Transitions of blood immune endotypes and improved outcome by anakinra in COVID-19 pneumonia: an analysis of the SAVE-MORE randomized controlled trial

doi:10.1186/s13054-024-04852-z

Randomized Controlled Trial

. 2024 Mar 12;28(1):73.

doi: 10.1186/s13054-024-04852-z.

Transitions of blood immune endotypes and improved outcome by anakinra in COVID-19 pneumonia: an analysis of the SAVE-MORE randomized controlled trial

Evdoxia Kyriazopoulou¹, Yehudit Hasin-Brumshtein², Uros Midic², Garyfallia Poulakou³, Haralampos Milionis⁴, Simeon Metallidis⁵, Myrto Astriti⁶, Archontoula Fragkou⁷, Aggeliki Rapti⁸, Eleonora Taddei⁹, Ioannis Kalomenidis¹⁰, Georgios Chrysos¹¹, Andrea Angheben¹², Ilias Kainis¹³, Zoi Alexiou¹⁴, Francesco Castelli¹⁵, Francesco Saverio Serino¹⁶, Petros Bakakos¹⁷, Emanuele Nicastri¹⁸, Vasiliki Tzavara¹⁹, Sofia Ioannou²⁰, Lorenzo Dagna²¹, Katerina Dimakou²², Glykeria Tzatzagou²³, Maria Chini²⁴, Matteo Bassetti²⁵, Vasileios Kotsis²⁶, Dionysios G Tsoukalas²⁷, Carlo Selmi²⁸, Alexandra Konstantinou²⁹, Michael Samarkos³⁰, Michael Doumas³¹, Aikaterini Masgala³², Konstantinos Pagkratis³³, Aikaterini Argyraki³⁴, Karolina Akinosoglou³⁵, Styliani Symbardi³⁶, Mihai G Netea^{37

38}, Periklis Panagopoulos³⁹, George N Dalekos⁴⁰, Oliver Liesenfeld², Timothy E Sweeney², Purvesh Khatri^{41

