Immunosenescence and inflamm-ageing in COVID-19.

The destructive effects of coronavirus disease 2019 (COVID-19) on the elderly and people with cardiovascular disease have been proven. New findings shed light on the role of aging pathways on life span and health age. New therapies that focus on aging-related pathways may positively impact the treatment of this acute respiratory infection. Using new therapies that boost the level of the immune system can support the elderly with co-morbidities against the acute form of COVID-19. This article discusses the effect of the aging immune system against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the pathways affecting this severity of infection.

Systematic Review of Biologic Correlates of Frailty in Solid Tumors: Implications for Brain Tumors

BACKGROUND: Cancer and cancer treatments contribute to accelerated aging and frailty, which is present in over 50% of adult cancer survivors and increases vulnerability to poor outcomes. Biomarkers of frailty would allow for early identification and timely interventions. The purpose of this review is to synthesize the current literature examining biomarkers of frailty across solid tumor patients, including primary brain tumors (PBT). METHOD(S): The systematic review was conducted using preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines. PubMed, Web of Science, and Embase, were searched by the medical librarian (D.C.) of all reports from the inception to December 08, 2021. Inclusion criteria were: a) English language, b) biomarkers of aging hallmarks, c) association between biomarkers and frailty. Studies were limited to human solid tumors. Two reviewers (D.S. and B.P.S.) independently screened titles, s, and full-text articles using Covidence platform with conflict resolution by the third researcher (T.S.A.). Included studies were independently evaluated for quality assessment using NIH tools for Observational Cohort, Cross-Sectional and Case-Control studies. RESULT(S): In total, 915 reports were screened and 15 full-text articles were included for the review. Studies were most commonly in breast tumors with no PBTs identified. Most were cross-sectional using small sample sizes. Fried, Balducci, and Leuven Oncogeriatric Frailty tools and cytokines (i.e. Interleukin-6 and C-reactive protein) were commonly used. Increased inflammatory response was the prevalent identified mechanism. Threats to internal validity of the studies were the use of unvalidated cut-off scores or modification of existing tools in about 50% of studies. Only six studies were rated as good using quality assessment ratings. CONCLUSION(S): Varied use of frailty measures and nonspecific blood biomarkers limited conclusions for mechanisms of frailty in cancer survivors. There are missed opportunities in neuro-oncology;inclusion of frailty assessment and biomarkers is instrumental to advancing science in PBTs.

Single-center experience in robotic-assisted Colorectal Surgery during COVID pandemic: First 72 cases

Aim: To present an analysis of The first 2-years' experience of robotic-assisted Colorectal procedures (RACp) using The DaVinci Xi platform. Method(s): This data were prospectively collected and include 72 RACp between February 2020 and December 2021.Indications were: malignancy in 74.3%, diverticular disease 10%, inflammatory bowel disease 8.6%, rectal prolapse 4.3%, intussusception 1.4% and recurrent volvulus 1.4%. Result(s): Over The 13-month study period, 72 RACp were performed including elective 57 cases and 15 semi-elective cases. These comprised: 25 right hemicolectomies, 25 high anterior resections, 6 extended right hemicolectomies,4 low anterior resections, 4 subtotal colectomies 2 restorative proctectomies, 3 abdominoperineal excisions of The rectum, 3 rectopexies that were performed. 51.2% were female and 48.6% were male with a median age of 45 years (22-85 years) and The median body mass index was 31 (18-46) kg/m2. Preoperative American Society of Anaesthesiology scores were reported as 1-2 in 72.9% (n=51) of patients and 27.1%(n=19) as 3. The median length of stay was 5 days (1-35), with readmission rate within 30 days of 8.6% (n=6) that were resolved conservatively. The mean operating time was 268 minutes and The mean console operative time was 158 minutes, with only 3 (4.3%) reported cases of conversion to open. The incidence of postoperative complications was 24.3% (Clavien-Dindo (CD) I/II-12.9%, CD III-10%, and CD V-1 case with superimposed COVID 19 within 30 days. Conclusion(s): RACp is a safe and viable modality in The treatment of Colorectal conditions and can be introduced safely with appropriate guidance and proctorship.

Immunosenescence is a therapeutic target for frailty in older adults: a narrative review.

