d-Alanine as a biomarker and a therapeutic option for severe influenza virus infection and COVID-19.

Since the outbreak of coronavirus disease 2019 (COVID-19), biomarkers for evaluating severity, as well as supportive care to improve clinical course, remain insufficient. We explored the potential of d-amino acids, rare enantiomers of amino acids, as biomarkers for assessing disease severity and as protective nutrients against severe viral infections. In mice infected with influenza A virus (IAV) and in patients with severe COVID-19 requiring artificial ventilation or extracorporeal membrane oxygenation, blood levels of d-amino acids, including d-alanine, were reduced significantly compared with those of uninfected mice or healthy controls. In mice models of IAV infection or COVID-19, supplementation with d-alanine alleviated severity of clinical course, and mice with sustained blood levels of d-alanine showed favorable prognoses. In severe viral infections, blood levels of d-amino acids, including d-alanine, decrease, and supplementation with d-alanine improves prognosis. d-Alanine has great potentials as a biomarker and a therapeutic option for severe viral infections.