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Remodeling of the Immune Response With Aging: Immunosenescence and Its Potential Impact on COVID-19 Immune Response.
Front Immunol. 2020; 11:1748.FI

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.

Authors+Show Affiliations

Department of Medicine, Escola Paulista de Medicina, Federal University of São Paulo, São Paulo, Brazil.Division of Rheumatology, Escola Paulista de Medicina, Federal University of São Paulo, São Paulo, Brazil.Schuster Transplantation Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.Renal Division, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States.Division of Nephrology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States. Department of Surgery, Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA, United States.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

32849623

Citation

Cunha, Lucas Leite, et al. "Remodeling of the Immune Response With Aging: Immunosenescence and Its Potential Impact On COVID-19 Immune Response." Frontiers in Immunology, vol. 11, 2020, p. 1748.
Cunha LL, Perazzio SF, Azzi J, et al. Remodeling of the Immune Response With Aging: Immunosenescence and Its Potential Impact on COVID-19 Immune Response. Front Immunol. 2020;11:1748.
Cunha, L. L., Perazzio, S. F., Azzi, J., Cravedi, P., & Riella, L. V. (2020). Remodeling of the Immune Response With Aging: Immunosenescence and Its Potential Impact on COVID-19 Immune Response. Frontiers in Immunology, 11, 1748. https://doi.org/10.3389/fimmu.2020.01748
Cunha LL, et al. Remodeling of the Immune Response With Aging: Immunosenescence and Its Potential Impact On COVID-19 Immune Response. Front Immunol. 2020;11:1748. PubMed PMID: 32849623.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Remodeling of the Immune Response With Aging: Immunosenescence and Its Potential Impact on COVID-19 Immune Response. AU - Cunha,Lucas Leite, AU - Perazzio,Sandro Felix, AU - Azzi,Jamil, AU - Cravedi,Paolo, AU - Riella,Leonardo Vidal, Y1 - 2020/08/07/ PY - 2020/04/20/received PY - 2020/06/30/accepted PY - 2020/8/28/entrez PY - 2020/8/28/pubmed PY - 2020/9/22/medline KW - COVID-19 KW - SARS-CoV-2 KW - immunopathogenesis KW - immunosenescence KW - inflammaging SP - 1748 EP - 1748 JF - Frontiers in immunology JO - Front Immunol VL - 11 N2 - 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. SN - 1664-3224 UR - https://www.unboundmedicine.com/medline/citation/32849623/Remodeling_of_the_Immune_Response_With_Aging:_Immunosenescence_and_Its_Potential_Impact_on_COVID_19_Immune_Response_ L2 - https://doi.org/10.3389/fimmu.2020.01748 DB - PRIME DP - Unbound Medicine ER -