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The Impact of Long COVID-19 on Muscle Health

  • Montserrat Montes-Ibarra
    Affiliations
    Human Nutrition Research Unit, Department of Agricultural, Food, & Nutritional Science, University of Alberta, 113 Street and 87 Avenue NW, 2-004 Li Ka Shing Center for Health Research Innovation, Edmonton, Alberta, Canada
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  • Camila L.P. Oliveira
    Affiliations
    Human Nutrition Research Unit, Department of Agricultural, Food, & Nutritional Science, University of Alberta, 113 Street and 87 Avenue NW, 2-004 Li Ka Shing Center for Health Research Innovation, Edmonton, Alberta, Canada
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  • Camila E. Orsso
    Affiliations
    Human Nutrition Research Unit, Department of Agricultural, Food, & Nutritional Science, University of Alberta, 113 Street and 87 Avenue NW, 2-004 Li Ka Shing Center for Health Research Innovation, Edmonton, Alberta, Canada
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  • Francesco Landi
    Affiliations
    Department of Geriatrics, Neurosciences and Orthopaedics, Catholic University of the Sacred Heart, Rome, Italy

    Geriatric Department, Fondazione Policlinico Universitario Agostino Gemelli’ IRCCS, Rome, Italy

    Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy

    Center for Geriatric Medicine (Ce.M.I.), Università Cattolica del Sacro Cuore, L.go F. Vito 1, Rome 00168, Italy
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  • Emanuele Marzetti
    Affiliations
    Center for Geriatric Medicine (Ce.M.I.), Università Cattolica del Sacro Cuore, L.go F. Vito 1, Rome 00168, Italy

    Department of Geriatrics and Orthopedics, Università Cattolica del Sacro Cuore, Rome, Italy

    Orthogeriatric Unit, Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS, Rome, Italy
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  • Carla M. Prado
    Correspondence
    Corresponding author.
    Affiliations
    Human Nutrition Research Unit, Department of Agricultural, Food, & Nutritional Science, University of Alberta, 113 Street and 87 Avenue NW, 2-004 Li Ka Shing Center for Health Research Innovation, Edmonton, Alberta, Canada
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Published:March 20, 2022DOI:https://doi.org/10.1016/j.cger.2022.03.004

      Keywords

      Key points

      • Long COVID negatively impacts muscle mass, function, and quality of life.
      • Longitudinal studies, including long-term assessment of muscle mass and function, can help identify the impact of long COVID on muscle health.
      • Respiratory muscle dysfunction may be a marker of muscle wasting and recovery outcome during long COVID.
      • Age differences should be explored in future studies to better understand how long COVID affects muscle health across the life course.

      Introduction

      The World Health Organization (WHO) has recently created a clinical case definition to frame a condition of symptom persistence following a coronavirus disease 2019 (COVID-19).
      World Health Organization. (2021). A clinical case definition of post COVID-19 condition by a Delphi consensus, 6 October 2021. World Health Organization.
      The condition, known as post-COVID-19, postacute sequelae of COVID-19, or long COVID, develops in individuals with a history of probable or confirmed SARS-CoV-2 infection in the past 3 months and encompasses a wide range of signs and symptoms that persists for weeks or months and cannot be explained by an alternative diagnosis. Long COVID symptoms can develop de novo after acute COVID-19 or persist from the initial illness. Common symptoms include, but are not limited to shortness of breath, fatigue, weakness, cognitive dysfunction, body aches, sore throat, cough, diarrhea, anosmia, and dysgeusia.
      • Greenhalgh T.
      • Knight M.
      • A'Court C.
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      Management of post-acute covid-19 in primary care.
      ,
      NICE
      Covid-19 rapid guideline: managing the long-term effects of covid-19.
      It has been estimated that up to 80% of people who recovered from a COVID-19 episode experience at least one long-term symptom.
      • Lopez-Leon S.
      • Wegman-Ostrosky T.
      • Perelman C.
      • et al.
      More than 50 long-term effects of COVID-19: a systematic review and meta-analysis.
      ,
      • Soraas A.
      • Kalleberg K.T.
      • Dahl J.A.
      • et al.
      Persisting symptoms three to eight months after non-hospitalized COVID-19, a prospective cohort study.
      Long COVID has been shown to negatively impact several organs and body systems, including skeletal muscle.
      • Piotrowicz K.
      • Gasowski J.
      • Michel J.P.
      • et al.
      Post-COVID-19 acute sarcopenia: physiopathology and management.
      This organ is essential for movement, balance, posture, daily activities, and a variety of metabolic functions.
      • Tieland M.
      • Trouwborst I.
      • Clark B.C.
      Skeletal muscle performance and ageing.
      Indeed, more than 60% of individuals presenting with long COVID have reported fatigue, lower mobility, and weakness.
      • Karaarslan F.
      • Guneri F.D.
      • Kardes S.
      Long COVID: rheumatologic/musculoskeletal symptoms in hospitalized COVID-19 survivors at 3 and 6 months.
      ,
      • Huang C.
      • Huang L.
      • Wang Y.
      • et al.
      6-month consequences of COVID-19 in patients discharged from hospital: a cohort study.
      Interestingly, a high prevalence of skeletal muscle weakness and low physical performance has been reported in COVID-19 survivors without prior musculoskeletal problems.
      • Akbarialiabad H.
      • Taghrir M.H.
      • Abdollahi A.
      • et al.
      Long COVID, a comprehensive systematic scoping review.
      Older adults are at increased risk of developing musculoskeletal symptoms during long COVID,
      • Docherty A.B.
      • Harrison E.M.
      • Green C.A.
      • et al.
      Features of 20 133 UK patients in hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: prospective observational cohort study.
      ,
      • Welch C.
      • Greig C.
      • Masud T.
      • et al.
      COVID-19 and acute sarcopenia.
      possibly because of the combined effect of viral infection and preexisting age-related declines in muscle mass and function.
      The purpose of this narrative review is to describe the potential long-term effects of COVID-19 on muscle health in adults. We used the term muscle health to describe muscle mass and function (ie, strength and performance). Here, we describe muscle health outcomes in people with long COVID presenting with different degrees of disease severity and assessed by different body composition and physical function methods. In addition, we report the impact of long COVID on quality of life (QoL) related to muscle health.

