EBioMedicine (Jan 2025)
Safety of baricitinib in vaccinated patients with severe and critical COVID-19 sub study of the randomised Bari-SolidAct trialResearch in context
- Hans-Kittil Viermyr,
- Kristian Tonby,
- Erica Ponzi,
- Sophie Trouillet-Assant,
- Julien Poissy,
- José R. Arribas,
- Virginie Dyon-Tafani,
- Maude Bouscambert-Duchamp,
- Lambert Assoumou,
- Bente Halvorsen,
- Nuriye Basdag Tekin,
- Alpha Diallo,
- Lucie De Gastines,
- Ludvig A. Munthe,
- Sarah Louise Murphy,
- Thor Ueland,
- Annika E. Michelsen,
- Fridtjof Lund-Johansen,
- Pål Aukrust,
- Joy Mootien,
- Benjamin Dervieux,
- Yoann Zerbib,
- Jean-Christophe Richard,
- Renaud Prével,
- Denis Malvy,
- Jean-François Timsit,
- Nathan Peiffer-Smadja,
- Damien Roux,
- Lionel Piroth,
- Hafid Ait-Oufella,
- Cesar Vieira,
- Olav Dalgard,
- Lars Heggelund,
- Karl Erik Müller,
- Jannicke Horjen Møller,
- Anders Benjamin Kildal,
- Vegard Skogen,
- Saad Aballi,
- Jonas Daniel Sjøberg Øgaard,
- Anne Ma Dyrhol-Riise,
- Anders Tveita,
- Amin Alirezaylavasani,
- Dominique Costagliola,
- Yazdan Yazdanpanah,
- Inge Christoffer Olsen,
- Tuva Børresdatter Dahl,
- Hassen Kared,
- Aleksander Rygh Holten,
- Marius Trøseid
Affiliations
- Hans-Kittil Viermyr
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Section for Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway
- Kristian Tonby
- Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Infectious Diseases, Oslo University Hospital Ullevål, Oslo, Norway
- Erica Ponzi
- Department of Research Support for Clinical Trials, Oslo University Hospital, Oslo, Norway
- Sophie Trouillet-Assant
- Centre International de Recherche en Infectiologie (CIRI), Université Claude Bernard Lyon 1, Inserm, U1111, CNRS, UMR5308, ENS Lyon, Lyon, France; Joint Research Unit Hospices Civils de Lyon-bioMerieux S.A., Hôpital Lyon Sud, Pierre-Bénite, France
- Julien Poissy
- Université Lille, Inserm U1285, CHU Lille, Pôle de Médecine Intensive-Réanimatin, CNRS, UMR 8576, France; Université Lille, Unité de Glycobiologie Structurale et Fonctionnelle (UGSF), F-59000, Lille, France
- José R. Arribas
- Infectious Diseases Unit, Internal Medicine Department, La Paz University Hospital, IdiPAZ, Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Madrid, Spain
- Virginie Dyon-Tafani
- Centre International de Recherche en Infectiologie (CIRI), Université Claude Bernard Lyon 1, Inserm, U1111, CNRS, UMR5308, ENS Lyon, Lyon, France
- Maude Bouscambert-Duchamp
- Hospices Civils de Lyon, Laboratoire de Virologie, Institut des Agents Infectieux de Lyon, Centre National de Référence des Virus Respiratoires France Sud, F-69317, Lyon, France; Université Claude Bernard Lyon 1, Virpath, CIRI, INSERM U1111, CNRS UMR5308, ENS Lyon, F-69372, Lyon, France
- Lambert Assoumou
- Sorbonne Université, INSERM, Institut Pierre Louis d’Épidémiologie et de Santé Publique (IPLESP), Paris, France
- Bente Halvorsen
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Nuriye Basdag Tekin
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Alpha Diallo
- ANRS, Maladies Infectieuses Emergentes, F-75015, Paris, France; Institut National de la Santé et de la Recherche Médicale, INSERM, F-75013, Paris, France
- Lucie De Gastines
- ANRS, Maladies Infectieuses Emergentes, F-75015, Paris, France; Institut National de la Santé et de la Recherche Médicale, INSERM, F-75013, Paris, France
- Ludvig A. Munthe
- Department of Immunology, Oslo University Hospital, Oslo, Norway; KG Jebsen Centre for B Cell Malignancies, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Precision Immunotherapy Alliance, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Sarah Louise Murphy
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Thor Ueland
