{"paper_id":"8d0049ec-87e3-4c46-96e1-c229a25d3ba0","body_text":"The relationship of cytomegalovirus with physical functioning and health-related quality of life in older adults | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The relationship of cytomegalovirus with physical functioning and health-related quality of life in older adults Frances A Kirkham, Phu Sabei Shwe, Ekow Mensah, C Rajkumar This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5937387/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 5 You are reading this latest preprint version Abstract Methods 210 participants in the south of England with mean age 69.8 years underwent demographic and medical questionnaires, measures of body composition (bioimpedance analysis), handgrip strength and the short form 36 item survey of quality of life (SF36). All participants had peripheral venepuncture to assess CMV serology and inflammatory markers. Measures of sarcopenia were calculated using European Working Group definitions. Results 51.7% of participants were positive for CMV IgG. There were no significant differences between CMV positive and negative groups in age, gender, measures of sarcopenia or inflammatory markers. CMV positive groups had lower scores in all domains of the SF36, with significantly lower physical function score (88.7 vs 81.3, p = 0.003) as well as total score, limitations due to physical health, energy/fatigue, social functioning and pain. Physical functioning score was significantly correlated with measures of sarcopenia including handgrip strength (r = 0.155 p = 0.026) and appendicular skeletal muscle mass index (r = 0.201, p = 0.005). On linear regression, CMV status was significantly associated with SF36 physical function score (p = 0.004) after adjustment for age, gender, BMI, CRP and handgrip strength. Conclusion CMV positivity is significantly associated with physical function and health-related quality of life in older adults, although its direct relationship to sarcopenia is yet to be fully ascertained. Cytomegalovirus sarcopenia frailty quality of life Figures Figure 1 Key summary points Aim The aim of this paper is to show the relationship between cytomegalovirus with physical functioning and health-related quality of life in older adults. Finding CMV status is independently associated with physical functioning, as measured by the SF36 CMV positive groups had lower values on all domains of health-related quality of life compared to CMV negative groups SF36 physical functioning correlates with measures of sarcopenia and may represent a way of detecting early signs of sarcopenia Message This paper adds to our understanding of the role CMV exposure plays in changes to muscle mass and function and the subsequent development of sarcopenia. This paper shows that interventions to reduce the burden of CMV (e.g. vaccines) may have a role in reducing subsequent sarcopenia. This paper shows that SF36 measures of physical function may be a method by which precursors of sarcopenia may be detected in this cohort. Introduction Cytomegalovirus (CMV) is a pro-inflammatory herpes virus that is highly prevalent across the world and can establish persistent and latent infections. CMV has been associated with cardiovascular disease 1 , cognitive decline and mortality 2 , postulated to contribute to chronic inflammation and immunosenescence. To date, most studies have focused on the impact of CMV on vascular and endothelial smooth muscle, looking to explain its deleterious impact on the cardiovascular system 3 . Sarcopenia is defined as loss of muscle mass with age beyond that due to reduced physical activity. It has been an increasing area of research due to its role in the frailty syndrome and emerging studies demonstrating its association with poor health outcomes and mortality 4–6 . Evidence is growing to suggest that clinical interventions may reduce the negative consequences of sarcopenia, but these are not routinely offered. There remain difficulties defining thresholds for sarcopenia and creating a globally accepted consensus on diagnosis and management, although progress has been made recently 7 . The most recent European Working Group definition focuses on muscle function rather than mass, partly due to difficulty and lack of routine measurement of muscle mass 8 . Grip strength is inexpensive to perform, not invasive or laborious and can be easily incorporated into routine practice 9 . Measures of muscle mass are used to confirm diagnosis, and bioimpedance analysis is accepted as equivalent in accuracy to DEXA or CT measurements 10 . There have been numerous studies linking CMV to general frailty and a small number investigating its relationship to sarcopenia. One study to date has investigated the relationship between grip-strength and CMV status, finding no association, but suggesting there may be an association between muscle cross-sectional area and CMV status in men only 11 . In patients with HIV, CMV positivity has been shown to be linked to worse physical performance but not muscle density 12 . Physical function has been shown to be a strong correlate of measures of quality of life 13 , but the implications of sarcopenia and reduced muscle mass on quality of life and physical functioning has yet to be investigated in the context of CMV positivity. This study aimed to explore the relationship between CMV status, sarcopenia and health-related quality of life in a healthy cohort of over 60s in the UK. We sought to investigate the association of CMV exposure with reduced muscle mass and reduction in physical function and quality of life. Methods Participants aged 60 years or over were recruited through the primary care research network and general practices in Southeast England. Inclusion criteria: White British and age 60 years or older. Exclusion criteria: pre-existing immunodeficiency, organ transplant, use of immunosuppressive or immune-modulating drugs in the last year, cancer or treatment for cancer in the last 5 years, insulin-dependent diabetes, moderate or advanced renal failure, liver disease, endocrine disorders (except corrected thyroid dysfunction), manifest autoimmune disease, dementia/lack of capacity to consent, known alcoholism or other drug abuse, acute infection or illness in the last 4 weeks, raised body temperature (> 37.5°C), moderate or severe heart failure (NYHA III or IV), inability to lie flat. Participants were asked for a detailed medical history, including demographic and lifestyle factors and medications. Participants underwent physical examination, height, weight, blood pressure measurement and assessment of vascular stiffness by the cardio-ankle vascular index (CAVI - VaSera VS-1500 N, Fukuda Denshi, Tokyo, Japan). Blood samples were taken by peripheral venepuncture and CMV immunoglobulin G (IgG) serology (Architect CMV IgG, Abbot, Maidenhead, UK) was performed at the Brighton and Sussex University Hospital Trust virology laboratory using a routine assay. Participants whose serum samples exceeded the assay threshold for positive IgG are referred to as 'CMV positive’. C-reactive protein (mg/l) was also measured. Grip strength was measured using a standard dynamometer as the average of three readings from the dominant hand. Grip strength was also adjusted for BMI to give an alternative measure. Cut-offs for reduced grip strength were < 27 kg for men and < 16 kg for women, as defined in British cohorts by Dodds et al 14 . Studenski’s cut-offs for adjusted grip strength were also used - <0.1 for men and < 0.56 for women 15 . Bioimpedance analysis (BC-418, Tanita, Tokyo) was used to measure body composition. Appendicular skeletal muscle mass (ASM) was assessed and appendicular skeletal muscle mass index (ASMI) was calculated, adjusting ASM for height squared. An alternative measure of ASMI was calculated by adjusting ASM for BMI, as recommended by Studenski et al 15 . Reduced ASM was defined using the Sergi Eq. 1 6,17 with cut-offs of < 20kg and < 15kg for men and women respectively. Reduced ASMI was defined as < 0.789 for men and < 0.512 for women, taken from the FNIH sarcopenia project, based on a large European population 15 . European Working Group (EWG) definitions of sarcopenia were used with probable sarcopenia defined by reduced grip strength and definite sarcopenia defined by the addition of reduced ASM or ASMI. The EWG also included a further characterization of severe sarcopenia with the addition of reduced physical performance as measured by a timed up and go test or gait speed, however these measures were not taken in our cohort. In order to assess health-related quality of life and self-reported physical functioning, the RAND 36 item short-form survey (SF36 version 1.0) was performed on all participants and scored according to the creators' guidelines 18 to give overall scores and scores in seven domains: physical functioning, role limitations due to physical health, role limitations due to emotional health, energy/fatigue, emotional wellbeing, social functioning, pain and general health. Answers given are scored from 0-100 and relevant questions combined. Higher scores indicate better quality of life. The SF36 has been shown to be equal in performance to other widely used measures of quality of life 19 Statistical Analysis Statistical analysis was performed using SPSS v29.0.1.0 (IBM, Armonk, NY), with p < .05 considered statistically significant. Values are expressed as mean ± standard deviation. Independent samples t-test was used to compare baseline characteristics between participants according to CMV status and sarcopenia status. Linear regression was performed to determine whether SF36 physical functioning score (dependent variable) was associated with CMV status independent of potential confounders (smoking history, age, gender, BMI). Bivariate correlation was used to evaluate the correlation between variables. Results 210 participants took part with mean age 69.8 years (±7.3), including 108 females (51%) and 102 males (49%). Past medical history: a small proportion of the cohort reported previous medical issues: previous stroke – 2 (1%), previous Transient Ischaemic Attack – 5 (2%), hypertension – 74 (36%), atrial fibrillation – 18 (9%), congestive heart failure – 4 (2%), ischaemic heart disease – 11 (5%), Chronic Obstructive Pulmonary Disease – 3 (1%), malignancy – 13 (6%), arthritis – 47 (23%), diabetes mellitus – 11 (5%), hyperlipidaemia – 58 (28%). In terms of lifestyle factors, 7% of the cohort were current smokers and 49% were ex-smokers. 108 participants had positive CMV serology (51.7%). Table 1 compares characteristics between the total cohort and CMV positive and negative groups. There were no statistically significant differences between CMV groups in terms of age, gender, smoking history, blood pressure, arterial stiffness (measured by CAVI) or CRP. There were no significant differences in measures of sarcopenia between CMV groups. Table 1 – comparison of baseline characteristics between total cohort and CMV positive and negative groups (p values based on independent samples t test) Total cohort CMV negative CMV positive P value Age in years 69.8 (7.3) 69.5 (7.5) 70.0 (7.1) 0.614 Gender (%f:m) 51:49 51:49 51:49 0.936 Combined pack years 9.1 (15.7) 8.3 (13.4) 9.8 (17.5) 0.499 Systolic Blood Pressure (lying) (mmHg) 137.5 (17.8) 138.9 (17.5) 136.1 (18.1) 0.261 Diastolic Blood Pressure (lying) (mmHg) 76.2 (10.1) 76.9 (9.5) 75.5 (10.6) 0.336 Average Cardio-Ankle Vascular Index 9.25 (1.2) 9.23 (1.1) 9.28 (1.3) 0.775 C-Reactive Protein (mg/l) 2.71 (6.09) 2.63 (6.46) 2.78 (5.75) 0.864 Handgrip strength (kg) 27.3 (10.7) 26.9 (11.0) 27.7 (10.4) 0.598 Appendicular skeletal muscle mass (kg) 21.0 (5.1) 21.0 (5.5) 21.0 (4.8) 0.972 Appendicular skeletal muscle mass index 0.80 (0.17) 0.79 (0.17) 0.80 (0.18) 0.818 Prevalence of sarcopenia varied depending on the definition used. According to the EWG definition of probable sarcopenia, prevalence was 23.9% overall, with 24.5% for females and 23.2% males. Definite sarcopenia had a prevalence of 8.8% overall, with 7.5% of females and 10.2% of males meeting this definition. When using measures of either muscle strength or muscle quantity, there was a prevalence of sarcopenia of 31.2% overall, with 31.1% for females and 31.3% for males. There were no statistically significant differences in handgrip strength, adjusted handgrip strength, ASM or ASMI between CMV positive and negative groups for either males or females (supplementary material Table 1). There were significant differences in SF36 scores between CMV groups in the following domains: total score, physical functioning, limitations due to physical health, energy/fatigue, social functioning and pain (Table 2). CMV positive groups had lower values in all SF36 domains compared to CMV negative groups (Figure 1). Table 2 – comparison in SF36 scores between CMV negative and positive groups on independent samples t test Total cohort CMV negative CMV positive P value SF36 Total score 2964.1 (510.0) 3075.5 (387.5) 2860.0 (585.3) 0.002** Physical functioning 84.9 (18.5) 88.7 (15.0) 81.3 (20.8) 0.003** Limitations due to physical health 83.3 (33.6) 89.1 (29.0) 77.8 (36.7) 0.015* Limitations due to emotional health 92.7 (22.2) 95.0 (18.5) 90.4 (25.0) 0.132 Energy/fatigue 71.9 (17.9) 74.9 (16.1) 69.2 (19.1) 0.022* Emotional wellbeing 85.7 (12.4) 87.4 (9.9) 84.1 (14.3) 0.056 Social functioning 91.0 (16.5) 93.9 (13.1) 88.3 (18.9) 0.014* Pain 82.6 (21.2) 87.3 (16.7) 78.1 (24.0) 0.002** General health 74.6 (17.1) 75.6 (15.2) 73.7 (18.8) 0.403 *indicates p<0.05 **indicates p<0.01 Bivariate correlation was performed to assess correlation of SF36 domains with other variables. Total score was significantly correlated with age and ASMI, while physical functioning was significantly correlated with age, BMI, handgrip strength and ASMI. Other significant correlations are highlighted in Table 3. Table 3 – Bivariate correlations of SF36 domains with age, BMI and measures of sarcopenia Age BMI Handgrip strength ASM ASMI SF36 Total r=-.184** p=.007 r=-.123 p=.076 r=.099 p=.159 r=.100 p=.160 r=0.169 p=0.017* Physical functioning r=-.284** p=<.001 r=-.152* p=.028 r=.155* p=.026 r=.099 p=.164 r=0.201 p=0.005** Limitations due to physical health r=-.122 p=.079 r=-.024 p=.733 r=.070 p=.320 r=.089 p=.210 r=0.099 p=0.163 Limitations due to emotional health r=-.043 p=.535 r=-.104 p=.136 r=.024 p=.734 r=.069 p=.337 r=0.131 p=0.066 Energy/fatigue r=-.099 p=.155 r=-.147 p=.033 * r=.056 p=.426 r=.048 p=.503 r=0.010 p=0.122 Emotional wellbeing r=.008 p=.910 r=-.041 p=.552 r=.124 p=.077 r=.135 p=.059 r=0.156 p=0.028* Social functioning r=-.202** p=.003 r=-.150* p=.030 r=.083 p=.236 r=.088 p=.219 r=0.169 p=0.017* Pain r=-.032 p=.643 r=-.096 p=.169 r=.033 p=.634 r=.085 .p=232 r=0.140 p=0.050 General health r=-.070 p=.310 r=.003 p=.964 r=-.062 p=.376 r=-.028 p=.700 r=-0.046 p=0.515 *indicates p<0.05 **indicates