      Mechanisms of muscle damage in long COVID

      After entering the human body, the spike protein of SARS-CoV-2 binds to the cell membrane receptor angiotensin converter enzyme 2 (ACE2) using the transmembrane protease, serine 2 (TMPRSS2) to deliver its genetic material.
      • Benton D.J.
      • Wrobel A.G.
      • Xu P.
      • et al.
      Receptor binding and priming of the spike protein of SARS-CoV-2 for membrane fusion.
      ,
      • Hoffmann M.
      • Kleine-Weber H.
      • Schroeder S.
      • et al.
      SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease Inhibitor.
      Upon cellular entry, the virus replicates and causes disruption of cellular functions, leading to cell death and tissue dysfunction.
      • Disser N.P.
      • De Micheli A.J.
      • Schonk M.M.
      • et al.
      Musculoskeletal consequences of COVID-19.
      Because ACE2 and TMPRSS2 are expressed in most tissues and organs, SARS-CoV-2 can invade and cause damage to almost all body systems, including the skeletal muscle.
      • Finsterer J.
      • Scorza F.A.
      SARS-CoV-2 myopathy.
      In addition to direct virus-mediated injury, other factors contributing to muscle damage during a COVID-19 episode include systemic inflammation, electrolyte disturbances, critical ill myopathy, drugs (eg, corticosteroids), and hypoxia.
      • Finsterer J.
      • Scorza F.A.
      SARS-CoV-2 myopathy.
      Some of these mechanisms and factors are likely to play a role in musculoskeletal damage and its related outcomes in long COVID.
      Inflammation is advocated as one of the primary factors associated with muscle catabolism in patients with long COVID.
      • Akbarialiabad H.
      • Taghrir M.H.
      • Abdollahi A.
      • et al.
      Long COVID, a comprehensive systematic scoping review.
      Systemic inflammation sustained by increased blood levels of interferon gamma, C-reactive protein, interleukin (IL) 6, IL-2, IL-10, and tumor necrosis factor α has been described in people with long COVID.
      • Malik P.
      • Patel K.
      • Pinto C.
      • et al.
      Post-acute COVID-19 syndrome (PCS) and health-related quality of life (HRQoL)-A systematic review and meta-analysis.
      ,
      • Liu J.
      • Li S.
      • Liu J.
      • et al.
      Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients.
      These proinflammatory cytokines are well known for their ability to negatively impact muscle protein metabolism through triggering catabolic pathways and suppressing anabolism.
      • Webster J.M.
      • Kempen L.J.A.P.
      • Hardy R.S.
      • et al.
      Inflammation and skeletal muscle wasting during cachexia.
      The mechanisms underlying the transition from acute to chronic inflammation after a COVID-19 episode are largely unknown. Anomalous microclots enriched in acute-phase inflammatory molecules and resistant to fibrinolysis have been found in blood samples of individuals with long COVID.
      • Pretorius E.
      • Vlok M.
      • Venter C.
      • et al.
      Persistent clotting protein pathology in Long COVID/Post-Acute Sequelae of COVID-19 (PASC) is accompanied by increased levels of antiplasmin.
      Hence, it is plausible that inflammatory cytokines trapped within microclots may leak into the circulation, thereby maintaining a state of chronic inflammation. SARS-CoV-2 infection was also shown to cause long-term proinflammatory reprogramming of macrophages, possibly via epigenetic modifications.
      • Theobald S.J.
      • Simonis A.
      • Georgomanolis T.
      • et al.
      Long-lived macrophage reprogramming drives spike protein-mediated inflammasome activation in COVID-19.
      In older COVID-19 survivors, SARS-CoV-2–induced long-term inflammation may superimpose to the age-dependent chronic inflammation (inflamm-aging), leading to more severe disruption of muscle metabolic homeostasis.
      • Soraas A.
      • Kalleberg K.T.
      • Dahl J.A.
      • et al.
      Persisting symptoms three to eight months after non-hospitalized COVID-19, a prospective cohort study.
      Over time, proinflammatory cytokines lead to muscle fiber proteolysis, decreased protein synthesis, hindered capacity of satellite cells to proliferate and differentiate, and eventually fibrosis.
      • Disser N.P.
      • De Micheli A.J.
      • Schonk M.M.
      • et al.
      Musculoskeletal consequences of COVID-19.
      Muscular issues in long COVID are more likely to occur in patients with more severe diseases who had been admitted to the intensive care unit (ICU).
      • Schefold J.C.
      • Wollersheim T.
      • Grunow J.J.
      • et al.
      Muscular weakness and muscle wasting in the critically ill.
      ,
      • Soares M.N.
      • Eggelbusch M.
      • Naddaf E.
      • et al.
      Skeletal muscle alterations in patients with acute Covid-19 and post-acute sequelae of Covid-19.
      However, Doykov and colleagues
      • Doykov I.
      • Hällqvist J.
      • Gilmour K.C.
      • et al.
      The long tail of Covid-19' - the detection of a prolonged inflammatory response after a SARS-CoV-2 infection in asymptomatic and mildly affected patients.
      observed an increase in proinflammatory biomarkers and disruption of muscle metabolic homeostasis 40 to 60 days after initial diagnosis in individuals who had mild and asymptomatic COVID-19.
      Physical inactivity potentially exacerbated by quarantine and hospitalization has also a major impact on muscle mass and function.
      • Piotrowicz K.
      • Gasowski J.
      • Michel J.P.
      • et al.
      Post-COVID-19 acute sarcopenia: physiopathology and management.
      Lastly, inadequate dietary intake and poor nutritional status, which are common during a COVID-19 episode, negatively impact skeletal muscle during recovery.
      • Barazzoni R.
      • Bischoff S.C.
      • Breda J.
      • et al.
      ESPEN expert statements and practical guidance for nutritional management of individuals with SARS-CoV-2 infection.
      ,
      • Gerard M.
      • Mahmutovic M.
      • Malgras A.
      • et al.
      Long-term Evolution of malnutrition and loss of muscle strength after COVID-19: a major and Neglected Component of long COVID-19.
      Bedock and colleagues
      • Bedock D.
      • Bel Lassen P.
      • Mathian A.
      • et al.
      Prevalence and severity of malnutrition in hospitalized COVID-19 patients.
      observed that ∼42% of hospitalized patients with COVID-19 were malnourished and the prevalence increased to ∼67% in those admitted to ICU. It has been hypothesized that reduced food intake caused by COVID-19 symptoms (ie, anorexia, diarrhea, vomiting, nausea, abdominal pain, anosmia, and dysgeusia) and increased nutritional needs are main factors leading to malnutrition.
      • Barazzoni R.
      • Bischoff S.C.
      • Breda J.
      • et al.
      ESPEN expert statements and practical guidance for nutritional management of individuals with SARS-CoV-2 infection.
      ,
      • Bedock D.
      • Bel Lassen P.
      • Mathian A.
      • et al.
      Prevalence and severity of malnutrition in hospitalized COVID-19 patients.
      ,
      • Wischmeyer P.E.
      Nutrition therapy in sepsis.
      Fig. 1 illustrates some of the mechanisms associated with muscle damage in individuals with long COVID.
      Figure thumbnail gr1
      Fig. 1Potential mechanisms of muscle damage in patients with long COVID-19. Systemic inflammatory state during the acute phase results in chronic release of proinflammatory cytokines, contributing to imbalances in muscle protein metabolism and impaired muscle health. In addition, physical inactivity due to hospitalization and quarantine as well as inadequate nutrition intake may also negatively impact muscle mass, quality, and function.
      (From Servier Medical Art. Servier. Available at https://smart.servier.com/; under Creative Commons Attribution 3.0 Unported License)

