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Abstract
Background and Purpose: COVID-19 has become the ongoing public health crisis of our time. Although it was first presented as a respiratory infection, extrapulmonary manifestations are increasingly reported. However, no effective therapeutic strategy for COVID-19 extrapulmonary involvement is currently available. The current study aims to analyze the pathogenesis of COVID-19 extrapulmonary complications to evaluate the rationale for proposing organ-specific treatment as a novel therapeutic strategy to manage these multisystemic complications.
Experimental Approach: In this study, differentially expressed genes (DEGs) of SARS-CoV-2 infected extrapulmonary organs including human pluripotent stem cells (hPSCs)-derived liver organoids, hPSCs-derived pancreatic endocrine cells, and human-induced pluripotent stem cells (hiPSCs)-derived choroid plexus organoids were analyzed. First, pathway enrichment analysis is done based on the identified DEGs to compare the underlying biological pathways enriched upon SARS-CoV-2 infection in different organs to confirm the need for developing organ-specific treatment strategies. Then, these lists of DEGs are used in a connectivity map-based drug repurposing experiment to propose novel organ-specific therapeutic options.
Key Results: The results reveal different biological pathways and networks responsible for SARS-CoV-2 multisystemic pathogenesis based on the organ involved that highlight the need for considering organ-specific treatments. Besides, some FDA-approved drugs are proposed as the potential therapeutic candidates for each infected cell line.
Conclusion and Implications: Although COVID-19 extrapulmonary manifestations are increasing, management of these complications is still challenging. Traditional therapeutic strategies and already repurposed antiviral agents are not effective. In this situation, organ-specific treatment, or in other words personalized therapy might be a promising solution.
