Longitudinal assessment of IFN-I activity and immune profile in critically ill COVID-19 patients with acute respiratory distress syndrome
Fabienne Venet,
Martin Cour,
Thomas Rimmelé,
Sebastien Viel,
Hodane Yonis,
Remy Coudereau,
Camille Amaz,
Paul Abraham,
Céline Monard,
Jean-Sebastien Casalegno,
Karen Brengel-Pesce,
Anne-Claire Lukaszewicz,
Laurent Argaud,
Guillaume Monneret,
the RICO study group
Affiliations
Fabienne Venet
Immunology Laboratory, Hôpital E. Herriot - Hospices Civils de Lyon
Martin Cour
Medical Intensive Care Department, Edouard Herriot Hospital, Hospices Civils de Lyon
Thomas Rimmelé
Joint Research Unit HCL-bioMérieux, EA 7426 “Pathophysiology of Injury-Induced Immunosuppression” (Université Claude Bernard Lyon 1 - Hospices Civils de Lyon - bioMérieux)
Sebastien Viel
Centre International de Recherche en Infectiologie (CIRI), Inserm U1111, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Université Claude
Hodane Yonis
Medical Intensive Care Department, Croix-Rousse University Hospital, Hospices Civils de Lyon
Remy Coudereau
Immunology Laboratory, Hôpital E. Herriot - Hospices Civils de Lyon
Camille Amaz
Centre d’Investigation Clinique de Lyon (CIC 1407 Inserm), Hospices Civils de Lyon
Paul Abraham
Anesthesia and Critical Care Medicine Department, Edouard Herriot Hospital, Hospices Civils de Lyon
Céline Monard
Anesthesia and Critical Care Medicine Department, Edouard Herriot Hospital, Hospices Civils de Lyon
Jean-Sebastien Casalegno
Virology Laboratory, Croix-Rousse University Hospital, Hospices Civils de Lyon
Karen Brengel-Pesce
Joint Research Unit HCL-bioMérieux, EA 7426 “Pathophysiology of Injury-Induced Immunosuppression” (Université Claude Bernard Lyon 1 - Hospices Civils de Lyon - bioMérieux)
Anne-Claire Lukaszewicz
Joint Research Unit HCL-bioMérieux, EA 7426 “Pathophysiology of Injury-Induced Immunosuppression” (Université Claude Bernard Lyon 1 - Hospices Civils de Lyon - bioMérieux)
Laurent Argaud
Medical Intensive Care Department, Edouard Herriot Hospital, Hospices Civils de Lyon
Guillaume Monneret
Immunology Laboratory, Hôpital E. Herriot - Hospices Civils de Lyon
Abstract Background Since the onset of the pandemic, only few studies focused on longitudinal immune monitoring in critically ill COVID-19 patients with acute respiratory distress syndrome (ARDS) whereas their hospital stay may last for several weeks. Consequently, the question of whether immune parameters may drive or associate with delayed unfavorable outcome in these critically ill patients remains unsolved. Methods We present a dynamic description of immuno-inflammatory derangements in 64 critically ill COVID-19 patients including plasma IFNα2 levels and IFN-stimulated genes (ISG) score measurements. Results ARDS patients presented with persistently decreased lymphocyte count and mHLA-DR expression and increased cytokine levels. Type-I IFN response was initially induced with elevation of IFNα2 levels and ISG score followed by a rapid decrease over time. Survivors and non-survivors presented with apparent common immune responses over the first 3 weeks after ICU admission mixing gradual return to normal values of cellular markers and progressive decrease of cytokines levels including IFNα2. Only plasma TNF-α presented with a slow increase over time and higher values in non-survivors compared with survivors. This paralleled with an extremely high occurrence of secondary infections in COVID-19 patients with ARDS. Conclusions Occurrence of ARDS in response to SARS-CoV2 infection appears to be strongly associated with the intensity of immune alterations upon ICU admission of COVID-19 patients. In these critically ill patients, immune profile presents with similarities with the delayed step of immunosuppression described in bacterial sepsis.