p<0.01 Linear regression was performed to assess whether CMV status contributes to physical functioning score of SF36 independent of other variables (smoking, age, sex, BMI, CRP and handgrip strength). CMV status remained a significant contributor to physical functioning score (p=0.003) with smoking history, age and BMI also remaining significant (Table 4). Table 4 – linear regression with physical functioning domain of SF-36 as dependent variable. R squared for model=0.232, F=8.216, p<0.001 Independent variables Unstandardised B Significance Smoking pack years -.313 <.001** Age -.694 <.001** Gender 4.260 .228 BMI -.761 .011* CRP -.094 .630 CMV status -6.938 .004** Handgrip strength 0.064 0.706 *indicates p<0.05 **indicates p<0.01 Discussion Our results show a clear relationship between CMV status and health-related quality of life, particularly the physical domains as measured in the SF36 survey. However, while the physical functioning domains of the SF36 correlate with measures of sarcopenia, there was no direct association of CMV status with measures of sarcopenia. The prevalence of sarcopenia in our cohort mirrors that found in previous European studies. Our prevalence of 8.8%, according to the full EWG definition of reduced muscle function and mass, is similar to that found in the large FNIH study of ambulatory males (3-8%) 20 . In a significantly older cohort, reduced grip strength was found in 23% of males and 26.6% of females 14 , while our younger cohort demonstrated reduced grip strength in 23.2% of males and 24.5% of females. The optimal cut offs are still debated, with Lauretani suggesting higher values for grip strength as providing the ideal balance of sensitivity and specificity for detecting reduced physical function 21 . Loss of strength has been shown to be an accurate predictor of future worsening mobility 22 . Timed up and go tests and other clinical measures of physical function are time consuming and difficult to perform, thus finding simple correlates that can be routinely measured to detect impaired function could be a huge clinical relevance. CMV and sarcopenia Our study did not find a significant difference in handgrip strength or measures of sarcopenia between CMV groups. However, our study did show significant differences in SF36 scores between CMV groups, particularly in physical function. This may suggest that CMV exposure has an impact on physical function that may predate measurable changes in muscle strength or mass. Previous research has demonstrated a relationship between health-related quality of life and sarcopenia. Low grip strength (in both sexes) was found to be associated with poor scores on all SF36 domains, remaining associated with reduced physical functioning after adjustment 23 . One Spanish study of predominantly older women found that probable sarcopenia was associated with lower SF36 domains, including physical functioning 24 . Interestingly, the associations were less pronounced for participants with definite sarcopenia, suggesting that such scoring systems are more useful at an early stage in the disease process. However, the study used cut offs for sarcopenia based on Skeletal Mass Index (SMI) taken from community-dwelling older people in Taiwan. These cut offs may be inappropriate in a European population which may not have comparable characteristics in terms of body composition. A Turkish study compared sarcopenic/sarcopenic obese patients to non-sarcopenic/non-obese groups, finding only a small difference in SF36 physical function (64.6 ± 29.06 vs 63.4 ± 29.92). It is questionable how comparable these scores are, as the absolute values are extremely low (compared to other similar studies) which may suggest their scoring system was non-conventional. They did find a positive correlation of BMI with physical functioning r=-0.324 p<0.05, similar to our results. On binary logistic regression, SF36 domains were not able to predict sarcopenia 25 , suggesting that the relationship is complex and requires further delineation. Similarly, a Belgian study of over 65s also found very low values for both sarcopenic and non-sarcopenic groups (52.0 ±29.2 vs 65.2 ±25.9 p=0.001) – this may be because participants were recruited from outpatient clinics and had high levels of comorbid disease (average of 4.34 concomitant diseases) compared to our generally healthy population 26 . A Portuguese study of older women did not find significant differences in SF36 scores for sarcopenic or sarcopenic obese, but showed a clear trend towards lower scores for sarcopenic groups and did find a positive correlation between handgrip strength and physical functioning 27 . In a small Brazilian cohort, worse physical functioning and pain scores were found in sarcopenic compared to non-sarcopenic participants, although European thresholds and definitions were used, likely due to lack of population-specific data 28 . A small longitudinal study found that declining physical quality of life, defined by SF36 domains, was associated independently with physical performance and muscle cross-sectional area over 3-year follow up 29 . This suggests that the SF36 may be a useful early indicator of worsening mobility and subsequent muscle loss, underlining the importance of interventions to maintain skeletal muscle health in older populations. The majority of previous studies have focused on quality of life in the context of general frailty, often using SF36 30,31 . In the context of CMV, there have been limited studies looking at the relationship of CMV status and frailty, with different measures of frailty used. CMV reactivation was shown to be associated with an odds ratio of 6.13 for frailty compared to non-frail Brazilian females 32 .Schmaltz et al found higher levels of frailty in CMV positive older women, suggesting this association may be modified by IL6, as a higher association was found in those with higher IL6 levels 33 . However, they were not able to show a statistically significant association of CMV status with grip strength, although there was a trend towards increased weakness. Another study of women found an association between CMV status and both frailty (hazard ratio 3.45, 95% confidence interval 1.45-8.27) and mortality (HR 2.79, 95% CI 1.64-8.83), but only the highest quintile of antibody titres remained significant in predicting mortality after adjustment and the association with frailty became non-significant 34 . Similarly, using Fried’s criteria, a Belgian study of the oldest old found no association between pre-frailty and CMV status with only IL6 age and sex found to be predictors of the pre-frail phenotype 35 .The BELFRAIL study, also of over 80s in Belgium, counterintuitively found a negative association of CMV serology with frailty 36 . They suggest that a survival effect may result from the older age of their population, meaning that those more susceptible to the damage of CMV have died at earlier ages. They also found no association of CMV status with IL6 levels, although IL6 itself was associated with frailty and functional impairment. The level of association of CMV with all elements of frailty is significant, as there is increasing belief that frailty is to some degree reversible at the pre-frail stage, thus clinical interventions and CMV vaccines may have a role to play in reducing the burden of frailty. Measures of quality of life The SF36 is a commonly used measure of health-related quality of life but is not specific to older people and has some limitations. Currently, there are no defined thresholds to identify reduced physical function, although cut offs for some mental health components have been proposed 37 . To give our figures some context, one large study used the US general population as a baseline for comparison, finding that the mean physical function score was 90 (±17) 38 . In a much younger population of healthy controls (mean age 30-40), the mean physical functioning score was 92.6±14.2 39 . It would appear reasonable, given the older average age of our cohort, that the CMV negative group had a slightly lower score (88.7±15) and shows that the CMV positive group had a significantly lower value (81.3±20.8). A UK study of younger Cushing’s syndrome patients and healthy controls had an almost identical value of 88.7±14.8 in the healthy group compared to 80±19.5 for those with Cushing’s syndrome 40 , suggesting that the impact of CMV may be comparable to major diseases. It has been determined that the minimal clinically impactful difference in the SF36 is a difference of 3-5 on each scale 18 , thus the differences highlighted in our study represent clinically impactful figures. SarQoL is a sarcopenia-specific measure of quality of life, which has been shown to correlate well in detecting robust vs frail vs prefrail individuals 41 . However, one study found that the SF36 was similarly able to detect differences between patients and controls when compared to SarQoL and was found to be superior to SARC-F 40 , a survey designed for use in case-finding for sarcopenia. Our study is focused on identifying individuals who may be vulnerable to the detrimental effects of CMV exposure and so finding diagnostic tools that highlight such individuals at an early stage (before clinical sarcopenia or frailty has developed) could be of benefit to clinicians. The SF36 provides a simple, effective tool for this purpose and further studies to validate its use in this context are needed. Possible mechanisms Inflammation and immunosenescence have been proposed as mechanisms by which CMV may contribute to reduced muscle function and quantity. One study identified a ‘cluster’ of the oldest old with an immunosenescent profile which included CMV positivity and T cell senescence 42 . However, similarly to ours, this study failed to find a relationship to muscle loss or sarcopenia over 5 years. It is debatable whether 5 years is sufficient to detect changes relating to CMV exposure, which is likely to have occurred in childhood or adolescence. There was also a 40% loss to follow up which may have underpowered the final results. In a similar population of the oldest old, there was limited evidence to support immunosenescence as the key element driving the association of frailty and inflammation, with no association found between CMV status and frailty. This may support the idea of a survival effect in this older group 43 . Equally, the duration of CMV infection does not seem to affect the impact on the system 44 , suggesting that the damage may relate to some vulnerability factor in the host. Changes to the immune system occurring over time include reduced capacity to fight infection and increased inflammation (‘inflammageing’), which are postulated to relate to higher levels of IL6. In one study, IL6 levels strongly predicted grip-strength, suggesting a possible role in the development of sarcopenia 11 . However, there is the possibility raised by authors that cardiovascular disease may be a mediating factor, resulting in less physical activity and thus muscle depletion. It is also unclear whether CMV reactivation is the cause or effect of immunological changes with age. There is inevitably a cumulative impact of changes in nutrition, activity levels, endocrinological change and inflammatory changes contributing to frailty and its component parts including sarcopenia 45 . Again, authors propose IL6 as a major modulator of muscle density with a likely bidirectional interaction of chronic disease and immune function. In middle-aged patients with HIV and CMV coinfection, lower NAD levels were observed in skeletal muscle and there was an associated increase in frailty 46 , adding to the notion of inflammatory damage, but suggesting multiple modulating factors may be involved. Some studies have suggested that CMV may contribute to immunosenescence through clonal proliferation of terminally differentiated CMV-specific T cells, alongside chronic inflammation leading to persistent accumulation of inflammatory damage 47 . We have previously written about the increase in T memory cells, predominantly in men, in the CMV positive group of this cohort 48 . There is also the possibility of a dose-response relationship, with higher CMV IgG more strongly correlated with frailty 49 . Chronic low-grade inflammation may be a response to chronic or latent infections such as CMV, resulting in higher levels of circulating inflammatory markers including CRP. This has mainly been studied in the HIV population where CMV Infection is highly prevalent and CMV is the target of over 10% of circulating T cells in HIV-infected individuals 50 . Limitations This was a cross-sectional study of UK older people and thus cannot infer causality and may not be generalisable to other populations. However, the use of a linear scale to detect differences in SF36-assessed physical function offers advantages to simply categorising participants into frail/non-frail or sarcopenic/non-sarcopenic. We chose to use recommended measures and cut-offs for muscle quality and quantity based on European guidelines. BIA is recommended for use in assessing body composition but does have limitations as it is dependent on hydration and relies on specific population norms for comparison. The use of CMV antibodies also may not be sufficient to characterise the status of a large population, as 1 in 4 people may fail to generate a humoral response. In this case, it would be necessary to measure cellular immunity 24 . Conclusion Our study found an independent association of physical function domains of the SF36 with CMV status, but no clear relationship between CMV status and sarcopenia. Previous studies have suggested that CMV may contribute to overall frailty, but the relationship with muscle loss over time is yet to be determined. Future studies would be beneficial to assess whether changes in measures of physical function may predate the development of sarcopenia in this cohort, thus offering the potential for interventions to reduce the negative consequences of sarcopenia. The exact mechanism by which frailty, immune senescence and CMV-related inflammation are linked remains uncertain, likely due to the complex, heterogeneous interactions between these states. It is possible that the development of a CMV vaccine may have a valuable role in reducing the future burden of frailty, but further elucidation of these relationships is required. Declarations Funding sources and related paper presentations: This work was supported by The Dunhill Medical Trust, grant number R278/0213 On behalf of all authors, the corresponding author states that there is no conflict of interest. Acknowledgements We would like to thank all involved staff of the Clinical Investigation and Research Unit (CIRU) of Brighton and Sussex University Hospital Trust (BSUHT) for their continuous support. We are grateful to all participating GP practices and especially grateful to