Highlights • Clinical and pathophysiological relationships in sarcopenia and frailty. • Inflammaging in sarcopenia and frailty. • Physical inactivity in sarcopenia and frailty. • Reduced neutrophil ...migration and inflammation.
Whilst the majority of individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative pathogen of COVID-19, experience mild to moderate symptoms, approximately ...20% develop severe respiratory complications that may progress to acute respiratory distress syndrome, pulmonary failure and death. To date, single cell and high-throughput systems based analyses of the peripheral and pulmonary immune responses to SARS-CoV-2 suggest that a hyperactive and dysregulated immune response underpins the development of severe disease, with a prominent role assigned to neutrophils. Characterised in part by robust generation of neutrophil extracellular traps (NETs), the presence of immature, immunosuppressive and activated neutrophil subsets in the circulation, and neutrophilic infiltrates in the lung, a granulocytic signature is emerging as a defining feature of severe COVID-19. Furthermore, an assessment of the number, maturity status and/or function of circulating neutrophils at the time of hospital admission has shown promise as a prognostic tool for the early identification of patients at risk of clinical deterioration. Here, by summarising the results of studies that have examined the peripheral and pulmonary immune response to SARS-CoV-2, we provide a comprehensive overview of the changes that occur in the composition, phenotype and function of the neutrophil pool in COVID-19 patients of differing disease severities and discuss potential mediators of SARS-CoV-2-induced neutrophil dysfunction. With few specific treatments currently approved for COVID-19, we conclude the review by discussing whether neutrophils represent a potential therapeutic target for the treatment of patients with severe COVID-19.
Remodelling of the immune system with age - immunosenescence - is a substantial contributor to poor health in older adults, with increasing risk of infections, cancer and chronic inflammatory disease ...contributing to age-related multi-morbidity. What is seldom considered when examining the immune response of an aged individual is that the immune system is profoundly influenced by physical activity. Habitual physical activity levels decline with age, with significant consequences for muscle mass and function. Skeletal muscle is a major immune regulatory organ and generates a range of proteins, termed myokines, which have anti-inflammatory and immunoprotective effects. Several studies indicate that maintaining physical activity has immune benefits in older adults, for example, it reduces the systemic inflammation associated with chronic age-related diseases. Here, we discuss how physical activity can prevent or ameliorate age-related multi-morbidity by boosting immune function, and we consider whether physical activity could improve immunotherapy outcomes in age-related conditions such as cancer.
Highlights • Roles are emerging for natural killer (NK) cells beyond removing transformed cells. • These include immune regulation and the elimination of senescent cells. • Human ageing is associated ...with a decline in NK cell function. • We propose some aspects of human ageing are due in part to reduced NK cell function. • These include reduced vaccination efficacy and delayed resolution of inflammation.
Bearing a strong resemblance to the phenotypic and functional remodeling of the immune system that occurs during aging (termed immunesenescence), the immune response to severe acute respiratory ...syndrome coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus disease 2019 (COVID-19), is characterized by an expansion of inflammatory monocytes, functional exhaustion of lymphocytes, dysregulated myeloid responses and the presence of highly activated senescent T cells. Alongside advanced age, male gender and pre-existing co-morbidities e.g., obesity and type 2 diabetes (T2D) are emerging as significant risk factors for COVID-19. Interestingly, immunesenescence is more profound in males when compared to females, whilst accelerated aging of the immune system, termed premature immunesenescence, has been described in obese subjects and T2D patients. Thus, as three distinct demographic groups with an increased susceptibility to COVID-19 share a common immune profile,
Here, by focussing on three key aspects of an immune response, namely pathogen recognition, elimination and resolution, we address this question by discussing how immunesenescence may weaken or exacerbate the immune response to SARS-CoV-2. We also highlight how aspects of immunesenescence could render potential COVID-19 treatments less effective in older adults and draw attention to certain therapeutic options, which by reversing or circumventing certain features of immunesenescence may prove to be beneficial for the treatment of groups at high risk of severe COVID-19.