      Current evidence

      A summary of findings specifically related to body composition, muscle function, and QoL related to muscle health is shown in Table 1.
      Table 1Summary of findings related to body composition, muscle function, and quality of life related to muscle health in individuals with long COVID
      Body Composition
      ReferenceBody CompartmentTechniqueTimelineSelected Main Findings
      Tanriverdi et al,
      • Tanriverdi A.
      • Savci S.
      • Kahraman B.O.
      • et al.
      Extrapulmonary features of post-COVID-19 patients: muscle function, physical activity, mood, and sleep quality.
      2021
      FM and FFMBIA>3 mo after COVID-19
      • No differences in FM and FFM by disease severity.
      van den Borst et al,
      • van den Borst B.
      • Peters J.B.
      • Brink M.
      • et al.
      Comprehensive health assessment 3 Months after recovery from acute Coronavirus disease 2019 (COVID-19).
      2021
      FFMIBIA3 mo after COVID-19
      • 19% had low FFMI, prevalence not different by disease severity.
      van Gassel et al,
      • van Gassel R.J.J.
      • Bels J.
      • Remij L.
      • et al.
      Functional outcomes and their association with physical performance in mechanically ventilated Coronavirus disease 2019 survivors at 3 Months following hospital discharge: a cohort study.
      2021
      SMA, SMD, and IMATCT3 mo after hospital discharge
      • No differences in SMA and SMD between groups of physical performance.
      • IMAT was higher in patients with impaired physical performance.
      Farr et al,
      • Farr E.
      • Wolfe A.R.
      • Deshmukh S.
      • et al.
      Diaphragm dysfunction in severe COVID-19 as determined by neuromuscular ultrasound.
      2021
      Diaphragm muscle thickness and thickening ratioUltrasoundAdmitted to a rehabilitation after COVID-19
      • Muscle thickness was not different between cases and controls.
      • Thickening ratio was reduced in patients with COVID-19.
      Muscle Function
      ReferenceMuscle Function EvaluationAssessment TestTimelineSelected Main Findings
      van Gassel et al,
      • van Gassel R.J.J.
      • Bels J.
      • Remij L.
      • et al.
      Functional outcomes and their association with physical performance in mechanically ventilated Coronavirus disease 2019 survivors at 3 Months following hospital discharge: a cohort study.
      2021
      Muscle strength and physical performanceHandgrip strength3 mo after COVID-19
      • Trend for lower relative handgrip strength (no statistical difference in patients with impaired physical function).
      Tanriverdi et al,
      • Tanriverdi A.
      • Savci S.
      • Kahraman B.O.
      • et al.
      Extrapulmonary features of post-COVID-19 patients: muscle function, physical activity, mood, and sleep quality.
      2021
      Muscle strength and physical performanceHandgrip and quadriceps muscle strength, and

      4-m gait speed
      >3 mo after COVID-19
      • Disease severity did not relate to muscle weakness and function.
      van den Borst et al,
      • van den Borst B.
      • Peters J.B.
      • Brink M.
      • et al.
      Comprehensive health assessment 3 Months after recovery from acute Coronavirus disease 2019 (COVID-19).
      2021
      Physical performance6MWD3 mo after COVID-19
      • Greater impairment in individuals with moderate and severe disease.
      Mittal et al,
      • Mittal J.
      • Ghosh A.
      • Bhatt S.P.
      • et al.
      High prevalence of post COVID-19 fatigue in patients with type 2 diabetes: a case-control study.
      2021
      Muscle strengthHandgrip strengthNot specified.

      Average: 3 mo
      • Handgrip strength was significantly reduced in patients with COVID-19 with high fatigue scores.
      Bellan et al,
      • Bellan M.
      • Soddu D.
      • Balbo P.E.
      • et al.
      Respiratory and psychophysical sequelae among patients with COVID-19 four months after hospital discharge.
      2021
      Physical performanceSPPB and

      2MWT
      4- and 12-mo postdischarge
      • 31.5% and 7.1% of patients had poor physical function at 4- and 12-mo follow-up.
      • Decrease in the prevalence of impaired physical performance at 12 mo.
      Quality of Life
      ReferenceQOL TestTimelineSelected Main Findings
      van den Borst et al,
      • van den Borst B.
      • Peters J.B.
      • Brink M.
      • et al.
      Comprehensive health assessment 3 Months after recovery from acute Coronavirus disease 2019 (COVID-19).
      2021
      Nijmegen Clinical Screening Instrument3 mo after COVID-19
      • High prevalence of functional impairment, fatigue, and low QoL
      van Gassel et al,
      • van Gassel R.J.J.
      • Bels J.
      • Remij L.
      • et al.
      Functional outcomes and their association with physical performance in mechanically ventilated Coronavirus disease 2019 survivors at 3 Months following hospital discharge: a cohort study.
      2021
      EQ-5D3 mo after COVID-19
      • Lower QoL in patients with impaired physical performance.
      Cuerda et al,
      • Cuerda C.
      • Sanchez Lopez I.
      • Gil Martinez C.
      • et al.
      Impact of COVID-19 in nutritional and functional status of survivors admitted in intensive care units during the first outbreak. Preliminary results of the NUTRICOVID study.
      2021
      EQ-5D-5 LOngoing study: patients are being followed for 12 mo
      • 71.2% unable to move or with moderate impairment.
      • 75.5% with problems to perform daily activities.
      Vaes et al,
      • Vaes A.W.
      • Goertz Y.M.J.
      • Van Herck M.
      • et al.
      Recovery from COVID-19: a sprint or marathon? 6-month follow-up data from online long COVID-19 support group members.
      2021
      EQ-5D-5 L3 and 6 mo after COVID-19
      • 62% with moderate-to-extreme problems performing daily activities.
      Abbreviations: 6MWD, 6-minute walking distance; 2MWT, 2-minute walk test; BIA, bioelectrical impedance analysis; COVID-19, coronavirus disease, 2019; CT, computerized tomography; EQ-5D, European Quality of Life Five Dimension; EQ-5D-5L, 5-level European Quality of Life Five Dimension; FFMI, fat-free mass index; FFM, fat-free mass; FM, fat mass; IMAT, intermuscular adipose tissue; QoL, quality of life; SMA, skeletal muscle area; SMD, skeletal muscle radiodensity; SPPB, short physical performance battery.

