Lymphopenic community-acquired pneumonia is associated with a dysregulated immune response and increased severity and mortality

Objectives: Lymphopenic (<724 lymphocytes/mu L) community-acquired pneumonia (L-CAP) is an immunophenotype with an increased risk of mortality. We aimed to characterize the L-CAP immunophenotype though lymphocyte subsets and the inflammatory response and its relationship with severity at presentation and outcome. Methods: Prospective study of 217 immunocompetent patients hospitalized for CAP. Lymphocyte subsets (CD4(+), CD8(+), CD19(+), and natural killer [NK] cells) and inflammatory cytokines were analyzed on days 1 and 4, and immunoglobulin subclasses were analyzed on day 1 in a nested group. Results: 39% of patients showed L-CAP, with decreased levels of all lymphocyte subsets with a partial recovery of CD4(+) and CD8(+) cells by day 4. L-CAP patients exhibited higher initial severity and systemic levels of interleukin (IL)-8, IL-10, granulocyte colony-stimulating factor, and monocyte chemoattractant protein-1. Initial IgG2 levels were lower in patients with <724 lymphocytes/mu L and positively correlated with ALC, CD4(+), and CD19(+) cell counts. Low CD4(+) counts (<129 cells/mu L) also independently predicted 30-day mortality after adjusting for age, gender, and the CURB-65 score. Conclusions: L-CAP is characterized by CD4(+) depletion, a higher inflammatory response, and low IgG2 levels that correlated with greater severity at presentation and worse prognosis. L-CAP is an immunophenotype useful for rapidly recognizing severity. (C) 2019 Published by Elsevier Ltd on behalf of The British Infection Association.