Mass cytometry and artificial intelligence define CD169 as a specific marker of SARS-CoV2-induced acute respiratory distress syndrome

Acute respiratory distress syndrome (ARDS) is the main complication of COVID-19, requiring admission to Intensive Care Unit (ICU). Despite recent 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 question, we built 3 cohorts of patients categorized in COVID-19 neg ARDS pos , COVID-19 pos ARDS pos , and COVID-19 pos ARDS neg , 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 CD169 pos monocytes, plasmablasts, and Th1 cells was specifically found in COVID-19 pos ARDS pos , unlike COVID-19 neg ARDS pos patients. Moreover, this signature was shared by COVID-19 pos ARDS neg patients, suggesting severe COVID-19 patients, whatever they experienced or not ARDS, displayed similar immune dysfunctions. We also showed an increase in CD14 pos HLA-DR low and CD14 low CD16 pos 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. One Sentence Summary COVID-19-associated ARDS is biologically distinct from other causes of ARDS.