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

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

Nature Communications, 2025, vol. 16, issue 1, 1-13

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-63681-y

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