Respiratory viral infections remain a scourge, with seasonal influenza infecting millions and killing many thousands annually and viral pandemics, such as COVID-19, recurring every decade. Age, cardiovascular disease, and diabetes mellitus are risk factors for severe disease and death from viral infection. Immunometabolic therapies for these populations hold promise to reduce the risks of death and disability. Such interventions have pleiotropic effects that might not only target the virus itself but also enhance supportive care to reduce cardiopulmonary complications, improve cognitive resilience, and facilitate functional recovery. Ketone bodies are endogenous metabolites that maintain cellular energy but also feature drug-like signaling activities that affect immune activity, metabolism, and epigenetics. Here, we provide an overview of ketone body biology relevant to respiratory viral infection, focusing on influenza A and severe acute respiratory syndrome (SARS)-CoV-2, and discuss the opportunities, risks, and research gaps in the study of exogenous ketone bodies as novel immunometabolic interventions in these diseases. Graphical Abstract Stubbs et al. provide an overview of the known biological actions of ketone bodies that could be relevant to severe respiratory viral infection, using influenza A virus and SARS-CoV-2 as key examples, and describe how exogenous ketones could be a novel immunometabolic intervention in these diseases.
【저자키워드】 COVID-19, SARS-CoV-2, Cytokine storm, Influenza, ketones, ketone bodies, β-hydroxybutyrate, exogenous ketone, ketone ester, ketone salt, 【초록키워드】 Resilience, viral infection, therapy, Diseases, Cardiopulmonary, Diabetes Mellitus, influenza A virus, risk, cardiovascular disease, Intervention, risk factor, virus, influenza A, metabolism, immune, Population, activity, Research, death, Pandemics, complications, respiratory, metabolite, respiratory viral infection, cellular, Signaling, supportive care, severe disease, ketone body, Seasonal influenza, cognitive, acute respiratory syndrome, infecting, killing, Affect, ENhance, IMPROVE, facilitate, functional, maintain, reduce, pleiotropic effect, 【제목키워드】 respiratory, ketone, countermeasure, Body,