Single-cell transcriptomics reveal a hyperacute cytokine and immune checkpoint axis after cardiac arrest in patients with poor neurological outcome

Context and significance

Brain injury is the leading cause of death among patients hospitalized after out-of-hospital cardiac arrest. Although inflammation is associated with brain injury and mortality after cardiac arrest, the immune landscape after cardiac arrest is poorly understood. By examining peripheral blood at single-cell resolution, this study shows that examining the innate immune system just 6 h after cardiac arrest differentiates patients who eventually have good or poor neurological outcomes days later. Cardiac arrest triggers an early negative feedback loop in which pro- and anti-inflammatory cytokines induce immune checkpoints that limit inflammation. These findings support investigation of therapeutic approaches that augment protective immune mechanisms very early after cardiac arrest.