biostudies-literatureUnknown251Koh JYA dysregulated hyperinflammatory response is a key pathogenesis of severe COVID-19, but optimal immune modulator treatment has not been established. To evaluate the clinical effectiveness of double (glucocorticoids and tocilizumab) and triple (plus baricitinib) immune modulator therapy for severe COVID-19, a retrospective cohort study was conducted. For the immunologic investigation, a single-cell RNA sequencing analysis was performed in serially collected PBMCs and neutrophil specimens. Triple immune modulator therapy was a significant factor in a multivariable analysis for 30-day recovery. In the scRNA-seq analysis, type I and II IFN response-related pathways were suppressed by GC, and the IL-6-associated signature was additionally downregulated by TOC. Adding BAR to GC and TOC distinctlClinical immunology (Orlando, Fla.)109628https://www.ebi.ac.uk/biostudies/studies/S-EPMC10139747biostudies-literatureTriple immune modulator therapy for aberrant hyperinflammatory responses in severe COVID-19.PMC10139747Lee JSKang CIKim SHBae SKo JHPeck KRHuh KKoh JYLim SYCho SYChung CRChung DRfalseTriple immune modulator therapy for aberrant hyperinflammatory responses in severe COVID-19.A dysregulated hyperinflammatory response is a key pathogenesis of severe COVID-19, but optimal immune modulator treatment has not been established. To evaluate the clinical effectiveness of double (glucocorticoids and tocilizumab) and triple (plus baricitinib) immune modulator therapy for severe COVID-19, a retrospective cohort study was conducted. For the immunologic investigation, a single-cell RNA sequencing analysis was performed in serially collected PBMCs and neutrophil specimens. Triple immune modulator therapy was a significant factor in a multivariable analysis for 30-day recovery. In the scRNA-seq analysis, type I and II IFN response-related pathways were suppressed by GC, and the IL-6-associated signature was additionally downregulated by TOC. Adding BAR to GC and TOC distinctl2023-01-01T00:00:00Z2023 Jun2025-04-22T05:15:10.714Z2025-02-19T02:26:24.123ZS-EPMC101397473711995110.1016/j.clim.2023.109628