The injured monocyte: The link to chronic critical illness and mortality following injury

Abstract

Background This study aimed to understand the altered innate immune response in severely injured patients leading to chronic critical illness (CCI). Specifically, it focused on characterizing the monocyte populations and their correlation with CCI development and long-term complications. Methods Over a 3-year period, we monitored patients with severe injuries for up to 1-year post-injury. CCI was defined as an ICU stay exceeding 14 days with persistent organ failure. Blood samples were collected on days 1 and 5 for monocyte phenotypic expression analysis using cytometry by time flight. The monocyte subpopulations studied were classical (CL), intermediate (INT), and non-classical (NC), along with cell surface receptor expression and activation. Results Out of 80 enrolled patients, 26 (32.5%) developed CCI. Patients with CCI had more severe injuries (injury severity score 32.4 + 5.2 vs. 29.6 + 4.1, p = 0.01) and received a higher number of red blood cells (8.9 + 4.1 vs. 4.7 + 3.8 units, p < 0.01) compared to those without CCI. In patients with CCI, the NC monocytes were significantly reduced by over 2-fold early, and significantly increased later, compared to those without CCI. Moreover, significant changes in intracellular cytokine expression and cell receptors were observed within each monocyte subpopulation in patients with CCI, indicating an increased pro-inflammatory phenotype but decreased phagocytic capacity and antigen presentation. The development of CCI and the presence of this unique monocyte phenotype were associated with a significantly increased risk of infection, discharge to a long-term care facility, and 1-year mortality of 27%. Conclusions Development of CCI following severe injury is associated with significant long-term morbidity and unacceptably high mortality. The altered NC phenotype with reduced phagocytic capacity and antigen presentation in patients developing CCI after severe injury is appears partially responsible. Early identification of this unique phenotype may help predict and treat patients at risk for CCI, leading to improved outcomes. Level of Evidence Level III, Prognostic/Epidemiological