      Muscle Mass and Other Body Composition Compartments

      Body composition was assessed in 4 studies investigating long-term health sequelae of COVID-19 infection
      • van den Borst B.
      • Peters J.B.
      • Brink M.
      • et al.
      Comprehensive health assessment 3 Months after recovery from acute Coronavirus disease 2019 (COVID-19).
      • van Gassel R.J.J.
      • Bels J.
      • Remij L.
      • et al.
      Functional outcomes and their association with physical performance in mechanically ventilated Coronavirus disease 2019 survivors at 3 Months following hospital discharge: a cohort study.
      • Farr E.
      • Wolfe A.R.
      • Deshmukh S.
      • et al.
      Diaphragm dysfunction in severe COVID-19 as determined by neuromuscular ultrasound.
      • Tanriverdi A.
      • Savci S.
      • Kahraman B.O.
      • et al.
      Extrapulmonary features of post-COVID-19 patients: muscle function, physical activity, mood, and sleep quality.
      using the following techniques: bioelectrical impedance analysis (BIA),
      • van den Borst B.
      • Peters J.B.
      • Brink M.
      • et al.
      Comprehensive health assessment 3 Months after recovery from acute Coronavirus disease 2019 (COVID-19).
      ,
      • Tanriverdi A.
      • Savci S.
      • Kahraman B.O.
      • et al.
      Extrapulmonary features of post-COVID-19 patients: muscle function, physical activity, mood, and sleep quality.
      computed tomography (CT),
      • van Gassel R.J.J.
      • Bels J.
      • Remij L.
      • et al.
      Functional outcomes and their association with physical performance in mechanically ventilated Coronavirus disease 2019 survivors at 3 Months following hospital discharge: a cohort study.
      and ultrasound (US).
      • Farr E.
      • Wolfe A.R.
      • Deshmukh S.
      • et al.
      Diaphragm dysfunction in severe COVID-19 as determined by neuromuscular ultrasound.
      After 4 to 5 weeks of COVID-19 infection, Tanriverdi and colleagues
      • Tanriverdi A.
      • Savci S.
      • Kahraman B.O.
      • et al.
      Extrapulmonary features of post-COVID-19 patients: muscle function, physical activity, mood, and sleep quality.
      assessed fat mass and fat-free mass (FFM) using BIA in people who recovered from mild (n = 25) and moderate (n = 23) disease severity. The 2 body compartments were not different between individuals who suffered mild or moderate disease, although a sex-specific comparison was not presented.
      • Tanriverdi A.
      • Savci S.
      • Kahraman B.O.
      • et al.
      Extrapulmonary features of post-COVID-19 patients: muscle function, physical activity, mood, and sleep quality.
      Another study assessed the body composition of patients discharged after COVID-19 using BIA.
      • van den Borst B.
      • Peters J.B.
      • Brink M.
      • et al.
      Comprehensive health assessment 3 Months after recovery from acute Coronavirus disease 2019 (COVID-19).
      Patients were classified according to disease severity (mild: n = 27; moderate: n = 51; severe: n = 26; critical: n = 20).
      • van den Borst B.
      • Peters J.B.
      • Brink M.
      • et al.
      Comprehensive health assessment 3 Months after recovery from acute Coronavirus disease 2019 (COVID-19).
      Fat-free mass index (FFMI) was calculated as FFM/height2 and classified as low in 19% of the patients (7/27; 5/51; 7/26; 4/20).
      • van den Borst B.
      • Peters J.B.
      • Brink M.
      • et al.
      Comprehensive health assessment 3 Months after recovery from acute Coronavirus disease 2019 (COVID-19).
      No differences in FFMI or in the number of patients with low FFMI were observed among the 4 groups.
      • van den Borst B.
      • Peters J.B.
      • Brink M.
      • et al.
      Comprehensive health assessment 3 Months after recovery from acute Coronavirus disease 2019 (COVID-19).
      In a prospective cohort study, 46 patients who were admitted to the ICU and received mechanical ventilation were assessed 3 months after hospital discharge.
      • van Gassel R.J.J.
      • Bels J.
      • Remij L.
      • et al.
      Functional outcomes and their association with physical performance in mechanically ventilated Coronavirus disease 2019 survivors at 3 Months following hospital discharge: a cohort study.
      Thoracic CT scans at the 12th vertebra were used to quantify skeletal muscle area, skeletal muscle radiation attenuation (an index of muscle quality), and intermuscular adipose tissue (IMAT).
      • van Gassel R.J.J.
      • Bels J.
      • Remij L.
      • et al.
      Functional outcomes and their association with physical performance in mechanically ventilated Coronavirus disease 2019 survivors at 3 Months following hospital discharge: a cohort study.
      Patients were categorized based on their performance on the 6-min walk distance (6MWD) test as having normal (n = 24) or low physical performance (<80% of predicted, n = 22).
      • van Gassel R.J.J.
      • Bels J.
      • Remij L.
      • et al.
      Functional outcomes and their association with physical performance in mechanically ventilated Coronavirus disease 2019 survivors at 3 Months following hospital discharge: a cohort study.
      Both skeletal muscle area and skeletal muscle radiation did not differ between patient subgroups; however, IMAT was higher in those with low physical performance.
      • van Gassel R.J.J.
      • Bels J.
      • Remij L.
      • et al.
      Functional outcomes and their association with physical performance in mechanically ventilated Coronavirus disease 2019 survivors at 3 Months following hospital discharge: a cohort study.
      Physical performance remained significantly associated with IMAT after adjusting for age, sex, handgrip strength, and diffusing capacity for carbon monoxide.
      • van Gassel R.J.J.
      • Bels J.
      • Remij L.
      • et al.
      Functional outcomes and their association with physical performance in mechanically ventilated Coronavirus disease 2019 survivors at 3 Months following hospital discharge: a cohort study.
      US images of the diaphragm muscle were assessed in 21 patients admitted to rehabilitation after severe COVID-19 and compared with 11 non–COVID-19 controls who needed ventilator support during hospitalization.
      • Farr E.
      • Wolfe A.R.
      • Deshmukh S.
      • et al.
      Diaphragm dysfunction in severe COVID-19 as determined by neuromuscular ultrasound.
      Diaphragm muscle thickness was not different between cases and controls, but the thickening ratio (ie, maximal inspiration/end-expiration) was reduced in patients who had been diagnosed with COVID-19, suggesting reduced diaphragm function.
      • Farr E.
      • Wolfe A.R.
      • Deshmukh S.
      • et al.
      Diaphragm dysfunction in severe COVID-19 as determined by neuromuscular ultrasound.

