严重急性呼吸综合征冠状病毒2在主要组织相容性复合体I类不匹配的肺移植受者中的感染动态

SARS-CoV-2 infection dynamics in a MHCI-mismatched lung transplant recipient.

作者信息

Fuchs Jonas, Karl Vivien, Hettich Ina, Alvarado Jaime, Eckert Daniel, Jaki Lena, Kohl Ann-Kathrin, Kremser Anastasia, Maks Anastasija, Terschluse Charlott, Agarwal Prerana, Emmerich Florian, Fähndrich Sebastian, Flügler Annabelle, Hornuss Daniel, Kalbhenn Johannes, Kneidinger Nikolaus, Lau Inga, Lother Achim, Moneke Isabelle, Schibilsky David, Schygulla Elisabeth, Venhoff Nils, Zissel Gernot, Czerny Martin, Huzly Daniela, Kochs Georg, Neumann-Haefelin Christoph, Passlick Bernward, Stolz Daiana, Thimme Robert, Panning Marcus, Hofmann Maike, Frye Björn C

机构信息

Institute of Virology, Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Faculty of Biology, University of Freiburg, Freiburg, Germany.

出版信息

Nat Commun. 2025 Sep 16;16(1):8292. doi: 10.1038/s41467-025-63681-y.

DOI:10.1038/s41467-025-63681-y

PMID:40957936

Abstract

A 48-year-old patient underwent lung transplantation because of severe COVID-19, which aggravated his underlying interstitial lung disease, despite the presence of detectable SARS-CoV-2. Subsequently, the graft is re-infected early in the post-procedural phase, leading to viral persistence for more than five months. By analyzing viral evolution and effector immune response within the transplanted organ, we observe three main findings. First, virus evolution differs in the transplanted organ compared to that in the upper respiratory tract and is affected by monoclonal SARS-CoV-2-specific antibodies and molnupiravir. Second, we show the potential clinical relevance of T cell HLA restriction that may facilitate viral clearance in the upper respiratory tract compared to the ongoing viral replication in the HLA mismatch organ. Third, close monitoring and modulation of immunosuppressive and antiviral therapy enables viral clearance in a lung transplantation setting despite incomplete SARS-CoV-2 clearance prior to transplantation.

摘要

一名48岁的患者因严重的新型冠状病毒肺炎接受了肺移植，尽管检测到严重急性呼吸综合征冠状病毒2（SARS-CoV-2），但该疾病加重了他潜在的间质性肺病。随后，移植肺在术后早期再次感染，导致病毒持续存在超过五个月。通过分析移植器官内的病毒进化和效应免疫反应，我们观察到三个主要发现。第一，与上呼吸道相比，移植器官中的病毒进化有所不同，并且受到单克隆SARS-CoV-2特异性抗体和莫努匹韦的影响。第二，我们展示了T细胞HLA限制的潜在临床相关性，与HLA不匹配器官中持续的病毒复制相比，这可能有助于上呼吸道中的病毒清除。第三，尽管移植前SARS-CoV-2未完全清除，但密切监测和调整免疫抑制及抗病毒治疗能够在肺移植环境中实现病毒清除。