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 ( PKM, LDHA and PKM ) and PPP – related genes ( PGD and TKT ) 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 ( NSD1, KMT2E , and SETD2 ) and elevated transcription levels of genes involved in OXPHOS ( ATP6V1B2 , ATP5A1 , ATP5E , and ATP5B ), which may inhibit M2-like polarization. Plasma cells also expressed higher levels of the OXPHOS gene ATP13A3 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.
【저자키워드】 COVID-19, Inflammation, Peripheral blood mononuclear cells, metabolic changes, antibody secretion, 【초록키워드】 coronavirus disease, Monocytes, Coronavirus disease 2019, severe COVID-19, Transcription, memory B cells, progression, Single-cell RNA sequencing, monocyte, Peripheral blood, survival, plasmablasts, hyperinflammation, Patient, Peripheral blood mononuclear cells, lysine, immune cells, Severe patient, Degradation, differentiation, signaling pathways, change, mechanism, antibody secretion, Plasma cell, COVID-19 patients, memory B cell, mild patients, Plasma cells, Glycolysis, immune dysfunction, PBMCs, Immune cell, Pathways, severe disease, COVID-19 patient, mononuclear cells, lead, mononuclear cell, severe patients, plasmablast, CD14, sequencing data, mono, cell survival, cell population, ATP13A3, ATP6V1B2, KMT2E, LDHA, NSD1, SETD2, feature, Cell, involved, investigated, inhibit, elevated, exacerbated, reduced, contribute, expressed, promoted, biological processe, PGD, PKM, TKT, 【제목키워드】 Coronavirus disease 2019, RNA,