Impaired cytotoxic CD8+ T cell response in elderly COVID-19 patients

Abstract

SARS-CoV-2 infection induces a T cell response that most likely contributes to virus control in COVID-19 patients, but may also induce immunopathology. Until now, the cytotoxic T cell response has not been very well characterized in COVID-19 patients.Here, we analyzed the differentiation and cytotoxic profile of T cells in 30 cases of mild COVID-19 during acute infection. SARS-CoV-2 infection induced a cytotoxic response of CD8+ T cells, but not CD4+ T cells, characterized by the simultaneous production of granzyme A and B, as well as perforin within different effector CD8+ T cell subsets. PD-1 expressing CD8+ T cells also produced cytotoxic molecules during acute infection indicating that they were not functionally exhausted. However, in COVID-19 patients over the age of 80 years the cytotoxic T cell potential was diminished, especially in effector memory and terminally differentiated effector CD8+ cells, showing that elderly patients have impaired cellular immunity against SARS-CoV-2.Our data provides valuable information about T cell responses in COVID-19 patients that may also have important implications for vaccine development.ImportanceCytotoxic T cells are responsible for the elimination of infected cells and are key players for the control of viruses. CD8+ T cells with an effector phenotype express cytotoxic molecules and are able to perform target cell killing. COVID-19 patients with a mild disease course were analyzed for the differentiation status and cytotoxic profile of CD8+ T cells. SARS-CoV-2 infection induced a vigorous cytotoxic CD8+ T cell response. However, this cytotoxic profile of T cells was not detected in COVID-19 patients over the age of 80 years. Thus, the absence of a cytotoxic response in elderly patients might be a possible reason for the more frequent severity of COVID-19 in this age group in comparison to younger patients.

Characterization of T lymphocytes in severe COVID‐19 patients

“…We found no differences between elderly patients (defined as ≥80 years) and patients <80 years old concerning the immunological parameters analyzed, as reported recently in the literature 18,19 . These results could derive from the small number of patients analyzed and/or from the group of patients enrolled in the study with severe COVID‐19.…”

Immunological profiling of COVID-19 patients with pulmonary sequelae

“…Functional analysis further revealed that upregulation of degranulation capacity and cytotoxic molecules in CD4+ and CD8+ T cells in PPSs compared with NPSs. Our findings are in line with published papers(42)(43)(44).SARS-CoV-2 infection may induce a cytotoxic response, characterized by simultaneous production of GZMB and perforin in T cells, NK cells and γδ T cells inPPSs. Excessive activation of cytotoxic T, NK and γδ T cells is not protective but rather drives pulmonary damage after SARS-CoV-2 infection.Emerging evidence suggests that COVID-19 survivors have impaired lung function, with the development of pulmonary fibrosis(2,14).…”

SARS-CoV-2 infection paralyzes cytotoxic and metabolic functions of the immune cells

“…In contrast to our results, in young patients, granzyme A or B and perforin levels were increased in mild and moderate cases. Conversely, in elderly COVID-19 patients, there was a reduced expression of granzyme A and perforin [61]. Another study suggested that decreased perforin and granzyme A levels in CD4 þ T cells, CD8 þ T cell and NK cells is associated with severely afflicted COVID-19 patients [62].…”