COVID-19 outbreak, stress, atherosclerosis and immune function
Stress is a major factor that can alter the immune system. During the lockdown due to the pandemic, a huge number of persons have developed relevant signs of psychological suffering, that can significantly affect the capacity of the organism to react to external stimuli like those represented by microorganisms. It has been known for a long time that the immune response is regulated by soluble factors which include not only numerous cytokines and chemokines, but also a large number of hormones and neurotransmitters, whose receptors are found both on cells of innate and acquired immunity. Among these molecules, glucocorticoids play a fundamental role, and are responsible for a variety of immunological effects. Psychological stress, as well as several proinflammatory cytokines, acts at the hypothalamus level, provoking the production and release of corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) that, in turn, induce the anterior pituitary gland to synthesize adrenocorticotropin hormone (ACTH), which is able to stimulate steroidogenesis in adrenocortical cells. 5,6This is crucial to give origin to cortisol, the main corticosteroid. In turn, glucocorticoids trigger a negative feedback, according to which the hypothalamic–pituitary–adrenal axis is inhibited. In general, it can be well stated that the main physiological effects of glucocorticoids go in the direction to suppress immune responses. However, these are not the only important effects described for these molecules. Atherosclerosis is a process in which ACTH and cortisol may play an important role. Acting on proinflammatory or anti-inflammatory cytokines, they can regulate vascular endothelial functionality and recruit monocytes, that can enter the wall and differentiate first into macrophages, second into foam cells. Their capability to modulate the capacity of macrophages to remove the excess free cholesterol from the atherosclerotic plaque is also crucial for maintaining an efficient endothelial functionality. 6 The pathogenesis of COVID-19 is associated with elevation of several immune plays as well as inflammatory factors which contributes to cytokine storms.