      Muscle Function

      Muscle strength

      Muscle strength was evaluated by handgrip strength testing in 3 studies assessing the health impact in individuals diagnosed with long COVID.
      • van Gassel R.J.J.
      • Bels J.
      • Remij L.
      • et al.
      Functional outcomes and their association with physical performance in mechanically ventilated Coronavirus disease 2019 survivors at 3 Months following hospital discharge: a cohort study.
      ,
      • Tanriverdi A.
      • Savci S.
      • Kahraman B.O.
      • et al.
      Extrapulmonary features of post-COVID-19 patients: muscle function, physical activity, mood, and sleep quality.
      ,
      • Mittal J.
      • Ghosh A.
      • Bhatt S.P.
      • et al.
      High prevalence of post COVID-19 fatigue in patients with type 2 diabetes: a case-control study.
      In a prospective cohort study, handgrip strength was assessed in 46 COVID-19 survivors 3 months after ICU discharge.
      • van Gassel R.J.J.
      • Bels J.
      • Remij L.
      • et al.
      Functional outcomes and their association with physical performance in mechanically ventilated Coronavirus disease 2019 survivors at 3 Months following hospital discharge: a cohort study.
      Individuals who tested lower than predicted on the 6MWD test showed a trend for lower handgrip strength than those with a normal 6MWD test result.
      • van Gassel R.J.J.
      • Bels J.
      • Remij L.
      • et al.
      Functional outcomes and their association with physical performance in mechanically ventilated Coronavirus disease 2019 survivors at 3 Months following hospital discharge: a cohort study.
      Mittal and colleagues
      • Mittal J.
      • Ghosh A.
      • Bhatt S.P.
      • et al.
      High prevalence of post COVID-19 fatigue in patients with type 2 diabetes: a case-control study.
      compared handgrip strength of 52 patients with type 2 diabetes (T2D) who had mild to moderate COVID-19 and T2D patients who did not have COVID-19 (n = 56). Although no difference in strength was found between groups, handgrip strength was significantly reduced when patients with COVID-19 were categorized into high and low fatigue scores.
      • Mittal J.
      • Ghosh A.
      • Bhatt S.P.
      • et al.
      High prevalence of post COVID-19 fatigue in patients with type 2 diabetes: a case-control study.
      These findings indicate that neither patient group had significant dynapenia, but patients with T2D who had COVID-19 had higher fatigue and lower muscle strength than those who did not have COVID-19.
      Handgrip strength and quadriceps muscle strength were assessed in a cross-sectional study including patients recovering from mild (n = 25) and moderate (n = 23) interstitial pneumonia after at least 12 weeks from COVID-19 diagnosis.
      • Tanriverdi A.
      • Savci S.
      • Kahraman B.O.
      • et al.
      Extrapulmonary features of post-COVID-19 patients: muscle function, physical activity, mood, and sleep quality.
      The prevalence of quadriceps and handgrip weakness was not different between groups (mild: 35%; moderate: 43.5%; P = .597).
      • Tanriverdi A.
      • Savci S.
      • Kahraman B.O.
      • et al.
      Extrapulmonary features of post-COVID-19 patients: muscle function, physical activity, mood, and sleep quality.

      Physical performance

      The prevalence of impaired physical performance in long COVID was evaluated in 4 studies including participants with different degrees of disease severity.
      • van den Borst B.
      • Peters J.B.
      • Brink M.
      • et al.
      Comprehensive health assessment 3 Months after recovery from acute Coronavirus disease 2019 (COVID-19).
      ,
      • van Gassel R.J.J.
      • Bels J.
      • Remij L.
      • et al.
      Functional outcomes and their association with physical performance in mechanically ventilated Coronavirus disease 2019 survivors at 3 Months following hospital discharge: a cohort study.
      ,
      • Tanriverdi A.
      • Savci S.
      • Kahraman B.O.
      • et al.
      Extrapulmonary features of post-COVID-19 patients: muscle function, physical activity, mood, and sleep quality.
      ,
      • Bellan M.
      • Soddu D.
      • Balbo P.E.
      • et al.
      Respiratory and psychophysical sequelae among patients with COVID-19 four months after hospital discharge.
      Direct measures of physical performance included walking tests (ie, 6MWD, 4-m gait speed test, and 2-min walk test)
      • van den Borst B.
      • Peters J.B.
      • Brink M.
      • et al.
      Comprehensive health assessment 3 Months after recovery from acute Coronavirus disease 2019 (COVID-19).
      ,
      • van Gassel R.J.J.
      • Bels J.
      • Remij L.
      • et al.
      Functional outcomes and their association with physical performance in mechanically ventilated Coronavirus disease 2019 survivors at 3 Months following hospital discharge: a cohort study.
      ,
      • Tanriverdi A.
      • Savci S.
      • Kahraman B.O.
      • et al.
      Extrapulmonary features of post-COVID-19 patients: muscle function, physical activity, mood, and sleep quality.
      and the short physical performance battery (SPPB).
      • Bellan M.
      • Soddu D.
      • Balbo P.E.
      • et al.
      Respiratory and psychophysical sequelae among patients with COVID-19 four months after hospital discharge.
      In a prospective observational study of mild to critical COVID-19 cases (n = 124), 22% of patients presented with low performance on the 6MWD test (ie, <80% of predicted) at 10 weeks after hospital discharge.
      • van den Borst B.
      • Peters J.B.
      • Brink M.
      • et al.
      Comprehensive health assessment 3 Months after recovery from acute Coronavirus disease 2019 (COVID-19).
      Although the prevalence of low 6MWD performance was numerically greater in individuals with moderate (28%) and severe (32%) compared with mild (12%) and critical (5%) disease, no statistical difference was found among groups, possibly due to the small sample size.
      • van den Borst B.
      • Peters J.B.
      • Brink M.
      • et al.
      Comprehensive health assessment 3 Months after recovery from acute Coronavirus disease 2019 (COVID-19).
      Using the same criteria to define impaired physical performance, another study observed that 48% of patients who survived critical COVID-19 had low performance on the 6MWD test at 3 months after hospital discharge.
      • van Gassel R.J.J.
      • Bels J.
      • Remij L.
      • et al.
      Functional outcomes and their association with physical performance in mechanically ventilated Coronavirus disease 2019 survivors at 3 Months following hospital discharge: a cohort study.
      Notably, the greater proportion of functional impairment observed in the latter study was likely driven by patients who required mechanical ventilation during ICU stay. Tanrivedi and colleagues
      • Tanriverdi A.
      • Savci S.
      • Kahraman B.O.
      • et al.
      Extrapulmonary features of post-COVID-19 patients: muscle function, physical activity, mood, and sleep quality.
      compared physical performance between groups of disease severity, and found that survivors of mild (n = 25) and moderate (n = 23) COVID-19 had similar 4-m gait speed.
      The longest study evaluating physical performance in long COVID assessed 238 and 198 individuals after 4 and 12 months postdischarge, respectively.
      • Bellan M.
      • Soddu D.
      • Balbo P.E.
      • et al.
      Respiratory and psychophysical sequelae among patients with COVID-19 four months after hospital discharge.
      Using a cutoff of 10 on the SPPB, low physical performance was found in 22.3% and 18.7% of patients at 4 and 12 months of follow-up, respectively. Highly functioning individuals (ie, those who scored 10 or more on the SPPB) also performed a 2-min walk test at both time points; 31.5% and 7.1% of patients had a poor physical function at 4 months and 12 months follow-up, respectively. Furthermore, the proportion of patients with low performance on either the SPPB or the 2-min walk test) was smaller at 12 months (25.8%) than at 4 months (52.8%).
      • Bellan M.
      • Soddu D.
      • Balbo P.E.
      • et al.
      Respiratory and psychophysical sequelae among patients with COVID-19 four months after hospital discharge.
      This finding suggests that although some patients improved their physical function as they recovered, a significant proportion of individuals was still experiencing detrimental effects of COVID-19 after 12 months of hospital discharge.