42}, Evangelos J Giamarellos-Bourboulis^{43

44}

Affiliations

¹ 4th Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
² Inflammatix, Inc., Sunnyvale, CA, USA.
³ 3rd Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
⁴ 1st Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece.
⁵ 1st Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.
⁶ 1st Department of Internal Medicine, G. Gennimatas General Hospital of Athens, Athens, Greece.
⁷ Department of Internal Medicine, Elpis General Hospital, Athens, Greece.
⁸ 2nd Department of Pulmonary Medicine, Sotiria General Hospital of Chest Diseases, Athens, Greece.
⁹ Dipartimento Scienze di Laboratorio e Infettivologiche, Fondazione Policlinico Gemelli IRCCS, Rome, Italy.
¹⁰ 1st Department of Critical Care and Pulmonary Medicine, Medical School, National and Kapodistrian University of Athens, Evangelismos General Hospital, Athens, Greece.
¹¹ 2nd Department of Internal Medicine, Tzaneio General Hospital of Piraeus, Athens, Greece.
¹² Department of Infectious - Tropical Diseases and Microbiology, IRCSS Sacro Cuore Hospital, Negrar, Verona, Italy.
¹³ 10th Department of Pulmonary Medicine, Sotiria General Hospital of Chest Diseases of Athens, Athens, Greece.
¹⁴ 2nd Department of Internal Medicine, Thriasio General Hospital of Eleusis, Athens, Greece.
¹⁵ Spedali Civili, Brescia ASST Spedali Civili Hospital, University of Brescia, Brescia, Italy.
¹⁶ Department of Internal Medicine, Hospital of Jesolo, Jesolo, Italy.
¹⁷ 1st Department of Chest Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
¹⁸ Department of Internal Medicine, Spallanzani Institute of Rome, Rome, Italy.
¹⁹ 1st Department of Internal Medicine, Korgialeneion-Benakeion General Hospital, Athens, Greece.
²⁰ Department of Therapeutics, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
²¹ Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Milan, Italy.
²² 5th Department of Pulmonary Medicine, Sotiria General Hospital of Chest Diseases, Athens, Athens, Greece.
²³ 1st Department of Internal Medicine, Papageorgiou General Hospital of Thessaloniki, Thessaloniki, Greece.
²⁴ 3rd Department of Internal Medicine and Infectious Diseases Unit, Korgialeneion-Benakeion General Hospital, Athens, Greece.
²⁵ Infectious Diseases Clinic, Ospedale Policlinico San Martino IRCCS and Department of Health Sciences, University of Genova, Genova, Italy.
²⁶ 3rd Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.
²⁷ 4th Department of Pulmonary Medicine, Sotiria General Hospital of Chest Diseases, Athens, Greece.
²⁸ Department of Biomedical Sciences, Humanitas University and IRCCS Humanitas Research Hospital, Milan, Italy.
²⁹ 1st Department of Internal Medicine, Asklepieio General Hospital of Voula, Voula, Greece.
³⁰ 1st Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
³¹ 2nd Department of Propedeutic Medicine, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.
³² 2nd Department of Internal Medicine, Konstantopouleio General Hospital, Athens, Greece.
³³ Department of Pulmonary Medicine, General Hospital of Kerkyra, Corfu, Greece.
³⁴ Department of Internal Medicine, Sotiria General Hospital of Chest Diseases, Athens, Greece.
³⁵ Department of Internal Medicine, University of Patras, Patras, Greece.
³⁶ 1st Department of Internal Medicine, Thriasio General Hospital of Eleusis, Athens, Greece.
³⁷ Department of Internal Medicine and Center for Infectious Diseases, Radboud University, Nijmegen, The Netherlands.
³⁸ Department of Immunology and Metabolism, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany.
³⁹ 2nd Department of Internal Medicine, Medical School, Democritus University of Thrace, Alexandroupolis, Greece.
⁴⁰ Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, European Reference Network on Hepatological Diseases (ERN RARE-LIVER), General University Hospital of Larissa, Larissa, Greece.
⁴¹ Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA, USA.
⁴² Center for Biomedical Informatics Research, Department of Medicine, Stanford University, Stanford, CA, USA.
⁴³ 4th Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece. egiamarel@med.uoa.gr.
⁴⁴ 4th Department of Internal Medicine, ATTIKON University Hospital, 1 Rimini Street, 124 62, Athens, Greece. egiamarel@med.uoa.gr.

PMID: 38475786
PMCID: PMC10935809
DOI: 10.1186/s13054-024-04852-z

Randomized Controlled Trial

Transitions of blood immune endotypes and improved outcome by anakinra in COVID-19 pneumonia: an analysis of the SAVE-MORE randomized controlled trial

Evdoxia Kyriazopoulou et al. Crit Care. 2024.

. 2024 Mar 12;28(1):73.

doi: 10.1186/s13054-024-04852-z.

