Association of Kidney Comorbidities and Acute Kidney Failure with Unfavorable Outcomes after COVID-19 in Individuals with the Sickle Cell Trait

Anurag Verma, Jennifer E. Huffman, Lina Gao, Jessica Minnier, Wen Chih Wu, Kelly Cho, Yuk Lam Ho, Bryan R. Gorman, Saiju Pyarajan, Nallakkandi Rajeevan, Helene Garcon, Jacob Joseph, John E. McGeary, Ayako Suzuki, Peter D. Reaven, Emily S. Wan, Julie A. Lynch, Jeffrey M. Petersen, James B. Meigs, Matthew S. FreibergElise Gatsby, Kristine E. Lynch, Seyedeh Maryam Zekavat, Pradeep Natarajan, Sharvari Dalal, Darshana N. Jhala, Mehrdad Arjomandi, Robert A. Bonomo, Trevor K. Thompson, Gita A. Pathak, Jin J. Zhou, Curtis J. Donskey, Ravi K. Madduri, Quinn S. Wells, Joel Gelernter, Rose D.L. Huang, Renato Polimanti, Kyong Mi Chang, Katherine P. Liao, Philip S. Tsao, Yan V. Sun, Peter W.F. Wilson, Christopher J. O'Donnell, Adriana M. Hung, J. Michael Gaziano, Richard L. Hauger, Sudha K. Iyengar, Shiuh Wen Luoh

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Importance: Sickle cell trait (SCT), defined as the presence of 1 hemoglobin beta sickle allele (rs334-T) and 1 normal beta allele, is prevalent in millions of people in the US, particularly in individuals of African and Hispanic ancestry. However, the association of SCT with COVID-19 is unclear. Objective: To assess the association of SCT with the prepandemic health conditions in participants of the Million Veteran Program (MVP) and to assess the severity and sequelae of COVID-19. Design, Setting, and Participants: COVID-19 clinical data include 2729 persons with SCT, of whom 353 had COVID-19, and 129848 SCT-negative individuals, of whom 13488 had COVID-19. Associations between SCT and COVID-19 outcomes were examined using firth regression. Analyses were performed by ancestry and adjusted for sex, age, age squared, and ancestral principal components to account for population stratification. Data for the study were collected between March 2020 and February 2021. Exposures: The hemoglobin beta S (HbS) allele (rs334-T). Main Outcomes and Measures: This study evaluated 4 COVID-19 outcomes derived from the World Health Organization severity scale and phenotypes derived from International Classification of Diseases codes in the electronic health records. Results: Of the 132577 MVP participants with COVID-19 data, mean (SD) age at the index date was 64.8 (13.1) years. Sickle cell trait was present in 7.8% of individuals of African ancestry and associated with a history of chronic kidney disease, diabetic kidney disease, hypertensive kidney disease, pulmonary embolism, and cerebrovascular disease. Among the 4 clinical outcomes of COVID-19, SCT was associated with an increased COVID-19 mortality in individuals of African ancestry (n = 3749; odds ratio, 1.77; 95% CI, 1.13 to 2.77; P =.01). In the 60 days following COVID-19, SCT was associated with an increased incidence of acute kidney failure. A counterfactual mediation framework estimated that on average, 20.7% (95% CI, -3.8% to 56.0%) of the total effect of SCT on COVID-19 fatalities was due to acute kidney failure. Conclusions and Relevance: In this genetic association study, SCT was associated with preexisting kidney comorbidities, increased COVID-19 mortality, and kidney morbidity..

Original languageEnglish (US)
Pages (from-to)796-804
Number of pages9
JournalJAMA internal medicine
Issue number8
StatePublished - Aug 2022

ASJC Scopus subject areas

  • Internal Medicine


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