Aberrant hyperactivation of cytotoxic T-cell as a potential determinant of COVID-19 severity
clinical immunology/immunity inflammation
Authors: Kang, CK et al.
Journal/ Pre-Print: International Journal of Infectious Diseases
Tags: Clinical, Immunology/Immunity, Inflammation
1. At week 1, T cells from PBMCs of severe COVID-19 patients showed no differences from mild cases. At week 3, after the onset of deterioration in severe cases, total CD4+ and CD8+ T cells were lower, and Ki-67, PD-1, perforin and granzyme B expression were higher, indicating hyperactivation of the cell-mediated immune response.
2. The phenotype observed may be related to a lack of inhibitory effects from Tregs, since this population tended to decline in the severe group.
3. IL7Ralow effector-memory CD8+ T cells failed to contract in severe cases.
The research addressed the question of whether hyperactivation of the cell-mediated immune response in severe COVID-19 cases may explain the deterioration of symptoms. Although few differences were observed during week 1, both CD4+ and CD8+ T cells in the severe group displayed a decline in number and an increase in markers related with proliferation, activation and cytotoxicity at week 3, while cytokine secretion did not change. Also, the failure in the contraction of the effector population and the tendency towards decreased Treg inhibition support the observed phenotypes.
Impact for SARS-CoV2/COVID19 research efforts
Understand the immune response to SARS-CoV2/COVID19
> The article indicates that there is hyperactivation of cell-mediated immune responses in the late phase of severe COVID-19 patients.
Clinical symptoms and pathogenesis of SARS-Cov2/COVID19
> The immune population changes may explain the symptoms of severe COVID-19 cases.
· In vitro study
· Patient Case study
Strengths and limitations of the paper
The research focuses on the T-cell mediated immune response in COVID-19, raising a possible mechanism may lead to the development of severe COVID-19.
Standing in the field:
The result of the research (lymphopenia, inflammatory phenotypes in severe cases) is consistent with previous reports.
The comparison used: two-tailed Mann-Whitney U test or Wilcoxon signed rank test. However, the sample numbers in each group are low and imbalanced.
Viral model used:
PBMC from COVID-19 patients and healthy donors
Low chance of translation of the results.
> The research suffers from extremely low number of patients. Some of the patients are treated with drugs, which may further complicate the results.
> Lack of direct evidence of hyperactivation of cell-mediated immune response is the cause of severe symptoms or the consequence of cytokine storm in those patients.