Genetic Findings in COVID19-Positive Patients from a Cohort of Kidney and Liver Patients at Columbia University

Background: Patients with preexisting chronic kidney (CKD) and liver disease and liver are more at risk from COVID-19, but reasons for variability in disease susceptibility and severity is still poorly understood. Given the high infection rate in New York City, we conducted a COVID-19 assessment survey in a cohort of CKD and liver patients previously consented into genetic studies. Methods: Between March and August 2020, we completed 1601 unique IRBapproved COVID-19 assessment surveys. The survey covered COVID-19 symptoms, exposure risk, PCR and/or serology testing, and hospitalization. 298 of those patients were exome sequenced. We analyzed differences in COVID-19 PCR, serology and hospitalization rate and genetic analysis to identify possibly associated variants in the immune/coagulation pathways, suggested to be involved in COVID-19 susceptibility/ severity by recent publicationw. We also analyzed variants based on the American College of Medical Genetics and Genomics (ACMG) guidelines for clinical annotation of genetic results Results: Hispanic/Latino patients were more likely to have a positive COVID-19 PCR (Fisher Exact Test p: 0.01, 29.5% vs 16.7%), serology (Fisher Exact Test p: 0.02, 22.9% vs 9.7%) and hospitalization (Fisher Exact Test p: 0.01, 29.5% vs 16.7%). Patients with glomerulopathy had lower positive COVID-19 PCR tests (Fisher Exact Test p: 0.01, 14.7% vs 48.7%). Analysis of exome data identified an excess number of rare variants in genes in the immune dysregulation pathways among patients with positive COVID-19 PCR test, (fisher p: 0.01, 75% vs 18%). These results were mostly driven by rare variants in CASP10, which were more common among the Hispanic/Latino population. Conclusions: We confirm that Hispanic/Latino ethnicity is a significant risk factor for positive COVID-19 PCR, serology and hospitalization. The analysis of the genetic mechanisms in immune/coagulation pathways identified an excess of rare variants in the CASP10 gene, results that overlap with Hispanic/Latino ethnicity.