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宿主-微生物多组学分析揭示实体器官移植受者中独特的新冠病毒免疫失调情况。

Host-microbe multiomic profiling identifies distinct COVID-19 immune dysregulation in solid organ transplant recipients.

作者信息

Pickering Harry, Schaenman Joanna, Phan Hoang Van, Maguire Cole, Tsitsiklis Alexandra, Rouphael Nadine, Higuita Nelson Iván Agudelo, Atkinson Mark A, Brakenridge Scott, Fung Monica, Messer William, Salehi-Rad Ramin, Altman Matthew C, Becker Patrice M, Bosinger Steven E, Eckalbar Walter, Hoch Annmarie, Doni Jayavelu Naresh, Kim-Schulze Seunghee, Jenkins Meagan, Kleinstein Steven H, Krammer Florian, Maecker Holden T, Ozonoff Al, Diray-Arce Joann, Shaw Albert, Baden Lindsey, Levy Ofer, Reed Elaine F, Langelier Charles R

机构信息

David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.

University of California San Francisco, San Francisco, CA, USA.

出版信息

Nat Commun. 2025 Jan 10;16(1):586. doi: 10.1038/s41467-025-55823-z.

Abstract

Coronavirus disease 2019 (COVID-19) poses significant risks for solid organ transplant recipients, who have atypical but poorly characterized immune responses to infection. We aim to understand the host immunologic and microbial features of COVID-19 in transplant recipients by leveraging a prospective multicenter cohort of 86 transplant recipients age- and sex-matched with 172 non-transplant controls. We find that transplant recipients have higher nasal SARS-CoV-2 viral abundance and impaired viral clearance, and lower anti-spike IgG levels. In addition, transplant recipients exhibit decreased plasmablasts and transitional B cells, and increased senescent T cells. Blood and nasal transcriptional profiling demonstrate unexpected upregulation of innate immune signaling pathways and increased levels of several proinflammatory serum chemokines. Severe disease in transplant recipients, however, is characterized by a less robust induction of pro-inflammatory genes and chemokines. Together, our study reveals distinct immune features and altered viral dynamics in solid organ transplant recipients.

摘要

2019冠状病毒病(COVID-19)对实体器官移植受者构成重大风险,这些受者对感染具有非典型但特征不明的免疫反应。我们旨在通过利用一个前瞻性多中心队列,该队列中有86名年龄和性别与172名非移植对照匹配的移植受者,来了解移植受者中COVID-19的宿主免疫和微生物特征。我们发现移植受者的鼻腔严重急性呼吸综合征冠状病毒2(SARS-CoV-2)病毒载量更高且病毒清除受损,抗刺突IgG水平更低。此外,移植受者的浆母细胞和过渡性B细胞减少,衰老T细胞增加。血液和鼻腔转录谱分析表明先天性免疫信号通路意外上调,几种促炎血清趋化因子水平升高。然而,移植受者的重症疾病特征是促炎基因和趋化因子的诱导作用较弱。总之,我们的研究揭示了实体器官移植受者独特的免疫特征和改变的病毒动态。

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