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

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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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)

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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