all participating volunteers. We would also like to thank the Primary Care Research Network (PCRN) South-East for coordinating the recruitment process. Authors’ roles FA Kirkham – concept design, data collection, analysis, manuscript writing S – data collection, manuscript writing EM - data collection, manuscript writing C Rajkumar – study design, concept design, manuscript writing Conflicts of interest None Ethics Statement The study was approved by the UK National Research Ethics Service (NRES) 'London Centre' (Reference 13/LO/1270). Written informed consent was obtained from all participants. The study was conducted in accordance with the Declaration of Helsinki. References Wang H, Peng G, Bai J, et al. Cytomegalovirus Infection and Relative Risk of Cardiovascular Disease (Ischemic Heart Disease, Stroke, and Cardiovascular Death): A Meta-Analysis of Prospective Studies Up to 2016. J Am Heart Assoc . Jul 2017;6(7)doi:10.1161/JAHA.116.005025 Savva GM, Pachnio A, Kaul B, et al. Cytomegalovirus infection is associated with increased mortality in the older population. Aging Cell . Jun 2013;12(3):381-7. doi:10.1111/acel.12059 Yaiw KC, Mohammad AA, Taher C, et al. Human Cytomegalovirus Reduces Endothelin-1 Expression in Both Endothelial and Vascular Smooth Muscle Cells. Microorganisms . May 25 2021;9(6)doi:10.3390/microorganisms9061137 Xue QL, Walston JD, Fried LP, Beamer BA. Prediction of risk of falling, physical disability, and frailty by rate of decline in grip strength: the women's health and aging study. Arch Intern Med . Jun 27 2011;171(12):1119-21. doi:10.1001/archinternmed.2011.252 Newman AB, Kupelian V, Visser M, et al. Strength, but not muscle mass, is associated with mortality in the health, aging and body composition study cohort. J Gerontol A Biol Sci Med Sci . Jan 2006;61(1):72-7. doi:10.1093/gerona/61.1.72 Kirkham FA, Rankin P, Bunting E, Ali K, Rajkumar C. Using measures of sarcopenia to predict recurrent cerebrovascular events in stroke and TIA patients. J Stroke Cerebrovasc Dis . Apr 2023;32(4):106979. doi:10.1016/j.jstrokecerebrovasdis.2023.106979 Sayer AA, Cruz-Jentoft A. Sarcopenia definition, diagnosis and treatment: consensus is growing. Age Ageing . Oct 06 2022;51(10)doi:10.1093/ageing/afac220 Cruz-Jentoft AJ, Bahat G, Bauer J, et al. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing . Jul 01 2019;48(4):601. doi:10.1093/ageing/afz046 Ibrahim K, May CR, Patel HP, Baxter M, Sayer AA, Roberts HC. Implementation of grip strength measurement in medicine for older people wards as part of routine admission assessment: identifying facilitators and barriers using a theory-led intervention. BMC Geriatr . Mar 22 2018;18(1):79. doi:10.1186/s12877-018-0768-5 Barazzoni R, Jensen GL, Correia MITD, et al. Guidance for assessment of the muscle mass phenotypic criterion for the Global Leadership Initiative on Malnutrition (GLIM) diagnosis of malnutrition. Clin Nutr . Jun 2022;41(6):1425-1433. doi:10.1016/j.clnu.2022.02.001 Kilgour AH, Firth C, Harrison R, et al. Seropositivity for CMV and IL-6 levels are associated with grip strength and muscle size in the elderly. Immun Ageing . Aug 13 2013;10(1):33. doi:10.1186/1742-4933-10-33 Abidi MZ, Umbleja T, Overton ET, et al. Cytomegalovirus IgG is Associated With Physical Function But Not Muscle Density in People With HIV. J Acquir Immune Defic Syndr . Apr 15 2024;95(5):470-478. doi:10.1097/QAI.0000000000003377 Groessl EJ, Kaplan RM, Rejeski WJ, et al. Physical Activity and Performance Impact Long-term Quality of Life in Older Adults at Risk for Major Mobility Disability. Am J Prev Med . Jan 2019;56(1):141-146. doi:10.1016/j.amepre.2018.09.006 Dodds RM, Syddall HE, Cooper R, et al. Grip strength across the life course: normative data from twelve British studies. PLoS One . 2014;9(12):e113637. doi:10.1371/journal.pone.0113637 Studenski SA, Peters KW, Alley DE, et al. The FNIH sarcopenia project: rationale, study description, conference recommendations, and final estimates. J Gerontol A Biol Sci Med Sci . May 2014;69(5):547-58. doi:10.1093/gerona/glu010 Sergi G, De Rui M, Stubbs B, Veronese N, Manzato E. Measurement of lean body mass using bioelectrical impedance analysis: a consideration of the pros and cons. Aging Clin Exp Res . Aug 2017;29(4):591-597. doi:10.1007/s40520-016-0622-6 Yamada Y, Nishizawa M, Uchiyama T, et al. Developing and Validating an Age-Independent Equation Using Multi-Frequency Bioelectrical Impedance Analysis for Estimation of Appendicular Skeletal Muscle Mass and Establishing a Cutoff for Sarcopenia. Int J Environ Res Public Health . Jul 19 2017;14(7)doi:10.3390/ijerph14070809 Hays RD, Morales LS. The RAND-36 measure of health-related quality of life. Ann Med . Jul 2001;33(5):350-7. doi:10.3109/07853890109002089 Coons SJ, Rao S, Keininger DL, Hays RD. A comparative review of generic quality-of-life instruments. Pharmacoeconomics . Jan 2000;17(1):13-35. doi:10.2165/00019053-200017010-00002 De Buyser SL, Petrovic M, Taes YE, et al. Validation of the FNIH sarcopenia criteria and SOF frailty index as predictors of long-term mortality in ambulatory older men. Age Ageing . Sep 2016;45(5):602-8. doi:10.1093/ageing/afw071 Lauretani F, Russo CR, Bandinelli S, et al. Age-associated changes in skeletal muscles and their effect on mobility: an operational diagnosis of sarcopenia. J Appl Physiol (1985) . Nov 2003;95(5):1851-60. doi:10.1152/japplphysiol.00246.2003 Hicks GE, Shardell M, Alley DE, et al. Absolute strength and loss of strength as predictors of mobility decline in older adults: the InCHIANTI study. J Gerontol A Biol Sci Med Sci . Jan 2012;67(1):66-73. doi:10.1093/gerona/glr055 Sayer AA, Syddall HE, Martin HJ, Dennison EM, Roberts HC, Cooper C. Is grip strength associated with health-related quality of life? Findings from the Hertfordshire Cohort Study. Age Ageing . Jul 2006;35(4):409-15. doi:10.1093/ageing/afl024 Fábrega-Cuadros R, Hita-Contreras F, Martínez-Amat A, et al. Associations between the Severity of Sarcopenia and Health-Related Quality of Life in Community-Dwelling Middle-Aged and Older Adults. Int J Environ Res Public Health . Jul 29 2021;18(15)doi:10.3390/ijerph18158026 Öztürk ZA, Türkbeyler İ, Abiyev A, et al. Health-related quality of life and fall risk associated with age-related body composition changes; sarcopenia, obesity and sarcopenic obesity. Intern Med J . Aug 2018;48(8):973-981. doi:10.1111/imj.13935 Beaudart C, Reginster JY, Petermans J, et al. Quality of life and physical components linked to sarcopenia: The SarcoPhAge study. Exp Gerontol . Sep 2015;69:103-10. doi:10.1016/j.exger.2015.05.003 Silva Neto LS, Karnikowiski MG, Tavares AB, Lima RM. Association between sarcopenia, sarcopenic obesity, muscle strength and quality of life variables in elderly women. Rev Bras Fisioter . 2012;16(5):360-7. Silva Neto LS, Karnikowski MG, Osório NB, et al. Association between sarcopenia and quality of life in quilombola elderly in Brazil. Int J Gen Med . 2016;9:89-97. doi:10.2147/IJGM.S92404 Trombetti A, Reid KF, Hars M, et al. Age-associated declines in muscle mass, strength, power, and physical performance: impact on fear of falling and quality of life. Osteoporos Int . Feb 2016;27(2):463-71. doi:10.1007/s00198-015-3236-5 Sánchez-García S, Gallegos-Carrillo K, Espinel-Bermudez MC, et al. Comparison of quality of life among community-dwelling older adults with the frailty phenotype. Qual Life Res . Oct 2017;26(10):2693-2703. doi:10.1007/s11136-017-1630-5 Rizzoli R, Reginster JY, Arnal JF, et al. Quality of life in sarcopenia and frailty. Calcif Tissue Int . Aug 2013;93(2):101-20. doi:10.1007/s00223-013-9758-y Thomasini RL, Pereira DS, Pereira FSM, et al. Aged-associated cytomegalovirus and Epstein-Barr virus reactivation and cytomegalovirus relationship with the frailty syndrome in older women. PLoS One . 2017;12(7):e0180841. doi:10.1371/journal.pone.0180841 Schmaltz HN, Fried LP, Xue QL, Walston J, Leng SX, Semba RD. Chronic cytomegalovirus infection and inflammation are associated with prevalent frailty in community-dwelling older women. J Am Geriatr Soc . May 2005;53(5):747-54. doi:10.1111/j.1532-5415.2005.53250.x Wang GC, Kao WH, Murakami P, et al. Cytomegalovirus infection and the risk of mortality and frailty in older women: a prospective observational cohort study. Am J Epidemiol . May 15 2010;171(10):1144-52. doi:10.1093/aje/kwq062 Cao Dinh H, Bautmans I, Beyer I, et al. Association Between Immunosenescence Phenotypes and Pre-frailty in Older Subjects: Does Cytomegalovirus Play a Role? J Gerontol A Biol Sci Med Sci . Mar 14 2019;74(4):480-488. doi:10.1093/gerona/gly135 Matheï C, Vaes B, Wallemacq P, Degryse J. Associations between cytomegalovirus infection and functional impairment and frailty in the BELFRAIL Cohort. J Am Geriatr Soc . Dec 2011;59(12):2201-8. doi:10.1111/j.1532-5415.2011.03719.x Silveira E, Taft C, Sundh V, Waern M, Palsson S, Steen B. Performance of the SF-36 health survey in screening for depressive and anxiety disorders in an elderly female Swedish population. Qual Life Res . Jun 2005;14(5):1263-74. doi:10.1007/s11136-004-7753-5 Hays RD, Cunningham WE, Sherbourne CD, et al. Health-related quality of life in patients with human immunodeficiency virus infection in the United States: results from the HIV Cost and Services Utilization Study. Am J Med . Jun 15 2000;108(9):714-22. doi:10.1016/s0002-9343(00)00387-9 Schulte-van Maaren YW, Carlier IV, Zitman FG, et al. Reference values for generic instruments used in routine outcome monitoring: the Leiden Routine Outcome Monitoring Study. BMC Psychiatry . Nov 21 2012;12:203. doi:10.1186/1471-244X-12-203 Martel-Duguech L, Alonso-Jimenez A, Bascuñana H, et al. Prevalence of sarcopenia after remission of hypercortisolism and its impact on HRQoL. Clin Endocrinol (Oxf) . Nov 2021;95(5):735-743. doi:10.1111/cen.14568 Geerinck A, Locquet M, Bruyère O, Reginster JY, Beaudart C. Evaluating quality of life in frailty: applicability and clinimetric properties of the SarQoL. J Cachexia Sarcopenia Muscle . Apr 2021;12(2):319-330. doi:10.1002/jcsm.12687 Granic A, Martin-Ruiz C, Dodds RM, et al. Immunosenescence profiles are not associated with muscle strength, physical performance and sarcopenia risk in very old adults: The Newcastle 85+ Study. Mech Ageing Dev . Sep 2020;190:111321. doi:10.1016/j.mad.2020.111321 Collerton J, Martin-Ruiz C, Davies K, et al. Frailty and the role of inflammation, immunosenescence and cellular ageing in the very old: cross-sectional findings from the Newcastle 85+ Study. Mech Ageing Dev . Jun 2012;133(6):456-66. doi:10.1016/j.mad.2012.05.005 Samson LD, van den Berg SP, Engelfriet P, et al. Limited effect of duration of CMV infection on adaptive immunity and frailty: insights from a 27-year-long longitudinal study. Clin Transl Immunology . 2020;9(10):e1193. doi:10.1002/cti2.1193 Fulop T, Larbi A, Witkowski JM, et al. Aging, frailty and age-related diseases. Biogerontology . Oct 2010;11(5):547-63. doi:10.1007/s10522-010-9287-2 Tran T, Pencina KM, Schultz MB, et al. Reduced Levels of NAD in Skeletal Muscle and Increased Physiologic Frailty Are Associated With Viral Coinfection in Asymptomatic Middle-Aged Adults. J Acquir Immune Defic Syndr . Feb 01 2022;89(Suppl 1):S15-S22. doi:10.1097/QAI.0000000000002852 Leng SX. Role of chronic cytomegalovirus infection in T-cell immunosenescence and frailty: more questions than answers. J Am Geriatr Soc . Dec 2011;59(12):2363-5. doi:10.1111/j.1532-5415.2011.03815.x Kirkham F, Pera A, Simanek AM, et al. Cytomegalovirus infection is associated with an increase in aortic stiffness in older men which may be mediated in part by CD4 memory T-cells. Theranostics . 2021;11(12):5728-5741. doi:10.7150/thno.58356 Haeseker MB, Pijpers E, Dukers-Muijrers NH, et al. Association of cytomegalovirus and other pathogens with frailty and diabetes mellitus, but not with cardiovascular disease and mortality in psycho-geriatric patients; a prospective cohort study. Immun Ageing . Jul 23 2013;10(1):30. doi:10.1186/1742-4933-10-30 Leng SX, Margolick JB. Aging, sex, inflammation, frailty, and CMV and HIV infections. Cell Immunol . Feb 2020;348:104024. doi:10.1016/j.cellimm.2019.104024 Supplementary Files RIETable4.docx RIETable2.docx RIETable1.docx RIEFigure2.png RIEFigure1.png SupplementarymaterialTable1.docx Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Major revisions 14 Mar, 2025 Reviewers agreed at journal 13 Feb, 2025 Reviewers invited by journal 12 Feb, 2025 Editor assigned by journal 12 Feb, 2025 First submitted to journal 06 Feb, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {\"props\":{\"pageProps\":{\"initialData\":{\"identity\":\"rs-5937387\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":false,\"archivedVersions\":[],\"articleType\":\"Research Article\",\"associatedPublications\":[],\"authors\":[{\"id\":414685456,\"identity\":\"1d22c4c9-b615-4210-945a-54147ddb88c5\",\"order_by\":0,\"name\":\"Frances A Kirkham\",\"email\":\"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABCElEQVRIiWNgGAWjYHACxgM8DMxg1gcgljMAMw0s8OoBa+FhY2CcAeQYG4D1G0gQryVxA8RK3Fr425sPHHjbZi1nL998sLmi5k76dvb+oxt+FEgApboTsGmROHMs4eDctnRjHja2xMYzx57l7uw5zHazB+gwiTNnN2DTYiCRY3CYt+1wYg8bj/nDBrbDuRtuJLPd4AFqMZDIxaulvoeN/2Njw7/D6QZALTf/EKElgYeNh7GxEcgAabmNzxawX+acSzfsOZZm2NjYd9hww5nDZrdlDCR4cPkFGGIHH7wps5Znbz78sLHh22F5g+ONz26++WMjx9/ei1ULbsBDmvJRMApGwSgYBcgAAPXKZx6/lzKgAAAAAElFTkSuQmCC\",\"orcid\":\"https://orcid.org/0000-0001-8513-3627\",\"institution\":\"University Hospitals Sussex NHS Foundation Trust\",\"correspondingAuthor\":true,\"prefix\":\"\",\"firstName\":\"Frances\",\"middleName\":\"A\",\"lastName\":\"Kirkham\",\"suffix\":\"\"},{\"id\":414685457,\"identity\":\"4f3043f9-4ea6-4124-9cb3-cea049e9f050\",\"order_by\":1,\"name\":\"Phu Sabei Shwe\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Monash University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Phu\",\"middleName\":\"Sabei\",\"lastName\":\"Shwe\",\"suffix\":\"\"},{\"id\":414685458,\"identity\":\"e7f544da-cdaf-4f60-a5f0-00c3678fbd8e\",\"order_by\":2,\"name\":\"Ekow Mensah\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"University Hospitals Sussex NHS Foundation Trust\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Ekow\",\"middleName\":\"\",\"lastName\":\"Mensah\",\"suffix\":\"\"},{\"id\":414685459,\"identity\":\"a9db6eb3-b1d9-4177-92fc-13229a6b595a\",\"order_by\":3,\"name\":\"C Rajkumar\",\"email\":\"\",\"orcid\":\"https://orcid.org/0000-0002-6240-5121\",\"institution\":\"Brighton and Sussex Medical School\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"C\",\"middleName\":\"\",\"lastName\":\"Rajkumar\",\"suffix\":\"\"}],\"badges\":[],\"createdAt\":\"2025-01-31 15:38:07\",\"currentVersionCode\":1,\"declarations\":\"\",\"doi\":\"10.21203/rs.3.rs-5937387/v1\",\"doiUrl\":\"https://doi.org/10.21203/rs.3.rs-5937387/v1\",\"draftVersion\":[],\"editorialEvents\":[],\"editorialNote\":\"\",\"failedWorkflow\":false,\"files\":[{\"id\":76282805,\"identity\":\"2d78b978-c80e-4b76-b179-a1547c848c07\",\"added_by\":\"auto\",\"created_at\":\"2025-02-14 10:50:16\",\"extension\":\"png\",\"order_by\":1,\"title\":\"Figure 1\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":127287,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003ecomparison of SF36 domains between CMV positive and negative groups (*indicates p\\u0026lt;0.05, **indicates p\\u0026lt;0.01)\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"floatimage1.