Abstract

Background

A 10-day dexamethasone regimen has emerged as the internationally adopted standard-of-care for severe COVID-19 patients. However, the immune response triggered by SARS-CoV-2 infection remains a complex and dynamic phenomenon, leading to various immune profiles and trajectories. The immune status of severe COVID-19 patients following complete dexamethasone treatment has yet to be thoroughly documented.

Results

To analyze monocyte HLA-DR expression (mHLA-DR) and CD4 + T lymphocyte count (CD4) in critically ill COVID-19 patients after a dexamethasone course and evaluate their association with 28-day ICU mortality, adult COVID-19 patients (n = 176) with an ICU length of stay of at least 10 days and under dexamethasone treatment were included. Associations between each biomarker value (or in combination) measured at day 10 after ICU admission and 28-day mortality in ICU were evaluated. At day 10, the majority of patients presented decreased values of both parameters. A significant association between low mHLA-DR and 28-day mortality was observed. This association remained significant in a multivariate analysis including age, comorbidities or pre-existing immunosuppression (adjusted Hazard ratio (aHR) = 2.86 [1.30–6.32], p = 0.009). Similar results were obtained with decreased CD4 + T cell count (aHR = 2.10 [1.09–4.04], p = 0.027). When combining these biomarkers, patients with both decreased mHLA-DR and low CD4 presented with an independent and significant elevated risk of 28-day mortality (i.e., 60%, aHR = 4.83 (1.72–13.57), p = 0.001).

Conclusions

By using standardized immunomonitoring tools available in clinical practice, it is possible to identify a subgroup of patients at high risk of mortality at the end of a 10-day dexamethasone treatment. This emphasizes the significance of integrating immune monitoring into the surveillance of intensive care patients in order to guide further immumodulation approaches.

Details

Title
Monitoring monocyte HLA-DR expression and CD4 + T lymphocyte count in dexamethasone-treated severe COVID-19 patients
Author
Monneret, Guillaume 1   VIAFID ORCID Logo  ; Voirin, Nicolas 2 ; Richard, Jean-Christophe 3 ; Cour, Martin 4 ; Rimmelé, Thomas 5 ; Garnier, Lorna 6 ; Yonis, Hodane 3 ; Coudereau, Remy 1 ; Gossez, Morgane 7 ; Malcus, Christophe 1 ; Wallet, Florent 8 ; Delignette, Marie-Charlotte 9 ; Dailler, Frederic 10 ; Buisson, Marielle 11 ; Argaud, Laurent 3 ; Lukaszewicz, Anne-Claire 12 ; Venet, Fabienne 7 ; Pescarmona, Remi; Lombard, Christine; Perret, Magali; Villard, Marine; Groussaud, Marie; Itah, Laetitia; Boussaha, Inesse; Poitevin-Later, Françoise; Simon, Marie; Dargent, Auguste; Bertrand, Pierre-Jean; Stevic, Neven; Provent, Marion; Bignet, Laurie; Cerro, Valérie; Bitker, Laurent; Mezidi, Mehdi; Baboi, Loredana

1  Hospices Civils de Lyon, Edouard Herriot Hospital, Immunology Laboratory, Lyon, France (GRID:grid.412180.e) (ISNI:0000 0001 2198 4166); (Université Claude Bernard Lyon 1 - Hospices Civils de Lyon - bioMérieux), EA 7426 “Pathophysiology of Injury-Induced Immunosuppression”, Joint Research Unit HCL-bioMérieux, Lyon, France (GRID:grid.413852.9) (ISNI:0000 0001 2163 3825) 
2  Epimod, Dompierre Sur Veyle, France (GRID:grid.413852.9) 
3  Hospices Civils de Lyon, Croix-Rousse University Hospital, Medical Intensive Care Department, Lyon, France (GRID:grid.413852.9) (ISNI:0000 0001 2163 3825) 
4  Hospices Civils de Lyon, Edouard Herriot Hospital, Medical Intensive Care Department, Lyon, France (GRID:grid.412180.e) (ISNI:0000 0001 2198 4166) 
5  (Université Claude Bernard Lyon 1 - Hospices Civils de Lyon - bioMérieux), EA 7426 “Pathophysiology of Injury-Induced Immunosuppression”, Joint Research Unit HCL-bioMérieux, Lyon, France (GRID:grid.413852.9) (ISNI:0000 0001 2163 3825); Hospices Civils de Lyon, Edouard Herriot Hospital, Anesthesia and Critical Care Medicine Department, Lyon, France (GRID:grid.412180.e) (ISNI:0000 0001 2198 4166) 
6  Hospices Civils de Lyon, Lyon-Sud University Hospital, Immunology Laboratory, Pierre Bénite, France (GRID:grid.413852.9) (ISNI:0000 0001 2163 3825) 
7  Hospices Civils de Lyon, Edouard Herriot Hospital, Immunology Laboratory, Lyon, France (GRID:grid.412180.e) (ISNI:0000 0001 2198 4166); Ecole Normale Supérieure de Lyon, Université Claude, Centre International de Recherche en Infectiologie (CIRI), Inserm U1111, CNRS, UMR5308, Lyon, France (GRID:grid.15140.31) (ISNI:0000 0001 2175 9188) 
8  Hospices Civils de Lyon, Lyon-Sud University Hospital, Intensive Care Department, Pierre-Bénite, France (GRID:grid.413852.9) (ISNI:0000 0001 2163 3825) 
9  Hospices Civils de Lyon, Croix-Rousse University Hospital, Anesthesia and Critical Care Medicine Department, Lyon, France (GRID:grid.413852.9) (ISNI:0000 0001 2163 3825) 
10  Hospices Civils de Lyon, Pierre Wertheimer Hospital, Neurological Anesthesiology and Intensive Care Department, Lyon, France (GRID:grid.413852.9) (ISNI:0000 0001 2163 3825) 
11  Hospices Civils de Lyon, Centre d’Investigation Clinique de Lyon (CIC 1407 Inserm), Lyon, France (GRID:grid.413852.9) (ISNI:0000 0001 2163 3825) 
12  (Université Claude Bernard Lyon 1 - Hospices Civils de Lyon - bioMérieux), EA 7426 “Pathophysiology of Injury-Induced Immunosuppression”, Joint Research Unit HCL-bioMérieux, Lyon, France (GRID:grid.413852.9) (ISNI:0000 0001 2163 3825); Hospices Civils de Lyon, Edouard Herriot Hospital, Medical Intensive Care Department, Lyon, France (GRID:grid.412180.e) (ISNI:0000 0001 2198 4166) 
Pages
76
Publication year
2024
Publication date
Dec 2024
Publisher
Springer Nature B.V.
e-ISSN
21105820
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1186/s13613-024-01310-5
ProQuest document ID
3056256391
Copyright
© The Author(s) 2024. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.