Unique Differentiation and Homing Features of T Cells in Individuals with Long Covid
Topics in Antiviral Medicine
; 31(2):137, 2023.
Article
in English
| EMBASE | ID: covidwho-2320687
ABSTRACT
Background:
A significant portion of individuals experience persistent symptoms months after SARS-CoV-2 infection, broadly referred to as Long COVID (LC). Although the frequencies of subsets of SARS-CoV-2-specific T cells have been shown to differ in individuals with LC relative to those with complete recovery, a deep dive into phenotypic and functional features of total and SARSCoV- 2-specific T cells from individuals with LC has yet to be performed. Method(s) Here, we used CyTOF to characterize the phenotypes and effector functions of T cells from LIINC cohort. The median age was 46, the cohort was 55.8% female, and 9/43 had been hospitalized. Participants were reported a median of 7 LC symptoms at 8 months. SARS-CoV-2-specific total antibody levels were also measured in concurrent sera. Manual gating was used to define T cell subsets, SPICE analyses for polyfunctionality, T cell clustering for phenotypic features, and linear regression for correlation. Permutation tests, Student's t tests, and Welch's t test were used for statistical analysis. Result(s) SARS-CoV-2 total antibody responses were elevated in the LC group (p=0.043), and correlated with frequencies of SARS-CoV-2-specific T cells in those without LC (r=0.776, p< 0.001) but not those with LC. While the frequencies of total SARS-CoV-2-specific CD4+ and CD8+ T cells were similar between individuals with and without LC, those from individuals without LC tended to be more polyfunctional (co-expressing IFNgamma, TNFalpha, IL2, and/or MIP1beta). CD4+ T cells from individuals with LC harbored higher frequencies of Tcm (p=0.003), Tfh (p=0.037), and Treg subsets (p=0.0412), and preferentially expressed a variety of tissue homing receptors including CXCR4 and CXCR5 (p=0.037). SARS-CoV-2-specific CD4+ T cells producing IL6, albeit rare, were observed exclusively among those with LC (p=0.016). In addition, participants with LC harbored significantly higher frequencies of SARS-CoV-2-specific CD8+ T cells co-expressing exhaustion markers PD1 and CTLA4 (p=0.018). Conclusion(s) Long COVID is characterized by global phenotypic differences in the CD4+ T cell compartment in ways suggesting preferential migration of these cells to inflamed mucosal tissues. Individuals with LC also harbor higher numbers of exhausted SARS-CoV-2-specific CD8+ T cells, potentially implicating viral persistence. Finally, our data additionally suggest that individuals with LC may uniquely exhibit an uncoordinated T cell and antibody response during COVID-19 convalescence.
adult; antibody response; CD4+ T lymphocyte; CD8+ T lymphocyte; cell migration; clinical article; cohort analysis; conference abstract; controlled study; convalescence; coronavirus disease 2019; exhaustion; female; gene expression; gene frequency; homing behavior; human; human cell; linear regression analysis; long COVID; male; middle aged; mucosa; nonhuman; phenotype; protein expression; regulatory T lymphocyte; Severe acute respiratory syndrome coronavirus 2; spice; T lymphocyte; T lymphocyte subpopulation; CD4 antigen; chemokine receptor CXCR4; chemokine receptor CXCR5; cytotoxic T lymphocyte antigen 4; endogenous compound; gamma interferon; homing receptor; interleukin 2; interleukin 6; macrophage inflammatory protein 1beta; tumor necrosis factor
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Collection:
Databases of international organizations
Database:
EMBASE
Topics:
Long Covid
Language:
English
Journal:
Topics in Antiviral Medicine
Year:
2023
Document Type:
Article
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