VPB0109 - NLRP3 inflammasome activation and immunothrombosis in COVID-19.

Sunday, July 10, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: Virtual

Presenting Author(s)

Audrey Cambon, MD

Aix-Marseille Univ, INSERM, INRAE, C2VN, Department of Internal Medicine, HIA SAINTE ANNE, Toulon, France
Toulon, Provence-Alpes-Cote d'Azur, France

Co-Author(s)

CG

Christophe Guervilly

MD
Aix-Marseille Univ, APHM, Medical Intensive Care Unit, North Hospital - Center for Studies and Research on Health Services and Quality of Life, EA3279 Research Unit, Marseille, France
Marseille, Provence-Alpes-Cote d'Azur, France
CD

Clémence Delteil

MD
Aix-Marseille Univ, APHM, Institute of Legal Medicine, University Hospital La Timone, Marseille, France
Marseille, Rhone-Alpes, France
RB

Richard Bachelier

Research scientist
Aix-Marseille Univ, INSERM, INRAE, C2VN, Marseille, France
Marseille, Provence-Alpes-Cote d'Azur, France
NP

Nicola Potere

MD
Department of Innovative Technologies in Medicine and Dentistry, "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy.
Chieti, Abruzzi, Italy
EA

Evelyne Abdili

Engineer
Biogenopole, APHM
Marseille, Provence-Alpes-Cote d'Azur, France
JF

Jean-Marie Forel

MD
Aix-Marseille Univ, APHM, Medical Intensive Care Unit, North Hospital -Center for Studies and Research on Health Services and Quality of Life, EA3279 Research Unit, Marseille, France
Marseille, Provence-Alpes-Cote d'Azur, France
Françoise Dignat-George

Professor, Director at C2VN
Aix-Marseille University
Marseille, Provence-Alpes-Cote d'Azur, France
SH

Sami Hraiech

MD-Assistant Professor
Aix-Marseille Univ, APHM, Medical Intensive Care Unit, North Hospital - Center for Studies and Research on Health Services and Quality of Life, EA3279 Research Unit, Marseille, France
Marseille, Provence-Alpes-Cote d'Azur, France
RL

Romaric Lacroix, PharmD PhD

PharmD. PhD. - Professor of Immunology and Hematology
Aix-Marseille Univ, APHM, INSERM, INRAE, C2VN, Laboratory of Hematology and Vascular Biology, University Hospital La Conception, Marseille, France
Marseille, Provence-Alpes-Cote d'Azur, France
LP

Laurent Papazian

MD - Professor of Intensive Care Medicine
Aix-Marseille Univ, APHM, Medical Intensive Care Unit, North Hospital-Center for Studies and Research on Health Services and Quality of Life, EA3279 Research Unit, Marseille , France
Marseille, Provence-Alpes-Cote d'Azur, France
GK

Gilles Kaplanski

MD, PhD., Pr. of Immunology, Director of the Department of Internal Medicine and Clinical Immunology
Aix-Marseille Univ, APHM, INSERM, INRAE, C2VN, Department of Internal Medicine and Clinical Immunology, University Hospital La Conception, Marseille, France.
Marseille, Provence-Alpes-Cote d'Azur, France

Background: Immunothrombosis resulting from the crosstalk between activation of the innate immune system, coagulation and inflammation is thought to play an important role in severe COVID-19 pathogenesis. Activation of the NLRP3 inflammasome inducing caspase-1 activation and IL-1b processing, constitutes an important step of the inflammatory cascade and may be central in COVID-19 hyperinflammation and immunothrombosis.

Aims: We evaluated NLRP3 inflammasome activation in lung tissues and broncho-alveolar lavage fluid (BALF) during severe COVID-19 and studied its association with lung vasculopathy.

Methods: Postmortem lung biopsies from 40 patients deceased of acute respiratory distress syndrome (ARDS) complicating SARS-Cov 2 infection were collected. Histological analysis and activated caspase-1 expression by immunohistochemistry, were performed. In another cohort of 19 COVID-19 patients with ARDS, soluble NLRP3, activated caspase-1 and inflammatory cytokines were measured by ELISA in BALF collected within 48 hours of admission and compared with BALF of patients with lung cancer.

Results: Among lung biopsies, 33 presented evidence of vasculopathy consisting in thrombo-embolism (n=9), thrombotic microangiopathy (n=9), endothelitis (n=15), intima fibrosis (n=19) and intima edema (n=11). Among them, 16 expressed activated caspase-1, which appeared specifically located into endo-alveolar macrophages. Higher concentrations of soluble NLRP3, activated caspase-1, IL-1B, and IL-1Ra were observed in BALF from patients with COVID-19 ARDS compared to controls (p < 0.0001).

Conclusion(s): We observed NLRP3 inflammasome activation in endo-alveolar macrophages of COVID-19 patients with ARDS and high inflammatory cytokine secretion associated with lung vasculopathy. These observations suggest that NRLP3 inflammasome may constitute a therapeutic target in severe COVID-19.