Impaired ketogenesis which ties metabolism to T cell dysfunction in COVID-19

At least that is what the results of the current study suggest. "We found that patients with influenza infections produce ketone bodies in considerable quantities," explains Prof. Dr. Christoph Wilhelm from the Institute of Clinical Chemistry and Clinical Pharmacology at the University Hospital Bonn, who is also a member of the Immunosensation2 Cluster of Excellence at the University of Bonn. "In contrast, we saw hardly any increase in Covid-19 patients, at least in those with a moderate or severe course."

In addition, it was striking that those infected with the coronavirus had lower levels of inflammatory messengers in their blood. This was particularly true for interferon-gamma.

The researchers also saw similar effects in another important group of immune cells, the killer T cells. Apparently, the ketone bodies promote the function of mitochondria, metabolic powerhouses fueling the immune cells. This not only ensures improved energy production but also provides molecules that are needed for interferon production.

"Without an adequate supply of ketone bodies, on the other hand, the killer T cells and helper T cells show signs of exhaustion," Bode explains. "In this depleted state, they can no longer perform their function adequately." However, the researchers were able to revive the immune cells by placing diseased mice on a ketogenic diet (a diet low in carbohydrates and protein) or by administering ketone bodies directly.

The results therefore also raise hope for new treatment options. "It may be possible to increase the power of the body's own defenses through a targeted change in diet," says Wilhelm. However, the researchers expressly advise against self-experimentation with dietary supplements or diets - these could possibly do more harm than good.

Ref:

Fotios Karagiannis et al.: Impaired ketogenesis ties metabolism to T cell dysfunction in COVID-19. Nature; https://doi.org/10.1038/s41586-022-05128-8