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-5937387/v1/0fed6653e0adafc49ac4d750.png\"},{\"id\":76285954,\"identity\":\"9e708e51-892d-48cd-b9b6-cf6fbb27d52c\",\"added_by\":\"auto\",\"created_at\":\"2025-02-14 11:14:16\",\"extension\":\"pdf\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":1050313,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"manuscript.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-5937387/v1/398969ce-f0d6-41a2-bc93-f2b88ead0b1c.pdf\"},{\"id\":76282798,\"identity\":\"907f8706-b6f3-4ad6-841c-f2962f7926a5\",\"added_by\":\"auto\",\"created_at\":\"2025-02-14 10:50:16\",\"extension\":\"docx\",\"order_by\":1,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"supplement\",\"size\":14762,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"RIETable4.docx\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-5937387/v1/476c6070ae9bb827ab7d405d.docx\"},{\"id\":76282800,\"identity\":\"a76a2e6a-35ee-42c3-93f6-670bb1c4823a\",\"added_by\":\"auto\",\"created_at\":\"2025-02-14 10:50:16\",\"extension\":\"docx\",\"order_by\":2,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"supplement\",\"size\":15986,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"RIETable2.docx\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-5937387/v1/af90dd827344c9639439c7cf.docx\"},{\"id\":76282799,\"identity\":\"d18a56a9-2d58-4991-adf8-323f73766b7c\",\"added_by\":\"auto\",\"created_at\":\"2025-02-14 10:50:16\",\"extension\":\"docx\",\"order_by\":3,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"supplement\",\"size\":16585,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"RIETable1.docx\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-5937387/v1/1e1663cd298b3f67648776a5.docx\"},{\"id\":76282802,\"identity\":\"4b179da9-191c-40d7-b86a-52693cf8a9f7\",\"added_by\":\"auto\",\"created_at\":\"2025-02-14 10:50:16\",\"extension\":\"png\",\"order_by\":4,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"supplement\",\"size\":16164,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"RIEFigure2.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-5937387/v1/e174d48f1b66218d029a4229.png\"},{\"id\":76284574,\"identity\":\"608a6d3c-e7c7-4247-b3cd-db11637f3230\",\"added_by\":\"auto\",\"created_at\":\"2025-02-14 10:58:16\",\"extension\":\"png\",\"order_by\":5,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"supplement\",\"size\":29582,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"RIEFigure1.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-5937387/v1/15e64e21ed27d3fd613ccff3.png\"},{\"id\":76282806,\"identity\":\"bd0d8395-0a12-44f9-9547-af2243ebd32e\",\"added_by\":\"auto\",\"created_at\":\"2025-02-14 10:50:16\",\"extension\":\"docx\",\"order_by\":6,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"supplement\",\"size\":14745,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"SupplementarymaterialTable1.docx\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-5937387/v1/482d4741e550db4cc682405a.docx\"}],\"financialInterests\":\"\",\"formattedTitle\":\"The relationship of cytomegalovirus with physical functioning and health-related quality of life in older adults\",\"fulltext\":[{\"header\":\"Key summary points\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003eAim\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe aim of this paper is to show the relationship between cytomegalovirus with physical functioning and health-related quality of life in older adults.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eFinding\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cul\\u003e\\n \\u003cli\\u003eCMV status is independently associated with physical functioning, as measured by the SF36\\u003c/li\\u003e\\n \\u003cli\\u003eCMV positive groups had lower values on all domains of health-related quality of life compared to CMV negative groups\\u003c/li\\u003e\\n \\u003cli\\u003eSF36 physical functioning correlates with measures of sarcopenia and may represent a way of detecting early signs of sarcopenia\\u003c/li\\u003e\\n\\u003c/ul\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eMessage\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cul\\u003e\\n \\u003cli\\u003eThis paper adds to our understanding of the role CMV exposure plays in changes to muscle mass and function and the subsequent development of sarcopenia.\\u003c/li\\u003e\\n \\u003cli\\u003eThis paper shows that interventions to reduce the burden of CMV (e.g. vaccines) may have a role in reducing subsequent sarcopenia.\\u003c/li\\u003e\\n \\u003cli\\u003eThis paper shows that SF36 measures of physical function may be a method by which precursors of sarcopenia may be detected in this cohort.\\u003c/li\\u003e\\n\\u003c/ul\\u003e\"},{\"header\":\"Introduction\",\"content\":\"\\u003cp\\u003eCytomegalovirus (CMV) is a pro-inflammatory herpes virus that is highly prevalent across the world and can establish persistent and latent infections. CMV has been associated with cardiovascular disease\\u003csup\\u003e1\\u003c/sup\\u003e, cognitive decline and mortality\\u003csup\\u003e2\\u003c/sup\\u003e, postulated to contribute to chronic inflammation and immunosenescence. To date, most studies have focused on the impact of CMV on vascular and endothelial smooth muscle, looking to explain its deleterious impact on the cardiovascular system\\u003csup\\u003e3\\u003c/sup\\u003e.\\u003c/p\\u003e \\u003cp\\u003eSarcopenia is defined as loss of muscle mass with age beyond that due to reduced physical activity. It has been an increasing area of research due to its role in the frailty syndrome and emerging studies demonstrating its association with poor health outcomes and mortality\\u003csup\\u003e4\\u0026ndash;6\\u003c/sup\\u003e. Evidence is growing to suggest that clinical interventions may reduce the negative consequences of sarcopenia, but these are not routinely offered. There remain difficulties defining thresholds for sarcopenia and creating a globally accepted consensus on diagnosis and management, although progress has been made recently\\u003csup\\u003e7\\u003c/sup\\u003e. The most recent European Working Group definition focuses on muscle function rather than mass, partly due to difficulty and lack of routine measurement of muscle mass\\u003csup\\u003e8\\u003c/sup\\u003e. Grip strength is inexpensive to perform, not invasive or laborious and can be easily incorporated into routine practice\\u003csup\\u003e9\\u003c/sup\\u003e. Measures of muscle mass are used to confirm diagnosis, and bioimpedance analysis is accepted as equivalent in accuracy to DEXA or CT measurements\\u003csup\\u003e10\\u003c/sup\\u003e.\\u003c/p\\u003e \\u003cp\\u003eThere have been numerous studies linking CMV to general frailty and a small number investigating its relationship to sarcopenia. One study to date has investigated the relationship between grip-strength and CMV status, finding no association, but suggesting there may be an association between muscle cross-sectional area and CMV status in men only\\u003csup\\u003e11\\u003c/sup\\u003e. In patients with HIV, CMV positivity has been shown to be linked to worse physical performance but not muscle density\\u003csup\\u003e12\\u003c/sup\\u003e. Physical function has been shown to be a strong correlate of measures of quality of life\\u003csup\\u003e13\\u003c/sup\\u003e, but the implications of sarcopenia and reduced muscle mass on quality of life and physical functioning has yet to be investigated in the context of CMV positivity.\\u003c/p\\u003e \\u003cp\\u003eThis study aimed to explore the relationship between CMV status, sarcopenia and health-related quality of life in a healthy cohort of over 60s in the UK. We sought to investigate the association of CMV exposure with reduced muscle mass and reduction in physical function and quality of life.\\u003c/p\\u003e\"},{\"header\":\"Methods\",\"content\":\"\\u003cp\\u003eParticipants aged 60 years or over were recruited through the primary care research network and general practices in Southeast England. Inclusion criteria: White British and age 60 years or older. Exclusion criteria: pre-existing immunodeficiency, organ transplant, use of immunosuppressive or immune-modulating drugs in the last year, cancer or treatment for cancer in the last 5 years, insulin-dependent diabetes, moderate or advanced renal failure, liver disease, endocrine disorders (except corrected thyroid dysfunction), manifest autoimmune disease, dementia/lack of capacity to consent, known alcoholism or other drug abuse, acute infection or illness in the last 4 weeks, raised body temperature (\\u0026gt;\\u0026thinsp;37.5\\u0026deg;C), moderate or severe heart failure (NYHA III or IV), inability to lie flat.\\u003c/p\\u003e \\u003cp\\u003eParticipants were asked for a detailed medical history, including demographic and lifestyle factors and medications. Participants underwent physical examination, height, weight, blood pressure measurement and assessment of vascular stiffness by the cardio-ankle vascular index (CAVI - VaSera VS-1500 N, Fukuda Denshi, Tokyo, Japan). Blood samples were taken by peripheral venepuncture and CMV immunoglobulin G (IgG) serology (Architect CMV IgG, Abbot, Maidenhead, UK) was performed at the Brighton and Sussex University Hospital Trust virology laboratory using a routine assay. Participants whose serum samples exceeded the assay threshold for positive IgG are referred to as 'CMV positive\\u0026rsquo;. C-reactive protein (mg/l) was also measured.\\u003c/p\\u003e \\u003cp\\u003eGrip strength was measured using a standard dynamometer as the average of three readings from the dominant hand. Grip strength was also adjusted for BMI to give an alternative measure. Cut-offs for reduced grip strength were \\u0026lt;\\u0026thinsp;27 kg for men and \\u0026lt;\\u0026thinsp;16 kg for women, as defined in British cohorts by Dodds et al\\u003csup\\u003e14\\u003c/sup\\u003e. Studenski\\u0026rsquo;s cut-offs for adjusted grip strength were also used - \\u0026lt;0.1 for men and \\u0026lt;\\u0026thinsp;0.56 for women\\u003csup\\u003e15\\u003c/sup\\u003e.\\u003c/p\\u003e \\u003cp\\u003eBioimpedance analysis (BC-418, Tanita, Tokyo) was used to measure body composition. Appendicular skeletal muscle mass (ASM) was assessed and appendicular skeletal muscle mass index (ASMI) was calculated, adjusting ASM for height squared. An alternative measure of ASMI was calculated by adjusting ASM for BMI, as recommended by Studenski et al\\u003csup\\u003e15\\u003c/sup\\u003e. Reduced ASM was defined using the Sergi Eq.\\u0026nbsp;1\\u003csup\\u003e6,17\\u003c/sup\\u003e with cut-offs of \\u0026lt;\\u0026thinsp;20kg and \\u0026lt;\\u0026thinsp;15kg for men and women respectively. Reduced ASMI was defined as \\u0026lt;\\u0026thinsp;0.789 for men and \\u0026lt;\\u0026thinsp;0.512 for women, taken from the FNIH sarcopenia project, based on a large European population\\u003csup\\u003e15\\u003c/sup\\u003e.\\u003c/p\\u003e \\u003cp\\u003eEuropean Working Group (EWG) definitions of sarcopenia were used with probable sarcopenia defined by reduced grip strength and definite sarcopenia defined by the addition of reduced ASM or ASMI. The EWG also included a further characterization of severe sarcopenia with the addition of reduced physical performance as measured by a timed up and go test or gait speed, however these measures were not taken in our cohort.\\u003c/p\\u003e \\u003cp\\u003eIn order to assess health-related quality of life and self-reported physical functioning, the RAND 36 item short-form survey (SF36 version 1.0) was performed on all participants and scored according to the creators' guidelines\\u003csup\\u003e18\\u003c/sup\\u003e to give overall scores and scores in seven domains: physical functioning, role limitations due to physical health, role limitations due to emotional health, energy/fatigue, emotional wellbeing, social functioning, pain and general health. Answers given are scored from 0-100 and relevant questions combined. Higher scores indicate better quality of life. The SF36 has been shown to be equal in performance to other widely used measures of quality of life\\u003csup\\u003e19\\u003c/sup\\u003e\\u003c/p\\u003e \\u003cdiv id=\\\"Sec3\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eStatistical Analysis\\u003c/h2\\u003e \\u003cp\\u003eStatistical analysis was performed using SPSS v29.0.1.0 (IBM, Armonk, NY), with p\\u0026thinsp;\\u0026lt;\\u0026thinsp;.05 considered statistically significant. Values are expressed as mean\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;standard deviation. Independent samples t-test was used to compare baseline characteristics between participants according to CMV status and sarcopenia status. Linear regression was performed to determine whether SF36 physical functioning score (dependent variable) was associated with CMV status independent of potential confounders (smoking history, age, gender, BMI). Bivariate correlation was used to evaluate the correlation between variables.\\u003c/p\\u003e \\u003c/div\\u003e\"},{\"header\":\"Results\",\"content\":\"\\u003cp\\u003e210 participants took part with mean age 69.8 years (\\u0026plusmn;7.3), including 108 females (51%) and 102 males (49%). Past medical history: a small proportion of the cohort reported previous medical issues: previous stroke \\u0026ndash; 2 (1%), previous Transient Ischaemic Attack \\u0026ndash; 5 (2%), hypertension \\u0026ndash; 74 (36%), atrial fibrillation \\u0026ndash; 18 (9%), congestive heart failure \\u0026ndash; 4 (2%), ischaemic heart disease \\u0026ndash; 11 (5%), Chronic Obstructive Pulmonary Disease \\u0026ndash; 3 (1%), malignancy \\u0026ndash; 13 (6%), arthritis \\u0026ndash; 47 (23%), diabetes mellitus \\u0026ndash; 11 (5%), hyperlipidaemia \\u0026ndash; 58 (28%). In terms of lifestyle factors, 7% of the cohort were current smokers and 49% were ex-smokers.\\u003c/p\\u003e\\n\\u003cp\\u003e108 participants had positive CMV serology (51.7%). Table 1 compares characteristics between the total cohort and CMV positive and negative groups. There were no statistically significant differences between CMV groups in terms of age, gender, smoking history, blood pressure, arterial stiffness (measured by CAVI) or CRP. There were no significant differences in measures of sarcopenia between CMV groups.