ABSTRACT
Background: Chronic Kidney disease (CKD) is the risk factor that most increases the risk of lethal COVID-19. However, the underlying molecular mechanisms are unclear. CKD patients have an increased risk of multiple infections due to CKD-associated nonspecific immunodeficiency. Whether specific defects are related to the defense against SARS-CoV-2 is unknown. SARS-CoV-2 and coronavirus-associated receptors and factors (SCARFs) regulate coronavirus cell entry and/or replication. We hypothesized that CKD may alter the expression of SCARF genes. Method(s): A literature search identified 32 SARF genes of which 21 were directly related to SARS-CoV-2 or SARS-CoV infection and assessed their expression in target tissues of COVID-19 (kidneys, lungs, aorta and heart) in experimental CKD in mice fed adenine and compared them with controls. Result(s): Out of 21 SCARF genes, 19 (90%) were differentially expressed in at least one organ in CKD. 15 genes had a differential expression that would be expected to favor SARS-CoV-2 infection and/or severity in at least one organ. Of these, 13 were differentially expressed in the kidney. Only 2 genes reported to protect from SARS-CoV-2, Ifitm3 encoding interferon induced transmembrane protein 3 (IFITM3) and Ly6e encoding lymphocyte antigen 6 family member 6 (LY6E), were downregulated in at least two non-kidney target organs (lung and heart), potentially predisposing to more severe lung/ cardiovascular involvement in COVID-19 (Fig). The largest change was observed for Ifitm3. Conclusion(s): CKD is associated with the differential expression of multiple SCARF genes in target organs of COVID-19. The decreased expression of Ifitm3 and Ly6e in heart and/or lung may contribute to increase the severity of COVID-19 in CKD. These data may allow the development of interventions that decrease the risk of severe COVID-19 in CKD patients.