Work

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

Year: 2026

Type: article

Abstract: Critical illness states including COVID-19 and trauma induce profound immune dysregulation associated with morbidity and mortality. Direct comparison of these illnesses is crucial to identify shared pathobiological mechanisms that could 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, 20 trauma patients, and 18 healthy controls and analysed plasma proteins and immune cell phenotypes and responses to S. aureus coated bioparticles. An unsupervised multi-omics factor analysis (MOFA) identified shared sources of biological variation. Both patient cohorts 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 versus controls. Classical monocytes from patients were unable to upregulate CD11c, CD86, and SIRPα upon stimulation, and a novel 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 first direct comparison of viral sepsis (severe COVID-19) and trauma patients demonstrates many shared immune alterations between these distinct critical illnesses, which may benefit from targeted immunomodulation irrespective of clinical diagnosis.

Source: Nature Communications

DOI: 10.1038/s41467-026-75748-5