Metabolic and immune markers for precise monitoring of COVID-19 severity and treatment

Abstract

Deep understanding of the SARS-CoV-2 effects on host molecular pathways is paramount for the discovery of early biomarkers of outcome of coronavirus disease 2019 (COVID-19) and the identification of novel therapeutic targets. In that light, we generated metabolomic data from COVID-19 patient blood using high-throughput targeted nuclear magnetic resonance (NMR) spectroscopy and high-dimensional flow cytometry. We find considerable changes in serum metabolome composition of COVID-19 patients associated with disease severity, and response to tocilizumab treatment. We built a clinically annotated, biologically-interpretable space for precise time-resolved disease monitoring and characterize the temporal dynamics of metabolomic change along the clinical course of COVID-19 patients and in response to therapy. Finally, we leverage joint immuno-metabolic measurements to provide a novel approach for patient stratification and early prediction of severe disease. Our results show that high-dimensional metabolomic and joint immune-metabolic readouts provide rich information content for elucidation of the host response to infection and empower discovery of novel metabolic-driven therapies, as well as precise and efficient clinical action.

Proinflammatory innate cytokines and metabolomic signatures shape the T cell response in active COVID-19

“…We and others have reported that COVID-19 patients have altered metabolic pathways and dysregulation of energy production [15][16][17][18][19] . Since plasma metabolites substantially influence the immune cells in shaping protective immune responses, we tested whether levels of specific metabolites or metabolic pathways correlate with the antiviral immune responses.…”

“…Since an extensive interplay is reported between plasma metabolites and immune cell activation in COVID-19 patients (15)(16)(17)(18)(19), metabolic analysis in the plasma samples of longitudinal active COVID-19 patients pointed out a set of metabolites significantly correlate with the innate and adaptive immune responses.…”

Stratification of hypertensive COVID-19 patients by quantitative NMR spectroscopy of serum metabolites, lipoproteins and inflammation markers

“…As such, above all, increased ketone bodies (16), phenylalanine (16,17) and pronounced dyslipidemia with increased ABA1 ratio, decreased HDL cholesterol (16) and decreased apolipoprotein A1 (18) had been mentioned. These markers could help to predict response to therapy (16,19). This was investigated in these two studies with the IL-6 inhibitor tocilizumab, where under and after therapy, respectively, an approximation of the metabolic/lipoproteomic parameters of severe COVID-19 cases to the levels of milder cases was observed.…”

“…Accordingly, in hospitalized patients with positive outcome, i.e., in Baranovicova et al survivors without respiratory deterioration or mechanical ventilation, normalization of energy metabolism occurred more rapidly, as well as an increase in glutamine, than in patients with negative outcome (deterioration of respiratory situation with need for respiratory support or death). Furthermore, NMR technology has identified markers that may be indicative of a severe COVID-19 progression (10,(16)(17)(18). As such, above all, increased ketone bodies (16), phenylalanine (16,17) and pronounced dyslipidemia with increased ABA1 ratio, decreased HDL cholesterol (16) and decreased apolipoprotein A1 (18) had been mentioned.…”

“…Furthermore, NMR technology has identified markers that may be indicative of a severe COVID-19 progression (10,(16)(17)(18). As such, above all, increased ketone bodies (16), phenylalanine (16,17) and pronounced dyslipidemia with increased ABA1 ratio, decreased HDL cholesterol (16) and decreased apolipoprotein A1 (18) had been mentioned. These markers could help to predict response to therapy (16,19).…”