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eTable 1\\u003c/strong\\u003e \\u0026ndash; comparison of baseline characteristics between total cohort and CMV positive and negative groups (p values based on independent samples t test)\\u003c/p\\u003e\\n\\u003ctable border=\\\"0\\\" cellspacing=\\\"0\\\" cellpadding=\\\"0\\\" width=\\\"601\\\"\\u003e\\n \\u003ctbody\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003eTotal cohort\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003eCMV negative\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003eCMV positive\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003eP value\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003eAge in years\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e69.8 (7.3)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e69.5 (7.5)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e70.0 (7.1)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e0.614\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003eGender (%f:m)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e51:49\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e51:49\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e51:49\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e0.936\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003eCombined pack years\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e9.1 (15.7)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e8.3 (13.4)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e9.8 (17.5)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e0.499\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003eSystolic Blood Pressure (lying) (mmHg)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e137.5 (17.8)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e138.9 (17.5)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e136.1 (18.1)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e0.261\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003eDiastolic Blood Pressure (lying) (mmHg)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e76.2 (10.1)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e76.9 (9.5)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e75.5 (10.6)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e0.336\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003eAverage Cardio-Ankle Vascular Index\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e9.25 (1.2)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e9.23 (1.1)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e9.28 (1.3)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e0.775\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003eC-Reactive Protein (mg/l)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e2.71 (6.09)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e2.63 (6.46)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e2.78 (5.75)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e0.864\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003eHandgrip strength (kg)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e27.3 (10.7)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e26.9 (11.0)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e27.7 (10.4)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e0.598\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003eAppendicular skeletal muscle mass (kg)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e21.0 (5.1)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e21.0 (5.5)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e21.0 (4.8)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e0.972\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003eAppendicular skeletal muscle mass index\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e0.80 (0.17)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e0.79 (0.17)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e0.80 (0.18)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e0.818\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/tbody\\u003e\\n\\u003c/table\\u003e\\n\\u003cp\\u003ePrevalence of sarcopenia varied depending on the definition used. According to the EWG definition of probable sarcopenia, prevalence was 23.9% overall, with 24.5% for females and 23.2% males. Definite sarcopenia had a prevalence of 8.8% overall, with 7.5% of females and 10.2% of males meeting this definition. When using measures of either muscle strength or muscle quantity, there was a prevalence of sarcopenia of 31.2% overall, with 31.1% for females and 31.3% for males. There were no statistically significant differences in handgrip strength, adjusted handgrip strength, ASM or ASMI between CMV positive and negative groups for either males or females (supplementary material Table 1).\\u003c/p\\u003e\\n\\u003cp\\u003eThere were significant differences in SF36 scores between CMV groups in the following domains: total score, physical functioning, limitations due to physical health, energy/fatigue, social functioning and pain (Table 2). CMV positive groups had lower values in all SF36 domains compared to CMV negative groups (Figure 1).\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eTable 2\\u003c/strong\\u003e \\u0026ndash; comparison in SF36 scores between CMV negative and positive groups on independent samples t test\\u003c/p\\u003e\\n\\u003ctable border=\\\"0\\\" cellspacing=\\\"0\\\" cellpadding=\\\"0\\\" width=\\\"601\\\"\\u003e\\n \\u003ctbody\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003eTotal cohort\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003eCMV negative\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003eCMV positive\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003eP value\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eSF36 Total score\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e2964.1 (510.0)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e3075.5 (387.5)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e2860.0 (585.3)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e0.002**\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003ePhysical functioning\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e84.9 (18.5)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e88.7 (15.0)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e81.3 (20.8)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e0.003**\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eLimitations due to physical health\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e83.3 (33.6)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e89.1 (29.0)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e77.8 (36.7)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e0.015*\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003eLimitations due to emotional health\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e92.7 (22.2)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e95.0 (18.5)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e90.4 (25.0)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e0.132\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eEnergy/fatigue\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e71.9 (17.9)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e74.9 (16.1)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e69.2 (19.1)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e0.022*\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003eEmotional wellbeing\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e85.7 (12.4)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e87.4 (9.9)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e84.1 (14.3)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e0.056\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eSocial functioning\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e91.0 (16.5)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e93.9 (13.1)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e88.3 (18.9)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e0.014*\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003ePain\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e82.6 (21.2)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e87.3 (16.7)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e78.1 (24.0)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e0.002**\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003eGeneral health\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e74.6 (17.1)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e75.6 (15.2)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e73.7 (18.8)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20%;\\\"\\u003e\\n \\u003cp\\u003e0.403\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/tbody\\u003e\\n\\u003c/table\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e*indicates p\\u0026lt;0.05\\u003cbr\\u003e\\u0026nbsp;**indicates p\\u0026lt;0.01\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eBivariate correlation was performed to assess correlation of SF36 domains with other variables. Total score was significantly correlated with age and ASMI, while physical functioning was significantly correlated with age, BMI, handgrip strength and ASMI. Other significant correlations are highlighted in Table 3.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eTable 3\\u003c/strong\\u003e \\u0026ndash; Bivariate correlations of SF36 domains with age, BMI and measures of sarcopenia\\u003c/p\\u003e\\n\\u003ctable border=\\\"0\\\" cellspacing=\\\"0\\\" cellpadding=\\\"0\\\" width=\\\"601\\\"\\u003e\\n \\u003ctbody\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 19.9667%;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15.9734%;\\\"\\u003e\\n \\u003cp\\u003eAge\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15.9734%;\\\"\\u003e\\n \\u003cp\\u003eBMI\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 16.3062%;\\\"\\u003e\\n \\u003cp\\u003eHandgrip strength\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 16.1398%;\\\"\\u003e\\n \\u003cp\\u003eASM\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15.6406%;\\\"\\u003e\\n \\u003cp\\u003eASMI\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 19.9667%;\\\"\\u003e\\n \\u003cp\\u003eSF36 Total\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15.9734%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003er=-.184**\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003ep=.007\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15.9734%;\\\"\\u003e\\n \\u003cp\\u003er=-.123\\u003c/p\\u003e\\n \\u003cp\\u003ep=.076\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 16.3062%;\\\"\\u003e\\n \\u003cp\\u003er=.099\\u003c/p\\u003e\\n \\u003cp\\u003ep=.159\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 16.1398%;\\\"\\u003e\\n \\u003cp\\u003er=.100\\u003c/p\\u003e\\n \\u003cp\\u003ep=.160\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15.6406%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003er=0.169 p=0.017*\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 19.9667%;\\\"\\u003e\\n \\u003cp\\u003ePhysical functioning\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15.9734%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003er=-.284**\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003ep=\\u0026lt;.001\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15.9734%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003er=-.152*\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003ep=.028\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 16.3062%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003er=.155*\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003ep=.026\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 16.1398%;\\\"\\u003e\\n \\u003cp\\u003er=.099\\u003c/p\\u003e\\n \\u003cp\\u003ep=.164\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15.6406%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003er=0.201 p=0.005**\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 19.9667%;\\\"\\u003e\\n \\u003cp\\u003eLimitations due to physical health\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15.9734%;\\\"\\u003e\\n \\u003cp\\u003er=-.122\\u003c/p\\u003e\\n \\u003cp\\u003ep=.079\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15.9734%;\\\"\\u003e\\n \\u003cp\\u003er=-.024\\u003c/p\\u003e\\n \\u003cp\\u003ep=.733\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 16.3062%;\\\"\\u003e\\n \\u003cp\\u003er=.070\\u003c/p\\u003e\\n \\u003cp\\u003ep=.320\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 16.1398%;\\\"\\u003e\\n \\u003cp\\u003er=.089\\u003c/p\\u003e\\n \\u003cp\\u003ep=.210\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15.6406%;\\\"\\u003e\\n \\u003cp\\u003er=0.099 p=0.163\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 19.9667%;\\\"\\u003e\\n \\u003cp\\u003eLimitations due to emotional health\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15.9734%;\\\"\\u003e\\n \\u003cp\\u003er=-.043\\u003c/p\\u003e\\n \\u003cp\\u003ep=.535\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15.9734%;\\\"\\u003e\\n \\u003cp\\u003er=-.104\\u003c/p\\u003e\\n \\u003cp\\u003ep=.136\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 16.3062%;\\\"\\u003e\\n \\u003cp\\u003er=.024\\u003c/p\\u003e\\n \\u003cp\\u003ep=.734\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 16.1398%;\\\"\\u003e\\n \\u003cp\\u003er=.069\\u003c/p\\u003e\\n \\u003cp\\u003ep=.337\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15.6406%;\\\"\\u003e\\n \\u003cp\\u003er=0.131 p=0.066\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 19.9667%;\\\"\\u003e\\n \\u003cp\\u003eEnergy/fatigue\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15.9734%;\\\"\\u003e\\n \\u003cp\\u003er=-.099\\u003c/p\\u003e\\n \\u003cp\\u003ep=.155\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15.9734%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003er=-.147\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003ep=.033 \\u0026nbsp; \\u0026nbsp; \\u0026nbsp; \\u0026nbsp; \\u0026nbsp; \\u0026nbsp; \\u0026nbsp; \\u0026nbsp;*\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 16.3062%;\\\"\\u003e\\n \\u003cp\\u003er=.056\\u003cbr\\u003e\\u0026nbsp;p=.426\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 16.1398%;\\\"\\u003e\\n \\u003cp\\u003er=.048\\u003c/p\\u003e\\n \\u003cp\\u003ep=.503\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15.6406%;\\\"\\u003e\\n \\u003cp\\u003er=0.010 p=0.122\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 19.9667%;\\\"\\u003e\\n \\u003cp\\u003eEmotional wellbeing\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15.9734%;\\\"\\u003e\\n \\u003cp\\u003er=.008\\u003c/p\\u003e\\n \\u003cp\\u003ep=.910\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15.9734%;\\\"\\u003e\\n \\u003cp\\u003er=-.041\\u003c/p\\u003e\\n \\u003cp\\u003ep=.552\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 16.3062%;\\\"\\u003e\\n \\u003cp\\u003er=.124\\u003c/p\\u003e\\n \\u003cp\\u003ep=.077\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 16.1398%;\\\"\\u003e\\n \\u003cp\\u003er=.135\\u003c/p\\u003e\\n \\u003cp\\u003ep=.059\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15.6406%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003er=0.156 p=0.028*\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 19.9667%;\\\"\\u003e\\n \\u003cp\\u003eSocial functioning\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15.9734%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003er=-.202**\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003ep=.003\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15.9734%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003er=-.150*\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003ep=.030 \\u0026nbsp; \\u0026nbsp; \\u0026nbsp; \\u0026nbsp; \\u0026nbsp; \\u0026nbsp; \\u0026nbsp; \\u0026nbsp;\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 16.3062%;\\\"\\u003e\\n \\u003cp\\u003er=.083\\u003c/p\\u003e\\n \\u003cp\\u003ep=.236\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 16.1398%;\\\"\\u003e\\n \\u003cp\\u003er=.088\\u003c/p\\u003e\\n \\u003cp\\u003ep=.219\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15.6406%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003er=0.169 p=0.017*\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 19.9667%;\\\"\\u003e\\n \\u003cp\\u003ePain\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15.9734%;\\\"\\u003e\\n \\u003cp\\u003er=-.032\\u003c/p\\u003e\\n \\u003cp\\u003ep=.643\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15.9734%;\\\"\\u003e\\n \\u003cp\\u003er=-.096\\u003c/p\\u003e\\n \\u003cp\\u003ep=.169\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 16.3062%;\\\"\\u003e\\n \\u003cp\\u003er=.033\\u003c/p\\u003e\\n \\u003cp\\u003ep=.634\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 16.1398%;\\\"\\u003e\\n \\u003cp\\u003er=.085\\u003c/p\\u003e\\n \\u003cp\\u003e.p=232\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15.6406%;\\\"\\u003e\\n \\u003cp\\u003er=0.140 p=0.050\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 19.9667%;\\\"\\u003e\\n \\u003cp\\u003eGeneral health\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15.9734%;\\\"\\u003e\\n \\u003cp\\u003er=-.070\\u003c/p\\u003e\\n \\u003cp\\u003ep=.310\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15.9734%;\\\"\\u003e\\n \\u003cp\\u003er=.003\\u0026nbsp;\\u003c/p\\u003e\\n \\u003cp\\u003ep=.964\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 16.3062%;\\\"\\u003e\\n \\u003cp\\u003er=-.062\\u003c/p\\u003e\\n \\u003cp\\u003ep=.376\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 16.1398%;\\\"\\u003e\\n \\u003cp\\u003er=-.028\\u003c/p\\u003e\\n \\u003cp\\u003ep=.700\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15.6406%;\\\"\\u003e\\n \\u003cp\\u003er=-0.046 p=0.515\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/tbody\\u003e\\n\\u003c/table\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e*indicates p\\u0026lt;0.05\\u003cbr\\u003e\\u0026nbsp;**indicates p\\u0026lt;0.01\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eLinear regression was performed to assess whether CMV status contributes to physical functioning score of SF36 independent of other variables (smoking, age, sex, BMI, CRP and handgrip strength). CMV status remained a significant contributor to physical functioning score (p=0.003) with smoking history, age and BMI also remaining significant (Table 4).\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eTable 4\\u003c/strong\\u003e \\u0026ndash; linear regression with physical functioning domain of SF-36 as dependent variable. R squared for model=0.232, F=8.216, p\\u0026lt;0.001\\u003c/p\\u003e\\n\\u003ctable border=\\\"0\\\" cellspacing=\\\"0\\\" cellpadding=\\\"0\\\" width=\\\"601\\\"\\u003e\\n \\u003ctbody\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 33.2779%;\\\"\\u003e\\n \\u003cp\\u003eIndependent variables\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 33.2779%;\\\"\\u003e\\n \\u003cp\\u003eUnstandardised B\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 33.4443%;\\\"\\u003e\\n \\u003cp\\u003eSignificance\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 33.2779%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eSmoking pack years\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 33.2779%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e-.313\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 33.4443%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e\\u0026lt;.001**\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 33.2779%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eAge\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 33.2779%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e-.694\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 33.4443%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e\\u0026lt;.001**\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 33.2779%;\\\"\\u003e\\n \\u003cp\\u003eGender\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 33.2779%;\\\"\\u003e\\n \\u003cp\\u003e4.260\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 33.4443%;\\\"\\u003e\\n \\u003cp\\u003e.228\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 33.2779%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eBMI\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 33.2779%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e-.761\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 33.4443%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e.011*\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 33.2779%;\\\"\\u003e\\n \\u003cp\\u003eCRP\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 33.2779%;\\\"\\u003e\\n \\u003cp\\u003e-.094\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 33.4443%;\\\"\\u003e\\n \\u003cp\\u003e.630\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 33.2779%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eCMV status\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 33.2779%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e-6.938\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 33.4443%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e.004**\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 33.2779%;\\\"\\u003e\\n \\u003cp\\u003eHandgrip strength\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 33.2779%;\\\"\\u003e\\n \\u003cp\\u003e0.064\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 33.4443%;\\\"\\u003e\\n \\u003cp\\u003e0.706\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/tbody\\u003e\\n\\u003c/table\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e*indicates p\\u0026lt;0.05\\u003cbr\\u003e\\u0026nbsp;**indicates p\\u0026lt;0.01\\u003c/strong\\u003e\\u003c/p\\u003e\"},{\"header\":\"Discussion\",\"content\":\"\\u003cp\\u003eOur results show a clear relationship between CMV status and health-related quality of life, particularly the physical domains as measured in the SF36 survey. However, while the physical functioning domains of the SF36 correlate with measures of sarcopenia, there was no direct association of CMV status with measures of sarcopenia.\\u003c/p\\u003e\\n\\u003cp\\u003eThe prevalence of sarcopenia in our cohort mirrors that found in previous European studies. Our prevalence of 8.8%, according to the full EWG definition of reduced muscle function and mass, is similar to that found in the large FNIH study of ambulatory males (3-8%)\\u003csup\\u003e20\\u003c/sup\\u003e. In a significantly older cohort, reduced grip strength was found in 23% of males and 26.6% of females\\u003csup\\u003e14\\u003c/sup\\u003e, while our younger cohort demonstrated reduced grip strength in 23.2% of males and 24.5% of females. The optimal cut offs are still debated, with Lauretani suggesting higher values for grip strength as providing the ideal balance of sensitivity and specificity for detecting reduced physical function\\u003csup\\u003e21\\u003c/sup\\u003e. Loss of strength has been shown to be an accurate predictor of future worsening mobility\\u003csup\\u003e22\\u003c/sup\\u003e. Timed up and go tests and other clinical measures of physical function are time consuming and difficult to perform, thus finding simple correlates that can be routinely measured to detect impaired function could be a huge clinical relevance.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eCMV and sarcopenia\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eOur study did not find a significant difference in handgrip strength or measures of sarcopenia between CMV groups. However, our study did show significant differences in SF36 scores between CMV groups, particularly in physical function. This may suggest that CMV exposure has an impact on physical function that may predate measurable changes in muscle strength or mass. Previous research has demonstrated a relationship between health-related quality of life and sarcopenia. Low grip strength (in both sexes) was found to be associated with poor scores on all SF36 domains, remaining associated with reduced physical functioning after adjustment\\u003csup\\u003e23\\u003c/sup\\u003e. One Spanish study of predominantly older women found that probable sarcopenia was associated with lower SF36 domains, including physical functioning\\u003csup\\u003e24\\u003c/sup\\u003e. Interestingly, the associations were less pronounced for participants with definite sarcopenia, suggesting that such scoring systems are more useful at an early stage in the disease process. However, the study used cut offs for sarcopenia based on Skeletal Mass Index (SMI) taken from community-dwelling older people in Taiwan. These cut offs may be inappropriate in a European population which may not have comparable characteristics in terms of body composition. A Turkish study compared sarcopenic/sarcopenic obese patients to non-sarcopenic/non-obese groups, finding only a small difference in SF36 physical function (64.6 \\u0026plusmn; 29.06 vs 63.4 \\u0026plusmn; 29.92). It is questionable how comparable these scores are, as the absolute values are extremely low (compared to other similar studies) which may suggest their scoring system was non-conventional. They did find a positive correlation of BMI with physical functioning r=-0.324 p\\u0026lt;0.05, similar to our results. On binary logistic regression, SF36 domains were not able to predict sarcopenia\\u003csup\\u003e25\\u003c/sup\\u003e, suggesting that the relationship is complex and requires further delineation. Similarly, a Belgian study of over 65s also found very low values for both sarcopenic and non-sarcopenic groups (52.0 \\u0026plusmn;29.2 vs 65.2 \\u0026plusmn;25.9 p=0.001) \\u0026ndash; this may be because participants were recruited from outpatient clinics and had high levels of comorbid disease (average of 4.34 concomitant diseases) compared to our generally healthy population\\u003csup\\u003e26\\u003c/sup\\u003e.\\u003c/p\\u003e\\n\\u003cp\\u003eA Portuguese study of older women did not find significant differences in SF36 scores for sarcopenic or sarcopenic obese, but showed a clear trend towards lower scores for sarcopenic groups and did find a positive correlation between handgrip strength and physical functioning\\u003csup\\u003e27\\u003c/sup\\u003e. In a small Brazilian cohort, worse physical functioning and pain scores were found in sarcopenic compared to non-sarcopenic participants, although European thresholds and definitions were used, likely due to lack of population-specific data\\u003csup\\u003e28\\u003c/sup\\u003e. A small longitudinal study found that declining physical quality of life, defined by SF36 domains, was associated independently with physical performance and muscle cross-sectional area over 3-year follow up\\u003csup\\u003e29\\u003c/sup\\u003e. This suggests that the SF36 may be a useful early indicator of worsening mobility and subsequent muscle loss, underlining the importance of interventions to maintain skeletal muscle health in older populations.\\u003c/p\\u003e\\n\\u003cp\\u003eThe majority of previous studies have focused on quality of life in the context of general frailty, often using SF36\\u003csup\\u003e30,31\\u003c/sup\\u003e. In the context of CMV, there have been limited studies looking at the relationship of CMV status and frailty, with different measures of frailty used. CMV reactivation was shown to be associated with an odds ratio of 6.13 for frailty compared to non-frail Brazilian females\\u003csup\\u003e32\\u003c/sup\\u003e.Schmaltz et al found higher levels of frailty in CMV positive older women, suggesting this association may be modified by IL6, as a higher association was found in those with higher IL6 levels\\u003csup\\u003e33\\u003c/sup\\u003e. However, they were not able to show a statistically significant association of CMV status with grip strength, although there was a trend towards increased weakness. Another study of women found an association between CMV status and both frailty (hazard ratio 3.45, 95% confidence interval 1.45-8.27) and mortality (HR 2.79, 95% CI 1.64-8.83), but only the highest quintile of antibody titres remained significant in predicting mortality after adjustment and the association with frailty became non-significant\\u003csup\\u003e34\\u003c/sup\\u003e. Similarly, using Fried\\u0026rsquo;s criteria, a Belgian study of the oldest old found no association between pre-frailty and CMV status with only IL6 age and sex found to be predictors of the pre-frail phenotype\\u003csup\\u003e35\\u003c/sup\\u003e.The BELFRAIL study, also of over 80s in Belgium, counterintuitively found a negative association of CMV serology with frailty\\u003csup\\u003e36\\u003c/sup\\u003e. They suggest that a survival effect may result from the older age of their population, meaning that those more susceptible to the damage of CMV have died at earlier ages. They also found no association of CMV status with IL6 levels, although IL6 itself was associated with frailty and functional impairment. The level of association of CMV with all elements of frailty is significant, as there is increasing belief that frailty is to some degree reversible at the pre-frail stage, thus clinical interventions and CMV vaccines may have a role to play in reducing the burden of frailty.