Molecular Mechanism of ­Acute Sarcopenia in Elderly Patient with COVID - 19

I Gusti Putu Suka Aryana, Siti Setiati, Sandra Surya Rini


Coronavirus Disease 2019 (COVID-19) is an infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Case fatality rate has been on the rise among older adults. Muscle loss is a consequence of several chronic diseases (chronic sarcopenia) and recent theory also suggested that acute sarcopenia may caused by acute significant stressor such as an acute illness, surgery, infections, trauma or burns including COVID-19 infection leading to further muscle loss in elderly. Cytokine storm, the hallmark of COVID-19 pathogenesis will induce various pro-inflammatory cytokine such as IL-1 and IL-6 causing acute sarcopenia by activating negative regulators like NF-κB, atrogin-1, MURF-1. Long standing chronic inflammation also known as inflammaging along with acute inflammation during COVID-19 in elderly will cause reticulum endoplasmic and mitochondria stress activating caspase and finally increase both cytosolic and nuclear levels of AIF and EndoG to induce acute sarcopenia. Several precipitating factors shared same molecular pathway like physical inactivity and hormonal dysregulation which act through IGF-1-AKT-mTOR pathway. Physical inactivity during COVID-19 infection also induced myostatin and Atrogin-1/ MaFbx/ MuRF pathway. This review provides recent research advances dealing with molecular pathway modulating muscle mass in acute sarcopenia during COVID-19 infection.


COVID-19; acute sarcopenia; inflammation; aging


Susilo A, Rumende CM, Pitoyo CW, et al. Coronavirus disease 2019: tinjauan literatur terkini Coronavirus disease 2019. 2020;7:45–67.

World Health Organizarion. WHO Coronavirus disease (COVID-19). Dashboard. [accessed 2nd October 2021]. URL:

Satgas penanganan Covid-19. Data sebaran. [accessed 2nd October 2021]. URL:

Muhammad Khifzhon Azwar, Siti Setiati, Aulia Rizka, Ika Fitriana, Siti Rizny F. Saldi, Eka Dian Safitri. Clinical profile of elderly patients with COVID-19 hospitalised in Indonesia’s National General Hospital. Acta medica Indonesiana 52, 199–205.

Kang SJ, Jung SI. Age-related morbidity and mortality among patients with COVID-19. Infect Chemother. 2020;52:154.

United Nations. World population ageing 2019 highlights. New York: United Nations (2019).

Setiati, S., Dwimartutie, N. Buku ajar ilmu penyakit dalam. Jilid III. Edisi VI. Jakarta: Interna Publishing; 2014. p. 3719–27.

Welch CK, Hassan-Smith ZA, Greig CM, et al. Acute sarcopenia secondary to hospitalisation - an emerging condition affecting older adults. Aging and disease. 2018;9:151.

Zhang XM, et al. Sarcopenia as a predictor of mortality among the critically ill in an intensive care unit: a systematic review and meta-analysis. BMC Geriatr. 2021;21:339.

Weijs P.J, et al. Low skeletal muscle area is a risk factor for mortality in mechanically ventilated critically ill patients. Crit Care. 2014;18:R12.

Kou HW, et al. Sarcopenia is an effective predictor of difficult-to-wean and mortality among critically ill surgical patients. PLoS ONE. 2019;14:e0220699.

Giraudo, C. et al. Reduced muscle mass as predictor of intensive care unit hospitalization in COVID-19 patients. PLoS ONE. 2021;16:e0253433.

C. F., Isirdi A, Brusasco C, et al. Low diaphragm muscle mass predicts adverse outcome in patients hospitalized for Covid-19 pneumonia. 2020.

Welch C, Greig CA, Masud T, Pinkney T, Jackson TA. Protocol for understanding acute sarcopenia: a cohort study to characterise changes in muscle quantity and physical function in older adults following hospitalisation. BMC Geriatr. 2020;20:239.

Aiello A, et al. Immunosenescence and its hallmarks: How to oppose aging strategically? A review of potential options for therapeutic intervention. Front. Immunol. 2019;10:2247.

Franceschi C, Campisi J. Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J Gerontol Series A: Biol Sci Med Sci. 2014;69:S4–S9.

Perrotta F, et al. COVID-19 and the elderly: insights into pathogenesis and clinical decision-making. Aging Clin Exp Res. 2020;32:1599–608.

Diaz JH. Hypothesis: angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may increase the risk of severe COVID-19. J Travel Med. 2020;27:taaa041.

Baker, SA, Kwok S, Berry GJ, Montine TJ. Angiotensin-converting enzyme 2 (ACE2) expression increases with age in patients requiring mechanical ventilation. PLoS ONE. 2021;16:e0247060.

Rehman S, et al. Immunity, sex hormones, and environmental factors as determinants of COVID-19 disparity in women. Front Immunol. 2021;12:680845.

Ory J, et al. Understanding the complex relationship between androgens and SARS-CoV2. Urology. 2020;144:1–3.

Cruz-Jentoft AJ, et al. Sarcopenia: revised European consensus on definition and diagnosis. Age and Ageing. 2019;48:16–31.

Domingues R, Lippi A, Setz C, Outeiro TF, Krisko A. SARS-CoV-2, immunosenescence and inflammaging: partners in the COVID-19 crime. Aging. 2020;12:18778–89.