Authors

Affiliations

¹ 4th Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
² Inflammatix, Inc., Sunnyvale, CA, USA.
³ 3rd Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
⁴ 1st Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece.
⁵ 1st Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.
⁶ 1st Department of Internal Medicine, G. Gennimatas General Hospital of Athens, Athens, Greece.
⁷ Department of Internal Medicine, Elpis General Hospital, Athens, Greece.
⁸ 2nd Department of Pulmonary Medicine, Sotiria General Hospital of Chest Diseases, Athens, Greece.
⁹ Dipartimento Scienze di Laboratorio e Infettivologiche, Fondazione Policlinico Gemelli IRCCS, Rome, Italy.
¹⁰ 1st Department of Critical Care and Pulmonary Medicine, Medical School, National and Kapodistrian University of Athens, Evangelismos General Hospital, Athens, Greece.
¹¹ 2nd Department of Internal Medicine, Tzaneio General Hospital of Piraeus, Athens, Greece.
¹² Department of Infectious - Tropical Diseases and Microbiology, IRCSS Sacro Cuore Hospital, Negrar, Verona, Italy.
¹³ 10th Department of Pulmonary Medicine, Sotiria General Hospital of Chest Diseases of Athens, Athens, Greece.
¹⁴ 2nd Department of Internal Medicine, Thriasio General Hospital of Eleusis, Athens, Greece.
¹⁵ Spedali Civili, Brescia ASST Spedali Civili Hospital, University of Brescia, Brescia, Italy.
¹⁶ Department of Internal Medicine, Hospital of Jesolo, Jesolo, Italy.
¹⁷ 1st Department of Chest Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
¹⁸ Department of Internal Medicine, Spallanzani Institute of Rome, Rome, Italy.
¹⁹ 1st Department of Internal Medicine, Korgialeneion-Benakeion General Hospital, Athens, Greece.
²⁰ Department of Therapeutics, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
²¹ Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Milan, Italy.
²² 5th Department of Pulmonary Medicine, Sotiria General Hospital of Chest Diseases, Athens, Athens, Greece.
²³ 1st Department of Internal Medicine, Papageorgiou General Hospital of Thessaloniki, Thessaloniki, Greece.
²⁴ 3rd Department of Internal Medicine and Infectious Diseases Unit, Korgialeneion-Benakeion General Hospital, Athens, Greece.
²⁵ Infectious Diseases Clinic, Ospedale Policlinico San Martino IRCCS and Department of Health Sciences, University of Genova, Genova, Italy.
²⁶ 3rd Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.
²⁷ 4th Department of Pulmonary Medicine, Sotiria General Hospital of Chest Diseases, Athens, Greece.
²⁸ Department of Biomedical Sciences, Humanitas University and IRCCS Humanitas Research Hospital, Milan, Italy.
²⁹ 1st Department of Internal Medicine, Asklepieio General Hospital of Voula, Voula, Greece.
³⁰ 1st Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
³¹ 2nd Department of Propedeutic Medicine, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.
³² 2nd Department of Internal Medicine, Konstantopouleio General Hospital, Athens, Greece.
³³ Department of Pulmonary Medicine, General Hospital of Kerkyra, Corfu, Greece.
³⁴ Department of Internal Medicine, Sotiria General Hospital of Chest Diseases, Athens, Greece.
³⁵ Department of Internal Medicine, University of Patras, Patras, Greece.
³⁶ 1st Department of Internal Medicine, Thriasio General Hospital of Eleusis, Athens, Greece.
³⁷ Department of Internal Medicine and Center for Infectious Diseases, Radboud University, Nijmegen, The Netherlands.
³⁸ Department of Immunology and Metabolism, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany.
³⁹ 2nd Department of Internal Medicine, Medical School, Democritus University of Thrace, Alexandroupolis, Greece.
⁴⁰ Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, European Reference Network on Hepatological Diseases (ERN RARE-LIVER), General University Hospital of Larissa, Larissa, Greece.
⁴¹ Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA, USA.
⁴² Center for Biomedical Informatics Research, Department of Medicine, Stanford University, Stanford, CA, USA.
⁴³ 4th Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece. egiamarel@med.uoa.gr.
⁴⁴ 4th Department of Internal Medicine, ATTIKON University Hospital, 1 Rimini Street, 124 62, Athens, Greece. egiamarel@med.uoa.gr.

PMID: 38475786
PMCID: PMC10935809
DOI: 10.1186/s13054-024-04852-z

Abstract

Background: Endotype classification may guide immunomodulatory management of patients with bacterial and viral sepsis. We aimed to identify immune endotypes and transitions associated with response to anakinra (human interleukin 1 receptor antagonist) in participants in the SAVE-MORE trial.

Methods: Adult patients hospitalized with radiological findings of PCR-confirmed severe pneumonia caused by SARS-CoV-2 and plasma-soluble urokinase plasminogen activator receptor levels of ≥ 6 ng/ml in the SAVE-MORE trial (NCT04680949) were characterized at baseline and days 4 and 7 of treatment using a previously defined 33-messenger RNA classifier to assign an immunological endotype in blood. Endpoints were changes in endotypes and progression to severe respiratory failure (SRF) associated with anakinra treatment.