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eMeasures of quality of life\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe SF36 is a commonly used measure of health-related quality of life but is not specific to older people and has some limitations. Currently, there are no defined thresholds to identify reduced physical function, although cut offs for some mental health components have been proposed\\u003csup\\u003e37\\u003c/sup\\u003e. To give our figures some context, one large study used the US general population as a baseline for comparison, finding that the mean physical function score was 90 (\\u0026plusmn;17)\\u003csup\\u003e38\\u003c/sup\\u003e. In a much younger population of healthy controls (mean age 30-40), the mean physical functioning score was 92.6\\u0026plusmn;14.2\\u003csup\\u003e39\\u003c/sup\\u003e. \\u0026nbsp;It would appear reasonable, given the older average age of our cohort, that the CMV negative group had a slightly lower score (88.7\\u0026plusmn;15) and shows that the CMV positive group had a significantly lower value (81.3\\u0026plusmn;20.8). A UK study of younger Cushing\\u0026rsquo;s syndrome patients and healthy controls had an almost identical value of 88.7\\u0026plusmn;14.8 in the healthy group compared to 80\\u0026plusmn;19.5 for those with Cushing\\u0026rsquo;s syndrome\\u003csup\\u003e40\\u003c/sup\\u003e, suggesting that the impact of CMV may be comparable to major diseases. It has been determined that the minimal clinically impactful difference in the SF36 is a difference of 3-5 on each scale\\u003csup\\u003e18\\u003c/sup\\u003e, thus the differences highlighted in our study represent clinically impactful figures.\\u003c/p\\u003e\\n\\u003cp\\u003eSarQoL is a sarcopenia-specific measure of quality of life, which has been shown to correlate well in detecting robust vs frail vs prefrail individuals\\u003csup\\u003e41\\u003c/sup\\u003e. However, one study found that the SF36 was similarly able to detect differences between patients and controls when compared to SarQoL and was found to be superior to SARC-F\\u003csup\\u003e40\\u003c/sup\\u003e, a survey designed for use in case-finding for sarcopenia. Our study is focused on identifying individuals who may be vulnerable to the detrimental effects of CMV exposure and so finding diagnostic tools that highlight such individuals at an early stage (before clinical sarcopenia or frailty has developed) could be of benefit to clinicians. The SF36 provides a simple, effective tool for this purpose and further studies to validate its use in this context are needed.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003ePossible mechanisms\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eInflammation and immunosenescence have been proposed as mechanisms by which CMV may contribute to reduced muscle function and quantity. One study identified a \\u0026lsquo;cluster\\u0026rsquo; of the oldest old with an immunosenescent profile which included CMV positivity and T cell senescence\\u003csup\\u003e42\\u003c/sup\\u003e. However, similarly to ours, this study failed to find a relationship to muscle loss or sarcopenia over 5 years. It is debatable whether 5 years is sufficient to detect changes relating to CMV exposure, which is likely to have occurred in childhood or adolescence. There was also a 40% loss to follow up which may have underpowered the final results. In a similar population of the oldest old, there was limited evidence to support immunosenescence as the key element driving the association of frailty and inflammation, with no association found between CMV status and frailty. This may support the idea of a survival effect in this older group\\u003csup\\u003e43\\u003c/sup\\u003e. Equally, the duration of CMV infection does not seem to affect the impact on the system\\u003csup\\u003e44\\u003c/sup\\u003e, suggesting that the damage may relate to some vulnerability factor in the host.\\u003c/p\\u003e\\n\\u003cp\\u003eChanges to the immune system occurring over time include reduced capacity to fight infection and increased inflammation (\\u0026lsquo;inflammageing\\u0026rsquo;), which are postulated to relate to higher levels of IL6. In one study, IL6 levels strongly predicted grip-strength, suggesting a possible role in the development of sarcopenia\\u003csup\\u003e11\\u003c/sup\\u003e. However, there is the possibility raised by authors that cardiovascular disease may be a mediating factor, resulting in less physical activity and thus muscle depletion. \\u0026nbsp;It is also unclear whether CMV reactivation is the cause or effect of immunological changes with age. There is inevitably a cumulative impact of changes in nutrition, activity levels, endocrinological change and inflammatory changes contributing to frailty and its component parts including sarcopenia\\u003csup\\u003e45\\u003c/sup\\u003e. Again, authors propose IL6 as a major modulator of muscle density with a likely bidirectional interaction of chronic disease and immune function. In middle-aged patients with HIV and CMV coinfection, lower NAD levels were observed in skeletal muscle and there was an associated increase in frailty\\u003csup\\u003e46\\u003c/sup\\u003e, adding to the notion of inflammatory damage, but suggesting multiple modulating factors may be involved.\\u003c/p\\u003e\\n\\u003cp\\u003eSome studies have suggested that CMV may contribute to immunosenescence through clonal proliferation of terminally differentiated CMV-specific T cells, alongside chronic inflammation leading to persistent accumulation of inflammatory damage\\u003csup\\u003e47\\u003c/sup\\u003e. We have previously written about the increase in T memory cells, predominantly in men, in the CMV positive group of this cohort\\u003csup\\u003e48\\u003c/sup\\u003e. There is also the possibility of a dose-response relationship, with higher CMV IgG more strongly correlated with frailty\\u003csup\\u003e49\\u003c/sup\\u003e. Chronic low-grade inflammation may be a response to chronic or latent infections such as CMV, resulting in higher levels of circulating inflammatory markers including CRP. This has mainly been studied in the HIV population where CMV Infection is highly prevalent and CMV is the target of over 10% of circulating T cells in HIV-infected individuals\\u003csup\\u003e50\\u003c/sup\\u003e.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eLimitations\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThis was a cross-sectional study of UK older people and thus cannot infer causality and may not be generalisable to other populations. However, the use of a linear scale to detect differences in SF36-assessed physical function offers advantages to simply categorising participants into frail/non-frail or sarcopenic/non-sarcopenic. We chose to use recommended measures and cut-offs for muscle quality and quantity based on European guidelines. BIA is recommended for use in assessing body composition but does have limitations as it is dependent on hydration and relies on specific population norms for comparison. The use of CMV antibodies also may not be sufficient to characterise the status of a large population, as 1 in 4 people may fail to generate a humoral response. In this case, it would be necessary to measure cellular immunity\\u003csup\\u003e24\\u003c/sup\\u003e.\\u003c/p\\u003e\"},{\"header\":\"Conclusion\",\"content\":\"\\u003cp\\u003eOur study found an independent association of physical function domains of the SF36 with CMV status, but no clear relationship between CMV status and sarcopenia. Previous studies have suggested that CMV may contribute to overall frailty, but the relationship with muscle loss over time is yet to be determined. Future studies would be beneficial to assess whether changes in measures of physical function may predate the development of sarcopenia in this cohort, thus offering the potential for interventions to reduce the negative consequences of sarcopenia. The exact mechanism by which frailty, immune senescence and CMV-related inflammation are linked remains uncertain, likely due to the complex, heterogeneous interactions between these states. It is possible that the development of a CMV vaccine may have a valuable role in reducing the future burden of frailty, but further elucidation of these relationships is required.\\u003c/p\\u003e\"},{\"header\":\"Declarations\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003eFunding sources and related paper presentations:\\u0026nbsp;\\u003c/strong\\u003eThis work was supported by The Dunhill Medical Trust, grant number R278/0213\\u003c/p\\u003e\\n\\u003cp\\u003eOn behalf of all authors, the corresponding author states that there is no conflict of interest.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAcknowledgements\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eWe would like to thank all involved staff of the Clinical Investigation and Research Unit (CIRU) of Brighton and Sussex University Hospital Trust (BSUHT) for their continuous support. We are grateful to all participating GP practices and especially grateful to all participating volunteers. We would also like to thank the Primary Care Research Network (PCRN) South-East for coordinating the recruitment process.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAuthors\\u0026rsquo; roles\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eFA Kirkham\\u003cstrong\\u003e\\u0026nbsp;\\u0026ndash;\\u0026nbsp;\\u003c/strong\\u003econcept design, data collection, analysis, manuscript writing\\u003c/p\\u003e\\n\\u003cp\\u003eS \\u0026ndash; data collection, manuscript writing\\u003c/p\\u003e\\n\\u003cp\\u003eEM - data collection, manuscript writing\\u003c/p\\u003e\\n\\u003cp\\u003eC Rajkumar \\u0026ndash; study design, concept design, manuscript writing\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConflicts of interest\\u0026nbsp;\\u003c/strong\\u003eNone\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eEthics Statement\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe study was approved by the UK National Research Ethics Service (NRES) \\u0026apos;London Centre\\u0026apos; (Reference 13/LO/1270). Written informed consent was obtained from all participants. The study was conducted in accordance with the Declaration of Helsinki.\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col\\u003e\\n\\u003cli\\u003eWang H, Peng G, Bai J, et al. Cytomegalovirus Infection and Relative Risk of Cardiovascular Disease (Ischemic Heart Disease, Stroke, and Cardiovascular Death): A Meta-Analysis of Prospective Studies Up to 2016. \\u003cem\\u003eJ Am Heart Assoc\\u003c/em\\u003e. Jul 2017;6(7)doi:10.1161/JAHA.116.005025\\u003c/li\\u003e\\n\\u003cli\\u003eSavva GM, Pachnio A, Kaul B, et al. Cytomegalovirus infection is associated with increased mortality in the older population. \\u003cem\\u003eAging Cell\\u003c/em\\u003e. Jun 2013;12(3):381-7. doi:10.1111/acel.12059\\u003c/li\\u003e\\n\\u003cli\\u003eYaiw KC, Mohammad AA, Taher C, et al. Human Cytomegalovirus Reduces Endothelin-1 Expression in Both Endothelial and Vascular Smooth Muscle Cells. \\u003cem\\u003eMicroorganisms\\u003c/em\\u003e. May 25 2021;9(6)doi:10.3390/microorganisms9061137\\u003c/li\\u003e\\n\\u003cli\\u003eXue QL, Walston JD, Fried LP, Beamer BA. Prediction of risk of falling, physical disability, and frailty by rate of decline in grip strength: the women\\u0026apos;s health and aging study. \\u003cem\\u003eArch Intern Med\\u003c/em\\u003e. Jun 27 2011;171(12):1119-21. doi:10.1001/archinternmed.2011.252\\u003c/li\\u003e\\n\\u003cli\\u003eNewman AB, Kupelian V, Visser M, et al. Strength, but not muscle mass, is associated with mortality in the health, aging and body composition study cohort. \\u003cem\\u003eJ Gerontol A Biol Sci Med Sci\\u003c/em\\u003e. Jan 2006;61(1):72-7. doi:10.1093/gerona/61.1.72\\u003c/li\\u003e\\n\\u003cli\\u003eKirkham FA, Rankin P, Bunting E, Ali K, Rajkumar C. Using measures of sarcopenia to predict recurrent cerebrovascular events in stroke and TIA patients. \\u003cem\\u003eJ Stroke Cerebrovasc Dis\\u003c/em\\u003e. Apr 2023;32(4):106979. doi:10.1016/j.jstrokecerebrovasdis.2023.106979\\u003c/li\\u003e\\n\\u003cli\\u003eSayer AA, Cruz-Jentoft A. Sarcopenia definition, diagnosis and treatment: consensus is growing. \\u003cem\\u003eAge Ageing\\u003c/em\\u003e. Oct 06 2022;51(10)doi:10.1093/ageing/afac220\\u003c/li\\u003e\\n\\u003cli\\u003eCruz-Jentoft AJ, Bahat G, Bauer J, et al. Sarcopenia: revised European consensus on definition and diagnosis. \\u003cem\\u003eAge Ageing\\u003c/em\\u003e. Jul 01 2019;48(4):601. doi:10.1093/ageing/afz046\\u003c/li\\u003e\\n\\u003cli\\u003eIbrahim K, May CR, Patel HP, Baxter M, Sayer AA, Roberts HC. Implementation of grip strength measurement in medicine for older people wards as part of routine admission assessment: identifying facilitators and barriers using a theory-led intervention. \\u003cem\\u003eBMC Geriatr\\u003c/em\\u003e. Mar 22 2018;18(1):79. doi:10.1186/s12877-018-0768-5\\u003c/li\\u003e\\n\\u003cli\\u003eBarazzoni R, Jensen GL, Correia MITD, et al. Guidance for assessment of the muscle mass phenotypic criterion for the Global Leadership Initiative on Malnutrition (GLIM) diagnosis of malnutrition. \\u003cem\\u003eClin Nutr\\u003c/em\\u003e. Jun 2022;41(6):1425-1433. doi:10.1016/j.clnu.2022.02.001\\u003c/li\\u003e\\n\\u003cli\\u003eKilgour AH, Firth C, Harrison R, et al. Seropositivity for CMV and IL-6 levels are associated with grip strength and muscle size in the elderly. \\u003cem\\u003eImmun Ageing\\u003c/em\\u003e. Aug 13 2013;10(1):33. doi:10.1186/1742-4933-10-33\\u003c/li\\u003e\\n\\u003cli\\u003eAbidi MZ, Umbleja T, Overton ET, et al. Cytomegalovirus IgG is Associated With Physical Function But Not Muscle Density in People With HIV. \\u003cem\\u003eJ Acquir Immune Defic Syndr\\u003c/em\\u003e. Apr 15 2024;95(5):470-478. doi:10.1097/QAI.0000000000003377\\u003c/li\\u003e\\n\\u003cli\\u003eGroessl EJ, Kaplan RM, Rejeski WJ, et al. Physical Activity and Performance Impact Long-term Quality of Life in Older Adults at Risk for Major Mobility Disability. \\u003cem\\u003eAm J Prev Med\\u003c/em\\u003e. Jan 2019;56(1):141-146. doi:10.1016/j.amepre.2018.09.006\\u003c/li\\u003e\\n\\u003cli\\u003eDodds RM, Syddall HE, Cooper R, et al. Grip strength across the life course: normative data from twelve British studies. \\u003cem\\u003ePLoS One\\u003c/em\\u003e. 2014;9(12):e113637. doi:10.1371/journal.pone.0113637\\u003c/li\\u003e\\n\\u003cli\\u003eStudenski SA, Peters KW, Alley DE, et al. The FNIH sarcopenia project: rationale, study description, conference recommendations, and final estimates. \\u003cem\\u003eJ Gerontol A Biol Sci Med Sci\\u003c/em\\u003e. May 2014;69(5):547-58. doi:10.1093/gerona/glu010\\u003c/li\\u003e\\n\\u003cli\\u003eSergi G, De Rui M, Stubbs B, Veronese N, Manzato E. Measurement of lean body mass using bioelectrical impedance analysis: a consideration of the pros and cons. \\u003cem\\u003eAging Clin Exp Res\\u003c/em\\u003e. Aug 2017;29(4):591-597. doi:10.1007/s40520-016-0622-6\\u003c/li\\u003e\\n\\u003cli\\u003eYamada Y, Nishizawa M, Uchiyama T, et al. Developing and Validating an Age-Independent Equation Using Multi-Frequency Bioelectrical Impedance Analysis for Estimation of Appendicular Skeletal Muscle Mass and Establishing a Cutoff for Sarcopenia. \\u003cem\\u003eInt J Environ Res Public Health\\u003c/em\\u003e. Jul 19 2017;14(7)doi:10.3390/ijerph14070809\\u003c/li\\u003e\\n\\u003cli\\u003eHays RD, Morales LS. The RAND-36 measure of health-related quality of