Carly Welch1,2,3,*, Carolyn Greig2,4,5, Tahir Masud2,6,7, Daisy Wilson1,3, Thomas A Jackson1,2,3
1Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Birmingham, B15 2TT, UK. 2MRC-Versus Arthritis Centre for Musculoskeletal Ageing Research, University of Birmingham and University of Nottingham, UK. 3University Hospitals Birmingham NHS Trust, Birmingham, B15 2GW, UK. 4School of Sport, Exercise, and Rehabilitation Sciences, University of Birmingham, Birmingham, B15 2TT, UK. 5Birmingham Biomedical Research Centre, University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK. 6University of Nottingham, Nottingham, UK. 7Nottingham University Hospitals NHS Trust, Nottingham, UK.
The COVID-19 pandemic has had a devastating global impact, with older adults being most at risk of death from the disease. However, acute sarcopenia occurs in survivors of COVID-19; older adults and the most critically unwell patients are the most at risk. Acute sarcopenia is an under-recognised condition of acute muscle insufficiency, defined by declines in muscle function and/or quantity within six months, usually following a stressor event. This commentary reviews definition and mechanisms of acute sarcopenia in COVID-19 and suggests recommendations for research and clinical practice. Research should now focus on the longer-term consequences of acute sarcopenia in patients who have suffered from COVID-19. At the same time, clinicians need to be increasingly aware of the condition, and measurements of muscle strength, quantity, and physical performance should be embedded into clinical practice. Clinicians should consider the risks of acute sarcopenia when weighing up the risks and benefits of treatment (e.g. dexamethasone), and instigate multidisciplinary treatment including dietetics input.
Figure 1. Mechanisms of acute sarcopenia development with COVID-19. Precipitating factors for acute sarcopenia with COVID-19 are demonstrated by pathways and predisposing factors are shown separately. MPB = Muscle Protein Breakdown; MPS = Muscle Protein Synthesis
Cruz-Jentoft A (2016). Sarcopenia, the last organ insufficiency. Eur Geriatr Med, 7:195-196.
Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyère O, Cederholm T, et al. (2019). Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing, 48:16-31.
Beaudart C, Reginster JY, Petermans J, Gillain S, Quabron A, Locquet M, et al. (2015). Quality of life and physical components linked to sarcopenia: The SarcoPhAge study. Exp Gerontol, 69:103-110.
Bischoff-Ferrari HA, Orav JE, Kanis JA, Rizzoli R, Schlögl M, Staehelin HB, et al. (2015). Comparative performance of current definitions of sarcopenia against the prospective incidence of falls among community-dwelling seniors age 65 and older. Osteoporos Int, 26:2793-2802.
Landi F, Cruz-Jentoft AJ, Liperoti R, Russo A, Giovannini S, Tosato M, et al. (2013). Sarcopenia and mortality risk in frail older persons aged 80 years and older: results from ilSIRENTE study. Age Ageing, 42:203-209.
Wilson D, Jackson T, Sapey E, Lord JM (2017). Frailty and sarcopenia: The potential role of an aged immune system. Ageing Res Rev, 36:1-10.
Welch C, Hassan-Smith ZK, Greig CA, Lord JM, Jackson TA (2018). Acute Sarcopenia Secondary to Hospitalisation - An Emerging Condition Affecting Older Adults. Aging Dis, 9:151-164.
Cruz-Jentoft AJ, Sayer AA (2019). Sarcopenia. Lancet, 393:2636-2646.
Martinez BP, Batista AK, Gomes IB, Olivieri FM, Camelier FW, Camelier AA (2015). Frequency of sarcopenia and associated factors among hospitalized elderly patients. BMC Musculoskelet Disord, 16:108.
Rossi AP, Fantin F, Micciolo R, Bertocchi M, Bertassello P, Zanandrea V, et al. (2014). Identifying sarcopenia in acute care setting patients. J Am Med Dir Assoc, 15:303.e307-312.
