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, Georg Kochs
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.