Aging versus youth: Endocrine aspects of vulnerability for COVID-19

Abstract

Coronavirus Disease 2019 (COVID-19) is characterized with a wide range of clinical presentations from asymptomatic to severe disease. In patients with severe disease, the main causes of mortality have been acute respiratory distress syndrome, cytokine storm and thrombotic events. Although all factors that may be associated with disease severity are not yet clear, older age remains a leading risk factor. While age-related immune changes may be at the bottom of severe course of COVID-19, age-related hormonal changes have considerable importance due to their interactions with these immune alterations, and also with endothelial dysfunction and comorbid cardiometabolic disorders. This review aims to provide the current scientific evidence on the pathogenetic mechanisms underlying the pathway to severe COVID-19, from a collaborative perspective of age-related immune and hormonal changes together, in accordance with the clinical knowledge acquired thus far.

Keywords: Aging, biological; COVID-19; Endocrine System; Immunity; SARS-CoV-2; Senescence.

Fig. 1

The interrelation of age-related hormonal and immune alterations in severe COVID-19. Biological aging and interconnected age-related alterations in the immune and endocrine systems leave older adults vulnerable to infections such as COVID-19. COVID-19: Coronavirus disease 2019

Fig. 2

Immunosenescence mechanisms paving the way for severe COVID-19. Immunosenescence is the gradual unfavorable alterations in innate and adaptive immune mechanisms with aging. Diminished pathogen recognition, attenuated virus-induced IFN-I respose and dysfunctional macrophages/monocytes are the drawbacks of innate immunity that fail to provide the first line of defense to control viral replication. Impaired antigen presentation and costimulation further complicate generation of effective cellular and humoral immune responses by aging T&B cell populations. Dashed lines indicate the probable contributions of SARS-CoV-2 infection to these age-related immunological alterations. CD: cluster of differentiation; DC: dendritic cell; DN: double negative; GM-CSF: granulocyte–macrophage colony-stimulating factor; HLA-DR: human leukocyte antigen – DR isotype; IFN-I: type-I interferon; PD-1: Programmed Death 1; Th: helper T; TIM-3: T cell immunoglobulin mucin domain-3; TLR: toll-like receptor; Treg: regulatory T

Fig. 3

Age-related endocrine and immunologic factors leading to severe COVID-19. Unfavorable aging-related changes in the immune system, age-related hormonal alterations, increased number of comorbidities along with visceral adiposity and related disorders conspire to vulnerability of older adults to severe COVID-19. In addition, older age (cumulative oxidative stress and inflammaging) and certain comorbidities (e.g. diabetes and cardiovascular diseases) already characterized with endothelial dysfunction accompanied by age-related impairment in angiogenesis are the other links of this chain of events leading to severe COVID-19. COVID-19: Coronavirus disease 2019; ACE2: Angiotensin converting enzyme 2; Ang-II: Angiotensin-II; AT-1: Angiotensin receptor-1; RAAS: Renin–angiotensin–aldosterone system; GH: Growth hormone; DHEA: Dehydroepiandrosterone

Fig. 4

The possible causes and significance of sarcopenia and visceral obesity in poor COVID-19 outcomes. Increased physical inactivity and stress due to home confinement strategies during COVID-19 pandemic may have affected older adults in a more rapid and irrecoverable manner than the young. Along with comorbid diseases, stress-related overeating and age-related hormonal alterations may contribute to the emergence or worsening of visceral fat accumulation, sarcopenia/sarcopenic obesity, and related cardiometabolic disorders. In case of COVID-19, sarcopenia would further aggravate and might be related to severe COVID-19 and even death. COVID-19: Coronavirus disease 2019