Abstract
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.
Highlights
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continues to spread globally, causing widespread morbidity and mortality and showing a tremendously high transmission rate [1]
To characterize the metabolic features of these disproportionate cell types in patients with COVID-19, we identified the differentially-expressed genes (DEGs) (MAST algorithm; P < 0.01, logarithm of the fold change (logFC) > 0.25 or logFC < -0.25) in patients with mild or severe disease compared to healthy controls (HCs) and performed gene enrichment analysis (Table S4)
After performing pairwise comparison using Student’s t-test, we found that inflammation, IFN response, and S100 family were significantly upregulated and apoptosis, migration, and MHC class II were significantly downregulated in both mono-CD14+ and mono-CD14+CD16+ cells in COVID-19 patients compared to the corresponding cells in HCs (Figure 3A)
Summary
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continues to spread globally, causing widespread morbidity and mortality and showing a tremendously high transmission rate [1]. Severe coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 infection is often associated with older populations and individuals with preexisting conditions, such as cardiovascular disease, diabetes, chronic respiratory disease, and cancer [2]. In patients with severe COVID-19 but not in patients with mild disease, lymphopenia is a common feature, with drastically reduced numbers of CD4+ T cells and CD8+ T cells. Ill COVID-19 patients but not those with mild symptoms had high concentrations of a fucosylated IgG antibodies against SARS-CoV-2, amplifying proinflammatory cytokine release and acute-phase responses [11]. Antibodies, lymphopenia and inflammatory markers in monocytes may help identify COVID-19 cases and predict their severity
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