Does COVID‐19‐related cachexia mimic cancer‐related cachexia? Examining mechanisms, clinical biomarkers, and potential targets for clinical management

Cancer cachexia (CC) is a multi‐factorial, pathological disorder of striated muscle (skeletal and cardiac) and adipose tissue, characterized by the cardinal features of loss of skeletal muscle tissue or sarcopenia, with or without loss of adipose tissue, and often accompanied by anorexia, anaemia, asthenia, increased metabolism, altered immune function, decreased functional status, and decreased quality of life. 1–3 Overall, cancer cachexia may afflict 50–80% and cause up to 20% of deaths of cancer patients, with highest prevalence noted in pancreatic and gastric cancers. 3–6 More recently, guidelines to define each of the four stages of CC have been proposed. 5,6 CC begins initially in a pre‐cachectic stage involving unplanned weight loss followed by a more severe, irreversible and progressive loss of both muscle and fat, in addition to complications involving compromises in metabolic and immune processes, ultimately resulting in death. 7,8 Despite the clinical significance and decades of research to prevent progression of early stages of CC to the irreversible refractory stages, there is currently no defined standard of care to effectively mount a defence to the multi‐factorial disorders associated with CC. In addition to the diagnosis of cancer, CC is characterized by unplanned weight loss including loss of both skeletal and visceral muscles and fat stores, manifesting in the cardinal features of emaciation, anorexia, hypo albuminuria, myalgia, weakness affecting functional status, hypo albuminuria, significant increase in proinflammatory cytokines, dysfunction of the metabolic processes, and compromised quality of life. 1,3,19–26 Similarly, coronavirus disease (COVID‐19) is characterized by a pneumonic process of varying degree depending on the stage at diagnosis, significant increase in proinflammatory cytokines (cytokine storm), 14 anorexia, dysgeusia, anosmia, unplanned weight loss, sarcopenia, myalgia, hypo albuminuria, increased C‐reactive proteins, ferratin and proinflammatory cytokines‐TNF‐alpha, Il‐1 and Il‐6, 14,15,27 which are symptoms similar to cancer cachexia. 17,18,26,28–33 Being produced by both tumour and host, these pro‐inflammatory cytokines have frequently been suggested as possible mediators in cachexia. 32,33 It has been hypothesized that the cytokines that are important in the initiation of the acute phase response (APR) contribute to the genesis of CC. 26,31 Significant increases in TNF‐α have been observed specifically in cachec