Functional immune changes are conserved in COVID-19 and trauma patients receiving intensive care.

Abstract

Critical illness, including COVID-19 and trauma, induce immune dysregulation associated with morbidity and mortality. Direct comparison is crucial to identify shared pathobiological mechanisms to guide precision therapies. This prospective cohort study undertook a comprehensive, longitudinal comparison of innate immune cell function and plasma protein expression in critically ill patients at days 1, 3, and 5 of intensive care unit admission. We enrolled 26 COVID-19 patients, 20 trauma patients, and 18 healthy controls and analysed plasma proteins and immune cell phenotypes and responses to S. aureus bioparticles. An unsupervised multi-omics factor analysis (MOFA) identified shared sources of biological variation. Here we show shared, profound immune alterations, including neutrophilia, decreased non-classical monocytes and dendritic cells (DCs), and a hyper-phagocytic and reactive oxygen species producing neutrophil state in both patient cohorts compared to healthy controls. Classical monocytes from patients were unable to upregulate CD11c, CD86, and SIRPα upon stimulation, and a phagocytosis-impaired SIRPα^-CD11b^- DC population was enriched from day 1. Innate immune activation profiles could segregate patients and were associated with subsequent impaired innate/adaptive crosstalk. This direct comparison of severe COVID-19 and trauma patients demonstrates many shared immune alterations between these distinct critical illnesses, which may benefit from similar targeted immunomodulation.