Thrombomodulin as a Potentially Complementing Diagnostic Tool in Non-Pneumonic Bacterial Infections

Katharina Friedrich,1 Aurelia Hübner,2 Noa Galtung,2 Britta Hecke,1 Kai Kappert,1,3,4 Wolfgang Bauer2 1Institute of Diagnostic Laboratory Medicine, Clinical Chemistry and Pathobiochemistry, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; 2Department of Emergency Medicine, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; 3German Center for Cardiovascular Research (DZHK), Partner Site Berlin, Berlin, Germany; 4Department of Laboratory Medicine and Toxicology, Labor Berlin – Charité Vivantes GmbH, Berlin, GermanyCorrespondence: Wolfgang Bauer, Department of Emergency Medicine, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Hindenburgdamm 30, Berlin, 12203, Germany, Tel +49 030 450 552 897, Email [email protected]: Soluble thrombomodulin (TM) has been proposed as an endothelial injury marker with potential diagnostic value, particularly for severe pneumococcal community-acquired pneumonia (CAP). Its validation could enable clinically meaningful patient stratification and support biomarker-guided therapy. This retrospective study evaluated the associations between serum TM levels and disease severity/origin in 80 patients with suspected acute infection.Methods: Serum TM concentrations were measured in patients presenting to the emergency department and adjudicated by an expert panel as pneumococcal CAP, non-pneumococcal CAP, other bacterial infections (non-pneumonic), viral pneumonia, or patients with clinically ruled-out infection (controls).Results: TM levels did not differ significantly between CAP patients and controls or those with other bacterial infections. However, highest TM concentrations were observed in patients with bacterial infections without pneumonia, significantly exceeding control levels. TM levels were not correlated with disease severity in CAP, determined by National Early Warning Score 2 (NEWS2), but were significantly elevated in non-pneumonic bacterial infections of moderate severity (NEWS2 5– 6).Conclusion: In this cohort, TM was elevated in bacterial non-pneumonic infections but was not a specific marker for pneumococcal CAP. These findings indicate that TM predominantly reflects systemic endothelial injury, a hallmark of more severe bacterial infections, particularly those of non-pneumonic origin.Keywords: thrombomodulin, community-acquired pneumonia, severity of CAP, pneumococcal pneumonia, bacterial infections