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.
【저자키워드】 SARS-CoV-2, viral infection, 【초록키워드】 COVID-19, neutralizing antibody, Brazil, Evolution, Mutation, Neutralizing antibodies, B.1.351, neutralization, SARS-COV-2 infection, Sequencing, NGS, Genome, variant, SARS-CoV-2 variant, Infection, variants of concern, Immunocompromised patients, virus, variants, immune, Immunocompromised patient, sensitivity, RT-qPCR, South Africa, Viral, SARS-CoV-2 variants, protective immunity, B.1.1.7, mice, Next-generation sequencing, Patient, Re-infection, Immunocompromised, Evolution of SARS-CoV-2, Alpha, Beta, case study, respiratory, kidney transplant, Antibody neutralization, Antisera, respiratory specimens, viral genome, Immunosuppressed, Immunosuppressive treatment, persistent infections, specific neutralizing antibodies, neutralization titer, susceptible, identify, the patient, reduced, elicit, parental, resolved, exhibiting, Applying, 【제목키워드】 variant, Immune escape, Evolution of SARS-CoV-2, Immunosuppressed, COVID-19 patient,