Tuberc Respir Dis.  2026 Jan;89(1):38-54. 10.4046/trd.2025.0099.

T-Cell Immune Dysfunction and Progression to Severe COVID-19 in Asthma Revealed by Single-Cell RNA Sequencing

• Kim BG
• Kim Y
• Lee SH
• Lee S
• Choi M
• Lee B
• Jeong JS
• Kim SH
• Lee H
• Yoo KH

• KMID: 2575071
• DOI: http://doi.org/10.4046/trd.2025.0099

Abstract

Background
Little information is available on the immune signaling pathway that drives severe coronavirus disease 2019 (COVID-19) in asthma. Our study uses single-cell RNA sequencing (scRNA-seq) to evaluate the association between immune dysfunction and progression to severe COVID-19 in asthma.
Methods
Four patients with asthma and eight patients without asthma from three centers in South Korea were analyzed. Samples were collected from each patient over three-time points: at the time of COVID-19 infection, 1 week later, and 2 weeks later.
Results
Patients were classified into four groups according to the presence or absence of asthma and COVID-19 severity: non-asthma/mild COVID-19 (n=5), non-asthma/severe COVID-19 (n=3), asthma/mild COVID-19 (n=3), and asthma/severe COVID-19 (n=1) groups. A high-quality scRNA-seq dataset composed of 155,565 cells was generated that characterized peripheral immune cells. Analysis of the proportion of cell type by time points showed a decrease in T-cells at the second time point in the asthma/severe COVID-19 group, compared to the others. When the proportion of T-cell subtype was analyzed by time point, an increase in the proportion of CD8+ T-cell was shown at the second time point in the asthma/severe COVID-19 group compared to the other groups: in differentially expressed genes analysis, notably, we observed relatively higher levels of cytotoxicity-related genes in the asthma/severe COVID-19 group compared to the others.
Conclusion
Our study provides new insights into the mechanisms underlying the progression of COVID-19 infection in patients with asthma. A reduction in the proportion of T-cells while expanding cytotoxic CD8+ T-cell proportion was associated with severe COVID-19 presentation in asthma.

Keyword

COVID-19; Asthma; T-Cell; CD8+ T-Cell