S. Ryu, I. Shchukina, YH. Youm, H. Qing, B. Hilliard, T. Dlugos, X. Zhang, Y. Yasumoto, CJ. Booth, C. Fernández-Hernando, Y. Suárez, K. Khanna, TL. Horvath, MO. Dietrich, M. Artyomov, A. Wang, et al. (2021). Ketogenic diet restrains aging-induced exacerbation of coronavirus infection in mice. eLife, 10. https://doi.org/10.7554/eLife.66522

PubMed 34151773

[Abstract]
Increasing age is the strongest predictor of risk of COVID-19 severity and mortality. Immunometabolic switch from glycolysis to ketolysis protects against inflammatory damage and influenza infection in adults. To investigate how age compromises defense against coronavirus infection, and whether a pro-longevity ketogenic diet (KD) impacts immune surveillance, we developed an aging model of natural murine beta coronavirus (mCoV) infection with mouse hepatitis virus strain-A59 (MHV-A59). When inoculated intranasally, mCoV is pneumotropic and recapitulates several clinical hallmarks of COVID-19 infection. Aged mCoV-A59-infected mice have increased mortality and higher systemic inflammation in the heart, adipose tissue, and hypothalamus, including neutrophilia and loss of γδ T cells in lungs. Activation of ketogenesis in aged mice expands tissue protective γδ T cells, deactivates the NLRP3 inflammasome, and decreases pathogenic monocytes in lungs of infected aged mice. These data establish harnessing of the ketogenic immunometabolic checkpoint as a potential treatment against coronavirus infection in the aged.