Role of plasma and blood-cell co-metagenomic sequencing in precise diagnosis and severity evaluation of sepsis, a prospective cohort study in sepsis patients.

Summary

In 147 sepsis samples, plasma mNGS achieved 100% sensitivity for bacteria/fungi and 97% for viruses, outperforming blood-cell mNGS, while bc-mNGS aligned better with culture. Dual positivity (p-mNGS+ & bc-mNGS+) correlated with heightened immune activation signatures, worse SOFA/PCT/CRP, and lower survival. Co-mNGS was less affected by prior antibiotics than blood culture.

Key Findings

• Plasma mNGS sensitivity: 100% for bacteria/fungi and 97% for viruses; bc-mNGS: 88% and 71%, respectively
• bc-mNGS showed higher concordance with blood culture, suggesting viability inference
• Dual positivity (p-mNGS+ & bc-mNGS+) associated with higher SOFA, higher PCT/CRP, immune activation (low IFN-induced genes, high JAK-STAT), and lower survival
• Broad-spectrum antibiotics reduced culture yield more than p/bc-mNGS performance

Clinical Implications

Incorporate co-mNGS (plasma plus blood-cell) for diagnostic workups when cultures are negative or prior antibiotics were given, and consider dual-positivity as a red flag for severity and closer monitoring.

Limitations

• Moderate sample size and potential single-center bias
• Reference standards imperfect and mNGS contamination/interpretation challenges remain

Future Directions

Multicenter diagnostic-impact trials assessing time-to-appropriate therapy and outcomes, standardized reporting thresholds, and cost-effectiveness analyses for co-mNGS in sepsis pathways.