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. Variants of concerns arise from SARS-CoV-2 mutations poise as severe public health threats. Here the authors chronicle SARS-CoV-2 mutations onset and immune parameters in an immunocompromised patient with continuous virus-shedding, thereby hinting potential intra-host viral evolution and escape facilitated by ineffective T cell immunity.
【저자키워드】 SARS-CoV-2, Antimicrobial responses, Viral genetics, severe combined immunodeficiency, 【초록키워드】 COVID-19, public health, Evolution, Vaccine, coronavirus, Mutation, Immunity, VoC, Infection, variants of concern, viral shedding, RT-PCR, diagnostics, Immunocompromised patient, T cell, immune escape mutation, viral evolution, immune responses, Next-generation sequencing, VOCs, target, SARS-CoV-2 mutation, prolonged viral shedding, Non-synonymous mutation, Frequency, Non-synonymous, humoral, acute respiratory syndrome, Threats, immunocompromised individuals, SIGN, hosts, naso-pharyngeal swabs, populations, immunological, event, Seven, Course, described, analyzed, reported, facilitated, determine, specific mutation, immune parameter, the SARS-CoV-2 genome, 【제목키워드】 Immunity, Immunocompromised patient, viral evolution, SARS-CoV-2 mutation, Host, changes in,