Community-Acquired Pneumonia: Disease Course Prediction With a 5-Gene Signature

Area of Science:

• Genomics
• Infectious Diseases
• Critical Care Medicine

Background:

• Community-acquired pneumonia (CAP) poses a significant risk of organ dysfunction and mortality.
• Current clinical evaluation and scoring systems have limitations in identifying high-risk CAP patients.
• Early identification of patients requiring intensive care unit (ICU) admission is crucial to reduce mortality.

Purpose of the Study:

• To investigate if a transcriptomic signature can improve the identification of CAP patients at risk of severe outcomes.
• To compare the predictive performance of a novel gene signature against conventional clinical scores.

Main Methods:

• A prospective observational cohort study (PROGRESS trial) involving 455 hospitalized CAP patients.
• Time-course transcriptomic data from blood samples were analyzed.
• A 5-gene signature (STYCK) was developed and validated for predicting ICU admission or 28-day mortality.

Main Results:

• A 5-gene signature (STYCK) comprising SIGLEC14, TNFSF14, YOD1, CLEC4A, and KLRB1 was identified and validated.
• The STYCK signature demonstrated high predictive accuracy (AUCs > 0.80) for severe CAP.
• STYCK outperformed existing clinical scores and improved the Sequential Organ Failure Assessment (SOFA) score's predictive performance.

Conclusions:

• A 5-gene transcriptomic signature (STYCK) can accurately predict severe CAP course and mortality in hospitalized patients.
• STYCK offers superior prediction compared to conventional clinical scores and enhances existing risk assessment tools.
• This transcriptomic approach holds promise for earlier and more precise identification of high-risk CAP patients.