Investigating Ketone Bodies as Immunometabolic Countermeasures against Respiratory Viral Infections

There are multiple cellular and systemic mechanisms whereby ketone bodies might impact severe viral infections, such as influenza or SARS-CoV-2. Evidence across various model systems and/or clinical contexts support potentially relevant molecular mechanisms of ketone bodies, including provision of energetic support, attenuation of inflammation and oxidative stress, apoptosis resistance, maintenance of metabolic homeostasis, and others. These mechanisms have yet to be tested in the specific context of severe respiratory viral infection but could be hypothesized to prevent and mitigate disease as well as support recovery. Further investigation of ketone bodies in respiratory viral illness is warranted, informed by preclinical mechanistic work and with appropriate caution used in clinical studies. In considering the translatability of potential interventions, the natural history of ketone biology in humans provides strong evidence of safety, and the existence of multiple sources of exogenous ketones could facilitate translation. Consequently, exogenous ketone bodies represent a readily deployable tool that could impact multiple mechanisms directly linked to disease outcomes, making these compounds a priority for rapid investigation.