Transcriptome profile of delayed mortality in patients with invasive group A Streptococcal disease.

BACKGROUND: Our aim was to study the pathophysiological mechanisms of early (<7 days) and delayed sepsis mortality by transcriptome profiling of cases with invasive group A Streptococcal (iGAS) infections and possibly find predictors for delayed mortality. METHODS: We recruited cases with iGAS from June 2018 to June 2020. Whole blood samples were collected at the early timepoint (within two days after admission, timepoint A) and later timepoint (a week later, timepoint B) to perform transcriptome analysis. A comparison of gene expression against disease course was done using weighted genome correlation network analysis. RESULTS: We recruited 45 patients. Eight patients died within 90 days, four of whom within the first week. After RNA quality control 34 and 31 subjects at timepoints A and B remained, respectively. The gene expression profiles associated with a severe disease course differed markedly between timepoints A and B. High expression of necroptosis factors and low expression of HLA genes at timepoint B was associated with death. CONCLUSIONS: The seemingly different gene expression profile over time among patients with a severe iGAS disease may suggest distinct pathophysiological mechanisms for early and delayed sepsis mortality. However, as our sample size was small, these findings must be considered with caution and should not be interpreted as predictive.