Remodeling of the Immune Response With Aging: Immunosenescence and Its Potential Impact on COVID-19 Immune Response

Abstract

Elderly individuals are the most susceptible to an aggressive form of coronavirus disease (COVID-19), caused by SARS-CoV-2. The remodeling of immune response that is observed among the elderly could explain, at least in part, the age gradient in lethality of COVID-19. In this review, we will discuss the phenomenon of immunosenescence, which entails changes that occur in both innate and adaptive immunity with aging. Furthermore, we will discuss inflamm-aging, a low-grade inflammatory state triggered by continuous antigenic stimulation, which may ultimately increase all-cause mortality. In general, the elderly are less capable of responding to neo-antigens, because of lower naïve T cell frequency. Furthermore, they have an expansion of memory T cells with a shrinkage of the T cell diversity repertoire. When infected by SARS-CoV-2, young people present with a milder disease as they frequently clear the virus through an efficient adaptive immune response. Indeed, antibody-secreting cells and follicular helper T cells are thought to be effectively activated in young patients that present a favorable prognosis. In contrast, the elderly are more prone to an uncontrolled activation of innate immune response that leads to cytokine release syndrome and tissue damage. The failure to trigger an effective adaptive immune response in combination with a higher pro-inflammatory tonus may explain why the elderly do not appropriately control viral replication and the potential clinical consequences triggered by a cytokine storm, endothelial injury, and disseminated organ injury. Enhancing the efficacy of the adaptive immune response may be an important issue both for infection resolution as well as for the appropriate generation of immunity upon vaccination, while inhibiting inflamm-aging will likely emerge as a potential complementary therapeutic approach in the management of patients with severe COVID-19.

Prognostic role of nutritional status in elderly patients hospitalized for COVID-19: a monocentric study

“…The median age was 83 years (76-91.5). During a median follow-up of 11 (8)(9)(10)(11)(12)(13)(14)(15) days, 43 (39.4%) patients died. Most of the patients enrolled reported other underlying comorbidities: arterial hypertension (75.2%), cognitive impairment (44%) and atrial fibrillation (29.4%) were the most common.…”

“…The alterations of the immune system of the elderly patients may have an important prognostic role. Indeed, the remodelling of the immune response observed among the elderly could explain the increased prevalence of more aggressive clinical manifestations of COVID-19 in these patients [9]. In particular, the state of chronic inflammation when not under control loses its defensive role and turns into a damaging state to the whole organism; the practical consequence is that inflamm-aging predicts frailty, and is associated with higher mortality.…”

Clinical characteristics on admission predict in-hospital fatal outcome in patients aged ≥75 years with novel coronavirus disease (COVID-19): a retrospective cohort study

“…The immunosenescence and malnutrition could lead to a deficiency in control of viral replication. The elderly are more prone to an uncontrolled activation of innate immune response that leads to cytokine release syndrome and tissue damage [21]. Nutritional deficits are most prevalent in older population, thus contributing to weakening of the immune system [22].…”

Critical care triage during the COVID-19 pandemic in South Africa: A constitutional imperative!

“…This is likely to contribute to the significantly higher COVID-19-related mortality observed in elderly people. [9,18,19] However, chronological age should not be the sole criterion for determining ICU admission, and this is certainly not advocated by the CCSSA. [4,8] Bioethicists have argued that poor prognosis based on current and underlying disease should be the main allocation criterion for treatment during a crisis and, if advanced age correlates with this criterion, to use it as a prioritising factor should not be regarded as unfairly discriminatory.…”