Sousa AS, Guerra RS, Fonseca I, Pichel F, Amaral TF (2015). Sarcopenia among hospitalized patients - A cross-sectional study. Clin Nutr, 34:1239-1244.
Smoliner C, Sieber CC, Wirth R (2014). Prevalence of sarcopenia in geriatric hospitalized patients. J Am Med Dir Assoc, 15:267-272.
Du Y, Karvellas CJ, Baracos V, Williams DC, Khadaroo RG (2014). Sarcopenia is a predictor of outcomes in very elderly patients undergoing emergency surgery. Surgery, 156:521-527.
Huang DD, Wang SL, Zhuang CL, Zheng BS, Lu JX, Chen FF, et al. (2015). Sarcopenia, as defined by low muscle mass, strength and physical performance, predicts complications after surgery for colorectal cancer. Colorectal Dis, 17:O256-264.
Lieffers JR, Bathe OF, Fassbender K, Winget M, Baracos VE (2012). Sarcopenia is associated with postoperative infection and delayed recovery from colorectal cancer resection surgery. Br J Cancer, 107:931-936.
Reisinger KW, van Vugt JL, Tegels JJ, Snijders C, Hulsewé KW, Hoofwijk AG, et al. (2015). Functional compromise reflected by sarcopenia, frailty, and nutritional depletion predicts adverse postoperative outcome after colorectal cancer surgery. Ann Surg, 261:345-352.
Deniz O, Coteli S, Karatoprak NB, Pence MC, Varan HD, Kizilarslanoglu MC, et al. (2020). Diaphragmatic muscle thickness in older people with and without sarcopenia. Aging Clin Exp Res.
Supinski GS, Morris PE, Dhar S, Callahan LA (2018). Diaphragm Dysfunction in Critical Illness. Chest, 153:1040-1051.
Narici MV, Maffulli N (2010). Sarcopenia: characteristics, mechanisms and functional significance. Br Med Bull, 95:139-159.
Murton AJ, Greenhaff PL (2009). Muscle atrophy in immobilization and senescence in humans. Curr Opin Neurol, 22:500-505.
Markofski MM, Dickinson JM, Drummond MJ, Fry CS, Fujita S, Gundermann DM, et al. (2015). Effect of age on basal muscle protein synthesis and mTORC1 signaling in a large cohort of young and older men and women. Exp Gerontol, 65:1-7.
Wall BT, Gorissen SH, Pennings B, Koopman R, Groen BBL, Verdijk LB, et al. (2015). Aging Is Accompanied by a Blunted Muscle Protein Synthetic Response to Protein Ingestion. PLOS ONE, 10:e0140903.
British Association of Parenteral and Enteral Nutrition. 2016. Nutritional Assessment.
Gajic O, Ahmad SR, Wilson ME, Kaufman DA (2018). Outcomes of critical illness: what is meaningful? Curr Opin Crit Care, 24:394-400.
De Biase S, Cook L, Skelton DA, Witham M, ten Hove R (2020). The COVID-19 rehabilitation pandemic. Age Ageing.
World Health Organization. 2020. Naming the coronavirus disease (COVID-19) and the virus that causes it.
Emanuel EJ, Persad G, Upshur R, Thome B, Parker M, Glickman A, et al. (2020). Fair Allocation of Scarce Medical Resources in the Time of Covid-19. N Engl J Med, 382:2049-2055.
Docherty AB, Harrison EM, Green CA, Hardwick HE, Pius R, Norman L, et al. (2020). Features of 20?133 UK patients in hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: prospective observational cohort study. BMJ, 369:m1985.
Greenhalgh T, Knight M, A’Court C, Buxton M, Husain L (2020). Management of post-acute covid-19 in primary care. BMJ, 370:m3026.
Morley JE, Kalantar-Zadeh K, Anker SD (2020). COVID-19: a major cause of cachexia and sarcopenia? J Cachexia Sarcopenia Muscle, 11:863-865.
