Genetic Determinants of Renal Complications of COVID-19

Simone Sanna-Cherchi, Florence Irving Assistant Professor of Medicine

Patients with COVID-19 have high prevalence of renal complications, including acute kidney injury (AKI), proteinuria, and, more recently described, glomerulonephritis (collapsing FSGS). Proteinuria is also a marker of severity and an indicator of the inflammatory storm in COVID-19.

We have conducted large-scale GWAS for common variants, and exome/genome sequencing rare-variant collapsing analyses in proteinuric kidney disease (focal segmental glomerulosclerosis, FSGS; and minimal change disease, MCD), and identified multiple novel significant and suggestive loci and genes. Transcriptomic analysis of tissues from COVID-19 patients and co-expression studies point to multiple genes involved in the pathogenesis of FSGS/MCD (from previous and our studies, including APOL1), as differentially regulated by SARS-CoV-2.

Here we plan to conduct comprehensive genetic studies for common and rare variants in the NYP/Columbia COVID-19 biobank and aggregate data with collaborating Institutions in the US and Europe. We will benefit from our unique cohorts of thousands of patients with proteinuric kidney disease already subjected to GWAS and exome/genome sequencing for dissecting the genetic architecture of proteinuria in the context of COVID-19 disease. The identification of variants and genes associated to proteinuria and kidney disease in COVID-19 holds the promises to shed light on the renal and podocyte response to viral infection from SARS-CoV-2 and at large, but also to identify genes and variants that are linked to the severity of COVID-19, of which proteinuria is a marker. These studies are therefore poised to identify novel potential targets for intervention.