Background and Objective: Aging refers to a progressive decrease in functional performance, leading to increased mortality risk. At present, life expectancy is increasing worldwide and is expected to exceed 80 years by 2040. However, this increase in life expectancy also indicates a rise in the incidence and prevalence of diseases, such as cardiovascular, neurological, musculoskeletal, and oncological diseases, which are associated with aging. The exact underlying mechanisms of aging remain unknown, and whether it is a programmed process or the consequence of an accumulation of stress events remains unclear. Thus, more scientific research is needed to improve the management of complex and frail patients. Methods: Several databases were searched with the following key words: immunosenescence, inflamm-aging, frailty, sarcopenia and skeletal muscle, etc. Key Content and Findings: Skeletal muscle is the core phenotype of frailty and sarcopenia. Immune aging and skeletal muscle decline interplay with each other and form a vicious circle. Maintaining muscle health is beneficial for immune function and delays the onset of frailty. Particularly, in the context of the ongoing corona virus disease (COVID)-19 pandemic, studies have shown that the elderly are more prone to the consequences of the SARS-CoV-2 virus. It has been reported that the rates of hospitalization in the 65-74, 75-84, and ≥85 years old group were 5×, 8×, and 10× greater than the 18-29 years old group, with corresponding COVID-19-related deaths being 60×, 140×, and 330× that of the younger reference group, respectively. Considering the above, this review aims to discuss the relationship between immunosenescence, skeletal muscle, and frailty, and to explore immunosenescence as a potential therapeutic target to prevent frailty and extend healthspan, with some emphasis on the effects of the COVID-19 pandemic on the elderly. Conclusions: Immunosenescence is a promising potential therapeutic target for frailty and is worthy of further investigation.

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.

Triple jeopardy in ageing: COVID-19, co-morbidities and inflamm-ageing.

Covid-19 endangers lives, has disrupted normal life, changed the way medicine is practised and is likely to alter our world for the foreseeable future. Almost two years on since the presumptive first diagnosis of COVID-19 in China, more than two hundred and fifty million cases have been confirmed and more than five million people have died globally, with the figures rising daily. One of the most striking aspects of COVID-19 illness is the marked difference in individuals' experiences of the disease. Some, most often younger groups, are asymptomatic, whereas others become severely ill with acute respiratory distress syndrome (ARDS), pneumonia or proceed to fatal organ disease. The highest death rates are in the older and oldest age groups and in people with co-morbidities such as diabetes, heart disease and obesity. Three major questions seem important to consider. What do we understand about changes in the immune system that might contribute to the older person's risk of developing severe COVID-19? What factors contribute to the higher morbidity and mortality in older people with COVID-19? How could immunocompetence in the older and the frailest individuals and populations be supported and enhanced to give protection from serious COVID-19 illness?

Different aspects of frailty and COVID-19: points to consider in the current pandemic and future ones.

BACKGROUND: Older adults at a higher risk of adverse outcomes and mortality if they get infected with Severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2). These undesired outcomes are because ageing is associated with other conditions like multimorbidity, frailty and disability. This paper describes the impact of frailty on coronavirus disease 2019 (COVID-19) management and outcomes. We also try to point out the role of inflamm-ageing, immunosenescence and reduced microbiota diversity in developing a severe form of COVID-19 and a different response to COVID-19 vaccination among older frail adults. Additionally, we attempt to highlight the impact of frailty on intensive care unit (ICU) outcomes, and hence, the rationale behind using frailty as an exclusion criterion for critical care admission. Similarly, the importance of using a time-saving, validated, sensitive, and user-friendly tool for frailty screening in an acute setting as COVID-19 triage. We performed a narrative review. Publications from 1990 to March 2021 were identified by searching the electronic databases MEDLINE, CINAHL and SCOPUS. Based on this search, we have found that in older frail adults, many mechanisms contribute to the severity of COVID-19, particularly cytokine storm; those mechanisms include lower immunological capacity and status of ongoing chronic inflammation and reduced gut microbiota diversity. Higher degrees of frailty were associated with poor outcomes and higher mortality rates during and after ICU admission. Also, the response to COVID-19 vaccination among frail older adults might differ from the general population regarding effectiveness and side effects. Researches also had shown that there are many tools for identifying frailty in an acute setting that could be used in COVID-19 triage, and before ICU admission, the clinical frailty scale (CFS) was the most recommended tool. CONCLUSION: Older frail adults have a pre-existing immunopathological base that puts them at a higher risk of undesired outcomes and mortality due to COVID-19 and poor response to COVID-19 vaccination. Also, their admission in ICU should depend on their degree of frailty rather than their chronological age, which is better to be screened using the CFS.

