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.
Highlights
The origin of SARS-CoV-2 variants of concern remains unclear
A 58-year-old male with a history of autosomal dominant polycystic kidney disease was admitted to our university hospital, for renal transplantation performed on March 2020
On March 2020, the patient tested positive for SARS-CoV-2 by reverse transcription-quantitative polymerase chain reaction (RTqPCR)
Summary
The origin of SARS-CoV-2 variants of concern remains unclear. Here, we test whether intrahost 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. The recent emergence of SARS-CoV-2 alpha- (B.1.1.7), beta- (B.1.351), and gamma- (P.1) variants[3,4,5] pose a global threat due to their increased transmissibility and resistance to neutralizing antibodies[2]. The origin of these virus variants remains unclear, but long-term-infected immunocompromised individuals are a likely source, allowing prolonged viral replication and unhindered adaption to the host[6,7]. A late virus variant isolated from the patient elicited a considerable protective immune response in experimentally infected mice, suggesting that convalescent individuals might become resistant against reinfection by emerging variants of concern
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