Implication of Aging Related Chronic Neuroinflammation on COVID-19 Pandemic

Abstract

SARS-CoV-2, the virus responsible for the COVID-19 pandemic, leads to a respiratory syndrome and other manifestations. Most affected people show no or mild symptoms, but the risk of severe disease and death increases in older people. Here, we report a narrative review on selected studies targeting aging-related chronic neuroinflammation in the COVID-19 pandemic. A hyperactivation of the innate immune system with elevated levels of pro-inflammatory cytokines occurs during severe COVID-19, pointing to an important role of the innate immune dysregulation in the disease outcome. Aging is characterized by a general condition of low-grade inflammation, also connected to chronic inflammation of the brain (neuroinflammation), which is involved in frailty syndrome and contributes to several age-associated diseases, including neurodegenerative and neuropsychiatric disorders. Since neuroinflammation can be induced or worsened by the virus infection itself, as well as by stressful conditions like those linked to the recent pandemic, the role of neuroinflammatory mechanisms could be central in a vicious circle leading to an increase in the mortality risk in aged COVID-19 patients. Furthermore, triggered neuroinflammatory pathways and consequent neurodegenerative and neuropsychiatric conditions might be potential long-term complications of COVID-19. In order to provide insights to help clinicians in identifying patients who progress to a more severe case of the disease, this review underlines the potential implications of aging-related neuroinflammation in COVID-19 pandemic.

Involvement of Interleukin-1 Receptor-Associated Kinase 4 and Interferon Regulatory Factor 5 in the Immunopathogenesis of SARS-CoV-2 Infection: Implications for the Treatment of COVID-19

“…Similar reasoning may be applied to initial high viral load or prolonged exposure, which could overwhelm adaptive immunity and push the balance toward increased, but less effective, innate immune activation and "cytokine storm." A related unresolved difficulty is management of chronic COVID-19 symptoms, especially if associated with identifiable chronic inflammation, including neurological sequelae (115). Indeed, the predisposing conditions for hyperinflammatory COVID-19 are likely to overlap with at least some of those responsible for post-infection sequelae.…”

“…Changes in T and B cell function in metabolic inflammation, as well as in the elderly and, more acutely, in COVID-19 are all broadly similar, in that innate function is relatively preserved, but T cell and B cell compartments exhibit features of "exhaustion" or "senescence" (73, 113,114). Therefore, pre-existing metabolic inflammation across a variety of chronic conditions presages an unfavorable course and outcome of COVID-19 (115,116).…”

Neurologic and Neuroscientific Evidence in Aged COVID-19 Patients

“…Inflammaging is characterized by a hyperactive yet ineffective alert system with age-related process of systemic inflammation and autoimmune predisposition (Thomas et al, 2020 ). Emerging literature suggests that chronic systemic comorbidities and aging (known risk factors for severe COVID-19 disease) are associated with upregulation of inflammation and predisposition to neuroinflammatory and neurodegenerative conditions (Bossù et al, 2020 ; Scheiblich et al, 2020 ). Neuroinflammation also results from sustained anti-viral immune response with propagation of inflammation from the periphery to the brain through various pathways as previously described (Dantzer et al, 2008 ; Capuron and Miller, 2011 ).…”

COVID-19: a new emerging respiratory disease from the neurological perspective

“…it is worthy to mention that neuropsychiatric aspects of COVID-19, even in healthy individuals, must be taken into consideration. Such disorders can occur due to prolonged stressful situations (e.g., the fear of infection, social distancing, and economic pressure) that may induce post-traumatic stress disorder and other neuropsychiatric syndromes (Bossù et al 2020 ).…”