Abstract
Objective: Recently emerged beta-coronavirus SARS-CoV-2, has resulted in the current pandemic designated COVID-19. COVID-19 manifests as severe illness exhibiting systemic inflammatory response syndrome, acute respiratory distress syndrome (ARDS), thrombotic events, and shock, exacerbated further by co-morbidities and age. Recent clinical evidence suggests that the development of ARDS and subsequent pulmonary failure result from a complex interplay between cell types (endothelial, epithelial and immune) within the lung promoting inflammatory infiltration and a pro-coagulative state. How the complex molecular events mediated by SARS-CoV-2 in infected lung epithelial cells lead to thrombosis and pulmonary failure, is yet to be fully understood. Methods: We address these questions here, using publicly available transcriptomic data in the context of lung epithelia affected by SARS-CoV-2 and other respiratory infections, in vitro. We then extend our results to the understanding of in vivo lung, using a publicly available COVID-19 lung transcriptomic study. Results and Conclusions: Our analysis indicates that there exists a complex interplay between the fibrinolytic system particularly plasmin, and the complement and platelet-activating systems upon SARS-CoV-2 infection, with a potential for therapeutic intervention.
Highlights
Recent studies [1], [2] have rapidly provided molecular insights into the pathogenicity of the SARS-CoV-2, mainly at the level of genomic, structural, and functional aspects of viral-host interactions
IMPACT STATEMENT Why does COVID-19 lead to thrombotic complications in critically ill patients? We address this question by reconstructing mechanisms unique to COVID-19, from lung-epithelial transcriptional data, leading to potential therapeutic interventions
COMPARING THE SARS-COV-2 TRANSCRIPTOMIC PROFILE WITH OTHER UPPER-RESPIRATORY TRACT INFECTIONS In this study, we utilized publicly available RNA-sequencing data [5] (GSE100457) from Normal Human Bronchial Epithelial (NHBE) cell lines infected with SARS-CoV-2 and compared it with lung epithelial cells infected with other respiratory infections, namely, respiratory syncytial virus (RSV), influenza (H1N1), and rhinovirus (RV16) using stringent study inclusion criterion
Summary
Recent studies [1], [2] have rapidly provided molecular insights into the pathogenicity of the SARS-CoV-2, mainly at the level of genomic, structural, and functional aspects of viral-host interactions. Studies have identified key pathophysiological and molecular events associated with infection pathogenesis and progression of COVID-19 including thrombocytopenia, lymphopenia, eosinophilia, and elevated lactate dehydrogenase and fibrinogen [3], [4]. Serine protease (TMPRSS2) [13], [14], contributing to the increased transmissibility and lower-lung pathogenicity in humans [15]. This observation led us to explore mechanisms unique to SARS-CoV-2 infection of lung epithelial cells and cause thrombotic events
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