Immune and Metabolic Signatures of COVID-19 Revealed by Transcriptomics Data Reuse

Abstract

The current pandemic of coronavirus disease 19 (COVID-19) has affected millions of individuals and caused thousands of deaths worldwide. The pathophysiology of the disease is complex and mostly unknown. Therefore, identifying the molecular mechanisms that promote progression of the disease is critical to overcome this pandemic. To address such issues, recent studies have reported transcriptomic profiles of cells, tissues and fluids from COVID-19 patients that mainly demonstrated activation of humoral immunity, dysregulated type I and III interferon expression, intense innate immune responses and inflammatory signaling. Here, we provide novel perspectives on the pathophysiology of COVID-19 using robust functional approaches to analyze public transcriptome datasets. In addition, we compared the transcriptional signature of COVID-19 patients with individuals infected with SARS-CoV-1 and Influenza A (IAV) viruses. We identified a core transcriptional signature induced by the respiratory viruses in peripheral leukocytes, whereas the absence of significant type I interferon/antiviral responses characterized SARS-CoV-2 infection. We also identified the higher expression of genes involved in metabolic pathways including heme biosynthesis, oxidative phosphorylation and tryptophan metabolism. A BTM-driven meta-analysis of bronchoalveolar lavage fluid (BALF) from COVID-19 patients showed significant enrichment for neutrophils and chemokines, which were also significant in data from lung tissue of one deceased COVID-19 patient. Importantly, our results indicate higher expression of genes related to oxidative phosphorylation both in peripheral mononuclear leukocytes and BALF, suggesting a critical role for mitochondrial activity during SARS-CoV-2 infection. Collectively, these data point for immunopathological features and targets that can be therapeutically exploited to control COVID-19.

In-depth blood proteome profiling analysis revealed distinct functional characteristics of plasma proteins between severe and non-severe COVID-19 patients

“…Specifically, a microarray-based study of SARS-CoV-2 infected a peripheral blood mononuclear cell (PMBC) and single cell analysis of epithelial and immune cells in COVID-19 patients revealed that the neutrophil markers were overexpressed, suggesting that the patients were under neutrophilia [9,10]. Furthermore, a meta-analysis based on gene network constructed from the published datasets derived several neutrophil-enriched genes [11]. Other articles have reported that neutrophils and their extracellular traps (Neutrophil extracellular traps, NETs) trigger COVID-19 [12,13].…”

Noncoding RNAs implication in cardiovascular diseases in the COVID-19 era

“…The reanalysis of a previously reported dataset identified, as expected, upregulated expression of chemokines and neutrophils in the lung tissue and bronchoalveolar lavage fluid of COVID-19 patients and, in addition, the upregulation of genes coordinating heme biosynthesis [ 135 ]. This effect, which has been shown in sepsis secondary to pneumonia to have a protective role against oxidative stress [ 136 ], could be responsible of pro-inflammatory cytokine production amplification [ 137 ] or cause intravascular coagulation [ 138 ].…”

Transcriptomic dysregulations associated with SARS-CoV-2 infection in human nasopharyngeal and peripheral blood mononuclear cells

“…This response was shown to be specific at the infection site, that likely reflect in complementary and systemic elements of immune response in the periphery, as indicated in this study. The infection by SARS-CoV-2 is marked by a systemic inflammatory response that affects various organs in different manners (Gardinassi et al, 2020). Although the elevated inflammatory response may be beneficial in fighting the infection, it may also lead to an over-production of pro-inflammatory cytokines that may cause damage to the olfactory epithelium, as well as adverse outcomes such as alveolar damage, respiratory failure and multiple organ dysfunction (Chen et al, 2017.;Huang et al, 2020;Xiong et al, 2020).…”