treatment and 59.2% comparators (hazard ratio, 0.30; 95% CI, 0.20–0.46) progressed into SRF; 30-day mortality was 11.5% and 22.3% respectively (hazard ratio 0.49; 95% CI 0.25–0.97). Anakinra was associated with decrease in circulating interleukin (IL)−6, sCD163 and sIL2-R; IL-10/IL-6 ratio on day 7 was inversely associated with SOFA score; patients were allocated to less severe WHO-CPS strata. Conclusions: Early suPAR-guided anakinra decreased SRF and restored the pro-/anti-inflammatory balance. Funding: This study was funded by the Hellenic Institute for the Study of Sepsis, Technomar Shipping Inc, Swedish Orphan Biovitrum, and the Horizon 2020 Framework Programme. Clinical trial number: NCT04357366.
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