Long Covid发病、症状持续和缓解的性别差异和免疫相关性

IF 15.8 1区 医学 Q1 CELL BIOLOGY
Rebecca E. Hamlin, Shaun M. Pienkos, Leslie Chan, Mikayla A. Stabile, Kassandra Pinedo, Mallika Rao, Philip Grant, Hector Bonilla, Marisa Holubar, Upinder Singh, Karen B. Jacobson, Prasanna Jagannathan, Yvonne Maldonado, Susan P. Holmes, Aruna Subramanian, Catherine A. Blish
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引用次数: 0

摘要

在急性冠状病毒病2019年最新注册送彩金(COVID-19)和Long Covid(LC)结果中观察到了性别差异,男性在急性感染期间的疾病严重程度和死亡率更高,而女性患LC的比例更高。我们假设,性别特异性免疫失调是导致LC发病的原因之一。为了研究 LC 发病和症状持续存在的免疫学基础,我们对严重急性呼吸系统综合征冠状病毒 2(SARS-CoV-2)急性感染期间以及感染后 3 个月和 12 个月获得的血液样本进行了多组学分析,这些样本包括 45 名患 LC 或已康复的参与者。几种性别特异性免疫途径与 LC 相关。后来患上 LC 的男性在急性感染期间表现出转化生长因子-β(TGF-β)信号转导增加,而后来患上 LC 的女性则表现出 TGFB1 表达减少。与康复的女性相比,患 LC 的女性在急性感染期间体内与自身免疫有关的 RNA 基因 XIST 的表达增加。LC 的许多免疫特征在不同性别间也是一致的,如单核细胞表型和活化状态的改变。在急性期和康复期,许多细胞类型的核因子κB(NF-κB)转录因子上调。淋巴细胞亚群中的ETS1表达减少,T细胞亚群中细胞内IL-4升高,这表明ETS1的改变可能会驱动淋巴瘤中T辅助细胞2样反应的异常升高。总之,这项研究描述了 LC 的多种先天性和适应性免疫相关性,其中一些相关性因性别而异,并为寻求有针对性的疗法提供了启示。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Sex differences and immune correlates of Long Covid development, symptom persistence, and resolution
Sex differences have been observed in acute coronavirus disease 2019 (COVID-19) and Long Covid (LC) outcomes, with greater disease severity and mortality during acute infection in males and greater proportions of females developing LC. We hypothesized that sex-specific immune dysregulation contributes to LC pathogenesis. To investigate the immunologic underpinnings of LC development and symptom persistence, we performed multiomic analyses on blood samples obtained during acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and 3 and 12 months after infection in a cohort of 45 participants who either developed LC or recovered. Several sex-specific immune pathways were associated with LC. Males who would later develop LC exhibited increases in transforming growth factor–β (TGF-β) signaling during acute infection, whereas females who would go on to develop LC had reduced TGFB1 expression. Females who developed LC demonstrated increased expression of XIST , an RNA gene implicated in autoimmunity, during acute infection compared with females who recovered. Many immune features of LC were also conserved across sexes, such as alterations in monocyte phenotype and activation state. Nuclear factor κB (NF-κB) transcription factors were up-regulated in many cell types at acute and convalescent time points. Those with ongoing LC demonstrated reduced ETS1 expression across lymphocyte subsets and elevated intracellular IL-4 in T cell subsets, suggesting that ETS1 alterations may drive aberrantly elevated T helper cell 2–like responses in LC. Altogether, this study describes multiple innate and adaptive immune correlates of LC, some of which differ by sex, and offers insights toward the pursuit of tailored therapeutics.
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来源期刊
Science Translational Medicine
Science Translational Medicine CELL BIOLOGY-MEDICINE, RESEARCH & EXPERIMENTAL
CiteScore
26.70
自引率
1.20%
发文量
309
审稿时长
1.7 months
期刊介绍: Science Translational Medicine is an online journal that focuses on publishing research at the intersection of science, engineering, and medicine. The goal of the journal is to promote human health by providing a platform for researchers from various disciplines to communicate their latest advancements in biomedical, translational, and clinical research. The journal aims to address the slow translation of scientific knowledge into effective treatments and health measures. It publishes articles that fill the knowledge gaps between preclinical research and medical applications, with a focus on accelerating the translation of knowledge into new ways of preventing, diagnosing, and treating human diseases. The scope of Science Translational Medicine includes various areas such as cardiovascular disease, immunology/vaccines, metabolism/diabetes/obesity, neuroscience/neurology/psychiatry, cancer, infectious diseases, policy, behavior, bioengineering, chemical genomics/drug discovery, imaging, applied physical sciences, medical nanotechnology, drug delivery, biomarkers, gene therapy/regenerative medicine, toxicology and pharmacokinetics, data mining, cell culture, animal and human studies, medical informatics, and other interdisciplinary approaches to medicine. The target audience of the journal includes researchers and management in academia, government, and the biotechnology and pharmaceutical industries. It is also relevant to physician scientists, regulators, policy makers, investors, business developers, and funding agencies.
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