Thoma A, Akter-Miah T, Reade RL, Lightfoot AP. Targeting reactive oxygen species (ROS) to combat the age-related loss of muscle mass and function. Biogerontol. 2020;21:475–84.

Dodds RM, Granic A, Robinson SM, Sayer AA. Sarcopenia, long‐term conditions, and multimorbidity: findings from UK Biobank participants. Journal of Cachexia, Sarcopenia and Muscle. 2020;11:62–8.

Cleasby ME, Jamieson PM, Atherton PJ. Insulin resistance and sarcopenia: mechanistic links between common co-morbidities. Journal of Endocrinology. 2016;229:R67–R81.

Welch C, Greig C, Masud T, Wilson D, Jackson TA. COVID-19 and acute sarcopenia. Aging and disease. 2020;11:1345.

Conti P. Induction of pro-inflammatory cytokines (IL-1 and IL-6) and lung inflammation by COVID-19: anti-inflammatory strategies. J Biol Regul Homeost Agents. 2020;34:1.

Stam H, Stucki G, Bickenbach J. Covid-19 and post intensive care syndrome: A call for action. J Rehabil Med. 2020;52:jrm00044.

Marzetti E, et al. Multiple pathways to the same end: Mechanisms of myonuclear apoptosis in sarcopenia of aging. Sci World J. 2010;10:340–9.

Ferrucci L, Fabbri E. Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty. Nat Rev Cardiol. 2018;15:505–22.

Dupont-Versteegden EE. Apoptosis in muscle atrophy: Relevance to sarcopenia. Experimental Gerontology. 2005;40:473–81.

García LF. Immune response, inflammation, and the clinical spectrum of COVID-19. Front Immunol. 2020;11:1441.

Piotrowicz K, Gąsowski J, Michel JP, Veronese N. Post-COVID-19 acute sarcopenia: physiopathology and management. Aging Clin Exp Res. 2021;33: 2887–98.

Kortebein P, et al. Functional impact of 10 days of bed rest in healthy older adults. J Gerontol Series A: Biol Sci Med Sci. 2008;63:1076–81.

Yoshida T, Delafontaine P. Mechanisms of IGF-1-mediated regulation of skeletal muscle hypertrophy and atrophy. Cells. 2020;9:1970.

Ali AM, Kunugi H. Physical frailty/sarcopenia as a key predisposing factor to Coronavirus disease 2019 (COVID-19) and its complications in older adults. BioMed. 2021;1:11–40.

Ilias I, et al. Covid-19 and growth hormone/insulin-like growth factor 1: Study in critically and non-critically ill patients. Front Endocrinol. 2021;12:644055.

Guertin DA, et al. Ablation in mice of the mTORC components raptor, rictor, or mLST8 reveals that mTORC2 is required for signaling to Akt-FOXO and PKCα, but Not S6K1. Developmental Cell. 2006;11:859–71.

Schiaffino S, et al. CT-derived chest muscle metrics for outcome prediction in patients with COVID-19. Radiology. 2021;300:E328–E336.

Martone AM, et al. The incidence of sarcopenia among hospitalized older patients: results from the Glisten study: Hospitalization and risk of incident sarcopenia. Journal of Cachexia, Sarcopenia and Muscle. 2017;8: 907–14.

Zhang XM, et al. Frailty as a predictor of mortality among patients with COVID-19: a systematic review and meta-analysis. BMC Geriatr. 2021;21:186.

Woolford SJ, et al. COVID-19 and associations with frailty and multimorbidity: a prospective analysis of UK Biobank participants. Aging Clin Exp Res. 2020;32:1897–905.

Yang Y, et al. The impact of frailty on COVID-19 outcomes: a systematic review and meta-analysis of 16 cohort studies. J Nutr Health Aging. 2021;25: 702–9.

Hewitt J, et al. The effect of frailty on survival in patients with COVID-19 (COPE): a multicentre, European, observational cohort study. The Lancet Public Health. 2020;5:e444–e451.

Hudson L, Chittams J, Griffith C, Compher C. Malnutrition identified by academy of nutrition and dietetics/american society for parenteral and enteral nutrition is associated with more 30-day readmissions, greater hospital mortality, and longer hospital stays: a retrospective analysis of nutrition A. J Parent Enter Nutr. 2018;42:892–7.

Vandewoude MFJ, Alish CJ, Sauer AC, Hegazi RA. Malnutrition-sarcopenia syndrome: is this the future of nutrition screening and assessment for older adults? J Aging Res. 2012;2012:1–8.

Cederholm T, Jägren C, Hellström K. Outcome of protein-energy malnutrition in elderly medical patients. Am J Med. 1995;98:67–74.

Locher JL, et al. Body mass index, weight loss, and mortality in community-dwelling older adults. J Gerontol Series A: Biol Sci Med Sci. 2007;62: 1389–92.

Newman AB, et al. Weight change and the conservation of lean mass in old age: the health, aging and body composition study. Am J Clin Nutr. 2005;82:872–8.

Neumann SA, Miller MD, Daniels L, Crotty M. Nutritional status and clinical outcomes of older patients in rehabilitation. J Hum Nutr Diet. 2005;18: 129–36.

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