1. Within-host evolution of SARS-CoV-2 in an immunosuppressed COVID-19 patient as a source of immune escape variants.
- Author
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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, and Huzly, Daniela
- Subjects
COVID-19 ,SARS-CoV-2 ,IMMUNOCOMPROMISED patients ,IMMUNOGLOBULINS ,VIRAL mutation ,VIRAL genomes ,NEUTRALIZATION tests ,VIRUS diseases - 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. Here, in a longitudinal case study, Weigang et al. demonstrate that evolution of SARS-CoV-2 within a persistently infected immunosuppressed patient can result in the emergence of novel variants with reduced sensitivity to antibody neutralization. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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