Results: At baseline, 23.2% of 393 patients were designated as inflammopathic, 41.1% as adaptive, and 35.7% as coagulopathic. Only 23.9% were designated as the same endotype at days 4 and 7 compared to baseline, while all other patients transitioned between endotypes. Anakinra-treated patients were more likely to remain in the adaptive endotype during 7-day treatment (24.4% vs. 9.9%; p < 0.001). Anakinra also protected patients with coagulopathic endotype at day 7 against SRF compared to placebo (27.8% vs. 55.9%; p = 0.013).

Conclusion: We identify an association between endotypes defined using blood transcriptome and anakinra therapy for COVID-19 pneumonia, with anakinra-treated patients shifting toward endotypes associated with a better outcome, mainly the adaptive endotype. Trial registration ClinicalTrials.gov, NCT04680949, December 23, 2020.

Keywords: Anakinra; COVID-19; Endotypes; Viral sepsis.

PubMed Disclaimer

Conflict of interest statement

GND is an advisor or lecturer for Pfizer, Roche, Sanofi, Sobi, and Genesis and received research grants from Gilead and has served as PI in studies for Gilead, Novo Nordisk, Genkyotex, Regulus Therapeutics Inc, Tiziana Life Sciences, Pfizer, Amyndas Pharmaceuticals, CymaBay Therapeutics Inc., Sobi and Intercept Pharmaceuticals. MGN is a scientific founder of TTxD, Biotrip and Lemba and was supported by an ERC Advanced Grant (#833247) and a Spinoza grant of the Netherlands Organization for Scientific Research. PK is a co-founder of, holds stock options of and a consultant to Inflammatix, Inc. YH-B, UM, OL and TES are employees and stock option holders of Inflammatix, Inc. EJGΒ has received honoraria from Abbott Products Operations, bioMérieux, Brahms GmbH, GSK, InflaRx GmbH and Swedish Orphan BioVitrum; independent educational grants from Abbott Products Operations, bioMérieux Inc, InCyte, Johnson & Johnson, MSD, UCB and Swedish Orphan BioVitrum; and funding from the Horizon 2020 European Grants ImmunoSep and RISCinCOVID and the Horizon Health grant EPIC-CROWN-2 (granted to the Hellenic Institute for the Study of Sepsis). All other authors do not declare conflicts of interest.

Figures

**Fig. 1**
Alluvial plots of distribution of endotype transitions of patients of the SAVE-MORE trial treated with standard-of-care (SoC) and anakinra (*left panel*) and standard-of-care (SoC) and placebo (*right panel*), from baseline endotype to the endotype of days 4 and 7 of treatment

**Fig. 2**
Endotype transitions between days of follow-up. *Upper panel:* Alluvial plot of distribution of endotype transitions of patients of the SAVE-MORE trial from baseline endotype to the endotype at days 4 and 7 of treatment. *Lower panel left:* Proportion of patients that develop severe respiratory failure (SRF) and/or die by day 28, as function of number of timepoints they spent in the adaptive endotype. *Lower panel right*: Kaplan–Meier curves for the time of progression to severe respiratory failure and/or death by day 28 of patients with adaptive endotype at baseline and treated with Standard-of-Care (SoC) and placebo or SoC and anakinra. Abbreviations: CI, confidence interval; HR, hazard ratio

**Fig. 3**
Stabilization over the first 7 days of follow-up to the adaptive endotype. The upper panel shows the univariate and multivariate logistic regression analyses of variables associated with the stabilization of patients in the adaptive endotype between baseline day 1 and follow-up days 4 and 7. The lower panel shows the Kaplan–Meier curves for the time of progression to severe respiratory failure and/or death by day 28 between patients of the entire SAVE-MORE cohort remaining by day 7 in the adaptive endotype and those not stabilized by day 7 in adaptive endotype. Abbreviations: BMI, body mass index; CCI, Charlson’s comorbidity index; CI, confidence interval; HR, hazard ratio; n, number; OR, odds ratio; SOFA, sequential organ failure assessment score; SRF, severe respiratory failure; suPAR, soluble urokinase plasminogen activator receptor

