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Association of Kidney Comorbidities and Acute Kidney Failure With Unfavorable Outcomes After COVID-19 in Individuals With the Sickle Cell Trait.

Publication ,  Journal Article
Verma, A; Huffman, JE; Gao, L; Minnier, J; Wu, W-C; Cho, K; Ho, Y-L; Gorman, BR; Pyarajan, S; Rajeevan, N; Garcon, H; Joseph, J; McGeary, JE ...
Published in: JAMA Intern Med
August 1, 2022

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 129 848 SCT-negative individuals, of whom 13 488 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 132 577 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.

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Published In

JAMA Intern Med

DOI

EISSN

2168-6114

Publication Date

August 1, 2022

Volume

182

Issue

8

Start / End Page

796 / 804

Location

United States

Related Subject Headings

  • Sickle Cell Trait
  • Kidney
  • Humans
  • Hemoglobins
  • COVID-19
  • Black or African American
  • Acute Kidney Injury
  • 4203 Health services and systems
  • 3202 Clinical sciences
  • 1117 Public Health and Health Services
 

Citation

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Verma, A., Huffman, J. E., Gao, L., Minnier, J., Wu, W.-C., Cho, K., … VA Million Veteran Program COVID-19 Science Initiative, . (2022). Association of Kidney Comorbidities and Acute Kidney Failure With Unfavorable Outcomes After COVID-19 in Individuals With the Sickle Cell Trait. JAMA Intern Med, 182(8), 796–804. https://doi.org/10.1001/jamainternmed.2022.2141
Verma, Anurag, Jennifer E. Huffman, Lina Gao, Jessica Minnier, Wen-Chih Wu, Kelly Cho, Yuk-Lam Ho, et al. “Association of Kidney Comorbidities and Acute Kidney Failure With Unfavorable Outcomes After COVID-19 in Individuals With the Sickle Cell Trait.JAMA Intern Med 182, no. 8 (August 1, 2022): 796–804. https://doi.org/10.1001/jamainternmed.2022.2141.
Verma A, Huffman JE, Gao L, Minnier J, Wu W-C, Cho K, et al. Association of Kidney Comorbidities and Acute Kidney Failure With Unfavorable Outcomes After COVID-19 in Individuals With the Sickle Cell Trait. JAMA Intern Med. 2022 Aug 1;182(8):796–804.
Verma, Anurag, et al. “Association of Kidney Comorbidities and Acute Kidney Failure With Unfavorable Outcomes After COVID-19 in Individuals With the Sickle Cell Trait.JAMA Intern Med, vol. 182, no. 8, Aug. 2022, pp. 796–804. Pubmed, doi:10.1001/jamainternmed.2022.2141.
Verma A, Huffman JE, Gao L, Minnier J, Wu W-C, Cho K, Ho Y-L, Gorman BR, Pyarajan S, Rajeevan N, Garcon H, Joseph J, McGeary JE, Suzuki A, Reaven PD, Wan ES, Lynch JA, Petersen JM, Meigs JB, Freiberg MS, Gatsby E, Lynch KE, Zekavat SM, Natarajan P, Dalal S, Jhala DN, Arjomandi M, Bonomo RA, Thompson TK, Pathak GA, Zhou JJ, Donskey CJ, Madduri RK, Wells QS, Gelernter J, Huang RDL, Polimanti R, Chang K-M, Liao KP, Tsao PS, Sun YV, Wilson PWF, O’Donnell CJ, Hung AM, Gaziano JM, Hauger RL, Iyengar SK, Luoh S-W, VA Million Veteran Program COVID-19 Science Initiative. Association of Kidney Comorbidities and Acute Kidney Failure With Unfavorable Outcomes After COVID-19 in Individuals With the Sickle Cell Trait. JAMA Intern Med. 2022 Aug 1;182(8):796–804.

Published In

JAMA Intern Med

DOI

EISSN

2168-6114

Publication Date

August 1, 2022

Volume

182

Issue

8

Start / End Page

796 / 804

Location

United States

Related Subject Headings

  • Sickle Cell Trait
  • Kidney
  • Humans
  • Hemoglobins
  • COVID-19
  • Black or African American
  • Acute Kidney Injury
  • 4203 Health services and systems
  • 3202 Clinical sciences
  • 1117 Public Health and Health Services