Ketogenesis: Beneficial for Older Patient with COVID-19

Increasing age is the strongest analyst of COVID-19 severity. Unregulated cytokine storm and impaired immunometabolic response lead to the highest mortality in the elderly infected with SARS-CoV-2. A study claims that a ketogenic diet is capable of mitigating clinical outcomes of COVID-19 in elderly people by improving immune-metabolic functions and reducing inflammation. Since the emergence of the COVID-19 pandemic, several studies have identified age as the strongest risk factor associated with a high mortality rate in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections.

In the United States, about 80% of COVID-19 related deaths occurred in people who were more than 65 years old. The current study was conducted on a mouse model of natural murine beta coronavirus infection that outlines clinical outcomes of COVID-19 in older adults. It was observed that both old and adult mCoV-A59-infected mice had an almost similar viral load in the lungs; however, old mice displayed higher body weight loss, hypoxemia, and anorexia. The immunohistochemical analysis revealed that old infected mice had severe perivascular inflammation, edema formation, fibrosis, pneumonia, pulmonary thrombosis, and hemorrhage compared to that in young infected mice similar to elderly patients.

The observation was based on this study depicted that ketogenic diet-induced elevation in beta-hydroxybutyrate levels prevented the assembly of the inflammasome complex, leading to the prevention of inflammasome activation and reduction of inflammation. Interestingly, they observed that old mCoV-A59-infected mice fed with a ketogenic diet exhibited only mild ketosis, designating the preservation of lipid metabolism. These mice were protected from infection-related weight loss and hypoxemia and showed deactivation of the inflammasome.

Suggestively, the ketogenic diet elevated the level of γδ T cells in the lungs of mCoV-A59-infected old mice. Single-cell RNA sequencing using whole lung tissue revealed that ketogenic diet protects against mCoV-A59-induced inflammatory changes by significantly increasing goblet cells and γδ T cells and reducing proliferative myeloid cells and monocytes. 

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