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 iGAS cases from June 2018 to July 2020. Whole blood samples for transcriptome analysis and standard clinical laboratory tests were collected at the early timepoint (within two days after admission, timepoint A) and later timepoint (a week later, timepoint B). Gene expression was compared against disease course using weighted genome correlation network analysis.
Results
Forty-five patients were enrolled. After disqualifying degraded or impure RNAs we had 34 and 31 subjects at timepoints A and B, 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 markedly different gene expression profile over time among patients with a severe iGAS disease may suggest distinct pathophysiological mechanisms for early and delayed sepsis mortality. The gene expression profile appears to predict delayed death better than CRP level.