An untargeted metabolomic approach to identify antiviral defense mechanisms in memory leukocytes secreting in vitro IgG anti-SARS-Cov-2

Available knowledge shows that individuals infected by SARS-CoV-2 undergo an altered metabolic state in multiple organs. Metabolic activities are directly involved in modulating the immune responses against infectious diseases, yet our understanding remains limited on how host metabolism relates with inflammatory responses. To better elucidate the underlying biochemistry of leukocytes response, we focused our analysis on the possible relationships between SARS-CoV-2 post-infection stages and distinct metabolic pathways. Indeed, in cultures of peripheral blood mononuclear cells (PBMC, n=48) obtained 60-90 days after infection and showing in vitro IgG antibody memory for spike-S1 antigen (n=19), we observed a significant altered metabolism of tryptophan and urea cycle pathways. This work for the first time identifies metabolic routes in cell metabolism possibly related to later stages of immune defense against SARS-Cov-2 infection, namely when circulating antibodies may be absent, but an antibody memory is present. The results suggest a reprogramming of leukocyte metabolism after viral pathogenesis through activation of specific amino acid pathways possibly related to protective immunity against SARS-CoV-2. ### Competing Interest Statement The authors have declared no competing interest.