Accumulation of mutations in antibody and CD8 T cell epitopes in a B cell depleted lymphoma patient with chronic SARS-CoV-2 infection

Elham Khatamzas (), Markus H. Antwerpen, Alexandra Rehn, Alexander Graf, Johannes Christian Hellmuth, Alexandra Hollaus, Anne-Wiebe Mohr, Erik Gaitzsch, Tobias Weiglein, Enrico Georgi, Clemens Scherer, Stephanie-Susanne Stecher, Stefanie Gruetzner, Helmut Blum, Stefan Krebs, Anna Reischer, Alexandra Leutbecher, Marion Subklewe, Andrea Dick, Sabine Zange, Philipp Girl, Katharina Müller, Oliver Weigert, Karl-Peter Hopfner, Hans-Joachim Stemmler, Michael Bergwelt-Baildon, Oliver T. Keppler, Roman Wölfel, Maximilian Muenchhoff and Andreas Moosmann
Additional contact information
Elham Khatamzas: University Hospital, Ludwig-Maximilians University Munich
Markus H. Antwerpen: Bundeswehr, Institute of Microbiology Munich
Alexandra Rehn: Bundeswehr, Institute of Microbiology Munich
Alexander Graf: Gene Center, Ludwig-Maximilians University Munich
Johannes Christian Hellmuth: University Hospital, Ludwig-Maximilians University Munich
Alexandra Hollaus: University Hospital, Ludwig-Maximilians University Munich
Anne-Wiebe Mohr: University Hospital, Ludwig-Maximilians University Munich
Erik Gaitzsch: University Hospital, Ludwig-Maximilians University Munich
Tobias Weiglein: University Hospital, Ludwig-Maximilians University Munich
Enrico Georgi: Bundeswehr, Institute of Microbiology Munich
Clemens Scherer: University Hospital, Ludwig-Maximilians University Munich
Stephanie-Susanne Stecher: University Hospital, Ludwig-Maximilians University Munich
Stefanie Gruetzner: University of Augsburg
Helmut Blum: Gene Center, Ludwig-Maximilians University Munich
Stefan Krebs: Gene Center, Ludwig-Maximilians University Munich
Anna Reischer: University Hospital, Ludwig-Maximilians University Munich
Alexandra Leutbecher: University Hospital, Ludwig-Maximilians University Munich
Marion Subklewe: University Hospital, Ludwig-Maximilians University Munich
Andrea Dick: University of Munich, LMU
Sabine Zange: Bundeswehr, Institute of Microbiology Munich
Philipp Girl: Bundeswehr, Institute of Microbiology Munich
Katharina Müller: Bundeswehr, Institute of Microbiology Munich
Oliver Weigert: University Hospital, Ludwig-Maximilians University Munich
Karl-Peter Hopfner: Ludwig-Maximilians-Universität München
Hans-Joachim Stemmler: University Hospital, Ludwig-Maximilians University Munich
Michael Bergwelt-Baildon: University Hospital, Ludwig-Maximilians University Munich
Oliver T. Keppler: University Hospital, Ludwig-Maximilians University Munich
Roman Wölfel: Bundeswehr, Institute of Microbiology Munich
Maximilian Muenchhoff: University Hospital, Ludwig-Maximilians University Munich
Andreas Moosmann: University Hospital, Ludwig-Maximilians University Munich

Nature Communications, 2022, vol. 13, issue 1, 1-12

Abstract: Abstract Antibodies against the spike protein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can drive adaptive evolution in immunocompromised patients with chronic infection. Here we longitudinally analyze SARS-CoV-2 sequences in a B cell-depleted, lymphoma patient with chronic, ultimately fatal infection, and identify three mutations in the spike protein that dampen convalescent plasma-mediated neutralization of SARS-CoV-2. Additionally, four mutations emerge in non-spike regions encoding three CD8 T cell epitopes, including one nucleoprotein epitope affected by two mutations. Recognition of each mutant peptide by CD8 T cells from convalescent donors is reduced compared to its ancestral peptide, with additive effects resulting from double mutations. Querying public SARS-CoV-2 sequences shows that these mutations have independently emerged as homoplasies in circulating lineages. Our data thus suggest that potential impacts of CD8 T cells on SARS-CoV-2 mutations, at least in those with humoral immunodeficiency, warrant further investigation to inform on vaccine design.

Date: 2022
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DOI: 10.1038/s41467-022-32772-5

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