Disser NP, De Micheli AJ, Schonk MM, Konnaris MA, Piacentini AN, Edon DL, et al. (2020). Musculoskeletal Consequences of COVID-19. J Bone Joint Surg Br, 102:1197-1204.
Bagnato S, Boccagni C, Marino G, Prestandrea C, D’Agostino T, Rubino F (2020). Critical illness myopathy after COVID-19. Int J Infect Dis.
Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. (2020). Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet, 395:497-506.
Lang CH, Frost RA, Nairn AC, MacLean DA, Vary TC (2002). TNF-alpha impairs heart and skeletal muscle protein synthesis by altering translation initiation. Am J Physiol Endocrinol Metab, 282:E336-347.
Foletta VC, White LJ, Larsen AE, Léger B, Russell AP (2011). The role and regulation of MAFbx/atrogin-1 and MuRF1 in skeletal muscle atrophy. Pflugers Arch, 461:325-335.
Coppé J-P, Desprez P-Y, Krtolica A, Campisi J (2010). The senescence-associated secretory phenotype: the dark side of tumor suppression. Annu Rev Pathol, 5:99-118.
Ceglia L (2009). Vitamin D and its role in skeletal muscle. Curr Opin Clin Nutr Metab Care, 12:628-633.
Hansdottir S, Monick MM (2011). Vitamin D effects on lung immunity and respiratory diseases. Vitam Horm, 86:217-237.
Kostoglou-Athanassiou I, Pantazi E, Kontogiannis S, Kousouris D, Mavropoulos I, Athanassiou P (2018). Vitamin D in acutely ill patients. J Int Med Res, 46:4246-4257.
Hastie CE, Mackay DF, Ho F, Celis-Morales CA, Katikireddi SV, Niedzwiedz CL, et al. (2020). Vitamin D concentrations and COVID-19 infection in UK Biobank. Diabetes Metab Syndr, 14:561-565.
D’Avolio A, Avataneo V, Manca A, Cusato J, De Nicolò A, Lucchini R, et al. (2020). 25-Hydroxyvitamin D Concentrations Are Lower in Patients with Positive PCR for SARS-CoV-2. Nutrients, 12:1359.
Public Health England. 2020. Excess Weight and COVID-19
Batsis JA, Villareal DT (2018). Sarcopenic obesity in older adults: aetiology, epidemiology and treatment strategies. Nat Rev Endocrinol, 14:513-537.
Luo M, Cao S, Wei L, Tang R, Hong S, Liu R, et al. (2020). Precautions for Intubating Patients with COVID-19. Anesthesiology, 132:1616-1618.
Mira JC, Gentile LF, Mathias BJ, Efron PA, Brakenridge SC, Mohr AM, et al. (2017). Sepsis Pathophysiology, Chronic Critical Illness, and Persistent Inflammation-Immunosuppression and Catabolism Syndrome. Crit Care Med, 45:253-262.
Clegg A, Young J, Iliffe S, Rikkert MO, Rockwood K (2013). Frailty in elderly people. Lancet, 381:752-762.
Meng X, Deng Y, Dai Z, Meng Z (2020). COVID-19 and anosmia: A review based on up-to-date knowledge. Am J Otolaryngol, 41:102581-102581.
Grunfeld C, Zhao C, Fuller J, Pollack A, Moser A, Friedman J, et al. (1996). Endotoxin and cytokines induce expression of leptin, the ob gene product, in hamsters. J Clin Investig, 97:2152-2157.
Cox NJ, Morrison L, Ibrahim K, Robinson SM, Sayer AA, Roberts HC (2020). New horizons in appetite and the anorexia of ageing. Age Ageing, 49:526-534.
Yoshida M, Tsuga K (2020). Sarcopenia and Mastication. Curr Oral Health Rep, 7:179-187.
Woods JA, Hutchinson NT, Powers SK, Roberts WO, Gomez-Cabrera MC, Radak Z, et al. (2020). The COVID-19 pandemic and physical activity. J Sport Health Sci, 2:55-64.
