IMMUNOLOGY2025™ Conference Recordings-Learning the rulls of human immune tolerance through the lenses of single-cell genomics

Learning the rulls of human immune tolerance through the lenses of single-cell genomics

Video Transcription

Video Summary

The speaker presented a large, early-pandemic SARS-CoV-2 cohort to study sepsis-like immune dysfunction. Using 705 samples from 351 hospitalized patients, the team generated single-cell multi-omics, plasma protein, autoantibody, viral titer, and neutralizing antibody data from over 2.2 million cells. They modeled immune changes by age, sex, infection status, time, and disease severity.<br /><br />Key findings showed that severe disease was marked by impaired viral clearance and a shift from antiviral programs toward tissue repair and damage responses. In B cells, severe cases had persistent ISG-high subsets and atypical age-associated B cells, along with reduced BCR signaling. In T cells, severe disease was linked to reduced cytotoxic programs, lower TCR signaling, altered clonal selection, and age-related TCR diversity loss. In myeloid cells, severe cases showed loss of antigen presentation and emergence of sepsis-like monocyte states, strongly associated with IL-6 and other inflammatory proteins.<br /><br />To test causality, the speaker analyzed a small cohort treated with tocilizumab (IL-6 receptor blockade). In responders, the sepsis-like myeloid programs diminished, antigen presentation recovered, and dysfunctional inflammatory states reversed. The talk concluded that severe COVID can reveal shared sepsis biology, and that IL-6-driven immune dysregulation may be therapeutically reversible when treated in time.

Keywords

SARS-CoV-2

sepsis-like immune dysfunction

single-cell multi-omics

severe COVID-19

IL-6 blockade

tocilizumab

antigen presentation