Metabolic Landscape of Bronchoalveolar Lavage Fluid in Coronavirus Disease 2019 at Single Cell Resolution

Abstract

Abnormal function of immune cells is one of the key mechanisms leading to severe clinical symptoms in coronavirus disease 2019 patients, and metabolic pathways can destroy the function of the immune system by affecting innate and adaptive immune responses. However, the metabolic characteristics of the immune cells of the SARS-CoV-2 infected organs in situ remaining elusive. We reanalyzed the metabolic-related gene profiles in single-cell RNA sequencing data, drew the metabolic landscape in bronchoalveolar lavage fluid immune cells, and elucidated the metabolic remodeling mechanism that might lead to the progression of COVID-19 and the cytokine storm. Enhanced glycolysis is the most important common metabolic feature of all immune cells in COVID-19 patients. CCL2+ T cells, Group 2 macrophages with high SPP1 expression and myeloid dendritic cells are among the main contributors to the cytokine storm produced by infected lung tissue. Two metabolic analysis methods, including Compass, showed that glycolysis, fatty acid metabolism, bile acid synthesis and purine and pyrimidine metabolism levels of CCL2+ T cells, Group 2 macrophages and myeloid dendritic cells were upregulated and correlated with cytokine storms of COVID-19 patients. This might be the key metabolic regulatory factor for immune cells to produce large quantities of cytokines.

COVID-19: A complex disease with a unique metabolic signature

“…Remarkably, i) these pathways include the possible disease markers experimentally identified by our NMR approach (e.g. phenylalanine and mannose) and ii) a large body of literature identified perturbations of the metabolites belonging to these pathways as possible metabolic responses to the COVID-19 disease state [42][43][44][45][46]. Our data also suggest the presence of system-level differences in the metabolic network of males and females in response to COVID-19 disease.…”