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.

Public health concerns and increased risk of severe COVID-19 disease through androgen use

“…Because of this, De Lorenzo et al [19] outlined some of the nutritional demands and supplementation, as well as physical therapy and motor rehabilitation, that is necessary for recovering patients. In light of this article's specific purpose, and in the context of androgen use and COVID-19, there is also emerging evidence (although conceptual/suppositional) that testosterone, and potentially estrogen, repurposing may be particularly useful for those recovering from severe COVID-19 symptoms as an anabolic agent [20,21]. This argument is, perhaps, especially relevant when the work of Rastrelli et al [22] is taken into account.…”

“…Here, they analysed data related to 31 male patients affected by COVID-19 pneumonia who had subsequently recovered. Whilst a limited sample, Rastrelli et al [22] indicated that patients who had lower testosterone concentrations were subject to worse outcomes from COVID-19 infection, especially within older adults for whom hormone replacement therapy may be indicated [21,[23][24][25].…”

Dementia, infections and vaccines: 30 years of controversy

“…Several age-related endocrine and immunologic factors predispose older individuals to being disproportionately affected by long-COVID. These include cellular and immuno-senescence, inflammaging, lower levels of physical activity, undernutrition, and more frequent comorbidities [ 85 ]. Importantly, the general symptoms in older individuals frequently feature cognitive impairment, the mechanisms of which are multiple.…”

“…Second, COVID-19 infection may trigger reactivation of latent herpesviruses, compounding the inflammation. Third, there may be disruption of the integrity of the blood–brain-barrier, causing neuroinflammation and injury [ 85 ]. A recent retrospective cohort study in over 6.2 million adults aged 65 years and over found that people with COVID-19 had a significantly increased risk of new onset AD within a year after the initial COVID-19 diagnosis (hazard ratio HR:1.69, 95% CI 1.53–1.72) [ 86 , 87 ].…”

Revisiting the endocrine and metabolic manifestations of COVID-19 two years into the pandemic

“…The increasingly recognized prognostic role of these common metabolic conditions has raised further attention to the importance of nutritional aspects before, during and after COVID-19 [9,10]. Male sex and advanced age were also associated with disease severity although the role of sex hormones is not yet completely clarified [11,12].…”