Integrated analysis of plasma and single immune cells uncovers metabolic changes in individuals with COVID-19.

Lee, Jihoon W; Su, Yapeng; Baloni, Priyanka; Chen, Daniel; Pavlovitch-Bedzyk, Ana Jimena; Yuan, Dan; Duvvuri, Venkata R; Ng, Rachel H; Choi, Jongchan; Xie, Jingyi; Zhang, Rongyu; Murray, Kim; Kornilov, Sergey; Smith, Brett; Magis, Andrew T; Hoon, Dave S B; Hadlock, Jennifer J; Goldman, Jason D; Price, Nathan D; Gottardo, Raphael; Davis, Mark M; Hood, Leroy; Greenberg, Philip D; Heath, James R

A better understanding of the metabolic alterations in immune cells during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may elucidate the wide diversity of clinical symptoms experienced by individuals with coronavirus disease 2019 (COVID-19). Here, we report the metabolic changes associated with the peripheral immune response of 198 individuals with COVID-19 through an integrated analysis of plasma metabolite and protein levels as well as single-cell multiomics analyses from serial blood draws collected during the first week after clinical diagnosis. We document the emergence of rare but metabolically dominant T cell subpopulations and find that increasing disease severity correlates with a bifurcation of monocytes into two metabolically distinct subsets. This integrated analysis reveals a robust interplay between plasma metabolites and cell-type-specific metabolic reprogramming networks that is associated with disease severity and could predict survival.