      Quality of Life Related to Muscle Health

      QoL is related to several factors, and not only muscle health or physical performance. However, in this article, we focused only on studies assessing QoL related to muscle health. QoL of patients diagnosed with long COVID has been reported in 4 studies that assessed muscle function.
      • van den Borst B.
      • Peters J.B.
      • Brink M.
      • et al.
      Comprehensive health assessment 3 Months after recovery from acute Coronavirus disease 2019 (COVID-19).
      ,
      • van Gassel R.J.J.
      • Bels J.
      • Remij L.
      • et al.
      Functional outcomes and their association with physical performance in mechanically ventilated Coronavirus disease 2019 survivors at 3 Months following hospital discharge: a cohort study.
      ,
      • Cuerda C.
      • Sanchez Lopez I.
      • Gil Martinez C.
      • et al.
      Impact of COVID-19 in nutritional and functional status of survivors admitted in intensive care units during the first outbreak. Preliminary results of the NUTRICOVID study.
      ,
      • Vaes A.W.
      • Goertz Y.M.J.
      • Van Herck M.
      • et al.
      Recovery from COVID-19: a sprint or marathon? 6-month follow-up data from online long COVID-19 support group members.
      Two studies used the Euro-QoL-5D (EQ-5D) questionnaire.
      • van Gassel R.J.J.
      • Bels J.
      • Remij L.
      • et al.
      Functional outcomes and their association with physical performance in mechanically ventilated Coronavirus disease 2019 survivors at 3 Months following hospital discharge: a cohort study.
      ,
      • Vaes A.W.
      • Goertz Y.M.J.
      • Van Herck M.
      • et al.
      Recovery from COVID-19: a sprint or marathon? 6-month follow-up data from online long COVID-19 support group members.
      This instrument evaluates 5 dimensions of a person’s QoL (ie, mobility, self-care, daily activities, pain, and anxiety/depression).
      • van Gassel R.J.J.
      • Bels J.
      • Remij L.
      • et al.
      Functional outcomes and their association with physical performance in mechanically ventilated Coronavirus disease 2019 survivors at 3 Months following hospital discharge: a cohort study.
      ,
      • Cuerda C.
      • Sanchez Lopez I.
      • Gil Martinez C.
      • et al.
      Impact of COVID-19 in nutritional and functional status of survivors admitted in intensive care units during the first outbreak. Preliminary results of the NUTRICOVID study.
      Van Gassel and colleagues
      • van Gassel R.J.J.
      • Bels J.
      • Remij L.
      • et al.
      Functional outcomes and their association with physical performance in mechanically ventilated Coronavirus disease 2019 survivors at 3 Months following hospital discharge: a cohort study.
      assessed the QoL of 46 patients 3 months after hospital discharge using the EQ-5D. Health-related QoL was lower in people with low performance on the 6MWD test (n = 22) compared with those presenting with a normal test result (n = 24). The second study is an ongoing multicenter observational study including 176 COVID-19 survivors.
      • Cuerda C.
      • Sanchez Lopez I.
      • Gil Martinez C.
      • et al.
      Impact of COVID-19 in nutritional and functional status of survivors admitted in intensive care units during the first outbreak. Preliminary results of the NUTRICOVID study.
      Preliminary results showed that 71.2% of participants were unable to move or presented with moderate impairment and 75.5% reported problems to perform daily activities.
      • Cuerda C.
      • Sanchez Lopez I.
      • Gil Martinez C.
      • et al.
      Impact of COVID-19 in nutritional and functional status of survivors admitted in intensive care units during the first outbreak. Preliminary results of the NUTRICOVID study.
      QoL of 239 patients with long COVID was assessed 3 and 6 months after the onset of COVID-19-related symptoms using the 5-level EuroQol-5 Dimensions version (EQ-5D-5 L).
      • Vaes A.W.
      • Goertz Y.M.J.
      • Van Herck M.
      • et al.
      Recovery from COVID-19: a sprint or marathon? 6-month follow-up data from online long COVID-19 support group members.
      This questionnaire is similar to the EQ-5D but with higher sensitivity
      • Vaes A.W.
      • Goertz Y.M.J.
      • Van Herck M.
      • et al.
      Recovery from COVID-19: a sprint or marathon? 6-month follow-up data from online long COVID-19 support group members.
      ; 61.9% of the patients reported they were receiving physiotherapy and 11.7% rehabilitation between 3 and 6 months of follow-up. However, 62% of the patients still presented with moderate-to-extreme problems performing daily activities, and 49% experienced moderate-to-severe pain/discomfort.
      • Vaes A.W.
      • Goertz Y.M.J.
      • Van Herck M.
      • et al.
      Recovery from COVID-19: a sprint or marathon? 6-month follow-up data from online long COVID-19 support group members.
      Lastly, QoL was assessed using the Nijmegen Clinical Screening Instrument in 124 patients with symptoms persisting for more than 6 weeks who attended a COVID-19 aftercare facility.
      • van den Borst B.
      • Peters J.B.
      • Brink M.
      • et al.
      Comprehensive health assessment 3 Months after recovery from acute Coronavirus disease 2019 (COVID-19).
      Patients were divided into 4 groups (mild: n = 27; moderate: n = 51; severe: n = 26; and critical: n = 20). Functional impairment was observed in 64% of the patients, fatigue in 69%, and reduced QoL in 72%.
      • van den Borst B.
      • Peters J.B.
      • Brink M.
      • et al.
      Comprehensive health assessment 3 Months after recovery from acute Coronavirus disease 2019 (COVID-19).

