Handgrip strength is associated with adverse outcomes in patients hospitalized for COVID-19-associated pneumonia.

Handgrip strength (HGS), a simple tool for the evaluation of muscular strength, is independently associated with negative prognosis in many diseases. It is unknown whether HGS is prognostically relevant in COVID-19. We evaluated the ability of HGS to predict clinical outcomes in people with COVID-19-related pneumonia. 118 patients (66% men, 63 ± 12 years), consecutively hospitalized to the "Santa Maria" Terni University Hospital for COVID-19-related pneumonia and respiratory failure, underwent HGS measurement (Jamar hand-dynamometer) at ward admission. HGS was normalized to weight2/3 (nHGS) The main end-point was the first occurrence of death and/or endotracheal intubation at 14 days. Twenty-two patients reached the main end-point. In the Kaplan-Meyer analysis, the Log rank test showed significant differences between subjects with lower than mean HGS normalized to weight2/3 (nHGS) (< 1.32 kg/Kg2/3) vs subjects with higher than mean nHGS. (p = 0.03). In a Cox-proportional hazard model, nHGS inversely predicted the main end-point (hazard ratio, HR = 1.99 each 0.5 kg/Kg2/3 decrease, p = 0.03), independently from age, sex, body mass index, ratio of partial pressure arterial oxygen and fraction of inspired oxygen (PaO2/FiO2 ratio), hypertension, diabetes, estimated glomerular filtration rate and history of previous cardiovascular cardiovascular disease. These two latter also showed independent association with the main end-point (HR 1.30, p = 0.03 and 3.89, p < 0.01, respectively). In conclusion, nHGS measured at hospital admission, independently and inversely predicts the risk of poor outcomes in people with COVID-19-related pneumonia. The evaluation of HGS may be useful in early stratifying the risk of adverse prognosis in COVID-19.

Associations of Dynapenic Obesity and Sarcopenic Obesity with the Risk of Complications in COVID-19.

Ageing is associated with changes in body composition, such as low muscle mass (sarcopenia), decreased grip strength or physical function (dynapenia), and accumulation of fat mass. When the accumulation of fat mass synergistically accompanies low muscle mass or reduced grip strength, it results in sarcopenic obesity and dynapenic obesity, respectively. These types of obesity contribute to the increased risk of cardiovascular disease and mortality in the elderly, which could increase the damage caused by COVID-19. In this review, we associated factors that could generate a higher risk of COVID-19 complications in dynapenic obesity and sarcopenic obesity. For example, skeletal muscle regulates the expression of inflammatory cytokines and supports metabolic stress in pulmonary disease; hence, the presence of dynapenic obesity or sarcopenic obesity could be related to a poor prognosis in COVID-19 patients.

