Role of Aging and the Immune Response to Respiratory Viral Infections: Potential Implications for COVID-19

Abstract

Aging impairs immunity to promote diseases, especially respiratory viral infections. The current COVID-19 pandemic, resulting from SARS-CoV-2, induces acute pneumonia, a phenotype that is alarmingly increased with aging. In this article, we review findings of how aging alters immunity to respiratory viral infections to identify age-impacted pathways common to several viral pathogens, permitting us to speculate about potential mechanisms of age-enhanced mortality to COVID-19. Aging generally leads to exaggerated innate immunity, particularly in the form of elevated neutrophil accumulation across murine and large animal studies of influenza infection. COVID-19 patients who succumb exhibit a 2-fold increase in neutrophilia, suggesting that exaggerated innate immunity contributes to age-enhanced mortality to SARS-CoV-2 infection. Further investigation in relevant experimental models will elucidate the mechanisms by which aging impacts respiratory viral infections, including SARS-CoV-2. Such investigation could identify therapies to reduce the suffering of the population at large, but especially among older people, infected with respiratory viruses.

Innate Immunity and Influenza A Virus Pathogenesis: Lessons for COVID-19

“…There is also extensive evidence that myeloid cells contribute to damaging inflammation in the specific setting of severe IAV in some cases without improving control of the virus. Excessive neutrophil infiltration was found to underlie the increased mortality from IAV in older adults (Kulkarni et al, 2019;Chen et al, 2020). In contrast to alveolar macrophages, recruited monocytes do not necessarily mediate dampening effects on inflammation and can do the opposite (Lin et al, 2008(Lin et al, , 2011.…”

“…Clearly further research on how known risk factors for severe IAV infection impact innate immunity is an important direction for future research. Severe COVID 19 appears to share a number of the same risk factors, including cardiovascular disease, COPD, diabetes, obesity, and old age (Chen et al, 2020). There is a striking association of severe COVID 19 illness with thrombosis which may have similar underpinnings as thrombosis occurring with severe IAV.…”

“…For instance although obesity can adversely impact adaptive immunity it can also be linked to an underlying inflammatory bias that may predispose to excessive inflammatory response to infection (Hagau et al, 2010;Almond et al, 2013). Similarly old age is associated both with impaired adaptive immunity and, in some subjects, an underlying inflammatory state (termed "inflammaging" by some) (Elias et al, 2017;Chen et al, 2020). These two features may be linked.…”

Cellular senescence: friend or foe to respiratory viral infections?

“…Given this, how cellular senescence impacts the host response to acute respiratory viral infections is particularly relevant. Older people experience increased susceptibility to respiratory viruses such as influenza, respiratory syncytial virus (RSV), SARS, and now SARS-CoV-2 [88][89][90][91][92]. With COVID-19, the disease that results from SARS-CoV-2 infection, older people are ~20 fold more likely to die than younger people [93].…”

“…Specifically, both CD4 + and CD8 + T cells from aged hosts (e.g., rodents and humans) exhibit a reduced proliferative capacity associated with downregulation of surface costimulatory receptors, CD27 and CD28, which is accompanied by shortened telomeres. Collectively, these alterations within the immune system with aging result in an impaired ability to fight viral infections and lead to reduced vaccine efficiency [90]. In addition to natural aging, chronic viral infections (e.g., HIV and cytomegalovirus infection) also induce a phenotype of reduced T cell function (i.e., reduced proliferation and cytokine secretion) that shares features with immunosenescence [100,101].…”