Aging, Immunity, and COVID-19: How Age Influences the Host Immune Response to Coronavirus Infections?

Abstract

The novel coronavirus severe acute respiratory syndrome coronavirus 2 causing the Coronavirus disease (COVID-19) pandemic has ravaged the world with over 72 million total cases and over 1.6 million deaths worldwide as of early December 2020. An overwhelming preponderance of cases and deaths is observed within the elderly population, and especially in those with pre-existing conditions and comorbidities. Aging causes numerous biological changes in the immune system, which are linked to age-related illnesses and susceptibility to infectious diseases. Age-related changes influence the host immune response and therefore not only weaken the ability to fight respiratory infections but also to mount effective responses to vaccines. Immunosenescence and inflamm-aging are considered key features of the aging immune system wherein accumulation of senescent immune cells contribute to its decline and simultaneously increased inflammatory phenotypes cause immune dysfunction. Age-related quantitative and qualitative changes in the immune system affect cells and soluble mediators of both the innate and adaptive immune responses within lymphoid and non-lymphoid peripheral tissues. These changes determine not only the susceptibility to infections, but also disease progression and clinical outcomes thereafter. Furthermore, the response to therapeutics and the immune response to vaccines are influenced by age-related changes within the immune system. Therefore, better understanding of the pathophysiology of aging and the immune response will not only help understand age-related diseases but also guide targeted management strategies for deadly infectious diseases like COVID-19.

Keywords: COVID-19; SARS-CoV; aging; coronavirus; immune response; immunity; infection.

FIGURE 1

Schematic shows age-related changes in the innate and adaptive immune system with relevance to COVID-19. As the SARS-CoV-2 enters parenchymal cells expressing the ACE2 receptor, it activates PRR of the innate immune system. With aging, there is an imbalance in cellular functions and signaling, decreasing innate activation of an already weakened adaptive immune system. These imbalances lead to “inflammaging” from proinflammatory innate immune responses and immunosenescence of the adaptive immune response.

FIGURE 2

Aging and tissues in immunity. Aging is accompanied by the decline in function of lymphoid and non-lymphoid tissues involved in the host immune response. Degeneration of primary lymphoid organs lowers production of naive T and B lymphocytes which results in reduced migration to secondary lymphoid organs and to sites of antigen encounter. Additionally, the lungs and extrapulmonary organs are susceptible to accumulation of proinflammatory cells and mediators.