Overactive Immune Response Linked to Severe COVID-19
Summary
In this scholarly inquiry, the authors explore the plausible function of T lymphocytes in severe COVID-19 manifestations, amalgamating single-cell transcriptomic and proteomic methodologies with mechanistic examinations. They pinpoint highly activated CD16+ T cells exhibiting augmented cytotoxic capabilities in severe COVID-19, where CD16 expression facilitates immune-complex-mediated, T cell receptor-independent degranulation and cytotoxicity, a phenomenon absent in alternative maladies. These CD16+ T cells instigate microvascular endothelial cell damage and the liberation of neutrophil and monocyte chemoattractants. The investigators demonstrate that the proportions of activated CD16+ T cells and plasma concentrations of antecedent complement proteins, such as those preceding C3a, correlate with fatal consequences in COVID-19 cases, insinuating a pathological contribution of intensified cytotoxicity and complement activation.
Fig.1 Graphical abstract. (Georg, 2022)
Research Criteria
The research idea of this article is to assess pathogenic T cell functions and inducing signals in severe COVID-19 patients using single-cell transcriptomics and single-cell proteomics combined with mechanistic studies.
Fig.2 Experimental design. (Georg, 2022)
Sample Type
Cells from blood
Result—Single-Cell Transcriptomics Demonstrate a Shift in T Cells' Cytotoxic and Degranulation Capabilities in COVID-19 Patients
In the present investigation, scholars employed single-cell RNA sequencing examination of peripheral blood mononuclear cell specimens and isolated CD38+ T lymphocytes derived from acutely afflicted and convalescent individuals with mild and severe SARS-CoV-2 infection, alongside FLI, HBV, and control cohorts. Through Gene Ontology enrichment scrutiny, it was discerned that T cells from mildly impacted patients demonstrated an augmentation of cellular reactions to type I interferon and antiviral defense, in contrast to T cells from severely affected patients, which displayed a particular enhancement of genes implicated in degranulation. This noteworthy revelation was substantiated via Gene Set Enrichment Analysis and corroborated by single-cell RNA sequencing information from an auxiliary assemblage. The research underscored the existence of a distinct faction of highly stimulated CD16+ T cells, possessing elevated cytotoxicity-associated transcriptional schemes in severely afflicted COVID-19 patients.
Fig.3 Single-cell transcriptomics of T cells during acute mild and severe COVID-19. (Georg, 2022)
Result—T Cell Clones Expressing FCGR3A that were Generated During Acute Severe COVID-19 Survive and Retain Their Heightened Cytotoxic Capacity
The research aimed to assess the clonal persistence and differentiation of CD16+ T cells with enhanced cytotoxicity in severe COVID-19 patients after clearance of acute infection. Researchers utilized VDJ sequence data and gene expression profiles from acute and convalescent mild and severe COVID-19 patients, FLI, HBV, and controls. The results demonstrated clonal enrichment of FCGR3A expressing scRNA-seq clusters 8, 9, and 10 during acute COVID-19 infection, with up to 50% of TCR clones persisting in convalescent samples. These T cell clones matured into clusters 11 and 12, retaining FCGR3A expression and high cytotoxic potential, while there was no significant iNKT cell enrichment in COVID-19 T cell clusters 7-10. During convalescence, CD16+ CD8+ T cells persisted, acquired a more differentiated CD62L- phenotype, but maintained high cytotoxic potential. This research advances our understanding of severe COVID-19 infections' long-term effects.
Fig.4 Time-dependent evolution and phenotype of COVID-19-expanded T cell clones. (Georg, 2022)
Creative Biolabs' Services
Single Cell RNA Sequencing Service
Single-cell RNA sequencing provides insights into transcriptome diversity in heterogeneous samples. Creative Biolabs offers comprehensive workflows, including sample preparation, library construction, and data analysis, to optimize your project's flexibility, speed, and data accuracy.
Learn more
Single Cell TCR Profiling Service
Creative Biolabs provides a diverse range of customized and high-quality services for single-cell T cell receptor (TCR) profiling. These services are tailored to support global scientific research endeavors in the fields of immunology and biomedical sciences.
Learn moreCreative Biolabs offers various single cell analysis services, including single cell RNA sequencing and single cell TCR profiling. Single cell RNA sequencing enables scientists to study gene expression at the individual cell level, providing a comprehensive understanding of cellular heterogeneity and function. Meanwhile, single cell TCR profiling offers a detailed characterization of T-cell receptors at a single cell level, facilitating the detection of rare T-cell subpopulations and immune responses. These services are invaluable tools for scientific research, drug development, and diagnostic testing, and Creative Biolabs is equipped with the latest technologies and a team of expert scientists to provide high-quality data and insights.
For any information, please contact us.
Reference
- Georg, P.; et al. Complement activation induces excessive T cell cytotoxicity in severe COVID-19. Cell. 2022, 185(3): 493-512.