life. \\u003cem\\u003eAnn Med\\u003c/em\\u003e. Jul 2001;33(5):350-7. doi:10.3109/07853890109002089\\u003c/li\\u003e\\n\\u003cli\\u003eCoons SJ, Rao S, Keininger DL, Hays RD. A comparative review of generic quality-of-life instruments. \\u003cem\\u003ePharmacoeconomics\\u003c/em\\u003e. Jan 2000;17(1):13-35. doi:10.2165/00019053-200017010-00002\\u003c/li\\u003e\\n\\u003cli\\u003eDe Buyser SL, Petrovic M, Taes YE, et al. Validation of the FNIH sarcopenia criteria and SOF frailty index as predictors of long-term mortality in ambulatory older men. \\u003cem\\u003eAge Ageing\\u003c/em\\u003e. Sep 2016;45(5):602-8. doi:10.1093/ageing/afw071\\u003c/li\\u003e\\n\\u003cli\\u003eLauretani F, Russo CR, Bandinelli S, et al. Age-associated changes in skeletal muscles and their effect on mobility: an operational diagnosis of sarcopenia. \\u003cem\\u003eJ Appl Physiol (1985)\\u003c/em\\u003e. Nov 2003;95(5):1851-60. doi:10.1152/japplphysiol.00246.2003\\u003c/li\\u003e\\n\\u003cli\\u003eHicks GE, Shardell M, Alley DE, et al. Absolute strength and loss of strength as predictors of mobility decline in older adults: the InCHIANTI study. \\u003cem\\u003eJ Gerontol A Biol Sci Med Sci\\u003c/em\\u003e. Jan 2012;67(1):66-73. doi:10.1093/gerona/glr055\\u003c/li\\u003e\\n\\u003cli\\u003eSayer AA, Syddall HE, Martin HJ, Dennison EM, Roberts HC, Cooper C. Is grip strength associated with health-related quality of life? Findings from the Hertfordshire Cohort Study. \\u003cem\\u003eAge Ageing\\u003c/em\\u003e. Jul 2006;35(4):409-15. doi:10.1093/ageing/afl024\\u003c/li\\u003e\\n\\u003cli\\u003eF\\u0026aacute;brega-Cuadros R, Hita-Contreras F, Mart\\u0026iacute;nez-Amat A, et al. Associations between the Severity of Sarcopenia and Health-Related Quality of Life in Community-Dwelling Middle-Aged and Older Adults. \\u003cem\\u003eInt J Environ Res Public Health\\u003c/em\\u003e. Jul 29 2021;18(15)doi:10.3390/ijerph18158026\\u003c/li\\u003e\\n\\u003cli\\u003e\\u0026Ouml;zt\\u0026uuml;rk ZA, T\\u0026uuml;rkbeyler İ, Abiyev A, et al. Health-related quality of life and fall risk associated with age-related body composition changes; sarcopenia, obesity and sarcopenic obesity. \\u003cem\\u003eIntern Med J\\u003c/em\\u003e. Aug 2018;48(8):973-981. doi:10.1111/imj.13935\\u003c/li\\u003e\\n\\u003cli\\u003eBeaudart C, Reginster JY, Petermans J, et al. Quality of life and physical components linked to sarcopenia: The SarcoPhAge study. \\u003cem\\u003eExp Gerontol\\u003c/em\\u003e. Sep 2015;69:103-10. doi:10.1016/j.exger.2015.05.003\\u003c/li\\u003e\\n\\u003cli\\u003eSilva Neto LS, Karnikowiski MG, Tavares AB, Lima RM. Association between sarcopenia, sarcopenic obesity, muscle strength and quality of life variables in elderly women. \\u003cem\\u003eRev Bras Fisioter\\u003c/em\\u003e. 2012;16(5):360-7.\\u003c/li\\u003e\\n\\u003cli\\u003eSilva Neto LS, Karnikowski MG, Os\\u0026oacute;rio NB, et al. Association between sarcopenia and quality of life in quilombola elderly in Brazil. \\u003cem\\u003eInt J Gen Med\\u003c/em\\u003e. 2016;9:89-97. doi:10.2147/IJGM.S92404\\u003c/li\\u003e\\n\\u003cli\\u003eTrombetti A, Reid KF, Hars M, et al. Age-associated declines in muscle mass, strength, power, and physical performance: impact on fear of falling and quality of life. \\u003cem\\u003eOsteoporos Int\\u003c/em\\u003e. Feb 2016;27(2):463-71. doi:10.1007/s00198-015-3236-5\\u003c/li\\u003e\\n\\u003cli\\u003eS\\u0026aacute;nchez-Garc\\u0026iacute;a S, Gallegos-Carrillo K, Espinel-Bermudez MC, et al. Comparison of quality of life among community-dwelling older adults with the frailty phenotype. \\u003cem\\u003eQual Life Res\\u003c/em\\u003e. Oct 2017;26(10):2693-2703. doi:10.1007/s11136-017-1630-5\\u003c/li\\u003e\\n\\u003cli\\u003eRizzoli R, Reginster JY, Arnal JF, et al. Quality of life in sarcopenia and frailty. \\u003cem\\u003eCalcif Tissue Int\\u003c/em\\u003e. Aug 2013;93(2):101-20. doi:10.1007/s00223-013-9758-y\\u003c/li\\u003e\\n\\u003cli\\u003eThomasini RL, Pereira DS, Pereira FSM, et al. Aged-associated cytomegalovirus and Epstein-Barr virus reactivation and cytomegalovirus relationship with the frailty syndrome in older women. \\u003cem\\u003ePLoS One\\u003c/em\\u003e. 2017;12(7):e0180841. doi:10.1371/journal.pone.0180841\\u003c/li\\u003e\\n\\u003cli\\u003eSchmaltz HN, Fried LP, Xue QL, Walston J, Leng SX, Semba RD. Chronic cytomegalovirus infection and inflammation are associated with prevalent frailty in community-dwelling older women. \\u003cem\\u003eJ Am Geriatr Soc\\u003c/em\\u003e. May 2005;53(5):747-54. doi:10.1111/j.1532-5415.2005.53250.x\\u003c/li\\u003e\\n\\u003cli\\u003eWang GC, Kao WH, Murakami P, et al. Cytomegalovirus infection and the risk of mortality and frailty in older women: a prospective observational cohort study. \\u003cem\\u003eAm J Epidemiol\\u003c/em\\u003e. May 15 2010;171(10):1144-52. doi:10.1093/aje/kwq062\\u003c/li\\u003e\\n\\u003cli\\u003eCao Dinh H, Bautmans I, Beyer I, et al. Association Between Immunosenescence Phenotypes and Pre-frailty in Older Subjects: Does Cytomegalovirus Play a Role? \\u003cem\\u003eJ Gerontol A Biol Sci Med Sci\\u003c/em\\u003e. Mar 14 2019;74(4):480-488. doi:10.1093/gerona/gly135\\u003c/li\\u003e\\n\\u003cli\\u003eMathe\\u0026iuml; C, Vaes B, Wallemacq P, Degryse J. Associations between cytomegalovirus infection and functional impairment and frailty in the BELFRAIL Cohort. \\u003cem\\u003eJ Am Geriatr Soc\\u003c/em\\u003e. Dec 2011;59(12):2201-8. doi:10.1111/j.1532-5415.2011.03719.x\\u003c/li\\u003e\\n\\u003cli\\u003eSilveira E, Taft C, Sundh V, Waern M, Palsson S, Steen B. Performance of the SF-36 health survey in screening for depressive and anxiety disorders in an elderly female Swedish population. \\u003cem\\u003eQual Life Res\\u003c/em\\u003e. Jun 2005;14(5):1263-74. doi:10.1007/s11136-004-7753-5\\u003c/li\\u003e\\n\\u003cli\\u003eHays RD, Cunningham WE, Sherbourne CD, et al. Health-related quality of life in patients with human immunodeficiency virus infection in the United States: results from the HIV Cost and Services Utilization Study. \\u003cem\\u003eAm J Med\\u003c/em\\u003e. Jun 15 2000;108(9):714-22. doi:10.1016/s0002-9343(00)00387-9\\u003c/li\\u003e\\n\\u003cli\\u003eSchulte-van Maaren YW, Carlier IV, Zitman FG, et al. Reference values for generic instruments used in routine outcome monitoring: the Leiden Routine Outcome Monitoring Study. \\u003cem\\u003eBMC Psychiatry\\u003c/em\\u003e. Nov 21 2012;12:203. doi:10.1186/1471-244X-12-203\\u003c/li\\u003e\\n\\u003cli\\u003eMartel-Duguech L, Alonso-Jimenez A, Bascu\\u0026ntilde;ana H, et al. Prevalence of sarcopenia after remission of hypercortisolism and its impact on HRQoL. \\u003cem\\u003eClin Endocrinol (Oxf)\\u003c/em\\u003e. Nov 2021;95(5):735-743. doi:10.1111/cen.14568\\u003c/li\\u003e\\n\\u003cli\\u003eGeerinck A, Locquet M, Bruy\\u0026egrave;re O, Reginster JY, Beaudart C. Evaluating quality of life in frailty: applicability and clinimetric properties of the SarQoL. \\u003cem\\u003eJ Cachexia Sarcopenia Muscle\\u003c/em\\u003e. Apr 2021;12(2):319-330. doi:10.1002/jcsm.12687\\u003c/li\\u003e\\n\\u003cli\\u003eGranic A, Martin-Ruiz C, Dodds RM, et al. Immunosenescence profiles are not associated with muscle strength, physical performance and sarcopenia risk in very old adults: The Newcastle 85+ Study. \\u003cem\\u003eMech Ageing Dev\\u003c/em\\u003e. Sep 2020;190:111321. doi:10.1016/j.mad.2020.111321\\u003c/li\\u003e\\n\\u003cli\\u003eCollerton J, Martin-Ruiz C, Davies K, et al. Frailty and the role of inflammation, immunosenescence and cellular ageing in the very old: cross-sectional findings from the Newcastle 85+ Study. \\u003cem\\u003eMech Ageing Dev\\u003c/em\\u003e. Jun 2012;133(6):456-66. doi:10.1016/j.mad.2012.05.005\\u003c/li\\u003e\\n\\u003cli\\u003eSamson LD, van den Berg SP, Engelfriet P, et al. Limited effect of duration of CMV infection on adaptive immunity and frailty: insights from a 27-year-long longitudinal study. \\u003cem\\u003eClin Transl Immunology\\u003c/em\\u003e. 2020;9(10):e1193. doi:10.1002/cti2.1193\\u003c/li\\u003e\\n\\u003cli\\u003eFulop T, Larbi A, Witkowski JM, et al. Aging, frailty and age-related diseases. \\u003cem\\u003eBiogerontology\\u003c/em\\u003e. Oct 2010;11(5):547-63. doi:10.1007/s10522-010-9287-2\\u003c/li\\u003e\\n\\u003cli\\u003eTran T, Pencina KM, Schultz MB, et al. Reduced Levels of NAD in Skeletal Muscle and Increased Physiologic Frailty Are Associated With Viral Coinfection in Asymptomatic Middle-Aged Adults. \\u003cem\\u003eJ Acquir Immune Defic Syndr\\u003c/em\\u003e. Feb 01 2022;89(Suppl 1):S15-S22. doi:10.1097/QAI.0000000000002852\\u003c/li\\u003e\\n\\u003cli\\u003eLeng SX. Role of chronic cytomegalovirus infection in T-cell immunosenescence and frailty: more questions than answers. \\u003cem\\u003eJ Am Geriatr Soc\\u003c/em\\u003e. Dec 2011;59(12):2363-5. doi:10.1111/j.1532-5415.2011.03815.x\\u003c/li\\u003e\\n\\u003cli\\u003eKirkham F, Pera A, Simanek AM, et al. Cytomegalovirus infection is associated with an increase in aortic stiffness in older men which may be mediated in part by CD4 memory T-cells. \\u003cem\\u003eTheranostics\\u003c/em\\u003e. 2021;11(12):5728-5741. doi:10.7150/thno.58356\\u003c/li\\u003e\\n\\u003cli\\u003eHaeseker MB, Pijpers E, Dukers-Muijrers NH, et al. Association of cytomegalovirus and other pathogens with frailty and diabetes mellitus, but not with cardiovascular disease and mortality in psycho-geriatric patients; a prospective cohort study. \\u003cem\\u003eImmun Ageing\\u003c/em\\u003e. Jul 23 2013;10(1):30. doi:10.1186/1742-4933-10-30\\u003c/li\\u003e\\n\\u003cli\\u003eLeng SX, Margolick JB. Aging, sex, inflammation, frailty, and CMV and HIV infections. \\u003cem\\u003eCell Immunol\\u003c/em\\u003e. Feb 2020;348:104024. doi:10.1016/j.cellimm.2019.104024\\u003c/li\\u003e\\n\\u003c/ol\\u003e\"}],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":true,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":false,\"hideJournal\":false,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":true,\"isAuthorSuppliedPdf\":false,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":true,\"isPdf\":false,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"european-geriatric-medicine\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":false,\"externalIdentity\":\"EGEM\",\"sideBox\":\"Learn more about [European Geriatric Medicine](https://www.springer.com/journal/41999)\",\"snPcode\":\"41999\",\"submissionUrl\":\"https://www.editorialmanager.com/egem/default2.aspx\",\"title\":\"European Geriatric Medicine\",\"twitterHandle\":\"\",\"acdcEnabled\":false,\"dfaEnabled\":true,\"editorialSystem\":\"em\",\"reportingPortfolio\":\"Springer Hybrid\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":false},\"keywords\":\"Cytomegalovirus, sarcopenia, frailty, quality of life\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-5937387/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-5937387/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003ch2\\u003eMethods\\u003c/h2\\u003e \\u003cp\\u003e210 participants in the south of England with mean age 69.8 years underwent demographic and medical questionnaires, measures of body composition (bioimpedance analysis), handgrip strength and the short form 36 item survey of quality of life (SF36). All participants had peripheral venepuncture to assess CMV serology and inflammatory markers. Measures of sarcopenia were calculated using European Working Group definitions.\\u003c/p\\u003e\\u003ch2\\u003eResults\\u003c/h2\\u003e \\u003cp\\u003e51.7% of participants were positive for CMV IgG. There were no significant differences between CMV positive and negative groups in age, gender, measures of sarcopenia or inflammatory markers. CMV positive groups had lower scores in all domains of the SF36, with significantly lower physical function score (88.7 vs 81.3, p\\u0026thinsp;=\\u0026thinsp;0.003) as well as total score, limitations due to physical health, energy/fatigue, social functioning and pain. Physical functioning score was significantly correlated with measures of sarcopenia including handgrip strength (r\\u0026thinsp;=\\u0026thinsp;0.155 p\\u0026thinsp;=\\u0026thinsp;0.026) and appendicular skeletal muscle mass index (r\\u0026thinsp;=\\u0026thinsp;0.201, p\\u0026thinsp;=\\u0026thinsp;0.005). On linear regression, CMV status was significantly associated with SF36 physical function score (p\\u0026thinsp;=\\u0026thinsp;0.004) after adjustment for age, gender, BMI, CRP and handgrip strength.\\u003c/p\\u003e\\u003ch2\\u003eConclusion\\u003c/h2\\u003e \\u003cp\\u003eCMV positivity is significantly associated with physical function and health-related quality of life in older adults, although its direct relationship to sarcopenia is yet to be fully ascertained.\\u003c/p\\u003e\",\"manuscriptTitle\":\"The relationship of cytomegalovirus with physical functioning and health-related quality of life in older adults\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2025-02-14 10:50:11\",\"doi\":\"10.21203/rs.3.rs-5937387/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0},{\"type\":\"decision\",\"content\":\"Major revisions\",\"date\":\"2025-03-14T06:29:01+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"reviewerAgreed\",\"content\":\"\",\"date\":\"2025-02-13T07:26:25+00:00\",\"index\":0,\"fulltext\":\"\"},{\"type\":\"reviewersInvited\",\"content\":\"\",\"date\":\"2025-02-12T10:02:37+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorAssigned\",\"content\":\"\",\"date\":\"2025-02-12T07:21:17+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"submitted\",\"content\":\"European Geriatric Medicine\",\"date\":\"2025-02-06T05:48:05+00:00\",\"index\":\"\",\"fulltext\":\"\"}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"european-geriatric-medicine\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":false,\"externalIdentity\":\"EGEM\",\"sideBox\":\"Learn more about [European Geriatric Medicine](https://www.springer.com/journal/41999)\",\"snPcode\":\"41999\",\"submissionUrl\":\"https://www.editorialmanager.com/egem/default2.aspx\",\"title\":\"European Geriatric Medicine\",\"twitterHandle\":\"\",\"acdcEnabled\":false,\"dfaEnabled\":true,\"editorialSystem\":\"em\",\"reportingPortfolio\":\"Springer Hybrid\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":false}}],\"origin\":\"\",\"ownerIdentity\":\"7cbdec2f-f376-47c9-8364-452ad853b489\",\"owner\":[],\"postedDate\":\"February 14th, 2025\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"under-review\",\"subjectAreas\":[],\"tags\":[],\"updatedAt\":\"2025-05-21T06:11:08+00:00\",\"versionOfRecord\":[],\"versionCreatedAt\":\"2025-02-14 10:50:11\",\"video\":\"\",\"vorDoi\":\"\",\"vorDoiUrl\":\"\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-5937387\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-5937387\",\"identity\":\"rs-5937387\",\"version\":[\"v1\"]},\"buildId\":\"8U1c8b4HqxoKbykW_rLl7\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}