Weigang, SebastianSebastianWeigangFuchs, JonasJonasFuchsZimmer, GertGertZimmerSchnepf, DanielDanielSchnepfKern, LisaLisaKernBeer, JuliusJuliusBeerLuxenburger, HendrikHendrikLuxenburgerAnkerhold, JakobJakobAnkerholdFalcone, ValeriaValeriaFalconeKemming, JanineJanineKemmingHofmann, MaikeMaikeHofmannThimme, RobertRobertThimmeNeumann-Haefelin, ChristophChristophNeumann-HaefelinUlferts, SvenjaSvenjaUlfertsGrosse, RobertRobertGrosseHornuss, DanielDanielHornussTanriver, YakupYakupTanriverRieg, SiegbertSiegbertRiegWagner, DirkDirkWagnerHuzly, DanielaDanielaHuzlySchwemmle, MartinMartinSchwemmlePanning, MarcusMarcusPanningKochs, GeorgGeorgKochs2024-10-092024-10-092021-11-04https://boris-portal.unibe.ch/handle/20.500.12422/67550The 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.en600 - Technology::630 - Agriculture500 - Science500 - Science::570 - Life sciences; biology500 - Science::590 - Animals (Zoology)600 - Technology::610 - Medicine & healtharticle10.48350/1656563473726610.1038/s41467-021-26602-3