TY - JOUR
T1 - Association of Kidney Comorbidities and Acute Kidney Failure with Unfavorable Outcomes after COVID-19 in Individuals with the Sickle Cell Trait
AU - Verma, Anurag
AU - Huffman, Jennifer E.
AU - Gao, Lina
AU - Minnier, Jessica
AU - Wu, Wen Chih
AU - Cho, Kelly
AU - Ho, Yuk Lam
AU - Gorman, Bryan R.
AU - Pyarajan, Saiju
AU - Rajeevan, Nallakkandi
AU - Garcon, Helene
AU - Joseph, Jacob
AU - McGeary, John E.
AU - Suzuki, Ayako
AU - Reaven, Peter D.
AU - Wan, Emily S.
AU - Lynch, Julie A.
AU - Petersen, Jeffrey M.
AU - Meigs, James B.
AU - Freiberg, Matthew S.
AU - Gatsby, Elise
AU - Lynch, Kristine E.
AU - Zekavat, Seyedeh Maryam
AU - Natarajan, Pradeep
AU - Dalal, Sharvari
AU - Jhala, Darshana N.
AU - Arjomandi, Mehrdad
AU - Bonomo, Robert A.
AU - Thompson, Trevor K.
AU - Pathak, Gita A.
AU - Zhou, Jin J.
AU - Donskey, Curtis J.
AU - Madduri, Ravi K.
AU - Wells, Quinn S.
AU - Gelernter, Joel
AU - Huang, Rose D.L.
AU - Polimanti, Renato
AU - Chang, Kyong Mi
AU - Liao, Katherine P.
AU - Tsao, Philip S.
AU - Sun, Yan V.
AU - Wilson, Peter W.F.
AU - O'Donnell, Christopher J.
AU - Hung, Adriana M.
AU - Gaziano, J. Michael
AU - Hauger, Richard L.
AU - Iyengar, Sudha K.
AU - Luoh, Shiuh Wen
N1 - Funding Information:
other (consulting) from Pfizer unrelated to COVID-19 outside the submitted work. Dr Lynch reports grants from Janssen Pharmaceuticals Inc outside the submitted work. Dr Natarajan reports grant support from Amgen, Apple, AstraZeneca, Boston Scientific, and Novartis; personal fees from Apple, AstraZeneca, Blackstone Life Sciences, Foresite Labs, Genentech/Roche, Novartis, and TenSixteen Bio; holding equity in TenSixteen Bio and Genexwell; and spousal employment at Vertex; all outside the submitted work. Dr Arjomandi reports salary support from US Department of Veterans Affairs during the conduct of the study; and grants from the Departments of Defense (W81XWH-20-1-0158) and Veterans Affairs (CXV-00125), the Flight Attendant Medical Research Institute (012500WG and CIA190001), and the California Tobacco-related Disease Research Program (T29IR0715) during the conduct of the study; and received research support from Guardant Health and Genentech. Mr Thompson reports grants from Vanderbilt University Medical Center Vanderbilt Medical Scholar during the conduct of the study. Dr O’Donnell is an employee of Novartis Institute for Biomedical Research. Dr Hung reports grants from Veterans Health Administration (CSR&D MVP Merit 5I01CX001897 Genetics of CKD and Hypertension—Risk Prediction and Drug Response in the MVP) and grants from MVP COVID-19 Science Program (MVP035) during the conduct of the study; and grants from Vertex to Vanderbilt University Medical Center outside the submitted work. No other disclosures were reported.
Funding Information:
from the Million Veteran Program, Office of Research and Development, Veterans Health Administration, and was supported by the MVP035 award and VA Grant BX 004831 (Drs Wilson and Cho).
Publisher Copyright:
© 2022 American Medical Association. All rights reserved.
PY - 2022/8
Y1 - 2022/8
N2 - 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..
AB - 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..
UR - http://www.scopus.com/inward/record.url?scp=85133434283&partnerID=8YFLogxK
U2 - 10.1001/jamainternmed.2022.2141
DO - 10.1001/jamainternmed.2022.2141
M3 - Article
C2 - 35759254
AN - SCOPUS:85133434283
SN - 2168-6106
VL - 182
SP - 796
EP - 804
JO - JAMA Internal Medicine
JF - JAMA Internal Medicine
IS - 8
ER -