Organ-specific or personalized treatment for COVID-19: rationale, evidence, and potential candidates

Although extrapulmonary manifestations of coronavirus disease 2019 (COVID-19) are increasingly reported, no effective therapeutic strategy for these multisystemic complications is available due to a poor understanding of the pathophysiology of COVID-19 multiorgan involvement. In this study, differentially expressed genes (DEGs) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected extrapulmonary organs including human pluripotent stem cells (hPSCs)-derived liver organoids and choroid plexus organoids besides transformed lung alveolar (A549) cells were analyzed. First, pathway enrichment analysis was done to compare the underlying biological pathways enriched upon SARS-CoV-2 infection in different organs. Then, these lists of DEGs were used in a connectivity map (CMap)-based drug repurposing experiment. Also, protein-protein interaction (PPI) network analysis was done to compare the associated hub genes. The results revealed different biological pathways and genes responsible for SARS-CoV-2 multisystemic pathogenesis based on the organ involved that highlighted the need for considering organ-specific treatments or even personalized therapy. Besides, some FDA-approved drugs were proposed as the potential therapeutic candidates for each infected cell line.