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is associated with a range of persistent symptoms impacting everyday functioning, known as post-COVID-19 condition or long ...COVID. We undertook a retrospective matched cohort study using a UK-based primary care database, Clinical Practice Research Datalink Aurum, to determine symptoms that are associated with confirmed SARS-CoV-2 infection beyond 12 weeks in non-hospitalized adults and the risk factors associated with developing persistent symptoms. We selected 486,149 adults with confirmed SARS-CoV-2 infection and 1,944,580 propensity score-matched adults with no recorded evidence of SARS-CoV-2 infection. Outcomes included 115 individual symptoms, as well as long COVID, defined as a composite outcome of 33 symptoms by the World Health Organization clinical case definition. Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) for the outcomes. A total of 62 symptoms were significantly associated with SARS-CoV-2 infection after 12 weeks. The largest aHRs were for anosmia (aHR 6.49, 95% CI 5.02-8.39), hair loss (3.99, 3.63-4.39), sneezing (2.77, 1.40-5.50), ejaculation difficulty (2.63, 1.61-4.28) and reduced libido (2.36, 1.61-3.47). Among the cohort of patients infected with SARS-CoV-2, risk factors for long COVID included female sex, belonging to an ethnic minority, socioeconomic deprivation, smoking, obesity and a wide range of comorbidities. The risk of developing long COVID was also found to be increased along a gradient of decreasing age. SARS-CoV-2 infection is associated with a plethora of symptoms that are associated with a range of sociodemographic and clinical risk factors.
Summary
It is widely accepted that aging is accompanied by remodelling of the immune system including thymic atrophy and increased frequency of senescent T cells, leading to immune compromise. ...However, physical activity, which influences immunity but declines dramatically with age, is not considered in this literature. We assessed immune profiles in 125 adults (55–79 years) who had maintained a high level of physical activity (cycling) for much of their adult lives, 75 age‐matched older adults and 55 young adults not involved in regular exercise. The frequency of naïve T cells and recent thymic emigrants (RTE) were both higher in cyclists compared with inactive elders, and RTE frequency in cyclists was no different to young adults. Compared with their less active counterparts, the cyclists had significantly higher serum levels of the thymoprotective cytokine IL‐7 and lower IL‐6, which promotes thymic atrophy. Cyclists also showed additional evidence of reduced immunesenescence, namely lower Th17 polarization and higher B regulatory cell frequency than inactive elders. Physical activity did not protect against all aspects of immunesenescence: CD28−veCD57+ve senescent CD8 T‐cell frequency did not differ between cyclists and inactive elders. We conclude that many features of immunesenescence may be driven by reduced physical activity with age.
Summary Improvements in the control of haemorrhage after trauma have resulted in the survival of many people who would otherwise have died from the initial loss of blood. However, the danger is not ...over once bleeding has been arrested and blood pressure restored. Two-thirds of patients who die following major trauma now do so as a result of causes other than exsanguination. Trauma evokes a systemic reaction that includes an acute, non-specific, immune response associated, paradoxically, with reduced resistance to infection. The result is damage to multiple organs caused by the initial cascade of inflammation aggravated by subsequent sepsis to which the body has become susceptible. This Series examines the biological mechanisms and clinical implications of the cascade of events caused by large-scale trauma that leads to multiorgan failure and death, despite the stemming of blood loss. Furthermore, the stark and robust epidemiological finding—namely, that age has a profound influence on the chances of surviving trauma irrespective of the nature and severity of the injury—will be explored. Advances in our understanding of the inflammatory response to trauma, the impact of ageing on this response, and how this information has led to new and emerging treatments aimed at combating immune dysregulation and reduced immunity after injury will also be discussed.
There has been increasing interest and research into sarcopenia in community-dwelling older adults since the European Working Group on Sarcopenia in Older People (EWGSOP) agreed a consensus ...definition in 2010. Sarcopenia has been defined as loss of muscle mass with loss of muscle function (strength or physical performance), with measurements two Standard Deviations (SDs) below the mean of a young reference population. This definition does not necessitate longitudinal measurements, or the absence of acute illness and diagnosis can be made from single measurements. We hypothesise that hospitalisation, due to a combination of acute inflammatory burden and muscle disuse, leads to an acute decline in muscle mass and function and may lead to some individuals meeting criteria for sarcopenia, acutely, based on the EWGSOP definition. This may be partially recoverable or may lead to increased risk of developing sarcopenia long-term. We have denoted the term "acute sarcopenia" to refer to acute loss of muscle mass and function associated with hospitalisation. This review discusses some of the current available research in this context and also identifies some of the knowledge gaps and potential areas for future research.
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