      Discussion

      Long COVID has recently only been recognized; therefore, available evidence on the impact of this condition on muscle health is limited. Overall, studies suggest that long COVID negatively impacts body composition, muscle function, and QoL.
      Body composition in individuals with long COVID was not found to differ based on disease severity.
      • van den Borst B.
      • Peters J.B.
      • Brink M.
      • et al.
      Comprehensive health assessment 3 Months after recovery from acute Coronavirus disease 2019 (COVID-19).
      ,
      • van Gassel R.J.J.
      • Bels J.
      • Remij L.
      • et al.
      Functional outcomes and their association with physical performance in mechanically ventilated Coronavirus disease 2019 survivors at 3 Months following hospital discharge: a cohort study.
      ,
      • Tanriverdi A.
      • Savci S.
      • Kahraman B.O.
      • et al.
      Extrapulmonary features of post-COVID-19 patients: muscle function, physical activity, mood, and sleep quality.
      However, this finding may be attributed to limitations of the body composition techniques used and small sample size, among others. Furthermore, the lack of body composition assessments during the acute phase and at hospital discharge hinders our understanding of whether people did experience changes in body composition, and at which disease phase. In one study, IMAT was found to be greater in patients with low physical performance.
      • van Gassel R.J.J.
      • Bels J.
      • Remij L.
      • et al.
      Functional outcomes and their association with physical performance in mechanically ventilated Coronavirus disease 2019 survivors at 3 Months following hospital discharge: a cohort study.
      This measurement is an estimate of skeletal muscle “quality” and has been associated with COVID-19 severity
      • Viddeleer A.R.
      • Raaphorst J.
      • Min M.
      • et al.
      Intramuscular adipose tissue at level Th12 is associated with survival in COVID-19.
      and physical function after recovery.
      • Besutti G.
      • Pellegrini M.
      • Ottone M.
      • et al.
      The impact of chest CT body composition parameters on clinical outcomes in COVID-19 patients.
      Notably, long COVID was associated with a reduction of the thickening ratio of the diaphragm muscle, which can be related to diaphragm dysfunction.
      • Farr E.
      • Wolfe A.R.
      • Deshmukh S.
      • et al.
      Diaphragm dysfunction in severe COVID-19 as determined by neuromuscular ultrasound.
      This is an interesting marker in COVID-19 survivors, as it relates to fatigue after the acute phase.
      • Shi Z.
      • de Vries H.J.
      • Vlaar A.P.J.
      • et al.
      Diaphragm pathology in critically ill patients with COVID-19 and postmortem findings from 3 medical Centers.
      In fact, 4 ongoing clinical trials are investigating how abnormal diaphragm muscle thickening ratio, which is related to muscle contractility, can impact QoL of individuals with long COVID.

      ClinicalTrials.gov. National Library of Medicine (U.S.). Respiratory Muscles After Hospitalisation for COVID-19 (REMAP-COVID-19) .Identifier NCT04854863. Available from: https://clinicaltrials.gov/ct2/show/NCT04854863?cond=NCT04854863&draw=2&rank=1

      ClinicalTrials.gov. National Library of Medicine (U.S.). Diaphragm Ultrasound Evaluation During Weaning From Mechanical Ventilation in the Positive COVID-19 Patient. Identifier NCT05019313. Available from:https://clinicaltrials.gov/ct2/show/NCT05019313?cond=NCT05019313&draw=2&rank=1

      ClinicalTrials.gov. National Library of Medicine (U.S.).Pulmonary Function in Patients Recovering From COVID19 Infection : a Pilot Study (EFRUPIC). Identifier NCT05074927. Available from: https://clinicaltrials.gov/ct2/show/NCT05074927?cond=NCT05074927&draw=2&rank=1

      ClinicalTrials.gov. National Library of Medicine (U.S.). Respiratory Muscle Function, Dyspnea, Exercise Capacity and Quality of Life in Severe COVID19 Patients. Identifier NCT04853940. Available from: https://clinicaltrials.gov/ct2/show/NCT04853940?cond=NCT04853940&draw=2&rank=1