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Thrombosis Research Center (TREC), Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway
- Annika E. Michelsen
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Fridtjof Lund-Johansen
- Department of Immunology, Oslo University Hospital, Oslo, Norway; Precision Immunotherapy Alliance, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Pål Aukrust
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Joy Mootien
- Intensive Care Unit, Antibiotic Stewardship Team, Groupe Hospitalier Région Mulhouse et Sud Alsace, Mulhouse, France
- Benjamin Dervieux
- Infectious Diseases Unit, Groupe Hospitalier Région Mulhouse et Sud Alsace, Mulhouse, France
- Yoann Zerbib
- Intensive Care Department, Amiens-Picardie University Hospital, Amiens, France
- Jean-Christophe Richard
- Medical Intensive Care Unit, Hospices Civils de Lyon, Croix-Rousse Hospital - Université Lyon 1, Lyon, France; CREATIS INSERM 1044 CNRS 5220, Villeurbanne, France
- Renaud Prével
- CHU Bordeaux, Medical Intensive Care Unit, Bordeaux, France; Univ Bordeaux, Centre de Recherche Cardio-Thoracique de Bordeaux, Inserm UMR 1045, Bordeaux, France
- Denis Malvy
- Department of Infectious and Tropical Diseases, University Hospital, UMR 1219 Inserm/EMR 271 IRD, University of Bordeaux, Bordeaux, France
- Jean-François Timsit
- AP-HP, Bichat Hospital, Medical and Infectious Diseases ICU (MI2), F-75018, Paris, France; Université Paris-Cité, INSERM, F-75018, Paris, France; OUCTOME REA Research Network, France
- Nathan Peiffer-Smadja
- Université Paris Cité, Inserm, IAME, Paris, 75018, France; Service de Maladies Infectieuses et Tropicales, Hôpital Bichat Claude Bernard, AP-HP, Paris, 75018, France
- Damien Roux
- Université Paris Cité, AP-HP, Hôpital Louis Mourier, DMU ESPRIT, Service de Médecine Intensive Réanimation, Colombes, France
- Lionel Piroth
- Infectious Diseases Department, University Hospital, Dijon, France; INSERM CIC 1432, University of Burgundy, Dijon, France
- Hafid Ait-Oufella
- Service de Médecine Intensive-Réanimation, Hôpital Saint-Antoine, AP-HP, Sorbonne Université, Paris, F-75012, France
- Cesar Vieira
- Centro Hospitalar Universitário de Lisboa Central, Hospital Curry Cabral, Department of Intensive Care Medicine - Lisbon, Portugal
- Olav Dalgard
- Department of Infectious Diseases, Oslo University Hospital Ullevål, Oslo, Norway; Department of Infectious Diseases, Akershus University Hospital, Norway
- Lars Heggelund
- Department of Internal Medicine, Drammen Hospital, Vestre Viken Hospital Trust, Norway; Department of Clinical Science, Bergen Integrated Diagnostic Stewardship Cluster, Faculty of Medicine, University of Bergen, Bergen, Norway
- Karl Erik Müller
- Department of Internal Medicine, Drammen Hospital, Vestre Viken Hospital Trust, Norway; Department of Clinical Science, Bergen Integrated Diagnostic Stewardship Cluster, Faculty of Medicine, University of Bergen, Bergen, Norway
- Jannicke Horjen Møller
- Department of Intensive Care Medicine, Stavanger University Hospital, Stavanger, Norway
- Anders Benjamin Kildal
- Department of Anesthesiology and Intensive Care, University Hospital of North Norway, Tromsø, Norway; Faculty of Health Sciences, UIT The Arctic University of Norway, Norway
- Vegard Skogen
- Department of Infectious Diseases, University Hospital of North Norway, Tromsø, Norway; Faculty of Health Sciences, UIT The Arctic University of Norway, Norway
- Saad Aballi
- Department of Infectious Diseases, Østfold Hospital Kalnes, Grålum, Norway
- Jonas Daniel Sjøberg Øgaard
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Anne Ma Dyrhol-Riise
- Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Infectious Diseases, Oslo University Hospital Ullevål, Oslo, Norway
