Immunosenescence and COVID-19.

Ageing is associated with modified function of both innate and adaptive immunity. It is believed that changes occurring in ageing immune system are responsible for increased severity and deadliness of COVID-19 in the elderly. Although supported by statistics and epidemiology, these finding do not compute at the mechanistic level as depending solely on chronological and biological ageing. The phenomena describing changes in the aging immune system are immunosenescence and inflammageing, which develop in time depending on challenges to the individual immune system (immunobiography). Thus, "richer" immunobiography (in addition to other factors, including genetic, epigenetics or metabolic) may adversely affect the reactivity to the SARS-CoV-2 not only at later decades of life, but also earlier, in young and middle-aged individuals. On the other hand, infection with SARS-CoV-2 is affecting the function of both innate and adaptive branches of the immune system, adding to the individual immunobiography. Summarizing, immunosenescence and inflammaging may aggravate, but also may be aggravated by SARS-CoV-2 infection.

Immunosenescence and Altered Vaccine Efficiency in Older Subjects: A Myth Difficult to Change.

Organismal ageing is associated with many physiological changes, including differences in the immune system of most animals. These differences are often considered to be a key cause of age-associated diseases as well as decreased vaccine responses in humans. The most often cited vaccine failure is seasonal influenza, but, while it is usually the case that the efficiency of this vaccine is lower in older than younger adults, this is not always true, and the reasons for the differential responses are manifold. Undoubtedly, changes in the innate and adaptive immune response with ageing are associated with failure to respond to the influenza vaccine, but the cause is unclear. Moreover, recent advances in vaccine formulations and adjuvants, as well as in our understanding of immune changes with ageing, have contributed to the development of vaccines, such as those against herpes zoster and SARS-CoV-2, that can protect against serious disease in older adults just as well as in younger people. In the present article, we discuss the reasons why it is a myth that vaccines inevitably protect less well in older individuals, and that vaccines represent one of the most powerful means to protect the health and ensure the quality of life of older adults.

Immune system aging and the aging-related diseases in the COVID-19 era.

The interest in the process of aging, and specifically in how aging affects the working of our immune system, has recently enormously grown among both specialists (immunologists and gerontologists) and representatives of other disciplines of health sciences. An obvious reason for this interest is the current pandemics of COVID-19, known to affect the elderly more than younger people. In this paper current knowledge about mechanisms and complex facets of human immune system aging is presented, stemming from the knowledge about the working of various parts of the immune system, and leading to understanding of immunological mechanisms of chronic, inflammatory, aging-related diseases and of COVID-19.

The dual role of the immune system in the course of COVID-19. The fatal impact of the aging immune system.

COVID-19 is a highly contagious respiratory disease caused by the novel coronavirus SARS-CoV-2. Since October 2020 the second wave of the pandemic has been observed around the world, as pathogen specific herd immunity has not been built yet. Moreover, the current, more contagious pathogen carrying the D614G mutation has become the globally dominant form of SARS-CoV-2. In this article we present the current state of knowledge on the impact of ACE2 and the reninangiotensin system (RAS) and the innate immune system on different outcomes of COVID-19. Especially, we point out the dual role of the immune system and ACE2 in pathogenesis of the disease. Namely, at the initial stage of the infection anti-viral activity of innate immunity is responsible for inhibition of SARS-CoV-2 replication. On the other hand, a dysregulated immune response may cause the detrimental hyperinflammation ("cytokine storm") responsible for the severe course of the disease. Concomitantly, we analyse the roles of ACE2 in both facilitation of infection and abrogation of its effects, as the major cellular entry receptor for SARS-CoV-2 and an important enzyme responsible for tissue protection, respectively. Finally, we discuss the dominant impact of aging on the fatal outcome of COVID-19.