BIOPHYTIS BIO101 IN SARCOPENIA: RESULTS OF THE PHASE 2 SARA-INT STUDY

Backgrounds: Sarcopenia is a geriatric condition characterized by a progressive loss of muscle mass and function, having high personal, social and economic burdens when untreated. Sarcopenia increases risk of falls and fractures;impairs ability to perform activities of daily living;is associated with cardiac and respiratory disease and cognitive impairment;leads to mobility disorders;and contributes to lowered quality of life, loss of independence or need for long-term care placement, and death. It is recognized as one of the five pillars of frailty. As of today, to our knowledge, only exercise and nutrition interventions seem somewhat effective interventions. Objectives: SARA-INT study is a Phase 2 study to develop a viable option to treat community-dwelling seniors suffering from age-related sarcopenia, including sarcopenic obesity. Methods: SARA-INT is a randomized double-blind three-arm study (BIO101 175 mg bid / BIO101 350 mg bid / placebo) with planned treatment duration of 6 Months;due to COVID-related measures, 49 patients continued up to 9 months of treatment. Main eligibility criteria for sarcopenia were meeting FNIH criteria and Short Physical Performance Battery (SPPB) score ≤ 8/12 in men and women aged ≥ 65 years. Primary analysis was the gait speed from the 400-meter walking test (400MWT) at month 6/9 in the FAS with secondary analyses at other timepoints, secondary endpoints were other physical activity assessments, muscle strength, muscle mass and Patient Reported Outcomes (PROs). Results: 233 participants were randomized in the study, 232 and 156 participants were included in the Full Analysis Set (FAS) and Per-Protocol (PP) populations, respectively. Due to COVID-19 pandemic, end-of-treatment assessments are missing for approximately half of the participants, impacting the treatment effect detection. In the primary analysis (at month 6/9 in the FAS population) of the primary parameter, the improvement in 400MWT compared to placebo was not statistically significant (0.0363 (0.03098) m/s and 0.0385 (0.02985) m/s in the BIO101 175 mg and 350 mg groups, p=0.2437 and p=0.2000, respectively). BIO101 350 mg bid treatment after 6 months showed a clinically relevant improvement in the 400MWT of 0.07 m/s in the FAS population (not significant) and of 0.09 m/s in the PP population (nominally statistically significant, p=0.008);this is close to the Minimal Clinically Important Difference (MCID) in sarcopenia (0.1 m/s). BIO101 350mg bid treatment effect on the 400MWT is confirmed in pre-defined sub-populations at higher risk of mobility disability such as slow walkers, obese and those with chair stand sub-score ≤2 from SPPB;trends were observed with other independent endpoints. BIO101 showed no difference in adverse events or safety laboratory parameters versus placebo (), and no severe adverse event associated with BIO101 treatment. Conclusions: After 6 to 9 months of treatment, BIO101 at 350 mg bid showed promising results with a clinically relevant improvement in the 400MWT gait speed, the primary endpoint of the study, confirmed in sub-populations at higher risk of mobility disability. BIO101 showed a very good safety profile at the doses of 175 and 350 mg bid. Biophytis is preparing to start a phase 3 program with BIO101 at 350 mg bid in 2022, targeting a similar patient population. Conflicts of interests: CT, WD, CM, RL, PD, RvM and SV are employees of Biophytis SA, AZ, and SA are employees of Biophytis Inc., JM is president of the Scientific Advisory Board of Biophytis, SDS is employee of BlueCompanion Ltd.

Skeletal Muscle in Hypoxia and Inflammation: Insights on the COVID-19 Pandemic.

SARS-CoV-2 infection is often associated with severe inflammation, oxidative stress, hypoxia and impaired physical activity. These factors all together contribute to muscle wasting and fatigue. In addition, there is evidence of a direct SARS-CoV-2 viral infiltration into skeletal muscle. Aging is often characterized by sarcopenia or sarcopenic obesity These conditions are risk factors for severe acute COVID-19 and long-COVID-19 syndrome. From these observations we may predict a strong association between COVID-19 and decreased muscle mass and functions. While the relationship between physical inactivity, chronic inflammation, oxidative stress and muscle dysfunction is well-known, the effects on muscle mass of COVID-19-related hypoxemia are inadequately investigated. The aim of this review is to highlight metabolic, immunity-related and redox biomarkers potentially affected by reduced oxygen availability and/or muscle fatigue in order to shed light on the negative impact of COVID-19 on muscle mass and function. Possible countermeasures are also reviewed.

Association of Obesity, Sarcopenia, and Sarcopenic Obesity With Hypertension in Adults: A Cross-Sectional Study From Ravansar, Iran During 2014-2017.

