Remodeling of the Immune Response With Aging: Immunosenescence and Its Potential Impact on COVID-19 Immune Response
Top Cited Papers
Open Access
- 7 August 2020
- journal article
- review article
- Published by Frontiers Media SA in Frontiers in Immunology
- Vol. 11, 1748
- https://doi.org/10.3389/fimmu.2020.01748
Abstract
Elderly individuals are the most susceptible to an aggressive form of coronavirus disease (COVID-19), caused by SARS-CoV-2. The remodeling of immune response that is observed among the elderly could explain, at least in part, the age gradient in lethality of COVID-19. In this review, we will discuss the phenomenon of immunosenescence, which entails changes that occur in both innate and adaptive immunity with aging. Furthermore, we will discuss inflamm-aging, a low-grade inflammatory state triggered by continuous antigenic stimulation, which may ultimately increase all-cause mortality. In general, the elderly are less capable of responding to neo-antigens, because of lower naïve T cell frequency. Furthermore, they have an expansion of memory T cells with a shrinkage of the T cell diversity repertoire. When infected by SARS-CoV-2, young people present with a milder disease as they frequently clear the virus through an efficient adaptive immune response. Indeed, antibody-secreting cells and follicular helper T cells are thought to be effectively activated in young patients that present a favorable prognosis. In contrast, the elderly are more prone to an uncontrolled activation of innate immune response that leads to cytokine release syndrome and tissue damage. The failure to trigger an effective adaptive immune response in combination with a higher pro-inflammatory tonus may explain why the elderly do not appropriately control viral replication and the potential clinical consequences triggered by a cytokine storm, endothelial injury, and disseminated organ injury. Enhancing the efficacy of the adaptive immune response may be an important issue both for infection resolution as well as for the appropriate generation of immunity upon vaccination, while inhibiting inflamm-aging will likely emerge as a potential complementary therapeutic approach in the management of patients with severe COVID-19.This publication has 131 references indexed in Scilit:
- Cell Host Response to Infection with Novel Human Coronavirus EMC Predicts Potential Antivirals and Important Differences with SARS CoronavirusmBio, 2013
- Granule exocytosis mediates immune surveillance of senescent cellsOncogene, 2012
- The inverted CD4/CD8 ratio and associated parameters in 66-year-old individuals: the Swedish HEXA immune studyAGE, 2012
- Ageing of the human metaorganism: the microbial counterpartAGE, 2011
- Intrinsic defects in B cell response to seasonal influenza vaccination in elderly humansVaccine, 2010
- Functionally distinct hematopoietic stem cells modulate hematopoietic lineage potential during aging by a mechanism of clonal expansionProceedings of the National Academy of Sciences of the United States of America, 2010
- B‐cell diversity decreases in old age and is correlated with poor health statusAging Cell, 2009
- Mechanism and Regulation of Class Switch RecombinationAnnual Review of Immunology, 2008
- Aging of the Immune System: How Much Can the Adaptive Immune System Adapt?Immunity, 2006
- Neutrophil Extracellular Traps Kill BacteriaScience, 2004