Metabolomic/lipidomic profiling of COVID-19 and individual response to tocilizumab

The current pandemic emergence of novel coronavirus disease (COVID-19) poses a relevant threat to global health. SARS-CoV-2 infection is characterized by a wide range of clinical manifestations, ranging from absence of symptoms to severe forms that need intensive care treatment. Here, plasma-EDTA samples of 30 patients compared with age- and sex-matched controls were analyzed via untargeted nuclear magnetic resonance (NMR)-based metabolomics and lipidomics. With the same approach, the effect of tocilizumab administration was evaluated in a subset of patients. Despite the heterogeneity of the clinical symptoms, COVID-19 patients are characterized by common plasma metabolomic and lipidomic signatures (91.7% and 87.5% accuracy, respectively, when compared to controls). Tocilizumab treatment resulted in at least partial reversion of the metabolic alterations due to SARS-CoV-2 infection. In conclusion, NMR-based metabolomic and lipidomic profiling provides novel insights into the pathophysiological mechanism of human response to SARS-CoV-2 infection and to monitor treatment outcomes. Author summary The current COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is markedly affecting the world population. Here we report about the small-molecule profile of patients hospitalized during the first wave of the COVID-19 pandemic in Florence (Italy). Using magnetic resonance spectroscopy, we showed that the infection induces profound changes in the metabolome. The analysis of the specific metabolite changes and correlations with clinical data enabled the identification of potential biochemical determinants of the disease fingerprint. We also followed how metabolic alterations revert towards those of the control group upon treatment with tocilizumab, a recombinant humanized monoclonal antibody against the interleukin-6 receptor. These results open up possibilities for the monitoring of novel patients and their individual response to treatment.