Aging correlates with lower threshold cycle values for RdRP/RdRP+S genes during molecular detection of SARS-CoV-2.

RT-qPCR is the most reliable molecular method for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we analyzed results of RT-qPCR obtained for 3044 patients diagnosed as SARS-CoV-2-positive using four different molecular tests utilizing five RNA sequences. The analysis showed that patients' age inversely correlates with threshold cycle (Ct) values for RdRP gene (LightMix® Modular Wuhan CoV RdRP-gene by Roche Diagnostics) and RdRP+S genes (MutaPLEX® Coronavirus RT-PCR kit by Immundiagnostic). At the same time, there was no correlation between age and Ct values for E, N, and ORF1ab genes. When patients were grouped by age, mean Ct values for RdRP gene in older patients were significantly lower compared with younger individuals. Collectively, our report indicates that older SARS-CoV-2-infected individuals exhibit higher viremia at diagnosis than younger patients, which may reflect impaired functioning of their immune response and predispose to more severe disease and worse prognosis.

The role of extracellular DNA in COVID-19: Clues from inflamm-aging.

Epidemiological data convey severe prognosis and high mortality rate for COVID-19 in elderly men affected by age-related diseases. These subjects develop local and systemic hyper-inflammation, which are associated with thrombotic complications and multi-organ failure. Therefore, understanding SARS-CoV-2 induced hyper-inflammation in elderly men is a pressing need. Here we focus on the role of extracellular DNA, mainly mitochondrial DNA (mtDNA) and telomeric DNA (telDNA) in the modulation of systemic inflammation in these subjects. In particular, extracellular mtDNA is regarded as a powerful trigger of the inflammatory response. On the contrary, extracellular telDNA pool is estimated to be capable of inhibiting a variety of inflammatory pathways. In turn, we underpin that telDNA reservoir is progressively depleted during aging, and that it is scarcer in men than in women. We propose that an increase in extracellular mtDNA, concomitant with the reduction of the anti-inflammatory telDNA reservoir may explain hyper-inflammation in elderly male affected by COVID-19. This scenario is reminiscent of inflamm-aging, the portmanteau word that depicts how aging and aging related diseases are intimately linked to inflammation.

Exploitation of Some Natural Products for the Prevention and/or Nutritional Treatment of SARS-CoV2 Infection.

Dietary habits strongly influence our health status, mostly in terms of maintenance of the inflammatory/anti-inflammatory homeostasis. High fat and high sugar diets account for the development of a low-grade inflammation, which is the pathogenic common denominator of various chronic diseases. Severe Acute Respiratory Syndrome Coronavirus (SARS)-CoV2 (COVID-19) infection affects all ages and especially frail elderly people and a nutritional intervention seems to be crucial in the course of this pandemic. The present review describes the properties of some vegetal products and their derivatives, such as Lupin sp., garlic, salvia and extra virgin olive oil (EVOO) that can be exploited for their beneficial effects, as preventive and/or nutritional treatment of coronavirus disease SARS-CoV2. Lupin, salvia, garlic and EVOO share overlapping properties, such as anti-oxidant, anti-inflammatory and anti-viral activities. Quite importantly, these products and their derivatives are able to recover the expression of angiotensin converting enzyme expression 2 on cell membrane, otherwise suppressed by COVID-19 binding and entry into cytoplasm. Dietary administration of the above nutraceuticals or their extracts may play a preventive or nutritional role in the course of SARS-CoV2 infection, even including the effects of the lockdown and the condition of inflamm-ageing.

Inflamm-aging: Why older men are the most susceptible to SARS-CoV-2 complicated outcomes.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is characterized by a high mortality of elderly men with age-related comorbidities. In most of these patients, uncontrolled local and systemic hyperinflammation induces severe and often lethal outcomes. The aging process is characterized by the gradual development of a chronic subclinical systemic inflammation (inflamm-aging) and by acquired immune system impairment (immune senescence). Here, we advance the hypothesis that four well-recognized features of aging contribute to the disproportionate SARS-CoV-2 mortality suffered by elderly men: i. the presence of subclinical systemic inflammation without overt disease, ii. a blunted acquired immune system and type I interferon response due to the chronic inflammation; iii. the downregulation of ACE2 (i.e. the SARS-CoV-2 receptor); and iv. accelerated biological aging. The high mortality rate of SARS-CoV-2 infection suggests that clarification of the mechanisms of inflamm-aging and immune senescence can help combat not only age-related disorders but also SARS-CoV-2 infection.