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      Covid-19 Pandemic: Maximizing Future Vaccination Treatments Considering Aging and Frailty

      brief-report
      1 , 2 , *
      Frontiers in Medicine
      Frontiers Media S.A.
      COVID-19, ageotype, frailty, vaccination, adherence to treatment, immunosenecence, inflammaging, immunology

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          Abstract

          The COVID-19 pandemic is proving to be a multiplier of inequalities. Especially toward the elderly population. A voiceless scream that comes from geriatrics, nursing homes, hospices from all over Italy. They call it the silent massacre: from North to South, the bulletin of coronavirus positive—or already deceased—elderly people continues to grow exponentially without a chance to counter it. Population aging and chronicity are a question that needs to be addressed. Frailty is the most challenging expression of population aging, with major consequences for public health and clinical practice. It is a geriatric syndrome which consists in a state of higher vulnerability to stressors attributed to a lower homeostatic reserve due to an age-related multisystem physiological change. People over 60, and especially over 80, are particularly vulnerable to severe or fatal infection. Moreover, the age-related dysregulation of the immune system in the elderly (i.e., immunosenescence and inflammaging) results in poorer responses to vaccination. Physical frailty is an effective health indicator and it has previously shown to predict the response to the seasonal flu vaccine. These findings suggest that assessing frailty in the elderly may identify those who are less likely to respond to immunization and be at higher risk for COVID-19 and its complications. Moreover, cognitive frailty and neurocognitive disorders, mental health and reduced awareness of illness negatively impact on adherence to complex medication regimens among elderly patients. A worldwide research and development blueprint have been initiated to accelerate the development of vaccines and therapeutics for the COVID-19 outbreak. Considered the above, I suggest the importance to consider aging in thinking about future Civud-19 vaccination and treatment, focusing on the possible impact of physical and cognitive frailty.

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          Most cited references75

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          Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty

          Most older individuals develop inflammageing, a condition characterized by elevated levels of blood inflammatory markers that carries high susceptibility to chronic morbidity, disability, frailty, and premature death. Potential mechanisms of inflammageing include genetic susceptibility, central obesity, increased gut permeability, changes to microbiota composition, cellular senescence, NLRP3 inflammasome activation, oxidative stress caused by dysfunctional mitochondria, immune cell dysregulation, and chronic infections. Inflammageing is a risk factor for cardiovascular diseases (CVDs), and clinical trials suggest that this association is causal. Inflammageing is also a risk factor for chronic kidney disease, diabetes mellitus, cancer, depression, dementia, and sarcopenia, but whether modulating inflammation beneficially affects the clinical course of non-CVD health problems is controversial. This uncertainty is an important issue to address because older patients with CVD are often affected by multimorbidity and frailty - which affect clinical manifestations, prognosis, and response to treatment - and are associated with inflammation by mechanisms similar to those in CVD. The hypothesis that inflammation affects CVD, multimorbidity, and frailty by inhibiting growth factors, increasing catabolism, and interfering with homeostatic signalling is supported by mechanistic studies but requires confirmation in humans. Whether early modulation of inflammageing prevents or delays the onset of cardiovascular frailty should be tested in clinical trials.
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            On the origin and continuing evolution of SARS-CoV-2

            ABSTRACT The SARS-CoV-2 epidemic started in late December 2019 in Wuhan, China, and has since impacted a large portion of China and raised major global concern. Herein, we investigated the extent of molecular divergence between SARS-CoV-2 and other related coronaviruses. Although we found only 4% variability in genomic nucleotides between SARS-CoV-2 and a bat SARS-related coronavirus (SARSr-CoV; RaTG13), the difference at neutral sites was 17%, suggesting the divergence between the two viruses is much larger than previously estimated. Our results suggest that the development of new variations in functional sites in the receptor-binding domain (RBD) of the spike seen in SARS-CoV-2 and viruses from pangolin SARSr-CoVs are likely caused by mutations and natural selection besides recombination. Population genetic analyses of 103 SARS-CoV-2 genomes indicated that these viruses evolved into two major types (designated L and S), that are well defined by two different SNPs that show nearly complete linkage across the viral strains sequenced to date. Although the L type (∼70%) is more prevalent than the S type (∼30%), the S type was found to be the ancestral version. Whereas the L type was more prevalent in the early stages of the outbreak in Wuhan, the frequency of the L type decreased after early January 2020. Human intervention may have placed more severe selective pressure on the L type, which might be more aggressive and spread more quickly. On the other hand, the S type, which is evolutionarily older and less aggressive, might have increased in relative frequency due to relatively weaker selective pressure. These findings strongly support an urgent need for further immediate, comprehensive studies that combine genomic data, epidemiological data, and chart records of the clinical symptoms of patients with coronavirus disease 2019 (COVID-19).
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              The World report on ageing and health: a policy framework for healthy ageing.

              Although populations around the world are rapidly ageing, evidence that increasing longevity is being accompanied by an extended period of good health is scarce. A coherent and focused public health response that spans multiple sectors and stakeholders is urgently needed. To guide this global response, WHO has released the first World report on ageing and health, reviewing current knowledge and gaps and providing a public health framework for action. The report is built around a redefinition of healthy ageing that centres on the notion of functional ability: the combination of the intrinsic capacity of the individual, relevant environmental characteristics, and the interactions between the individual and these characteristics. This Health Policy highlights key findings and recommendations from the report.
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                Author and article information

                Contributors
                Journal
                Front Med (Lausanne)
                Front. Med.
                Frontiers in Medicine
                Frontiers Media S.A.
                2296-858X
                18 September 2020
                2020
                18 September 2020
                : 7
                : 558835
                Affiliations
                [1] 1Department of Psychology, University of Turin , Turin, Italy
                [2] 2European Innovation Partnership on Active and Healthy Aging , Bruxelles, Belgium
                Author notes

                Edited by: Emanuele Marzetti, Catholic University of the Sacred Heart, Italy

                Reviewed by: Darryl Rolfson, University of Alberta, Canada; Liang-Yu Chen, Taipei Veterans General Hospital, Taiwan

                This article was submitted to Geriatric Medicine, a section of the journal Frontiers in Medicine

                Article
                10.3389/fmed.2020.558835
                7530612
                33072783
                869a1c22-d333-419f-b22f-e2e385b6e57d
                Copyright © 2020 Palermo.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 18 May 2020
                : 02 September 2020
                Page count
                Figures: 2, Tables: 0, Equations: 0, References: 88, Pages: 11, Words: 7963
                Categories
                Medicine
                Perspective

                covid-19,ageotype,frailty,vaccination,adherence to treatment,immunosenecence,inflammaging,immunology

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