Fig. 6: Association of lymphoid immune dysregulation with treatment.

a, Evaluation of 28-d mortality rate on the y axis stratified by high and low lymphoid dysregulation scores (defined by z-score ≥ 1.65) and anakinra (gold) versus placebo (gray) treatment in patients with COVID-19 in the SAVE-MORE clinical trial, using two-sided Fisher’s exact test unadjusted for multiple comparisons. Dysregulation was defined based on median scores across all noncritically ill, infected patients in SUBSPACE. Lymphoid dysregulation is associated with a disproportionate benefit from anakinra therapy relative to patients with low (balanced) lymphoid responses. b, Evaluation of Kaplan–Meier survival curve for 28-d survival in patients with lymphoid dysregulation stratified by anakinra (gold) and placebo (gray) in the SAVE-MORE trial. Cox’s proportional HR is adjusted for age, sex and SOFA score. c, Evaluation of 30-d mortality (y axis) in the VICTAS trial (a randomized controlled trial of vitamin C, thiamine and hydrocortisone in critically ill patients with sepsis) stratified by high and low lymphoid dysregulation score and treatment (red) versus placebo (gray). Dysregulation was defined by the median score across all infected, critically ill patients in SUBSPACE, and the significance was assessed using two-sided Fisher’s exact test unadjusted for multiple comparisons. The results indicate that lymphoid dysregulation was associated with disproportionate benefit from steroids, vitamin C and thiamine therapy. d, Evaluation of Kaplan–Meier survival curve for 30-d survival in patients with lymphoid dysregulation stratified by treatment (red) versus placebo (gray) in the VICTAS trial. Cox’s proportional HR is adjusted for age and sex. e, Evaluation of the 28-d mortality rate (y axis) in the VANISH trial (a clinical trial of hydrocortisone in patients with septic shock) stratified by high and low lymphoid dysregulation score (defined by median score) and randomized steroid treatment (red). The significance was assessed using two-sided Fisher’s exact test unadjusted for multiple comparisons. Patients with a low (balanced) lymphoid dysregulation score were disproportionately harmed by steroid therapy.