Association of Kidney Comorbidities and Acute Kidney Failure With Unfavorable Outcomes After COVID-19 in Individuals With the Sickle Cell Trait
Association of Kidney Comorbidities and Acute Kidney Failure With Unfavorable Outcomes After COVID-19 in Individuals With the Sickle Cell Trait
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DOI：
10.1001/jamainternmed.2022.2141
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发表时间：
2022-06-27
影响因子：
39
通讯作者：
Luoh, Shiuh-Wen
中科院分区：
文献类型：
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作者：
Verma, Anurag;Huffman, Jennifer E.;Luoh, Shiuh-Wen
重要性 镰状细胞性状 (SCT) 定义为存在 1 个血红蛋白 β 镰状等位基因 (rs3344) 和 1 个正常 β 等位基因，在数百万人中普遍存在，特别是在非洲和西班牙血统的个体中。然而，SCT 与 COVID-19 的关联尚不清楚。 目的 评估 SCT 与百万退伍军人计划 (MVP) 参与者大流行前健康状况的关联，并评估 COVID-19 的严重程度和后遗症。 设计、设置和参与者 COVID-19 临床数据包括 2729 名 SCT 患者，其中 353 人患有 COVID-19，以及 129 848 名 SCT 阴性个体，其中 13 488 人感染了 COVID-19。使用 firth 回归检查了 SCT 和 COVID-19 结果之间的关联。分析按血统进行，并根据性别、年龄、年龄平方和祖先主成分进行调整，以考虑人口分层。该研究的数据收集于 2020 年 3 月至 2021 年 2 月之间。暴露血红蛋白 β S (HbS) 等位基因 (rs334-T)。主要结果和措施本研究评估了源自世界卫生组织严重程度量表的 4 项 COVID-19 结果以及源自电子健康记录中的国际疾病分类代码的表型。结果 132 577 名 MVP 参与者中， COVID-19 数据，索引日期的平均 (SD) 年龄为 64.8 (13.1) 岁。 7.8% 的非洲血统个体存在镰状细胞特征，且与慢性肾病、糖尿病肾病、高血压肾病、肺栓塞和脑血管疾病病史相关。在 COVID-19 的 4 种临床结果中，SCT 与非洲血统个体的 COVID-19 死亡率增加相关（n = 3749；比值比，1.77；95% CI，1.13 至 2.77；P = .01）。在 COVID-19 发生后的 60 天内，SCT 与急性肾衰竭发病率增加有关。反事实中介框架估计，平均而言，SCT 对 COVID-19 死亡的总影响中有 20.7%（95% CI，-3.8% 至 56.0%）是由于急性肾衰竭所致。 结论和相关性 在这项遗传关联研究中，SCT 与先前存在的肾脏合并症有关。 COVID-19 死亡率和肾脏发病率增加。
IMPORTANCE Sickle cell trait (SCT), defined as the presence of 1 hemoglobin beta sickle allele (rs3344) 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.