Epidemiologic and Clinic Characteristics of the First Wave of the COVID-19 Pandemic in Hospitalized Patients from Galați County

The first cases of COVID-19 were reported in Wuhan Province, in China, in December 2019, spreading rapidly around the world. The World Health Organization (WHO) declared this pandemic at the beginning of March 2020 and, at the same time, the first patient in Galați County was confirmed. Both the global and the regional epidemiological evolutions have taken place with variations in incidence, which have been graphically recorded in several “waves”. We conducted a retrospective study on cases of COVID-19 infection, hospitalized between March and June 2020 in an infectious diseases clinic from Galati, in the south-east of Romania. The present paper describes the “first-wave” regional epidemiological and clinical-biological features and the evolution of the COVID-19 pandemic. A poor outcome was related to late presentation to hospital, old age, and over six comorbid conditions including Alzheimer’s disease. The high death rate among people from long-term care institutions is the consequence of the cumulative risk factors associated with immune senescence and inflammation, while COVID-19 is more likely a contributing factor to lower life expectancy.

End-Stage Renal Disease-Related Accelerated Immune Senescence: Is Rejuvenation of the Immune System a Therapeutic Goal?

End-stage renal disease (ESRD) patients exhibit clinical features of premature ageing, including frailty, cardiovascular disease, and muscle wasting. Accelerated ageing also concerns the immune system. Patients with ESRD have both immune senescence and chronic inflammation that are resumed in the so-called inflammaging syndrome. Immune senescence is particularly characterised by premature loss of thymic function that is associated with hyporesponsiveness to vaccines, susceptibility to infections, and death. ESRD-related chronic inflammation has multiple causes and participates to accelerated cardiovascular disease. Although, both characterisation of immune senescence and its consequences are relatively well-known, mechanisms are more uncertain. However, prevention of immune senescence/inflammation or/and rejuvenation of the immune system are major goal to ameliorate clinical outcomes of ESRD patients.

Vaccination as a preventative measure contributing to immune fitness

The primary goal of vaccination is the prevention of pathogen-specific infection. The indirect consequences may include maintenance of homeostasis through prevention of infection-induced complications; trained immunity that re-programs innate cells to respond more efficiently to later, unrelated threats; slowing or reversing immune senescence by altering the epigenetic clock, and leveraging the pool of memory B and T cells to improve responses to new infections. Vaccines may exploit the plasticity of the immune system to drive longer-term immune responses that promote health at a broader level than just the prevention of single, specific infections. In this perspective, we discuss the concept of “immune fitness” and how to potentially build a resilient immune system that could contribute to better health. We argue that vaccines may contribute positively to immune fitness in ways that are only beginning to be understood, and that life-course vaccination is a fundamental tool for achieving healthy aging.

Effects of Hormone Therapy and Flavonoids Capable on Reversal of Menopausal Immune Senescence

Menopause, probably the most important natural change in a woman’s life and a major component of female senescence, is characterized, inter alia, by cessation of ovarian estrogen and progesterone production, resulting in a gradual deterioration of the female immune system. Hormone replacement therapy (HRT) is used in postmenopausal women to relieve some of the peri- and postmenopausal symptoms, while there is also evidence that the therapy may additionally partially reverse menopausal immune senescence. Flavonoids, and especially isoflavones, are widely used for the treatment of menopausal symptoms, although it is not at present clear whether they can reverse or alleviate other menopausal changes. HRT reverses the menopausal CD4/CD8 ratio and also limits the general peri- and postmenopausal inflammatory state. Moreover, the increased levels of interleukins (IL)-1β, IL-6, and IL-8, as well as of tumor necrosis factor-α (TNF-α) are decreased after the initiation of HRT. However, some reports show no effect of HRT on IL-4, IL-10, and IL-12. It is thus evident that the molecular pathways connecting HRT and female immune senescence need to be clarified. Interestingly, recent studies have suggested that the anti-inflammatory properties of isoflavones possibly interact with inflammatory cytokines when applied in menopause treatments, thereby potentially reversing immune senescence. This narrative review presents the latest data on the effect of menopausal therapies, including administration of flavonoid-rich products, on age-associated immune senescence reversal with the aim of revealing possible directions for future research and treatment development.

Accelerated Immune Senescence and Biological Aging of T-cell Subsets Among ART-naive HIV-infected Men Who Have Sex With Men in Beijing, China: a Case-control Study

Background: The average lifespan of HIV-infected subjects remains shorter compared to uninfected individuals. Accelerated senescence may be responsible for this difference despite effective antiretroviral therapy (ART) with successful viral suppression. The present study aimed to assess the impact of HIV on immune and biological senescence of ART-naive HIV-infected men who have sex with men (MSM) in Beijing, China. Methods: A cross-sectional study was conducted that compared MSM HIV-infected patients and age-matched MSM HIV negative controls. Within the CD4 and CD8 population, the percentages of naive(TN), central memory(TCM), effector memory(TEM) and terminally differentiated memory(TemRA) subsets were studied and markers of senescence and activation in these cells were measured by multiparameter flow cytometry. Naive (CD45RA+) and memory (CD45RO+) CD8 T cells were purified by MACS technology. Telomere length was quantified by real-time PCR. Results: Within the CD8 T cell subsets, TN, TCM,TEM and TemRA cells showed more activation (HLA-DR+) and replicative senescence(CD28-CD57+) phenotypes in ART-naive MSM. However, in the CD4 T cell subsets, expect for TN, the percentage of senescent cells did not differ between ART-naive MSM and uninfected controls, but activated cells were upregulated in the former. The telomere length of naive and memory CD8 T cells was significantly shorter in ART-naive MSM than that of uninfected controls.Conclusion: Our results indicate that HIV-infected ART-naive MSM exhibit accelerated immune senescence with premature biological aging, which particularly affects the CD8 T-cell subsets. This highlights the strong impact of HIV on aging process of T-cell despite patient’s young age at infection and supports the importance of early control of HIV replication.

Blood Immunosenescence Signatures Reflecting Age, Frailty and Tumor Immune Infiltrate in Patients with Early Luminal Breast Cancer

Background: Immune/senescence-related host factors play a pivotal role in numerous biological and pathological process like aging, frailty and cancer. The assessment of these host factors via robust, non-invasive, and easy-to-measure blood biomarkers could improve insights in these processes. Here, we investigated in a series of breast cancer patients in which way single circulating biomarkers or biomarker panels relate to chronological age, frailty status, and tumor-associated inflammatory microenvironment. Methods: An extensive panel of blood immune/senescence markers and the tumor immune infiltrate was studied in young, middle-aged, and old patients with an early invasive hormone-sensitive, HER2-negative breast cancer. In the old group, clinical frailty was estimated via the G8-scores. Results: Several three-blood biomarker panels proved to be able to separate old chronological age from young age very efficiently. Clinically more important, several three-blood biomarker panels were strongly associated with clinical frailty. Performance of blood biomarker panels for prediction of the tumor immune infiltrate was lower. Conclusion: Immune/senescence blood biomarker panels strongly correlate with chronological age, and clinically more importantly with frailty status in early breast cancer patients. They require further investigation on their ability to provide a more complete picture on clinical frailty status and direct personalized therapy in older persons.