Kortebein P, Ferrando A, Lombeida J, Wolfe R, Evans WJ (2007). Effect of 10 days of bed rest on skeletal muscle in healthy older adults. JAMA, 297:1772-1774.
Tanner RE, Brunker LB, Agergaard J, Barrows KM, Briggs RA, Kwon OS, et al. (2015). Age-related differences in lean mass, protein synthesis and skeletal muscle markers of proteolysis after bed rest and exercise rehabilitation. J Physiol, 593:4259-4273.
Jones SW, Hill RJ, Krasney PA, O'Conner B, Peirce N, Greenhaff PL (2004). Disuse atrophy and exercise rehabilitation in humans profoundly affects the expression of genes associated with the regulation of skeletal muscle mass. FASEB J, 18:1025-1027.
Narici M, De Vito G, Franchi M, Paoli A, Moro T, Marcolin G, et al. (2020). Impact of sedentarism due to the COVID-19 home confinement on neuromuscular, cardiovascular and metabolic health: Physiological and pathophysiological implications and recommendations for physical and nutritional countermeasures. Eur J Sport Sci:1-22.
The RECOVERY Collaborative Group (2020). Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report. N Engl J Med.
Paddon-Jones D, Sheffield-Moore M, Cree MG, Hewlings SJ, Aarsland A, Wolfe RR, et al. (2006). Atrophy and Impaired Muscle Protein Synthesis during Prolonged Inactivity and Stress. J Clin Endocrinol Metab, 91:4836-4841.
Bodine SC, Latres E, Baumhueter S, Lai VK, Nunez L, Clarke BA, et al. (2001). Identification of ubiquitin ligases required for skeletal muscle atrophy. Science, 294:1704-1708.
Chan KS, Mourtzakis M, Aronson Friedman L, Dinglas VD, Hough CL, Ely EW, et al. (2018). Evaluating Muscle Mass in Survivors of Acute Respiratory Distress Syndrome: A 1-Year Multicenter Longitudinal Study. Crit Care Med, 46:1238-1246.
Rocheteau P, Chatre L, Briand D, Mebarki M, Jouvion G, Bardon J, et al. (2015). Sepsis induces long-term metabolic and mitochondrial muscle stem cell dysfunction amenable by mesenchymal stem cell therapy. Nat Commun, 6:10145.
Welch C, Greig CA, Masud T, Pinkney T, Jackson TA (2020). Protocol for understanding acute sarcopenia: a cohort study to characterise changes in muscle quantity and physical function in older adults following hospitalisation. BMC Geriatr, 20:239.
PHOSP-COVID Researchers. 2020. Long-term follow up of adults hospitalised with COVID-19.
Wilson D, Breen L, Lord JM, Sapey E (2018). The challenges of muscle biopsy in a community based geriatric population. BMC Res Notes, 11:830-830.
Rolland Y, Lauwers-Cances V, Cournot M, Nourhashémi F, Reynish W, Rivière D, et al. (2003). Sarcopenia, calf circumference, and physical function of elderly women: a cross-sectional study. J Am Geriatr Soc, 51:1120-1124.
MacKnight C, Rockwood K (1995). A Hierarchical Assessment of Balance and Mobility. Age Ageing, 24:126-130.
Hoffer LJ, Bistrian BR (2012). Appropriate protein provision in critical illness: a systematic and narrative review. Am J Clin Nutr, 96:591-600.
Brugliera L, Spina A, Castellazzi P, Cimino P, Arcuri P, Negro A, et al. (2020). Nutritional management of COVID-19 patients in a rehabilitation unit. Eur J Clin Nutr, 74:860-863.
Nir Barzilai, James C Appleby, Steven N Austad, Ana Maria Cuervo, Matt Kaeberlein, Christian Gonzalez-Billault, Stephanie Lederman, Ilia Stambler, Felipe Sierra. Geroscience in the Age of COVID-19[J]. Aging and disease, 2020, 11(4): 725-729.