Centenarians born before 1919 are resistant to COVID-19.

Although mortality from COVID-19 progressively increases with age, there are controversial data in the literature on the probability of centenarians dying from COVID-19. Moreover, it has been claimed that men in their 90s and 100s are more resilient than women. To gain insight into this matter, we analysed, according to gender, mortality data during the first year of pandemic of Sicilian nonagenarians and centenarians. We used mortality data from the 2019 as a control. The crude excess mortality between the two years was calculated. Data on deaths of Sicilian 90 + years show that, in line with what is known about the different response to infections between the two genders, oldest females are more resilient to COVID-19 than males. Moreover, centenarians born before 1919, but not "younger centenarians", are resilient to COVID-19. This latter datum should be related to the 1918 Spanish flu epidemic, although the mechanisms involved are not clear.

Role of Sex and Age in Fatal Outcomes of COVID-19: Women and Older Centenarians Are More Resilient.

In the present paper, we have analysed the role of age and sex in the fatal outcome of COVID-19, as there are conflicting results in the literature. As such, we have answered three controversial questions regarding this aspect of the COVID-19 pandemic: (1) Have women been more resilient than men? (2) Did centenarians die less than the remaining older people? (3) Were older centenarians more resistant to SARS-CoV-2 than younger centenarians? The literature review demonstrated that: (1) it is women who are more resilient, in agreement with data showing that women live longer than men even during severe famines and epidemics; however, there are conflicting data regarding centenarian men; (2) centenarians overall did not die less than remaining older people, likely linked to their frailty; (3) in the first pandemic wave of 2020, centenarians > 101 years old (i.e., born before 1919), but not "younger centenarians", have been more resilient to COVID-19 and this may be related to the 1918 Spanish flu epidemic, although it is unclear what the mechanisms might be involved.

Distribution of KIR Genes and Their HLA Ligands in Different Viral Infectious Diseases: Frequency Study in Sicilian Population.

Natural killer (NK) cells play a role in defence against viral infections by killing infected cells or by producing cytokines and interacting with adaptive immune cells. Killer immunoglobulin-like receptors (KIRs) regulate the activation of NK cells through their interaction with human leucocyte antigens (HLA). Ninety-six Sicilian patients positive to Human Immunodeficiency Virus-1 (HIV) and ninety-two Sicilian patients positive to SARS-CoV-2 were genotyped for KIRs and their HLA ligands. We also included fifty-six Sicilian patients with chronic hepatitis B (CHB) already recruited in our previous study. The aim of this study was to compare the distribution of KIR-HLA genes/groups of these three different infected populations with healthy Sicilian donors from the literature. We showed that the inhibitory KIR3DL1 gene and the KIR3DL1/HLA-B Bw4 pairing were more prevalent in individual CHB. At the same time, the frequency of HLA-C2 was increased in CHB compared to other groups. In contrast, the HLA-C1 ligand seems to have no contribution to CHB progression whereas it was significantly higher in COVID-19 and HIV-positive than healthy controls. These results suggest that specific KIR-HLA combinations can predict the outcome/susceptibility of these viral infections and allows to plan successful customized therapeutic strategies.

An immunologist's guide to immunosenescence and its treatment.

INTRODUCTION: Aging causes several changes in the immune system, although immune aging is strongly influenced by individual immunological history, as well as genetic and environmental factors leading to inter-individual variability. AREAS COVERED: We focused on the biological and clinical meaning of immunosenescence. SARS-CoV-2 and Yellow Fever vaccine have demonstrated the clinical relevance of immunosenescence, while inconsistent results, obtained from longitudinal studies aimed at looking for immune risk phenotypes, have revealed that immunosenescence is highly context-dependent. Large projects allowed the delineation of the drivers of immune system variance, including genetic and environmental factors, sex, smoking, and co-habitation. Therefore, it is difficult to identify the interventions that can be envisaged to maintain or improve immune function in older people. That suggests that drug treatment of immunosenescence should require personalized intervention. Regarding this, we discussed the role of changes in lifestyle as a potential therapeutic approach. EXPERT OPINION: Our review points out that age is only part of the problem of immunosenescence. Everyone ages differently because is unique in genetics and experience of life and this applies even more to the immune system (immunobiography). Finally, the review shows how appreciable results in the modification of immunosenescence biomarkers can be achieved with lifestyle modification.

Immunopathology and Immunosenescence, the Immunological Key Words of Severe COVID-19. Is There a Role for Stem Cell Transplantation?

The outcomes of Coronavirus disease-2019 (COVID-19) vary depending on the age, health status and sex of an individual, ranging from asymptomatic to lethal. From an immunologic viewpoint, the final severe lung damage observed in COVID-19 should be caused by cytokine storm, driven mainly by interleukin-6 and other pro-inflammatory cytokines. However, which immunopathogenic status precedes this "cytokine storm" and why the male older population is more severely affected, are currently unanswered questions. The aging of the immune system, i.e., immunosenescence, closely associated with a low-grade inflammatory status called "inflammageing," should play a key role. The remodeling of both innate and adaptive immune response observed with aging can partly explain the age gradient in severity and mortality of COVID-19. This review discusses how aging impacts the immune response to the virus, focusing on possible strategies to rejuvenate the immune system with stem cell-based therapies. Indeed, due to immunomodulatory and anti-inflammatory properties, multipotent mesenchymal stem cells (MSCs) are a worth-considering option against COVID-19 adverse outcomes.

The Role of Immunogenetics in COVID-19.

Coronavirus disease 2019 (COVID-19) is induced by SARS-CoV-2 and may arise as a variety of clinical manifestations, ranging from an asymptomatic condition to a life-threatening disease associated with cytokine storm, multiorgan and respiratory failure. The molecular mechanism behind such variability is still under investigation. Several pieces of experimental evidence suggest that genetic variants influencing the onset, maintenance and resolution of the immune response may be fundamental in predicting the evolution of the disease. The identification of genetic variants behind immune system reactivity and function in COVID-19 may help in the elaboration of personalized therapeutic strategies. In the frenetic look for universally shared treatment plans, those genetic variants that are common to other diseases/models may also help in addressing future research in terms of drug repurposing. In this paper, we discuss the most recent updates about the role of immunogenetics in determining the susceptibility to and the history of SARS-CoV-2 infection. We propose a narrative review of available data, speculating about lessons that we have learnt from other viral infections and immunosenescence, and discussing what kind of aspects of research should be deepened in order to improve our knowledge of how host genetic variability impacts the outcome for COVID-19 patients.