UNDERSTANDING LONG COVID AS CANCER METABOLISM SYNDROME

We know the terms by heart. Tumor necrosis factor alpha (TNFα), interleukin-6 and -1 (IL-6/IL-1) and interferon gamma. These are all hallmarks of COVID and Long COVID. They are also hallmarks of Cancer Metabolism Syndrome which we commonly know as Cancer Cachexia.

Metabolic reprogramming occurs in tumors to foster cancer cell proliferation, survival and metastasis, but as well at a systemic level affecting the whole organism, eventually leading to cancer cachexia. Indeed, as cancer cells rely on external sources of nitrogen and carbon skeleton to grow, systemic metabolic deregulation promoting tissue wasting and metabolites mobilization ultimately supports tumor growth. Cachectic patients experience a wide range of symptoms affecting several organ functions such as muscle, liver, brain, immune system and heart, collectively decreasing patients’ quality of life and worsening their prognosis.

These metabolic changes are also apparent in COVID-19 and Long COVID.

Taste misperceptions are also reported in Long COVID. TNFα has also been associated to the stimulation of bitterness perception,139 thus further inhibiting the willingness of food assumption.

The same metabolism is also responsible for inducing insulin resistance and diabetes in those with cancer cachexia, which we are seeing in Long COVID patients.

One of the factors identified for the induction of insulin resistance is TNF-α, which directly impairs insulin signaling and IRS-1 activation.

Additionally, the very recent paper showing gas exchange dysfunction in Long COVID patients is also directly related to cachexia. Chronic respiratory failure is a condition that results in the inability to effectively exchange carbon dioxide and oxygen, and induces chronically low oxygen levels or chronically high carbon dioxide levels. The condition is usually caused by chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD), chronic bronchitis, and idiopathic interstitial pneumonia. If diseases with chronic respiratory failure progress to their advanced stages, cachexia commonly occurs (Schols, 2002). Cachexia is characterized by physical and muscle wasting, increased metabolic rate, and decreased appetite. The presence of cachexia worsens the patients’ quality of life and prognosis.

The spike protein is implicated in initiating this metabolism in affected cells. Long COVID may be the initiation of this process in stable and permanent cells. The virus also disrupts autophagy, attempting to turn labile cells into immortal cancer cells.

Referenced/related papers

The Fatty Acid Lipid Metabolism Nexus in COVID-19

https://pubmed.ncbi.nlm.nih.gov/33440724/

Metabolic Alterations in SARS-CoV-2 Infection and Its Implication in Kidney Dysfunction

https://www.frontiersin.org/articles/10.3389/fphys.2021.624698/full

Is IL-6 a key cytokine target for therapy in COVID-19?

https://www.nature.com/articles/s41577-021-00553-8

Chapter Twenty-Five – Clinical Application of Ghrelin for Chronic Respiratory Diseases

https://www.sciencedirect.com/science/article/pii/B9780123812728000258