Mass Cytometry and Artificial Intelligence Define CD169 as a Marker of SARS-CoV2-Induced Acute Respiratory Distress Syndrome

Abstract

Acute respiratory distress syndrome (ARDS) is the main complication of COVID-19, requiring admission to Intensive Care Unit (ICU). Despite extensive immune profiling of COVID-19 patients, to what extent COVID-19-associated ARDS specifically differs from other causes of ARDS remains unknown. To address this crucial question, we built 3 cohorts of patients categorized in COVID-19neg ARDSpos, COVID-19pos ARDSpos, and COVID-19pos ARDSneg, and compared their immune landscape analyzed by high-dimensional mass cytometry on peripheral blood followed by artificial intelligence analysis. A cell signature associating S100A9/calprotectin-producing CD169pos monocytes, plasmablasts, and Th1 cells was specifically found in COVID-19pos ARDSpos, unlike COVID-19neg ARDSpos patients. Moreover, this signature was essentially shared with COVID-19pos ARDSneg patients, suggesting that severe COVID-19 patients, whatever they experienced or not ARDS, display similar immune profiles. We also showed an increase in CD14pos HLA-DRlow and CD14low CD16pos monocytes correlated to the occurrence of adverse events during ICU stay. Our study demonstrates that COVID-19-associated ARDS display a specific immune profile, and might benefit from personalized therapy in addition to standard ARDS management.Funding: This work was supported by the University hospital of Rennes, CFTR² (COVID-19 Fast Track Recherche Rennes) grant (to F.R.)and by the Fondation pour la Recherche Médicale (FRM) and the Agence Nationale de la Recherche (ANR), Flash Covid-19 joint grant (HARMONICOV to M.Cog.)Conflict of Interest: J.Fer., F.R., S.L.G., J.D., M.Le., M.G., N.B., C.V., M.La., I.B., M.Cor., S.L., J.Feu., M. Cog. declare no competing interest. M.R., S.C., V.K.T., J.M.T., and K.T. are the inventors of a patent EP 20305642.9 “A method for early detection of propensity to severe clinical manifestations Methods” submitted June 11th 2020 under University hospital of Rennes and Scailyte AG names.Ethical Approval: The study design was approved by our ethic committee (CHU Rennes, n°35RC20_9795_HARMONICOV, ClinicalTrials.gov Identifier: NCT04373200) and informed consent was obtained from patients in accordance with the Declaration of Helsinki.