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Published on: September 20, 2024
Dynamic blood single-cell immune responses in patients with COVID-19
Lulin Huang1,2,3, Yi Shi1,2,3, Bo Gong1,2,3
1The Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
Insights
This study reveals dynamic blood immune responses in COVID-19 patients, identifying key cell changes and activated pathways like type I interferon. These findings offer insights into potential therapeutic strategies for SARS-CoV-2 infection.
Area of Science:
- Immunology
- Virology
- Genomics
Background:
- The pathogenesis of COVID-19 remains unclear, necessitating deeper understanding of the immune response to SARS-CoV-2.
- Dynamic changes in blood immune cells and pathways during COVID-19 progression are not fully elucidated.
Purpose of the Study:
- To investigate dynamic changes in blood immune responses at different stages of COVID-19.
- To analyze single-cell transcriptome data, including T cell receptor (TCR) and B cell receptor (BCR) V(D)J sequences, for insights into immune cell dynamics and specificity.
- To identify key activated pathways and potential therapeutic targets for COVID-19.
Main Methods:
- Single-cell mRNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) from COVID-19 patients and controls.
- TCR and BCR V(D)J transcriptome analysis at single-cell resolution.
- Validation using gene expression, serum cytokine levels (interferon-α), and additional patient cohorts.
Main Results:
- Observed expansion of dendritic cells (DCs), CD14+ monocytes, and megakaryocyte progenitor cells (MP)/platelets, with a reduction in naïve CD4+ T lymphocytes.
- Significant decrease in CD8+ T lymphocytes and natural killer cells (NKs) in critically ill patients.
- Activation of type I interferon (IFN-I), mitogen-activated protein kinase (MAPK), and ferroptosis pathways during active disease, with gradual recovery post-improvement.
- Elevated mRNA levels of IFN-I-induced gene IFI27 and increased serum interferon-α (IFN-α) in COVID-19 patients.
- Evidence of specific immune responses against SARS-CoV-2 antigens through TCR and BCR sequence analysis.
Conclusions:
- The study delineates a dynamic immune landscape in response to SARS-CoV-2 infection.
- The type I interferon pathway plays a significant role in the immune response to COVID-19.
- Findings provide valuable insights into the pathogenesis of COVID-19 and suggest potential therapeutic avenues.
Abstract:
The 2019 coronavirus disease (COVID-19) outbreak caused by the SARS-CoV-2 virus is an ongoing global health emergency. However, the virus' pathogenesis remains unclear, and there is no cure for the disease. We investigated the dynamic changes of blood immune response in patients with COVID-19 at different stages by using 5' gene expression, T cell receptor (TCR), and B cell receptors (BCR) V(D)J transcriptome analysis at a single-cell resolution. We obtained single-cell mRNA sequencing (scRNA-seq) data of 341,420 peripheral blood mononuclear cells (PBMCs) and 185,430 clonotypic T cells and 28,802 clonotypic B cells from 25 samples of 16 patients with COVID-19 for dynamic studies. In addition, we used three control samples. We found expansion of dendritic cells (DCs), CD14+ monocytes, and megakaryocytes progenitor cells (MP)/platelets and a reduction of naïve CD4+ T lymphocytes in patients with COVID-19, along with a significant decrease of CD8+ T lymphocytes, and natural killer cells (NKs) in patients in critical condition. The type I interferon (IFN-I), mitogen-activated protein kinase (MAPK), and ferroptosis pathways were activated while the disease was active, and recovered gradually after patient conditions improved. Consistent with this finding, the mRNA level of IFN-I signal-induced gene IFI27 was significantly increased in patients with COVID-19 compared with that of the controls in a validation cohort that included 38 patients and 35 controls. The concentration of interferon-α (IFN-α) in the serum of patients with COVID-19 increased significantly compared with that of the controls in an additional cohort of 215 patients with COVID-19 and 106 controls, further suggesting the important role of the IFN-I pathway in the immune response of COVID-19. TCR and BCR sequences analyses indicated that patients with COVID-19 developed specific immune responses against SARS-CoV-2 antigens. Our study reveals a dynamic landscape of human blood immune responses to SARS-CoV-2 infection, providing clues for therapeutic potentials in treating COVID-19.
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