CD4+ T cells stratification unveils a dynamic pathogen landscape in severe pneumonia: a targeted next-generation sequencing-based cohort study.

Background: The host's immune status is a critical determinant of the pathogen profile in pulmonary infections, but quantitative indicators to delineate this dynamic association are lacking. This study aimed to use CD4+ T cells count as an objective parameter to systematically characterize the evolution of the pathogen profile in bronchoalveolar lavage fluid-targeted next-generation sequencing (BALF-tNGS) from patients with severe pneumonia. Methods: We retrospectively analyzed 286 adult patients who underwent BALF-tNGS for severe pneumonia. Patients were stratified into four strata based on CD4+ T cells count: severe immunosuppression, moderate immunosuppression, low-normal immunity, and immunocompetent. Cochran-Armitage trend test, cluster analysis, and Kruskal-Wallis test were used to analyze the associations between CD4+ T cells strata and pathogen detection rates/co-infection complexity. Results: The detection rates of Pneumocystis jirovecii (PJP) and Cytomegalovirus (CMV) showed a highly significant increasing trend with decreasing CD4+ T cells strata (p < 0.05). CD4+ T cells count < 100 cells/μL was the most significant risk factor for PJP infection (detection rate 39.6%). Meanwhile, as the CD4+ T cells count decreased, the number of pathogen species detected in the patient's BALF significantly increased, with a statistically significant difference between groups (p < 0.05). The median number in the severe immunosuppression stratum was significantly higher than that in the immunocompetent stratum. Conclusion: The CD4+ T cells count quantitatively defines the pathogen ecology in pulmonary infections. A CD4+ T cells count < 100 cells/μL represents a critical threshold for opportunistic infections and complex co-infections. These findings support the integration of CD4+ T cells counting into the initial assessment framework for severe pneumonia to guide precise empirical therapy and diagnostic strategies.