Abstract
Severe novel corona virus disease 2019 (COVID-19) infection is associated with a considerable activation of coagulation pathways, endothelial damage, and subsequent thrombotic microvascular injuries. These consistent observations may have serious implications for the treatment and management of this highly pathogenic disease. As a consequence, the anticoagulant therapeutic strategies, such as low molecular weight heparin, have shown some encouraging results. Cytokine burst leading to sepsis which is one of the primary reasons for acute respiratory distress syndrome (ARDS) drive that could be worsened with the accumulation of coagulation factors in the lungs of COVID-19 patients. However, the obscurity of this syndrome remains a hurdle in making decisive treatment choices. Therefore, an attempt to characterize shared biological mechanisms between ARDS and thrombosis using comprehensive transcriptomics meta-analysis is made. We conducted an integrated gene expression meta-analysis of two independently publicly available datasets of ARDS and venous thromboembolism (VTE). Datasets GSE76293 and GSE19151 derived from National Centre for Biotechnology Information–Gene Expression Omnibus (NCBI-GEO) database were used for ARDS and VTE, respectively. Integrative meta-analysis of expression data (INMEX) tool preprocessed the datasets and effect size combination with random effect modeling was used for obtaining differentially expressed genes (DEGs). Network construction was done for hub genes and pathway enrichment analysis. Our meta-analysis identified a total of 1,878 significant DEGs among the datasets, which when subjected to enrichment analysis suggested inflammation–coagulation–hypoxemia convolutions in COVID-19 pathogenesis. The top hub genes of our study such as tumor protein 53 (TP53), lysine acetyltransferase 2B (KAT2B), DExH-box helicase 9 (DHX9), REL-associated protein (RELA), RING-box protein 1 (RBX1), and proteasome 20S subunit beta 2 (PSMB2) gave insights into the genes known to be participating in the host–virus interactions that could pave the way to understand the various strategies deployed by the virus to improve its replication and spreading.
Highlights
The comprehensive understanding of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pathogenesis, responsible for the novel coronavirus disease 2019 (COVID-19)outbreak, is important for its management but will take cognizance of the other members of the coronavirus family that have the potential of such outbreaks in future
Our meta-analysis identified a total of 1,878 significant differentially expressed genes (DEG) among the datasets, which when subjected to enrichment analysis suggested inflammation–coagulation–hypoxemia convolutions in COVID-19 pathogenesis
This abnormality in blood coagulation proteins increases the propensities of venous thromboembolism (VTE), a secondary complication to several diseases including cancers and viral infections such as SARSCoV-2.4 Consistent observations of Acute respiratory distress syndrome (ARDS) associated with thrombosis in severe COVID-19 patients may have serious implications for treatment and management
Summary
The comprehensive understanding of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pathogenesis, responsible for the novel coronavirus disease 2019 (COVID-19)outbreak, is important for its management but will take cognizance of the other members of the coronavirus family that have the potential of such outbreaks in future. ARDS is a build-up of noncardiogenic pulmonary edema resulting in hypoxemia in the vital organs of the body It is a life-threatening condition that is always associated with a heterogeneous mix of other existing health problems such as sepsis.[7] Though ARDS in COVID-19 is received with a debate among the scientific community,[8,9] still its occurrence along with the endothelial injury in the severe COVID-19 patients cannot be overlooked.[10] Perhaps, the endothelial injury as a result of SARS-CoV-2 infection might have a major role in the development of VTE, as well as ARDS.[11] it becomes pertinent to ascertain the intrinsic factors responsible for ARDS and thrombotic events in the case of COVID-19 as it is clear that these complications coexist relatedly. This will aid in delineating the deregulated pathways driving COVID-19 pathophysiology that could further help in deriving standard laboratory tests and targeted therapeutic interventions
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