Aging, inflammaging and immunosenescence as risk factors of severe COVID-19

Abstract

Coronavirus disease 2019 (COVID-19) is a respiratory infectious disease caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 is characterized by having a heterogeneous disease course, ranging from asymptomatic and mild symptoms to more severe and critical cases. In most cases the severity of COVID-19 is related to host factors, especially deregulation of the immune response in patients. Even if COVID-19 indiscriminately affects individuals of different age group, ethnicity and economic status; most severe cases and disproportional mortality occur in elderly individuals. This point out that aging is one risk factor for unfavourable clinical outcomes among COVID-19 patients. The biology of aging is a complex process; Aging can alter the structure and function of cells, tissues, and organs resulting in impaired response to stress. Alongside with other systems, the immune system is also affected with the aging process. Immunosenescence is an age associated change in the immune system that affects the overall response to immunological challenges in the elderly. Similarly, apart from the normal inflammatory process, aging is associated with a low grade, sterile, chronic inflammation which is termed as inflammaging. We hypothesized that inflammaging and immunosenescence could play an important role in SARS-CoV-2 pathogenesis and poor recovery from COVID-19 in elderly individuals. This review summarizes the changes in the immune system with age and how these changes play part in the pathogenesis of SARS-CoV-2 and clinical outcome of COVID-19 which could add to the understanding of age associated targeted immunotherapy in the elderly.

Antibody response to third and fourth BNT162b2 mRNA booster vaccinations in healthcare workers in Tokyo, Japan

“…These data suggest that the effect of a second vaccination on the antibody response depends on the age of the recipient, while a third vaccination induces an antibody response regardless of age, through at least 7 months post-vaccination. Given the high risk of COVID-19 in elderly [ 24 ], administration of a third dose vaccine would therefore be a valuable option especially in the elderly.…”

Spontaneous onset of cellular markers of inflammation and genome instability during aging in the immune niche of the naturally short-lived turquoise killifish (Nothobranchius furzeri)

“…However, aging of the immune system is not solely associated with "lowered" immune effector function. Aging in the immune system is often characterized by hyperreactive immune responses 45 and autoimmune dysfunctions, where the immune system is no longer able to properly discriminate self from non-self, resulting in increased auto-reactivity, ultimately leading to organ failure. Aging in the immune system is further characterized by a generalized, systemic, and chronic low-grade inflammatory state that has been named "inflammaging" 7 .…”

Multiscale network analysis identifies potential receptors for SARS‐CoV‐2 and reveals their tissue‐specific and age‐dependent expression

“…For example, Pence [62] concluded that pathological monocyte response in COVID-19 showed a similar pattern to those in aging, suggesting that monocytes may contribute to the disproportionate severity of COVID-19 in older adults. Tizazu et al [63] seconded this finding of proinflammatory monocytes both in aging and in severe COVID-19 cases. The lack of enrichment of STSPR-AD tissues for the heart and kidney signatures in the study by Delorey et al [61] emphasizes the role of monocytes in the age-related pathology of COVID-19.…”