Title : Studies on the evolution of a SARS-CoV-2 variant of concern –The story of immune escape in an immunocompromised patient.
Abstract:
Different scenarios explaining the emergence of novel variants of concern (VOC) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported, including their evolution in scarcely monitored populations, in animals as alternative hosts, or in immunocompromised individuals. Here we report SARS-CoV- 2 immune escape mutations over a period of seven months in an immunocompromised patient with prolonged viral shedding. Signs of infection, viral shedding and mutation events are periodically analyzed using RT-PCR and next-generation sequencing based on naso-pharyngeal swabs, with the results complemented by immunological diagnostics to determine humoral and T cell immune responses. Throughout the infection course, 17 non-synonymous intra-host mutations are noted, with 15 (88.2%) having been previously described as prominent immune escape mutations (S:E484K, S:D950N, S:P681H, S:N501Y, S:del(9), N:S235F and S:H655Y) in VOCs. The high frequency of these non-synonymous mutations is consistent with multiple events of convergent evolution. Thus, our results suggest that specific mutations in the SARS-CoV-2 genome may represent positions with a fitness advantage, and may serve as targets in future vaccine and therapeutics development for COVID- 19.
Audience Take Away:
• This presentation is the story of the emergence of Variants of concern, which is highly interesting and important to know for the further control of SARS-CoV-2 and potential subsequent virological pathogens.
• Most importantly, our study points out the convergent intra-host evolution of specific mutations in SARS-CoV- 2, as they emerged independently in previously described VOC, VOIs and in the strain we studied. Those specific, convergently evolving mutations reveal those neuralgic positions in the SARS-CoV-2 genome that on the one hand represent its highest fitness advantage, but on the other hand also uncovers its highest vulnerability and should be considered as the probably most important points of attack in future vaccine and therapeutics development.
