Within-host evolution of SARS-CoV-2 in an immunosuppressed COVID-19 patient as a source of immune escape variants

Sebastian Weigang, Jonas Fuchs, Gert Zimmer, Daniel Schnepf, Lisa Kern, Julius Beer, Hendrik Luxenburger, Jakob Ankerhold, Valeria Falcone, Janine Kemming, Maike Hofmann, Robert Thimme, Christoph Neumann-Haefelin, Svenja Ulferts, Robert Grosse, Daniel Hornuss, Yakup Tanriver, Siegbert Rieg, Dirk Wagner, Daniela Huzly, Martin Schwemmle, Marcus Panning () and Georg Kochs ()
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Sebastian Weigang: University of Freiburg
Jonas Fuchs: University of Freiburg
Gert Zimmer: Institute of Virology and Immunology, Bern & Mittelhäusern, Switzerland, and Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern
Daniel Schnepf: University of Freiburg
Lisa Kern: University of Freiburg
Julius Beer: University of Freiburg
Hendrik Luxenburger: University of Freiburg
Jakob Ankerhold: University of Freiburg
Valeria Falcone: University of Freiburg
Janine Kemming: University of Freiburg
Maike Hofmann: University of Freiburg
Robert Thimme: University of Freiburg
Christoph Neumann-Haefelin: University of Freiburg
Svenja Ulferts: Freiburg University Medical Center, Faculty of Medicine, University of Freiburg
Robert Grosse: Freiburg University Medical Center, Faculty of Medicine, University of Freiburg
Daniel Hornuss: University of Freiburg
Yakup Tanriver: University of Freiburg
Siegbert Rieg: University of Freiburg
Dirk Wagner: University of Freiburg
Daniela Huzly: University of Freiburg
Martin Schwemmle: University of Freiburg
Marcus Panning: University of Freiburg
Georg Kochs: University of Freiburg

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: Abstract The origin of SARS-CoV-2 variants of concern remains unclear. Here, we test whether intra-host virus evolution during persistent infections could be a contributing factor by characterizing the long-term SARS-CoV-2 infection dynamics in an immunosuppressed kidney transplant recipient. Applying RT-qPCR and next-generation sequencing (NGS) of sequential respiratory specimens, we identify several mutations in the viral genome late in infection. We demonstrate that a late viral isolate exhibiting genome mutations similar to those found in variants of concern first identified in UK, South Africa, and Brazil, can escape neutralization by COVID-19 antisera. Moreover, infection of susceptible mice with this patient’s escape variant elicits protective immunity against re-infection with either the parental virus and the escape variant, as well as high neutralization titers against the alpha and beta SARS-CoV-2 variants, B.1.1.7 and B.1.351, demonstrating a considerable immune control against such variants of concern. Upon lowering immunosuppressive treatment, the patient generated spike-specific neutralizing antibodies and resolved the infection. Our results suggest that immunocompromised patients could be a source for the emergence of potentially harmful SARS-CoV-2 variants.

Date: 2021
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DOI: 10.1038/s41467-021-26602-3

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