Single-cell RNA sequencing of blood antigen-presenting cells in severe COVID-19 reveals multi-process defects in antiviral immunity

Saichi et al. performed single-cell RNA-seq analysis of antigen-presenting cells (APCs) isolated from the peripheral blood of patients with moderate and severe COVID-19 and uncovered defects in antiviral immune response in specific APC subsets. COVID-19 can lead to life-threatening respiratory failure, with increased inflammatory mediators and viral load. Here, we perform single-cell RNA-sequencing to establish a high-resolution map of blood antigen-presenting cells (APCs) in 15 patients with moderate or severe COVID-19 pneumonia, at day 1 and day 4 post admission to intensive care unit or pulmonology department, as well as in 4 healthy donors. We generated a unique dataset of 81,643 APCs, including monocytes and rare dendritic cell (DC) subsets. We uncovered multi-process defects in antiviral immune defence in specific APCs from patients with severe disease: (1) increased pro-apoptotic pathways in plasmacytoid DCs (pDCs, key effectors of antiviral immunity), (2) a decrease of the innate sensors TLR9 and DHX36 in pDCs and CLEC9a(+) DCs, respectively, (3) downregulation of antiviral interferon-stimulated genes in monocyte subsets and (4) a decrease of major histocompatibility complex (MHC) class II-related genes and MHC class II transactivator activity in cDC1c(+) DCs, suggesting viral inhibition of antigen presentation. These novel mechanisms may explain patient aggravation and suggest strategies to restore the defective immune defence.

Automated summary

Saichi et al. conducted single-cell RNA-seq analysis on APCs isolated from COVID-19 patients, revealing defects in antiviral immune response in specific APC subsets. The study identified multiple mechanisms contributing to these defects, such as increased pro-apoptotic pathways, decreased innate sensor expression, downregulation of antiviral interferon-stimulated genes, and inhibition of antigen presentation. These findings may explain disease progression in severe patients and suggest potential strategies to restore immune defense.