Abstract: FR-PO014
CKD Results in Differential Expression of SCARF Genes That Potentially Facilitate SARS-CoV-2 Cell Entry and/or Replication
Session Information
- COVID-19: AKI Outcomes, Biomarkers, Treatments, Case Reports
November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Coronavirus (COVID-19)
- 000 Coronavirus (COVID-19)
Authors
- Carriazo, Sol Maria, Hospital Universitario Fundacion Jimenez Diaz, Madrid, Madrid, Spain
- Ribagorda, Marta, Instituto de Investigacion Sanitaria de la Fundacion Jimenez Diaz, Madrid, Madrid, Spain
- Pintor Chocano, Aranzazu, Instituto de Investigacion Sanitaria de la Fundacion Jimenez Diaz, Madrid, Madrid, Spain
- Ortiz, Alberto, Hospital Universitario Fundacion Jimenez Diaz, Madrid, Madrid, Spain
- Sanchez-Nino, Maria Dolores, Instituto de Investigacion Sanitaria de la Fundacion Jimenez Diaz, Madrid, Madrid, Spain
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 non-specific 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.
Methods
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.
Results
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
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.