Longitudinal assessment of IFN-I activity and immune profile in critically ill COVID-19 patients with acute respiratory distress syndrome.


Journal

Critical care (London, England)
ISSN: 1466-609X
Titre abrégé: Crit Care
Pays: England
ID NLM: 9801902

Informations de publication

Date de publication:
12 04 2021
Historique:
received: 27 01 2021
accepted: 30 03 2021
entrez: 13 4 2021
pubmed: 14 4 2021
medline: 20 4 2021
Statut: epublish

Résumé

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. 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. 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. 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.

Sections du résumé

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.

Identifiants

pubmed: 33845874
doi: 10.1186/s13054-021-03558-w
pii: 10.1186/s13054-021-03558-w
pmc: PMC8040759
doi:

Substances chimiques

Biomarkers 0
IFNA2 protein, human 0
Interferon-alpha 0

Types de publication

Clinical Trial Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

140

Investigateurs

Remi Pescarmona (R)
Lorna Garnier (L)
Christine Lombard (C)
Magali Perret (M)
Marine Villard (M)
Valérie Cheynet (V)
Filippo Conti (F)
Marie Groussaud (M)
Marielle Buisson (M)
Laetitia Itah (L)
Inesse Boussaha (I)
Françoise Poitevin-Later (F)
Christophe Malcus (C)
Morgane Gossez (M)
Florent Wallet (F)
Marie-Charlotte Delignette (MC)
Frederic Dailler (F)
Marie Simon (M)
Auguste Dargent (A)
Pierre-Jean Bertrand (PJ)
Neven Stevic (N)
Marion Provent (M)
Laurie Bignet (L)
Valérie Cerro (V)
Jean-Christophe Richard (JC)
Laurent Bitker (L)
Mehdi Mezidi (M)
Loredana Baboi (L)

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Auteurs

Fabienne Venet (F)

Immunology Laboratory, Hôpital E. Herriot - Hospices Civils de Lyon, 5 place d'Arsonval, 69437, Lyon Cedex 03, France. fabienne.venet@chu-lyon.fr.
Joint Research Unit HCL-bioMérieux, EA 7426 "Pathophysiology of Injury-Induced Immunosuppression" (Université Claude Bernard Lyon 1 - Hospices Civils de Lyon - bioMérieux), 69003, Lyon, France. fabienne.venet@chu-lyon.fr.
Centre International de Recherche en Infectiologie (CIRI), Inserm U1111, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Université Claude, Bernard-Lyon 1, Lyon, France. fabienne.venet@chu-lyon.fr.

Martin Cour (M)

Medical Intensive Care Department, Edouard Herriot Hospital, Hospices Civils de Lyon, 69437, Lyon, France.

Thomas Rimmelé (T)

Joint Research Unit HCL-bioMérieux, EA 7426 "Pathophysiology of Injury-Induced Immunosuppression" (Université Claude Bernard Lyon 1 - Hospices Civils de Lyon - bioMérieux), 69003, Lyon, France.
Anesthesia and Critical Care Medicine Department, Edouard Herriot Hospital, Hospices Civils de Lyon, 69437, Lyon, France.

Sebastien Viel (S)

Centre International de Recherche en Infectiologie (CIRI), Inserm U1111, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Université Claude, Bernard-Lyon 1, Lyon, France.
Immunology Laboratory, Lyon-Sud University Hospital, Hospices Civils de Lyon, 69495, Pierre-Bénite, France.

Hodane Yonis (H)

Medical Intensive Care Department, Croix-Rousse University Hospital, Hospices Civils de Lyon, 69004, Lyon, France.

Remy Coudereau (R)

Immunology Laboratory, Hôpital E. Herriot - Hospices Civils de Lyon, 5 place d'Arsonval, 69437, Lyon Cedex 03, France.
Joint Research Unit HCL-bioMérieux, EA 7426 "Pathophysiology of Injury-Induced Immunosuppression" (Université Claude Bernard Lyon 1 - Hospices Civils de Lyon - bioMérieux), 69003, Lyon, France.

Camille Amaz (C)

Centre d'Investigation Clinique de Lyon (CIC 1407 Inserm), Hospices Civils de Lyon, 69677, Lyon, France.

Paul Abraham (P)

Anesthesia and Critical Care Medicine Department, Edouard Herriot Hospital, Hospices Civils de Lyon, 69437, Lyon, France.

Céline Monard (C)

Anesthesia and Critical Care Medicine Department, Edouard Herriot Hospital, Hospices Civils de Lyon, 69437, Lyon, France.

Jean-Sebastien Casalegno (JS)

Virology Laboratory, Croix-Rousse University Hospital, Hospices Civils de Lyon, 69004, Lyon, France.

Karen Brengel-Pesce (K)

Joint Research Unit HCL-bioMérieux, EA 7426 "Pathophysiology of Injury-Induced Immunosuppression" (Université Claude Bernard Lyon 1 - Hospices Civils de Lyon - bioMérieux), 69003, Lyon, France.

Anne-Claire Lukaszewicz (AC)

Joint Research Unit HCL-bioMérieux, EA 7426 "Pathophysiology of Injury-Induced Immunosuppression" (Université Claude Bernard Lyon 1 - Hospices Civils de Lyon - bioMérieux), 69003, Lyon, France.
Anesthesia and Critical Care Medicine Department, Edouard Herriot Hospital, Hospices Civils de Lyon, 69437, Lyon, France.

Laurent Argaud (L)

Medical Intensive Care Department, Edouard Herriot Hospital, Hospices Civils de Lyon, 69437, Lyon, France.

Guillaume Monneret (G)

Immunology Laboratory, Hôpital E. Herriot - Hospices Civils de Lyon, 5 place d'Arsonval, 69437, Lyon Cedex 03, France.
Joint Research Unit HCL-bioMérieux, EA 7426 "Pathophysiology of Injury-Induced Immunosuppression" (Université Claude Bernard Lyon 1 - Hospices Civils de Lyon - bioMérieux), 69003, Lyon, France.

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