Patho-Physiology of Aging and Immune-Senescence: Possible Correlates With Comorbidity and Mortality in Middle-Aged and Old COVID-19 Patients

Abstract

During the last 2 years, the entire world has been severely devastated by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic (COVID-19) as it resulted in several million deaths across the globe. While the virus infects people indiscriminately, the casualty risk is higher mainly in old, and middle-aged COVID-19 patients. The incidences of COVID-19 associated co-morbidity and mortality have a great deal of correlation with the weakened and malfunctioning immune systems of elderly people. Presumably, due to the physiological changes associated with aging and because of possible comorbidities such as diabetes, hypertension, obesity, cardiovascular, and lung diseases, which are more common in elderly people, may be considered as the reason making the elderly vulnerable to the infection on one hand, and COVID-19 associated complications on the other. The accretion of senescent immune cells not only contributes to the deterioration of host defense, but also results in elevated inflammatory phenotype persuaded immune dysfunction. In the present review, we envisage to correlate functioning of the immune defense of older COVID-19 patients with secondary/super infection, increased susceptibility or aggravation against already existing cancer, infectious, autoimmune, and other chronic inflammatory diseases. Moreover, we have discussed how age-linked modulations in the immune system affect therapeutic response against administered drugs as well as immunological response to various prophylactic measures including vaccination in the elderly host. The present review also provides an insight into the intricate pathophysiology of the aging and the overall immune response of the host to SARS-CoV-2 infection. A better understanding of age-related immune dysfunction is likely to help us in the development of targeted preemptive strategies for deadly COVID-19 in elderly patients.

Keywords: COVID-19; SARS-CoV-2; comorbidities; immunosenescence; inflammaging; innate and adaptive immune system.

FIGURE 1

Age-linked modifications in the innate and adaptive immune systems with relevance to COVID-19 are depicted in this illustration. SARS-CoV-2 mediated infliction of parenchymal cells (through ACE2 receptor) ensues in activation of PRR of the innate immune system of the host. With age, cellular activities and signaling become deranged. This hampers the innate activation of an already diminished adaptive immune system. The abnormalities result in “inflammaging” from proinflammatory innate immune responses and adaptive immunological immunosenescence.

FIGURE 2

Effect of Immunosenescence on chronic viral infection and immunity. Major components of both the innate and adaptive immune systems alter as people age. Innate immune cells can activate IFN pathways in response to viral infection in order to clear virus-infected cells. Reduced IFN production can be caused by age-related abnormalities in innate immune cells. Persistent viral infection can lead to significant changes in adaptive immunity, particularly T cell composition and function. There are fewer naive T cells in the aged, but there are more senescent, inflationary, and or exhausted T cells that are functionally inert or dormant.