Real-world longitudinal validation of high-income-country-derived sepsis endotypes in sub-Saharan Africa: a nested prospective multicenter study
Authors' conclusion
Sepsis endotypes identified in HICs exhibit similar biological and clinical characteristics in sub-Saharan Africa. Longitudinal analysis revealed that the proportion of adverse endotype signatures decrease over time.
Study context
- Population
- Adults hospitalised with clinically suspected infection in Malawi and Uganda (African Research Collaboration on Sepsis (ARCS) Cohort and Cardiovascular Responses In Septic Patients (CRISP) studies); sepsis = modified Sequential Organ Failure Assessment (mSOFA) ≥ 2278 samples
- Participants
- 158 adults
- Exposure
- HIC-derived sepsis mRNA endotypes (Sepsis Response Signature (SRS), MARS, Inflammopathic-Coagulopathic-Adaptive): each adverse signature vs the others pooled
- Outcome
- 30-day mortality by endotype
- Follow-up
- 30 days
Methodological detailslongitudinal sampling (days 0, 2/3 and 28)
- Longitudinal sampling (days 0, 2/3 and 28)
Main finding
As reported in the abstract
30-day mortality
Hazard ratio (95% CI)
SRS1 vs Others pooled
2.81(1.17–6.77)
Mars2 vs Others pooled
3.11(1.24–7.79)
Inflammopathic vs Others pooled
2.66(1.09–6.52)
Observational data: associations, not effects.
Further findings
Signature frequency over all timepoints
- SRS2
- 63.3%
- Mars3
- 31.2%
- Coagulopathic
- 41.7%
- SRS3
- 16.5%
- Mars4
- 12.7%
- Adaptive
- 27.7%
Cohort characteristics
- HIV seropositivity
- 51.3%
- Sepsis prevalence (mSOFA ≥ 2)
- 56.3%
Longitudinal change in signatures · Follow-up samples
- Proportion of adverse signatures decreased, less severe ones increased
- Despite possible survivorship bias
Correlation between endotype systems
- Signatures of similar severity strongly correlated (Cramer’s V > 0.4)
- P < 0.001
Association with HIV status
- Signature classification not associated with HIV status
Parts of this Brief are withheld: the automatic checks could not confirm them against the abstract.
Original publication
Real-world longitudinal validation of high-income-country-derived sepsis endotypes in sub-Saharan Africa: a nested prospective multicenter study. Crit Care. Published 25 February 2026. doi:10.
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