BACKGROUND AND AIMS: Hypertension may lead to disability and death by increasing the risk of cardiovascular disease, kidney failure, and dementia. This study aimed to determine the association between obesity, sarcopenia and sarcopenic obesity, and hypertension in adults resident in Ravansar, a city in the west of Iran. METHODS: This cross-sectional study was conducted on 4,021 subjects from the baseline data of the Ravansar Non-Communicable Disease (RaNCD) cohort study, in the west region of Iran, from October 2014 up to February 2017. Body composition was categorized into obese, sarcopenia, sarcopenic obese, and normal based on measurements of muscle strength, skeletal muscle mass, and waist circumference. Univariate and multiple logistic regression models were used to examine the relationships, using the STATA 15 software. RESULTS: The mean age of the participant was 47.9 years (SD: 8.4), the body mass index (BMI) was 26.84 kg/m2 (SD: 4.44), and the prevalence of hypertension was 15.12%. The prevalence of obesity, sarcopenia, and sarcopenic obesity were 24.37, 22.01, and 6.91%, respectively. Body composition groups had significant differences in age, total calorie intake, BMI, skeletal muscle mass, and muscle strength (P-value ≤ 0.001). In crude model, the obese (OR = 2.64; 95% CI: 2.11-3.30), sarcopenic (OR = 2.45; 95% CI: 1.94-3.08), and sarcopenic obese (OR = 3.83; 95% CI: 2.81-5.22) groups had a higher odds of hypertension. However, in adjusted models, only the obese group had a higher likelihood of hypertension (OR = 2.18; 95% CI: 1.70-2.80). CONCLUSION: This study showed that obesity was associated with hypertension, whereas sarcopenia and sarcopenic obesity had no significant relationship with hypertension.

Sarcopenic obesity and the risk of hospitalization or death from coronavirus disease 2019: findings from UK Biobank.

Background: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2. The role of skeletal muscle mass in modulating immune response is well documented. Whilst obesity is well established as a key factor in COVID-19 and outcome, no study has examined the influence of both sarcopenia (low muscle mass) and obesity, termed 'sarcopenic obesity' on the risk of severe COVID-19. Methods: This study uses data from UK Biobank. Probable sarcopenia was defined as low handgrip strength. Sarcopenic obesity was mutually exclusively defined as the presence of obesity and low muscle mass [based on two established criteria: appendicular lean mass (ALM) adjusted for either (i) height or (ii) body mass index]. Severe COVID-19 was defined by a positive severe acute respiratory syndrome coronavirus 2 test result in a hospital setting and/or death with a primary cause reported as COVID-19. Fully adjusted logistic regression models were used to analyse the associations between sarcopenic status and severe COVID-19. This work was conducted under UK Biobank Application Number 52553. Results: We analysed data from 490 301 UK Biobank participants (median age 70.0 years, 46% male); 2203 (0.4%) had severe COVID-19. Individuals with probable sarcopenia were 64% more likely to have had severe COVID-19 (odds ratio 1.638; P < 0.001). Obesity increased the likelihood of severe COVID-19 by 76% (P < 0.001). Using either ALM index or ALM/body mass index to define low muscle mass, those with sarcopenic obesity were 2.6 times more likely to have severe COVID-19 (odds ratio 2.619; P < 0.001). Sarcopenia alone did not increase the risk of COVID-19. Conclusions: Sarcopenic obesity may increase the risk of severe COVID-19, over that of obesity alone. The mechanisms for this are complex but could be a result of a reduction in respiratory functioning, immune response, and ability to respond to metabolic stress.

The Role of Sarcopenic Obesity in Cancer and Cardiovascular Disease: A Synthesis of the Evidence on Pathophysiological Aspects and Clinical Implications.

Obesity is globally a serious public health concern and is associated with a high risk of cardiovascular disease (CVD) and various types of cancers. It is important to evaluate various types of obesity, such as visceral and sarcopenic obesity. The evidence on the associated risk of CVD, cancer and sarcopenic obesity, including pathophysiological aspects, occurrence, clinical implications and survival, needs further investigation. Sarcopenic obesity is a relatively new term. It is a clinical condition that primarily affects older adults. There are several endocrine-hormonal, metabolic and lifestyle aspects involved in the occurrence of sarcopenic obesity that affect pathophysiological aspects that, in turn, contribute to CVD and neoplasms. However, there is no available evidence on the role of sarcopenic obesity in the occurrence of CVD and cancer and its pathophysiological interplay. Therefore, this review aims to describe the pathophysiological aspects and the clinical and epidemiological evidence on the role of sarcopenic obesity related to the occurrence and mortality risk of various types of cancer and cardiovascular disease. This literature review highlights the need for further research on sarcopenic obesity to demonstrate the interrelation of these various associations.