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Abstract: PO0015

Renal Comorbidities and New Acute Kidney Failure Drive Unfavorable Outcomes Among COVID-19-Positive Sickle Cell Trait Carriers

Session Information

Category: Coronavirus (COVID-19)

  • 000 Coronavirus (COVID-19)

Authors

  • Iyengar, Sudha K., Louis Stokes Cleveland VA Medical Center, Cleveland, Ohio, United States
  • Minnier, Jessica, Biostatistics Shared Resource, Knight Cancer Institute, Oregon Health and Science University, Portland, Portland, Oregon, United States
  • Verma, Anurag, Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Luoh, Shiuh-Wen, Division of Hematology and Medical Oncology, Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon, United States

Group or Team Name

  • Million Veteran Program COVID-19 Disease Mechanisms Working Group
Background

The sickle cell trait (SCT) in the hemoglobin beta gene (HbS; rs334) affects millions of Americans, especially African Americans (AA; minor allele frequency [MAF]=7.8%) and Hispanic Americans (HA; MAF=1%). We investigated the impact of SCT on the severity and sequelae of COVID-19 infection in the Million Veteran Program (MVP). Pre-COVID diseases and laboratory findings present in electronic health records (EHR), as well as acute events following 60 days of COVID-19 infection, and their effect on COVID-19 mortality among SCT patients were examined.

Methods

COVID-19 clinical data on genotyped MVP participants (SCT+ = 2,729, SCT-= 129,848; COVID+=13,841, COVID-=118,736) was extracted from EHR. Outcomes analyzed were: severe disease (or mortality) vs. not severe (or survival). Ethnic-specific firth logistic regression for SCT was performed on European (EA), African (AA), Hispanic (HA) and Asian (ASA) groups, adjusting for sex, age, age2, and 20 genetic principal components. Ethnic-specific phenome-wide association (PheWAS and LabWAS) for SCT captured 20+ years of comorbidities and historical laboratory values and was used to contrast effects of COVID-19. Multiple testing corrections were applied.

Results

HbS is associated with increased COVID-19 mortality in AA (N=3,749; OR=1.8 [1.14-2.84], p=0.01) with a similar trend in HA. PheWAS revealed significant associations of rs334 with phecodes for pulmonary embolism, chronic renal disease, diabetic kidney disease, hypertensive renal disease, gout, sickle cell disease/trait, and hemolytic anemia (FDR p < 0.1). After adjusting for SCT, past renal disease was significantly associated with higher COVID-19 deaths among AA. Increased incidence of acute kidney failure (AKF) and chronic kidney disease (CKD) were seen within 60 days of infection with COVID-19. We estimated direct and indirect effects of AKF or CKD in AA SCT carriers via a mediation framework. On average 20.7% (95% CI: 3.8% - 56.0%) of the total effect of SCT on COVID-19 death was found to be mediated through AKF, and that for CKD was 12.4% (95% CI: 0% - 63%).

Conclusion

SCT is associated with an elevated risk of mortality with COVID-19 infection. Both pre-existing chronic medical conditions and new acute events after COVID-19 may contribute to adverse COVID-19 outcomes with SCT.

Funding

  • Veterans Affairs Support