Distinctive features of SARS-CoV-2-specific T cells predict recovery from severe COVID-19

Abstract

Although T cells are likely players in SARS-CoV-2 immunity, little is known about the phenotypic features of SARS-CoV-2-specific T cells associated with recovery from severe COVID-19. We analyze T cells from 34 COVID-19 patients with severities ranging from mild (outpatient) to critical culminating in death. Relative to patients that succumbed, individuals that recovered from severe COVID-19 harbor elevated and increasing numbers of SARS-CoV-2-specific T cells capable of homeostatic proliferation. In contrast, fatal COVID-19 displays elevated numbers of SARS-CoV-2-specific regulatory T cells and a time-dependent escalation in activated bystander CXCR4+ T cells as assessed by longitudinal sampling. Together with the demonstration of increased proportions of inflammatory CXCR4+ T cells in the lungs of severe COVID-19 patients, these results support a model whereby lung-homing T cells activated through bystander effects contribute to immunopathology, while a robust, non-suppressive SARS-CoV-2-specific T cell response limits pathogenesis and promotes recovery from severe COVID-19.

Mild SARS-CoV-2 infection in rhesus macaques is associated with viral control prior to antigen-specific T cell responses in tissues

“…PET/CT imaging showed regions of ground glass opacity and consolidation with elevated 18 FDG uptake in the lungs on day 3 after SARS-CoV-2 infection, which completely resolved by day 9. A longitudinal scRNAseq analysis identified early type I IFN responsive monocyte, macrophage, and dendritic cells in PBMC and BAL that mostly dissipated prior to the arrival of virus-specific CD8 and CD4 T cells.…”

“…), for a total dose of 2x10 6 TCID50 (Table 1). 18 FDG PET/CT imaging showed evidence of heterogeneous inflammatory foci with increased 18 FDG uptake (Fig 1A , B) and lesion density (Fig 1A, C) in the lungs of 5 of 6 animals at day 3 post-infection, which resolved by day 9. Total genomic Nucleocapsid (gN) and subgenomic Nucleocapsid (sgN) RNA levels from nasal and throat swabs peaked 1 to 2 days post-infection and decreased to undetectable levels by day 7 to 10 (Fig 1D).…”

“…Increased pro-inflammatory cytokines [1][2][3][4] , deficient type I interferon (IFN) responses [5][6][7] , activation of inflammasomes 8 , neutrophils [9][10][11] , and monocytes/macrophages 1,2,[11][12][13][14] have all been associated with severe COVID-19. Coordinated activation of CD8 and CD4 T cells, T cell activation state, and antigen (Ag)-specificity have all been linked to favorable outcomes of SARS-CoV-2 infection [15][16][17][18][19][20] . While neutralizing antibodies are clearly protective in immune hosts, T cell responses may also contribute to the protection provided by vaccination and natural infection [21][22][23][24] .…”

IL-7 in SARS-CoV-2 Infection and as a Potential Vaccine Adjuvant

“…In chronic HIV-infected individuals, IL-7Ra expression was significantly lower than in HAART-treated and healthy controls, suggesting the expansion of CD127 negative T cells in chronic viral infection (31). CyTOF analysis revealed that lower levels of IL-7Ra (CD127) were identified in severe COVID-19 patients compared to mild cases (32); patients who survived from severe SARS-CoV-2 illness showed elevated expression of IL-7Ra (CD127) compared to nonsurvivors (32). Thus, further studies are warranted to understand the relation between IL-7Ra (CD127) expression and plasma/serum levels of IL-7 in COVID-19 patients.…”

Monoclonal antibodies protect aged rhesus macaques from SARS-CoV-2-induced immune activation and neuroinflammation

“…In addition to comorbidities, COVID-19 also exhibits sex biases, with male patients being more susceptible to developing severe disease; hence future studies evaluating RBD-mAb therapy in male animals would be informative. Second, other factors, such as innate responses and host anti-viral responses, may be more challenging to discern because of variation in early viral replication and viral clearance (Neidleman et al, 2021). Thus, incorporating larger sample sizes may provide deeper insights into the effects of RBD-mAb on early immune dynamics.…”