Lumish Heidi S, Kim Eunyoung, Selvaggi Caitlin, Cao Tingyi, Gupta Aakriti, Foulkes Andrea S, Reilly Muredach P
Division of Cardiology, Columbia University, New York, NY, United States.
Biostatistics Center, Massachusetts General Hospital, Boston, MA, United States.
Front Cardiovasc Med. 2022 Apr 25;9:809997. doi: 10.3389/fcvm.2022.809997. eCollection 2022.
Studies examining outcomes among individuals with COronaVIrus Disease 2019 (COVID-19) have consistently demonstrated that men have worse outcomes than women, with a higher incidence of myocardial injury, respiratory failure, and death. However, mechanisms of higher morbidity and mortality among men remain poorly understood. We aimed to identify mediators of the relationship between sex and COVID-19-associated mortality.
Patients hospitalized at two quaternary care facilities, New York Presbyterian Hospital (CUIMC/NYPH) and Massachusetts General Hospital (MGH), for SARS-CoV-2 infection between February and May 2020 were included. Five independent biomarkers were identified as mediators of sex effects, including high-sensitivity cardiac troponin T (hs-cTNT), high sensitivity C-reactive protein (hs-CRP), ferritin, D-dimer, and creatinine.
In the CUIMC/NYPH cohort ( = 2,626, 43% female), male sex was associated with significantly greater mortality (26 vs. 21%, = 0.0146) and higher peak hs-cTNT, hs-CRP, ferritin, D-dimer, and creatinine ( < 0.001). The effect of male sex on the primary outcome of death was partially mediated by peak values of all five biomarkers, suggesting that each pathophysiological pathway may contribute to increased risk of death in men. Hs-cTnT, creatinine, and hs-CRP were the strongest mediators. Findings were highly consistent in the MGH cohort with the exception of D-dimer.
This study suggests that the effect of sex on COVID-19 outcomes is mediated by cardiac and kidney injury, as well as underlying differences in inflammation and iron metabolism. Exploration of these specific pathways may facilitate sex-directed diagnostic and therapeutic strategies for patients with COVID-19 and provides a framework for the study of sex differences in other complex diseases.
对2019冠状病毒病（COVID-19）患者预后的研究一致表明，男性的预后比女性差，心肌损伤、呼吸衰竭和死亡的发生率更高。然而，男性发病率和死亡率较高的机制仍知之甚少。我们旨在确定性别与COVID-19相关死亡率之间关系的介导因素。
纳入2020年2月至5月期间在纽约长老会医院（CUIMC/NYPH）和马萨诸塞州总医院（MGH）这两家四级医疗机构因感染严重急性呼吸综合征冠状病毒2（SARS-CoV-2）而住院的患者。确定了五种独立的生物标志物作为性别效应的介导因素，包括高敏心肌肌钙蛋白T（hs-cTNT）、高敏C反应蛋白（hs-CRP）、铁蛋白、D-二聚体和肌酐。
在CUIMC/NYPH队列（n = 2626，43%为女性）中，男性的死亡率显著更高（26%对21%，P = 0.0146），且hs-cTNT、hs-CRP、铁蛋白、D-二聚体和肌酐的峰值更高（P < = 0.001）。男性性别对主要死亡结局的影响部分由所有五种生物标志物的峰值介导，这表明每条病理生理途径可能都导致男性死亡风险增加。Hs-cTnT、肌酐和hs-CRP是最强的介导因素。除D-二聚体外，在MGH队列中的研究结果高度一致。
本研究表明，性别对COVID-19结局的影响是由心脏和肾脏损伤以及炎症和铁代谢的潜在差异介导的。对这些特定途径的探索可能有助于为COVID-19患者制定针对性别的诊断和治疗策略，并为研究其他复杂疾病中的性别差异提供框架。