      Muscle function of people with long COVID was shown to improve over 12 months.
      • Bellan M.
      • Soddu D.
      • Balbo P.E.
      • et al.
      Respiratory and psychophysical sequelae among patients with COVID-19 four months after hospital discharge.
      The negative effects of long COVID on muscle function were obvious after 4 months and 12 months posthospital discharge,
      • Tanriverdi A.
      • Savci S.
      • Kahraman B.O.
      • et al.
      Extrapulmonary features of post-COVID-19 patients: muscle function, physical activity, mood, and sleep quality.
      ,
      • Bellan M.
      • Soddu D.
      • Balbo P.E.
      • et al.
      Respiratory and psychophysical sequelae among patients with COVID-19 four months after hospital discharge.
      although one study showed improvements at 1-year follow-up.
      • Bellan M.
      • Soddu D.
      • Balbo P.E.
      • et al.
      Respiratory and psychophysical sequelae among patients with COVID-19 four months after hospital discharge.
      Inconsistency between the studies might be related to the degree of disease severity, age, and the presence of comorbidities.
      • Kirwan R.
      • McCullough D.
      • Butler T.
      • et al.
      Sarcopenia during COVID-19 lockdown restrictions: long-term health effects of short-term muscle loss.
      ,
      • Liu Y.
      • Mao B.
      • Liang S.
      • et al.
      Association between age and clinical characteristics and outcomes of COVID-19.
      Similarly to the findings observed by Huan and colleagues,
      • Huang C.
      • Huang L.
      • Wang Y.
      • et al.
      6-month consequences of COVID-19 in patients discharged from hospital: a cohort study.
      some studies hereby included reported worse physical performance in patients who recovered from severe COVID-19, when compared with those who had suffered a mild or moderate disease.
      • van Gassel R.J.J.
      • Bels J.
      • Remij L.
      • et al.
      Functional outcomes and their association with physical performance in mechanically ventilated Coronavirus disease 2019 survivors at 3 Months following hospital discharge: a cohort study.
      ,
      • Tanriverdi A.
      • Savci S.
      • Kahraman B.O.
      • et al.
      Extrapulmonary features of post-COVID-19 patients: muscle function, physical activity, mood, and sleep quality.
      ,
      • Mittal J.
      • Ghosh A.
      • Bhatt S.P.
      • et al.
      High prevalence of post COVID-19 fatigue in patients with type 2 diabetes: a case-control study.
      Notably, the presence of comorbidities also plays a critical role in long COVID. Cox and colleagues
      • Cox M.C.
      • Booth M.
      • Ghita G.
      • et al.
      The impact of sarcopenia and acute muscle mass loss on long-term outcomes in critically ill patients with intra-abdominal sepsis.
      observed that critically ill patients with low muscle mass who were recovering from sepsis experienced worse physical function 6 months after hospital discharge, when compared with critically ill patients with normal muscle mass. The presence of other comorbidities, such as obesity and pulmonary disease, has also been associated with symptoms of long COVID, including poor muscle function,
      • Aminian A.
      • Bena J.
      • Pantalone K.M.
      • et al.
      Association of obesity with postacute sequelae of COVID-19.
      and is therefore an important variable to assess in future studies investigating long COVID.
      Long COVID negatively affects QoL,
      • van den Borst B.
      • Peters J.B.
      • Brink M.
      • et al.
      Comprehensive health assessment 3 Months after recovery from acute Coronavirus disease 2019 (COVID-19).
      ,
      • van Gassel R.J.J.
      • Bels J.
      • Remij L.
      • et al.
      Functional outcomes and their association with physical performance in mechanically ventilated Coronavirus disease 2019 survivors at 3 Months following hospital discharge: a cohort study.
      ,
      • Cuerda C.
      • Sanchez Lopez I.
      • Gil Martinez C.
      • et al.
      Impact of COVID-19 in nutritional and functional status of survivors admitted in intensive care units during the first outbreak. Preliminary results of the NUTRICOVID study.
      ,
      • Vaes A.W.
      • Goertz Y.M.J.
      • Van Herck M.
      • et al.
      Recovery from COVID-19: a sprint or marathon? 6-month follow-up data from online long COVID-19 support group members.
      especially in individuals with impaired physical performance.
      • van Gassel R.J.J.
      • Bels J.
      • Remij L.
      • et al.
      Functional outcomes and their association with physical performance in mechanically ventilated Coronavirus disease 2019 survivors at 3 Months following hospital discharge: a cohort study.
      Some individuals still reported fatigue and difficulties in performing daily activities 6 months after hospital discharge and rehabilitation.
      • van den Borst B.
      • Peters J.B.
      • Brink M.
      • et al.
      Comprehensive health assessment 3 Months after recovery from acute Coronavirus disease 2019 (COVID-19).
      ,
      • Vaes A.W.
      • Goertz Y.M.J.
      • Van Herck M.
      • et al.
      Recovery from COVID-19: a sprint or marathon? 6-month follow-up data from online long COVID-19 support group members.
      According to Rios and colleagues
      • Rios T.C.
      • de Oliveira L.P.M.
      • da Costa M.L.V.
      • et al.
      A poorer nutritional status impacts quality of life in a sample population of elderly cancer patients.
      and Rives-Lange,
      • Rives-Lange C.
      • Zimmer A.
      • Merazka A.
      • et al.
      Evolution of the nutritional status of COVID-19 critically-ill patients: a prospective observational study from ICU admission to three months after ICU discharge.
      malnutrition is a possible contributor to low QoL during long COVID. The relationship between QoL and nutritional status has been previously investigated in other conditions and is associated with impaired functional status and delayed recovery.
      • Norman K.
      • Kirchner H.
      • Lochs H.
      • et al.
      Malnutrition affects quality of life in gastroenterology patients.
      However, reduced QoL is not entirely explained by reduced physical performance, QoL also depends on mental and cognitive factors.
      • Geense W.W.
      • de Graaf M.
      • Vermeulen H.
      • et al.
      Reduced quality of life in ICU survivors - the story behind the numbers: a mixed methods study.
      Although older adults are at greater risk for the detrimental effects of long COVID on muscle health, little is known regarding age-related differences, and whether the sequelae are worse in older compared with younger adults. Age differences should be explored in future studies to better understand how long COVID affects muscle health across the lifespan.
      Finally, despite the limited literature, long COVID directly or indirectly impacts muscle health. Muscle mass and function assessments can contribute toward the identification, diagnosis, and management of poor muscle health resulting from long COVID, consequently informing the design of targeted interventions.
      • Prado C.M.
      • Anker S.D.
      • Coats A.J.S.
      • et al.
      Nutrition in the spotlight in cachexia, sarcopenia and muscle: avoiding the wildfire.
      Early approaches to optimize muscle health throughout disease trajectory and the recovery period are essential and should involve a multidisciplinary team of health professionals.

      Summary

      Despite the relatively low number of studies and the presence of methodological limitations, available evidence suggests long COVID negatively impacts muscle health and QoL. These sequelae may be amplified in older adults due to preexisting age-related declines in muscle health. Acute and long-term assessments of these parameters are needed to optimize patient care. The mechanisms by which long COVID impacts muscle health are multifactorial and involve a combination of systemic inflammation, physical inactivity, poor nutritional status, and inadequate dietary intake. Other factors such as age, comorbidities, and degree of disease severity may also contribute to negative musculoskeletal outcomes during long COVID.
      Overall, the evidence to date suggests long COVID negatively impacts body composition, muscle function, and QoL. Recovery and rehabilitation services with adequate nutrition, mental and social support should be explored as potential multimodal interventions to improve muscle health of these patients.

      Clinics care points

      • Clinicians should be aware of the prevalence and deleterious impact of poor muscle health in individuals with long COVID.
      • People with long COVID can present with skeletal muscle symptoms 1 year after diagnosis.
      • Muscle health in long COVID is related to low quality of life

      Disclosure

      The authors have nothing to disclose.

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