Expansion of SARS-CoV-2 mutations in patient with B-cell lymphoma and rare combination of ACE2, TLR4, DDX58 and IFIH1 variations: A retrospective analysis of the virus-host interplay

Angelina Trifonova , Adelina Yosifova , Atanas Syarov , Andrey Velichkov , Martin Pasev , Svetlomir Takov , Kalina Madarzhieva , Krassimir Angelov , Radoslava Vazharova , Velislava Terzieva
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Abstract

Lessons from the COVID-19 outbreak suggest a highly variable individual clinical course of infection and unpredictable outcomes among infected individuals. In this retrospective study, we examined the intra-host viral evolution in an immunocompromised patient with B-cell lymphoma, severe COVID-19, and a two-stage, long-lasting in-hospital period with lethal outcome. The whole-genome sequencing profile demonstrated a dynamic accumulation of new viral mutations in the entire viral genome, mainly in S1-RBD and Nsp12, against the background of antiviral treatment and convalescent plasma transfusion. Long range-PCR and nanopore sequencing of ACE2, TLR7, TLR8, TLR4, DDX58, and IFIH1 genes revealed single nucleotide substitutions in the ACE2, TLR4, DDX58, IFIH1, and TLR7 receptors, negatively affecting the disease course from the onset. Our results demonstrate that genetic variations in host innate immunity and impaired adaptive immunity facilitate the accumulation of viral mutations that overcome antiviral treatment and passive antibody transfer, affecting the course of SARS-CoV-2 infection.
b细胞淋巴瘤患者中SARS-CoV-2突变的扩增和ACE2、TLR4、DDX58和IFIH1变异的罕见组合:病毒-宿主相互作用的回顾性分析
2019冠状病毒病疫情的教训表明,个体感染的临床过程变化很大,感染者的结果不可预测。在这项回顾性研究中,我们研究了一名免疫功能低下的b细胞淋巴瘤患者的宿主内病毒进化,该患者合并了严重的COVID-19,并出现了两期长期住院治疗的致命结果。全基因组测序显示,在抗病毒治疗和恢复期血浆输注的背景下,整个病毒基因组中出现了新的病毒突变的动态积累,主要集中在S1-RBD和Nsp12。ACE2、TLR7、TLR8、TLR4、DDX58和IFIH1基因的远程pcr和纳米孔测序显示,ACE2、TLR4、DDX58、IFIH1和TLR7受体的单核苷酸取代,从发病开始就对病程产生负面影响。我们的研究结果表明,宿主先天免疫和适应性免疫受损的遗传变异促进了病毒突变的积累,这些突变克服了抗病毒治疗和被动抗体转移,影响了SARS-CoV-2感染的过程。
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