Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the global pandemic of coronavirus disease 2019 (COVID-19) and particularly exhibits severe symptoms and mortality in elderly individuals. Mounting evidence shows that the characteristics of the age-related clinical severity of COVID-19 are attributed to insufficient antiviral immune function and excessive self-damaging immune reaction, involving T cell immunity and associated with pre-existing basal inflammation in the elderly. Age-related changes to T cell immunosenescence is characterized by not only restricted T cell receptor (TCR) repertoire diversity, accumulation of exhausted and/or senescent memory T cells, but also by increased self-reactive T cell- and innate immune cell-induced chronic inflammation, and accumulated and functionally enhanced polyclonal regulatory T (Treg) cells. Many of these changes can be traced back to age-related thymic involution/degeneration. How these changes contribute to differences in COVID-19 disease severity between young and aged patients is an urgent area of investigation. Therefore, we attempt to connect various clues in this field by reviewing and discussing recent research on the role of the thymus and T cells in COVID-19 immunity during aging (a synergistic effect of diminished responses to pathogens and enhanced responses to self) impacting age-related clinical severity of COVID-19. We also address potential combinational strategies to rejuvenate multiple aging-impacted immune system checkpoints by revival of aged thymic function, boosting peripheral T cell responses, and alleviating chronic, basal inflammation to improve the efficiency of anti-SARS-CoV-2 immunity and vaccination in the elderly.
Highlights
The global pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses a greater threat to elderly people than to children and young adults, as shown by a higher frequency of severe symptoms and mortality in elderly patients, while children and young adults usually present with mild disease [1,2]
Lower peripheral blood T cell counts are observed in severe COVID-19 patients [6,13], with further reductions in those admitted to intensive care units (ICUs) and in those over the age of 60 [32], whereas increased SARS-CoV-2-specific T cells are associated with disease recovery [33,34,35,36]
Induced Treg cells can be generated via transforming growth factor- β (TGF-β), while blocking TGF-β signaling impedes the conversion of CD4 T cells into iTreg cells and thereby facilitates immune responses abrogated by Treg suppression [129]
Summary
The global pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses a greater threat to elderly people than to children and young adults, as shown by a higher frequency of severe symptoms and mortality in elderly patients, while children and young adults usually present with mild disease [1,2]. Differences in clinical severity are likely associated with immune system age [3] Both the innate and adaptive immune systems are involved in antiviral responses. Rejuvenation of aged thymic function in combination with an improvement in the pre-existing aged peripheral T cell microenvironment and inflammaging could improve protective immunity and efficient vaccination against viruses, including SARS-CoV-2, in the elderly. We raise the hypothesis that thymic aging plays a potential role in clinical severity of aged COVID-19 patients based on aged T cell immune system features and the observed symptom disparities between children and young adults compared to elderly COVID-19 patients. Cells 2021, 10, x FOR PEER REVIEW insights into the potential contribution of the thymus to the clinical severity of COVID-19 pathology in young and aged patients
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