News Release 

High blood glucose levels may explain why some flu patients experience severe symptoms

O-GlcNAc transferase promotes influenza A virus-induced cytokine storm by targeting interferon regulatory factor-5

American Association for the Advancement of Science

Influenza A (a highly contagious virus that causes annual flu epidemics worldwide) may trigger an inflammatory "cytokine storm" - an excessive immune response that can lead to hospitalization or even death - by increasing glucose metabolism, according to a new study. As the novel coronavirus pandemic grips the globe, Qiming Wang and colleagues have separately, and fully apart from this study, begun investigating how glucose metabolism may affect patients with COVID-19. "We believe that glucose metabolism contributes to various COVID-19 outcomes since both influenza and COVID-19 can induce a cytokine storm, and since COVID-19 patients with diabetes have shown higher mortality," says Shi Liu, a researcher on the study. In general, the mechanisms that promote cytokine storms, causing some individuals to suffer more from influenza A (and, perhaps more from COVID-19) than others remain mysterious. Although glucose metabolism and inflammatory cytokine signal networks are known to have evolved together, it has not been clear whether they interact during flu infection. To learn whether glucose metabolism is related to the off-the-wall immune response brought on by influenza A, Wang et al. examined blood glucose levels and cytokine production in mice with the flu, finding that those treated with glucosamine produced significantly higher levels of inflammatory cytokines and chemokines than mice that did not receive glucosamine. Additionally, the researchers analyzed glucose levels in blood samples from patients diagnosed with influenza A and healthy patients, which were collected from volunteers during physical examinations at two Wuhan University hospitals between 2017 and 2019. They determined that the hexosamine biosynthesis pathway, which metabolizes a small portion of glucose, plays an essential role in cytokine storms triggered by the flu virus.

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