Prognostic Evaluation of Molecular Endotypes in Sepsis: A Multicenter Cohort Study in Brazil

Sepsis heterogeneity affects the identification of high-risk patients. Outcomes in low- and middle-income countries are worse than those in developed nations. This study aimed to assess the prognostic potential of the previously described molecular endotypes, Mars1, Mars2, Mars3, and Mars4, in a Brazilian cohort with sepsis.

This prospective, multicenter, observational study identified molecular expression-based endotypes in adults from four intensive care units in Brazil. Patients on their first 24-h diagnosis of sepsis based on the Sepsis 3 criteria were included. Health care workers were included in the control group. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to quantify the transcripted levels of eight genes and determine the four endotypes. The primary endpoint was 28-day mortality with a secondary analysis of diagnostic accuracy. Statistical significance was set at P  < 0.05.

One hundred sixty-eight participants and twenty-five controls were enrolled in this study. The overall mortality rate was 44%. The Mars1 group showed a higher 28-day mortality than the non-Mars1 group. The log-rank test showed a worst survival probability in Mars1 subgroup ( P  = 0.013), and the hazard ratio was 1.78 ( P  = 0.017). Compared to control, area-under-the-curve (AUC) of ROC curves for diagnosing sepsis were: 0.69 for Mars1 (SD 0.62-0.77 / P  = 0.0016), 0.89 for Mars2 (SD 0.85-0.94 / P  < 0.0001), 0.82 for Mars3 (SD 0.75-0.88 / P  < 0.0001), and 0.71 for Mars4 (SD 0.64-0.79 / P  < 0.0006).

The Mars1 endotype detected by qRT-PCR was associated with worse sepsis survival in low-to middle-income countries. We also identified the Mars 2 endotype as a potential diagnostic marker for sepsis.