**Fig. 4**
Association between the prevailing endotype at day 7 and 28-day outcome. Kaplan–Meier curves for the time of progression to severe respiratory failure and/or death by day 28 between patients treated with Standard-of-Care (SoC) and placebo versus Standard-of-Care (SoC) and anakinra and classified at day 7 into the coagulopathic endotype (*upper panel left*); the adaptive endotype (*upper panel right*); and the inflammopathic endotype (*lower panel*). Abbreviations: CI, confidence interval; HR, hazard ratio

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References

1. Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for sepsis and septic Shock (Sepsis-3) JAMA. 2016;315:801–810. doi: 10.1001/jama.2016.0287. - DOI - PMC - PubMed
1. Rudd KE, Johnson SC, Agesa KM, et al. Global, regional, and national sepsis incidence and mortality, 1990–2017: analysis 5 for the Global Burden of Disease Study. Lancet. 2020;395:200–211. doi: 10.1016/S0140-6736(19)32989-7. - DOI - PMC - PubMed
1. World Health Organization. Coronavirus disease (COVID-19) pandemic. https://www.who.int/emergencies/diseases/novel-coronavirus-2019?gclid=Cj....
1. Giamarellos-Bourboulis EJ, Netea MG, Rovina N, et al. Complex immune dysregulation in COVID-19 patients with severe respiratory failure. Cell Host Microbe. 2020;27:992–1000.e3. doi: 10.1016/j.chom.2020.04.009. - DOI - PMC - PubMed
1. Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395:1054–1062. doi: 10.1016/S0140-6736(20)30566-3. - DOI - PMC - PubMed

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[1] Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for sepsis and septic Shock (Sepsis-3) JAMA. 2016;315:801–810. doi: 10.1001/jama.2016.0287. - DOI - PMC - PubMed

[2] Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for sepsis and septic Shock (Sepsis-3) JAMA. 2016;315:801–810. doi: 10.1001/jama.2016.0287. - DOI - PMC - PubMed

[3] Rudd KE, Johnson SC, Agesa KM, et al. Global, regional, and national sepsis incidence and mortality, 1990–2017: analysis 5 for the Global Burden of Disease Study. Lancet. 2020;395:200–211. doi: 10.1016/S0140-6736(19)32989-7. - DOI - PMC - PubMed

[4] Rudd KE, Johnson SC, Agesa KM, et al. Global, regional, and national sepsis incidence and mortality, 1990–2017: analysis 5 for the Global Burden of Disease Study. Lancet. 2020;395:200–211. doi: 10.1016/S0140-6736(19)32989-7. - DOI - PMC - PubMed

[5] World Health Organization. Coronavirus disease (COVID-19) pandemic. https://www.who.int/emergencies/diseases/novel-coronavirus-2019?gclid=Cj....

[6] World Health Organization. Coronavirus disease (COVID-19) pandemic. https://www.who.int/emergencies/diseases/novel-coronavirus-2019?gclid=Cj....

[7] Giamarellos-Bourboulis EJ, Netea MG, Rovina N, et al. Complex immune dysregulation in COVID-19 patients with severe respiratory failure. Cell Host Microbe. 2020;27:992–1000.e3. doi: 10.1016/j.chom.2020.04.009. - DOI - PMC - PubMed

[8] Giamarellos-Bourboulis EJ, Netea MG, Rovina N, et al. Complex immune dysregulation in COVID-19 patients with severe respiratory failure. Cell Host Microbe. 2020;27:992–1000.e3. doi: 10.1016/j.chom.2020.04.009. - DOI - PMC - PubMed

[9] Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395:1054–1062. doi: 10.1016/S0140-6736(20)30566-3. - DOI - PMC - PubMed

[10] Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395:1054–1062. doi: 10.1016/S0140-6736(20)30566-3. - DOI - PMC - PubMed

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Transitions of blood immune endotypes and improved outcome by anakinra in COVID-19 pneumonia: an analysis of the SAVE-MORE randomized controlled trial

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Transitions of blood immune endotypes and improved outcome by anakinra in COVID-19 pneumonia: an analysis of the SAVE-MORE randomized controlled trial

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