COVID-19-induced sarcopenia and physical deconditioning may require reassessment of surgical risk for patients with cancer

Both muscle weakness and myalgia are well recognised in COVID-19 [15]. Studies of hospitalised patients have described biochemical evidence of muscle damage [16]. Several reports of severe rhabdomyolysis, even in the absence of respiratory symptoms, suggests skeletal muscle tissue is not immune from the disease process [17‐19]. Virus-induced myositis is seen with other pathogens including SARS-CoV-1 and influenza but is unclear whether immune-mediated injury due to myotoxic cytokines (such as CXCL-10, IFN-ϒ, IL-1β, IL-6, IL-17, and TNFα) or if direct viral infiltration is the predominant pathological process. SARS-CoV-2 viral particles have been detected by electron microscopy within skeletal muscle and cardiac muscle fibres whilst distressing case reports of fatal cardiac failure in children due to fulminant cardiomyopathy suggests the direct impact on muscle tissue can be profound [20]. SARS-CoV-2 enters host cells via the angiotensin-converting enzyme 2 (ACE2) receptor. Both skeletal and cardiac muscle exhibit robust expression on the ACE2 receptor on their surface as do many other tissues offering a potential viral route for direct tissue damage [21, 22]. Clinical parallels can be drawn from the SARS-CoV-1 pandemic in 2003 owing to its genetic and clinicopathological homology with SARS-CoV-2. Extensive myalgia and muscle dysfunction were reported in SARS patients. Widespread muscle fibre atrophy, fibre necrosis, myofibril disarray, and Z-disc streaming was demonstrated in post-mortem muscle tissue [23]. Furthermore, relatively fit SARS survivors were shown to have objective reductions in hand grip strength (32%) and 6-min walk test (13%) when followed up in clinic [24]. Similar functional outcomes measures in survivors of COVID-19 have also been described with measurable reductions in indices of muscle strength and physical function [25]. How long these impairment last for is unknown.

The indirect ability of the viral pandemic to cause physical deconditioning should also be considered. Some experts predict a pandemic-related increase in surgical morbidity and mortality due to social isolation and reduced activity levels in patients, where operations have been rescheduled or postponed [26, 27]. This deleterious effect will be more striking in the elderly or medically frail who also suffer psychological consequences and demotivation. For patients awaiting major cancer surgery, many community prehabilitation programs and local gymnasiums have closed evoking a rapid response to establish at-home exercise programs and telemedicine to minimise the effects of social isolation and pre-operative inactivity.

In conclusion, the ability of SARS-CoV-19 to cause physical decline is multifactorial and may be related to periods of convalescence, reduced appetite, chronic cardiorespiratory symptoms, social isolation, and reduced access to physical activity (Fig. 1). The direct and indirect impact on muscle strength, sarcopenia, and frailty may be underestimated and could, in part, explain the poor surgical outcomes seen in patients with previous SARS-CoV-2 infection. Functional outcome scales such as those proposed by Klok et al. may compliment standard assessment tools such as WHO performance status in assessing global functional recovery from the illness but remain unvalidated [28]. Pragmatic approaches to keep physically active prior to cancer surgery, such as home-based exercise programs, will become increasingly important as well as novel rehabilitation techniques for those worse effected by COVID-19 [29]. Going forward, we need a better understanding on how, and to what degree, COVID-19 causes physical deconditioning in mild, moderate, and severe cases alike. Whether this adjusts peri-operative risk for patients requiring cancer surgery requires further investigation to identify best timing for surgery and to tailor focussed prehabilitation for COVID-19 survivors.