Browsing by Subject "Sickle cell trait"

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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
    (American Medical Association, 2022) Verma, Anurag; Huffman, Jennifer E.; Gao, Lina; Minnier, Jessica; Wu, Wen-Chih; Cho, Kelly; Ho, Yuk-Lam; Gorman, Bryan R.; Pyarajan, Saiju; Rajeevan, Nallakkandi; Garcon, Helene; Joseph, Jacob; McGeary, John E.; Suzuki, Ayako; Reaven, Peter D.; Wan, Emily S.; Lynch, Julie A.; Petersen, Jeffrey M.; Meigs, James B.; Freiberg, Matthew S.; Gatsby, Elise; Lynch, Kristine E.; Zekavat, Seyedeh Maryam; Natarajan, Pradeep; Dalal, Sharvari; Jhala, Darshana N.; Arjomandi, Mehrdad; Bonomo, Robert A.; Thompson, Trevor K.; Pathak, Gita A.; Zhou, Jin J.; Donskey, Curtis J.; Madduri, Ravi K.; Wells, Quinn S.; Gelernter, Joel; Huang, Rose D. L.; Polimanti, Renato; Chang, Kyong-Mi; Liao, Katherine P.; Tsao, Philip S.; Sun, Yan V.; Wilson, Peter W. F.; O'Donnell, Christopher J.; Hung, Adriana M.; Gaziano, J. Michael; Hauger, Richard L.; Iyengar, Sudha K.; Luoh, Shiuh-Wen; VA Million Veteran Program COVID-19 Science Initiative; Medicine, School of Medicine
    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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    Sickle cell trait and risk of cognitive impairment in African-Americans: The REGARDS cohort
    (Elsevier, 2019-05-24) Cahill, Christina R.; Leach, Justin M.; McClure, Leslie A.; Irvin, Marguerite Ryan; Zakai, Neil A.; Naik, Rakhi; Unverzagt, Frederick; Wadley, Virginia G.; Hyacinth, Hyacinth I.; Manly, Jennifer; Judd, Suzanne E.; Winkler, Cheryl; Cushman, Mary; Psychiatry, School of Medicine
    Background: Sickle cell anemia may be associated with cognitive dysfunction, and some complications of sickle cell anemia might affect those with sickle cell trait (SCT), so we hypothesized that SCT is a risk factor for cognitive impairment. Methods: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) study enrolled a national cohort of 30,239 white and black Americans from 2003 to 7, who are followed every 6 months. Baseline and annual global cognitive function testing used the Six-Item Screener (SIS), a validated instrument (scores range 0-6; ≤ 4 indicates cognitive impairment). Participants with baseline cognitive impairment and whites were excluded. Logistic regression was used to calculate the association of SCT with incident cognitive impairment, adjusted for risk factors. Linear mixed models assessed multivariable-adjusted change in test scores on a biennially administered 3-test battery measuring learning, memory, and semantic and phonemic fluency. Findings: Among 7743 participants followed for a median of 7·1 years, 85 of 583 participants with SCT (14·6%) developed incident cognitive impairment compared to 902 of 7160 (12·6%) without SCT. In univariate analysis, the odds ratio (OR) of incident cognitive impairment was 1·18 (95% CI: 0·93, 1·51) for those with SCT vs. those without. Adjustment did not impact the OR. There was no difference in change on 3-test battery scores by SCT status (all p > 0·11). Interpretation: In this prospective cohort study of black Americans, SCT was not associated with incident cognitive impairment or decline in test scores of learning, memory and executive function. Funding: National Institutes of Health, American Society of Hematology.