Weigang, Sebastian; Fuchs, Jonas; Zimmer, Gert; Schnepf, Daniel; Kern, Lisa; Beer, Julius; Luxenburger, Hendrik; Ankerhold, Jakob; Falcone, Valeria; Kemming, Janine; Hofmann, Maike; Thimme, Robert; Neumann-Haefelin, Christoph; Ulferts, Svenja; Grosse, Robert; Hornuss, Daniel; Tanriver, Yakup; Rieg, Siegbert; Wagner, Dirk; Huzly, Daniela; ... (2021). Within-host evolution of SARS-CoV-2 in an immunosuppressed COVID-19 patient as a source of immune escape variants. Nature Communications, 12(1), p. 6405. Springer Nature 10.1038/s41467-021-26602-3
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Zimmer_Within-host_evolution_of_SARS-CoV-2_in_an_s41467-021-26602-3.pdf - Published Version Available under License Creative Commons: Attribution (CC-BY). Download (3MB) | Preview |
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.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Virology and Immunology 05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) |
UniBE Contributor: |
Zimmer, Gert |
Subjects: |
600 Technology > 630 Agriculture 500 Science 500 Science > 570 Life sciences; biology 500 Science > 590 Animals (Zoology) 600 Technology > 610 Medicine & health |
ISSN: |
2041-1723 |
Publisher: |
Springer Nature |
Language: |
English |
Submitter: |
Katharina Gerber-Paizs |
Date Deposited: |
08 Mar 2022 15:24 |
Last Modified: |
05 Dec 2022 16:09 |
Publisher DOI: |
10.1038/s41467-021-26602-3 |
PubMed ID: |
34737266 |
BORIS DOI: |
10.48350/165656 |
URI: |
https://boris.unibe.ch/id/eprint/165656 |
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