Erschienen in:
02.01.2021 | COVID-19 | Original Article
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SARS-CoV-2-Induced ARDS Associates with MDSC Expansion, Lymphocyte Dysfunction, and Arginine Shortage
verfasst von:
Florian Reizine, Mathieu Lesouhaitier, Murielle Gregoire, Kieran Pinceaux, Arnaud Gacouin, Adel Maamar, Benoit Painvin, Christophe Camus, Yves Le Tulzo, Pierre Tattevin, Matthieu Revest, Audrey Le Bot, Alice Ballerie, Berengère Cador-Rousseau, Mathieu Lederlin, Thomas Lebouvier, Yoann Launey, Maelle Latour, Clotilde Verdy, Delphine Rossille, Simon Le Gallou, Joelle Dulong, Caroline Moreau, Claude Bendavid, Mikael Roussel, Michel Cogne, Karin Tarte, Jean-Marc Tadié
Erschienen in:
Journal of Clinical Immunology
|
Ausgabe 3/2021
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Abstract
Purpose
The SARS-CoV-2 infection can lead to a severe acute respiratory distress syndrome (ARDS) with prolonged mechanical ventilation and high mortality rate. Interestingly, COVID-19-associated ARDS share biological and clinical features with sepsis-associated immunosuppression since lymphopenia and acquired infections associated with late mortality are frequently encountered. Mechanisms responsible for COVID-19-associated lymphopenia need to be explored since they could be responsible for delayed virus clearance and increased mortality rate among intensive care unit (ICU) patients.
Methods
A series of 26 clinically annotated COVID-19 patients were analyzed by thorough phenotypic and functional investigations at days 0, 4, and 7 after ICU admission.
Results
We revealed that, in the absence of any difference in demographic parameters nor medical history between the two groups, ARDS patients presented with an increased number of myeloid-derived suppressor cells (MDSC) and a decreased number of CD8pos effector memory cell compared to patients hospitalized for COVID-19 moderate pneumonia. Interestingly, COVID-19-related MDSC expansion was directly correlated to lymphopenia and enhanced arginase activity. Lastly, T cell proliferative capacity in vitro was significantly reduced among COVID-19 patients and could be restored through arginine supplementation.
Conclusions
The present study reports a critical role for MDSC in COVID-19-associated ARDS. Our findings open the possibility of arginine supplementation as an adjuvant therapy for these ICU patients, aiming to reduce immunosuppression and help virus clearance, thereby decreasing the duration of mechanical ventilation, nosocomial infection acquisition, and mortality.