PB0602 - Plasma NET markers kinetics in COVID-19 patients receiving immunomodulatory treatments

Monday, June 26, 2023

18:30 – 19:30 ET

Room: Exhibition

Presenting Author(s)

Geoffrey Garcia, PharmD (he/him/his)

PhD Student
University of Bordeaux, INSERM UMR 1034, Biology of cardiovascular diseases, Pessac, France
Bordeaux, Aquitaine, France

Co-Author(s)

AD

Antoine Dewitte

MD
CHU Bordeaux, Department of Anesthesia and Critical Care, F-33600 Pessac, France
Bordeaux, Aquitaine, France
SL

Sylvie Labrouche-Colomer

Assistant Professor
University of Bordeaux, INSERM UMR 1034, Biology of cardiovascular diseases, Pessac, France
Bordeaux, Aquitaine, France
CM

Christine Mouton

PharmD
Laboratoire Hématologie, Hôpital Haut-Lévêque, CHU Bordeaux, France
Bordeaux, Aquitaine, France
CD

Céline Delassasseigne

PharmD
Laboratoire Hématologie, Hôpital Haut-Lévêque, CHU Bordeaux, France
Bordeaux, Aquitaine, France
FM

Fanny Ménard

Haematologist
CH Bayonne, Laboratory of Hematology, Bayonne, France
Pau, Aquitaine, France
CV

Camille Vinclair

ICU physician
CH Bayonne, Intensive Care Unit, Bayonne, France
Pau, Aquitaine, France
EB

Erwan Begot

ICU physician
CH Bayonne, Intensive Care Unit, Bayonne, France
Pau, Aquitaine, France
LP

Laurent Petit

ICU physician
CHU Bordeaux, Department of Anesthesia and Critical Care, F-33000 Bordeaux, France
Bordeaux, Aquitaine, France
CC

Cédric Carrié

ICU physician
CHU Bordeaux, Department of Anesthesia and Critical Care, F-33000 Bordeaux, France
Bordeaux, Aquitaine, France
DM

Denis Malvy

Professor
INSERM UMR 1219, Bordeaux Population Health Research Centre, Bordeaux, France.
Bordeaux, Aquitaine, France
AD

Alexandre Duvignaud

Assistant Professor
INSERM UMR 1219, Bordeaux Population Health Research Centre, Bordeaux, France
Bordeaux, Aquitaine, France
CJ

Chloé James

Professor
University of Bordeaux, INSERM UMR 1034, Biology of cardiovascular diseases, Pessac, France
Pessac, Aquitaine, France
RP

Renaud Prével

M.D.
Univ Bordeaux, Centre de Recherche Cardio-Thoracique de Bordeaux, Inserm UMR 1045, F-33000 Bordeaux, France
Bordeaux, Aquitaine, France

Background: In COVID-19, dexamethasone (DXM) and tocilizumab are used to alleviate inflammation in patients requiring oxygen support. Increased immunothrombosis, and NETosis in particular, is exacerbated in severe COVID-19 patients. Whether the use of immunomodulatory drugs has any impact on NET kinetics is currently unknown. Whether mild patients may receive a benefit with the use of immunomodulatory drugs is being investigated in the COVERAGE trial (NCT04356495).

Aims: We aimed to characterize the kinetics of plasma NET markers in COVID-19 patients receiving immunomodulatory treatments.

Methods: one hundred and sixty-six early (≤ 7 days) COVID-19 outpatients were randomly allocated to placebo group (79 i.e. 48%), inhaled ciclesonide (48 i.e. 29%) or inhaled IFN-β-1b (39 i.e. 23%). Fifty-nine critically ill patients were included: 8 received placebo (14%), 42 (71%) DXM (6mg i.v. for ten days) and nine (15%) DXM + tocilizumab (8mg/kg I.v.). We quantified NET markers (MPO-DNA, H3Cit, H3cit-DNA) in plasma at inclusion, Day 3 and Day 7 for critically ill patients and at inclusion and Day 7 for outpatients.

Results: Inhaled IFN-β-1b, but not inhaled ciclesonide nor placebo, was linked to a decrease in plasma H3Cit levels (p: 0.02). DXM alone was not linked to a decrease in plasma NET markers levels but the association of DXM + tocilizumab was associated with decreased MPO-DNA levels (p: 0.03).

Conclusion(s): Inhaled IFN-β-1b treatment is associated with a decrease in plasma H3Cit levels in early ambulatory mild COVID-19 patients. DXM + tocilizumab, but not DXM alone, is associated with a decrease in plasma MPO-DNA levels in critically ill COVID-19 patients. NETosis appears to be a relevant adjunctive therapeutic target in COVID-19 patients but better characterization of DNase activity defect in patients and animal models are urgently warranted.