Comparative immune profiling of acute respiratory distress syndrome patients with or without SARS-CoV-2 infection

Highlights

• Machine-learning analysis of CyTOF data segregates COVID-19⁺ and COVID-19⁻ ARDS

• CD169⁺S100A9⁺ monocytes differentiate COVID-19 ARDS from other ARDS

• Monocyte compartment alterations correlate with other immune subset modifications

• CD14⁺HLA-DR^low and CD14^loCD16⁺ monocytes are markers of adverse COVID-19 evolution

Summary

Acute respiratory distress syndrome (ARDS) is the main complication of coronavirus disease 2019 (COVID-19), requiring admission to the intensive care unit (ICU). Despite extensive immune profiling of COVID-19 patients, to what extent COVID-19-associated ARDS differs from other causes of ARDS remains unknown. To address this question, here, we build 3 cohorts of patients categorized in COVID-19⁻ARDS⁺, COVID-19⁺ARDS⁺, and COVID-19⁺ARDS⁻, and compare, by high-dimensional mass cytometry, their immune landscape. A cell signature associating S100A9/calprotectin-producing CD169⁺ monocytes, plasmablasts, and Th1 cells is found in COVID-19⁺ARDS⁺, unlike COVID-19⁻ARDS⁺ patients. Moreover, this signature is essentially shared with COVID-19⁺ARDS⁻ patients, suggesting that severe COVID-19 patients, whether or not they experience ARDS, display similar immune profiles. We show an increase in CD14⁺HLA-DR^low and CD14^lowCD16⁺ monocytes correlating to the occurrence of adverse events during the ICU stay. We demonstrate that COVID-19-associated ARDS displays a specific immune profile and may benefit from personalized therapy in addition to standard ARDS management.