Background: Postoperative delirium (POD) is known to involve systemic inflammatory responses, but the characteristics of the immune cell types involved in these responses are unclear. 

Methods: In this prospective study, we compared relative abundances and transcriptomes of circulating immune cells between patients who experienced POD (n = 11) or not (n = 109) within 7 days after elective cardiac surgery with cardiopulmonary bypass. Blood was sampled before and at 24 h after surgery; features of immune cells were profiled using multi-channel spectral flow cytometry, 10× single-cell RNA sequencing, and measurement of plasma levels of cytokines. 

Results: Patients with POD were older and with higher incidence of congestive heart failure than patients without POD, and these risk factors in turn positively correlated with preoperative proportion of CD40+/HLA-DR+ monocytes and CD69+CD8+ T cells. In addition, preoperative activation of antigen presentation in monocytes and chemotaxis in CD8+ T cells, as well as elevated plasma levels of chemokines CCL3 and CXCL8, were detected in patients with POD. After cardiac surgery, activation of antigen presentation and chemotaxis were also found in patients with POD. 

Conclusions: This study described the perioperative landscape of immune cells in POD and found possible links between preoperative immune dysfunction and risk factors, which may guide future research to explore how the immune system contributes to POD and to design preventive strategies.