Single-Cell RNA Sequencing Analysis of the Immunometabolic Rewiring and Immunopathogenesis of Coronavirus Disease 2019.

Although immune dysfunction is a key feature of coronavirus disease 2019 (COVID-19), the metabolism-related mechanisms remain elusive. Here, by reanalyzing single-cell RNA sequencing data, we delineated metabolic remodeling in peripheral blood mononuclear cells (PBMCs) to elucidate the metabolic mechanisms that may lead to the progression of severe COVID-19. After scoring the metabolism-related biological processes and signaling pathways, we found that mono-CD14 cells expressed higher levels of glycolysis-related genes ( and ) and PPPrelated genes ( and ) in severe patients than in mild patients. These genes may contribute to the hyperinflammation in mono-CD14 cells of patients with severe COVID-19. The mono-CD16 cell population in COVID-19 patients showed reduced transcription levels of genes related to lysine degradation (, and ) and elevated transcription levels of genes involved in OXPHOS (, , , and ), which may inhibit M2-like polarization. Plasma cells also expressed higher levels of the OXPHOS gene in COVID-19 patients, which was positively associated with antibody secretion and survival of PCs. Moreover, enhanced glycolysis or OXPHOS was positively associated with the differentiation of memory B cells into plasmablasts or plasma cells. This study comprehensively investigated the metabolic features of peripheral immune cells and revealed that metabolic changes exacerbated inflammation in monocytes and promoted antibody secretion and cell survival in PCs in COVID-19 patients, especially those with severe disease.