Clinical and Immune Features of Pneumocystis Pneumonia with Acute Respiratory Distress Syndrome in Immunocompromised Children

Abstract

Pneumocystis jirovecii pneumonia (PJP) is a common opportunistic infection in immunocompromised children, often causing acute fulminant pneumonia with respiratory failure. The prognosis of PJP in human immunodeficiency virus (HIV)-negative children with acute respiratory distress syndrome (ARDS) remains unclear. This retrospective review (2015–2021) included 20 HIV-negative children with ARDS and PJP. Among them, 17 had hematological malignancies or solid tumors, and 3 had renal disease; 15 survived, 5 did not. Both groups had very low CD4+ T cell counts (<0.2×10⁹/L), severe ARDS (partial pressure of oxygen in arterial blood / fraction of inspired oxygen [PaO₂/FiO₂] ratio <150), and elevated lactate dehydrogenase (LDH) and (1,3)-β-D-glucan (BDG) levels. In non-survivors, anti-PJP therapy was initiated approximately 7 days later than in survivors. Single-cell sequencing revealed CD4+/CD8+ T cell ratios of 0.16 (survivors) vs 2.13 non-survivors), with a higher ratio of regulatory T cells (Tregs) to CD4⁺ T cells in non-survivors (33% vs. 10.6%). Non-survivors showed enrichment of neutrophil degranulation and activation pathways and expressed more proapoptotic and proinflammatory signals (e.g., FAS_FASLG, interferon-γ). Early treatment initiation is critical. Prolonged CD8+ T cell deficiency, high Treg expression with proapoptotic genes, and excessive inflammation may predict poor prognosis.