Profound dysregulation of T cell homeostasis and function in patients with severe COVID‐19

Abstract

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Follicular Helper T Cells in the Immunopathogenesis of SARS-CoV-2 Infection

“…Similarly, CD38 + HLA-DR + cTfh cells, activated CD4 + T cells and cytotoxic CD8 + T cells were expanded in COVID-19 patients, and increased CD38 + HLA-DR + cTfh cells indicated a recent antigen encounter and emigration from the GC of the patients (161). The frequencies of PD-1 + ICOS + cTfh, cytotoxic CD4 + T and exhausted T cells were strongly expanded in COVID-19 patients, particularly in severe patients compared to healthy individuals, which suggested that extensive T cell dysfunction was associated with COVID-19 severity (162). In severe COVID-19 patients, the frequencies of CCR6 + cTfh cells and CCR4 + cTfh cells were expanded, but CCR3 + cTfh cells and Th1 cells were low in severe COVID-19 patients compared to healthy individuals (163).…”

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

“…In chronic HIV-1 infected individuals, elevated levels of IL-7 and lower expression of IL-7Ra were reported as IL-7 downregulates its own receptor (22), and several studies confirmed the link between disease progression and increased plasma/serum levels of IL-7 (Figure 2). Elevated plasma/serum IL-7 concentration was also measured during SARS-CoV-2 infection together with other cytokines and chemokines (16,17,23,24). A study conducted in Zurich, Switzerland reported that severe COVID-19 patients exhibited profound loss of naïve T cells and impaired antiviral activity (23).…”

“…Elevated plasma/serum IL-7 concentration was also measured during SARS-CoV-2 infection together with other cytokines and chemokines (16,17,23,24). A study conducted in Zurich, Switzerland reported that severe COVID-19 patients exhibited profound loss of naïve T cells and impaired antiviral activity (23). Moreover, serum IL-7 levels were significantly higher in severe COVID-19 patients compared to healthy controls and patient with mild symptoms (23).…”

Interplay between Neutrophils, NETs and T-Cells in SARS-CoV-2 Infection—A Missing Piece of the Puzzle in the COVID-19 Pathogenesis?

“…In addition, the decrease in CD8+ T cells (cytotoxic T cells, CTLs) has been recorded. This is pivotal because CTLs kill virally infected cells via the production of granzymes and perforin, and the expression of the Fas ligand (FasL), all of which mediate cellular apoptosis [117]. In addition, patients with severe COVID-19 also showed a reduction in Several studies have confirmed that the severity of COVID-19 is correlated with the T CD3+ decrease [21,[113][114][115].…”

“…It is important to emphasize that the decrease in CTLs is recorded mainly within the CD8+ T cell compartment, but the reason for this remains uncertain [117]. The following possibilities have been enumerated: trafficking of CD8+ T cells into tissues with ongoing SARS-CoV-2 replication, increased elimination of this T cell's subset during the infection, or pre-existing low levels of this cell line in a severe course of the infection [117].…”