Immune Profiling and Rapid Molecular Diagnostics in Severe Respiratory Infections and Sepsis: The Potential Clinical Perspective of CD169 and CD64.

Acute respiratory infections and sepsis remain major causes of morbidity and mortality worldwide. Rapid pathogen identification and characterization of the host immune response are crucial for timely diagnosis and appropriate treatment. CD169 and CD64 have emerged as promising biomarkers for differentiating viral and bacterial infections. This study aimed to characterize hospitalized patients with severe respiratory infections and/or suspected sepsis by evaluating the potential diagnostic performance of CD169 and CD64 and describing pathogen-associated immune profiles. In this pilot study, nineteen patients admitted to Policlinico Tor Vergata were enrolled within the multicenter SIS-NET project together with healthy donors. Respiratory pathogens were identified on sputum and nasopharyngeal swabs using the FAST multiplex molecular assay. Clinical, biochemical, and immunological parameters were collected during hospitalization. Flow cytometry was performed to assess CD169 and CD64 expression and circulating leukocyte subsets. Patients showed marked etiological heterogeneity, including viral, bacterial, fungal, and mixed infections. Elevated inflammatory markers were commonly observed. CD169 expression on HLA-DR+ monocytes significantly increased in patients with only viral infections, especially COVID-19 (n = 4), whereas CD64 expression was higher in patients with only bacterial infections (n = 4). We have also analyzed the opportunistic infections in 5 people that live with HIV infection (PLWH) compared with the other subgroups. These findings support the integration of rapid molecular diagnostics and immune profiling to improve the characterization of severe respiratory infections and highlight CD169 and CD64 as useful biomarkers for patient stratification and clinical management.