- Anders Tveita
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Section for Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway; Department of Internal Medicine, Bærum Hospital, Vestre Viken Hospital Trust, 1346, Gjettum, Norway
- Amin Alirezaylavasani
- Department of Immunology, Oslo University Hospital, Oslo, Norway
- Dominique Costagliola
- Sorbonne Université, INSERM, Institut Pierre Louis d’Épidémiologie et de Santé Publique (IPLESP), Paris, France
- Yazdan Yazdanpanah
- Infectious and Tropical Diseases Department, Bichat - Claude Bernard Hospital, AP-HP Nord-Université Paris Cité, Paris, France; IAME INSERM UMR 1137, Université Paris Cité, Paris, France; ANRS, Maladies Infectieuses Emergentes, F-75015, Paris, France; Institut National de la Santé et de la Recherche Médicale, INSERM, F-75013, Paris, France
- Inge Christoffer Olsen
- Department of Research Support for Clinical Trials, Oslo University Hospital, Oslo, Norway
- Tuva Børresdatter Dahl
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Hassen Kared
- Department of Immunology, Oslo University Hospital, Oslo, Norway; KG Jebsen Centre for B Cell Malignancies, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Precision Immunotherapy Alliance, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Aleksander Rygh Holten
- Department of Infectious Diseases, Oslo University Hospital Ullevål, Oslo, Norway; Department of Acute Medicine, Oslo University Hospital, Oslo, Norway
- Marius Trøseid
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Section for Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway; Corresponding author. Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
- Journal volume & issue
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Vol. 111
p. 105511
Abstract
Summary: Background: The Bari-SolidAct randomized controlled trial compared baricitinib with placebo in patients with severe COVID-19. A post hoc analysis revealed a higher incidence of serious adverse events (SAEs) among SARS-CoV-2-vaccinated participants who had received baricitinib. This sub-study aimed to investigate whether vaccination influences the safety profile of baricitinib in patients with severe COVID-19. Methods: Biobanked samples from 146 participants (55 vaccinated vs. 91 unvaccinated) were analysed longitudinally for inflammation markers, humoral responses, tissue viral loads, and plasma viral antigens on days 1, 3, and 8. High-dimensional analyses, including RNA sequencing and flow cytometry, were performed on available samples. Mediation analyses were used to assess relationships between SAEs, baseline-adjusted biomarkers, and treatment-vaccination status. Findings: Vaccinated participants were older, more frequently hospitalized, had more comorbidities, and exhibited higher nasopharyngeal viral loads. Baricitinib treatment did not affect antibody responses or viral clearance, but reduced markers of T-cell and monocyte activation compared to placebo (sCD25, sCD14, sCD163, sTIM-3). Age, baseline levels of plasma viral antigen, and several inflammatory markers, as well as IL-2, IL-6, Neopterin, CXCL16, sCD14, and suPAR on day 8 were associated with the occurrence of SAEs. However, mediation analyses of markers linked to SAEs, baricitinib treatment, or vaccination status did not reveal statistically significant interactions between vaccination status and SAEs. Interpretation: This sub-study did not identify any virus- or host-related biomarkers significantly associated with the interaction between SARS-CoV-2 vaccination status and the safety of baricitinib. However, caution should be exercised due to the moderate sample size. Funding: EU Horizon 2020 (grant number 101015736).
