Kustova D D, Pochtovyi A A, Shpakova O G, Shtinova I A, Kuznetsova N A, Kleimenov D A, Komarov A G, Gushchin V A
National Research Centre for Epidemiology and Microbiology Named after Honorary Academician N.F. Gamaleya of the Ministry of Health of the Russian Federation.
Federal State Budgetary Educational Institution of Higher Education Lomonosov Moscow State University.
Vopr Virusol. 2024 Sep 26;69(4):329-340. doi: 10.36233/0507-4088-242.
For four years, SARS-CoV-2, the etiological agent of COVID-19, has been circulating among humans. By the end of the second year, an absence of immunologically naive individuals was observed, attributable to extensive immunization efforts and natural viral exposure. This study focuses on delineating the molecular and biological patterns that facilitate the persistence of SARS-CoV-2, thereby informing predictions on the epidemiological trajectory of COVID-19 toward refining pandemic countermeasures. The aim of this study was to describe the molecular biological patterns identified that contribute to the persistence of the virus in the human population.
For over three years since the beginning of the COVID-19 pandemic, molecular genetic monitoring of SARS-CoV-2 has been conducted, which included the collection of nasopharyngeal swabs from infected individuals, assessment of viral load, and subsequent whole-genome sequencing.
We discerned dominant genetic lineages correlated with rising disease incidence. We scrutinized amino acid substitutions across SARS-CoV-2 proteins and quantified viral loads in swab samples from patients with emerging COVID-19 variants. Our findings suggest a model of viral persistence characterized by 1) periodic serotype shifts causing substantial diminutions in serum virus-neutralizing activity (> 10-fold), 2) serotype-specific accrual of point mutations in the receptor-binding domain (RBD) to modestly circumvent neutralizing antibodies and enhance receptor affinity, and 3) a gradually increasing amount of virus being shed in mucosal surfaces within a single serotype.
This model aptly accounts for the dynamics of COVID-19 incidence in Moscow. For a comprehensive understanding of these dynamics, acquiring population-level data on immune tension and antibody neutralization relative to genetic lineage compositions is essential.
导致新冠肺炎的病原体严重急性呼吸综合征冠状病毒2（SARS-CoV-2）已在人类中传播了四年。到第二年年底，由于广泛的免疫接种努力和自然病毒暴露，未观察到免疫未接触过该病毒的个体。本研究重点描绘促进SARS-CoV-2持续存在的分子和生物学模式，从而为预测新冠肺炎的流行病学轨迹提供信息，以完善大流行应对措施。本研究的目的是描述所确定的有助于该病毒在人群中持续存在的分子生物学模式。
自新冠肺炎大流行开始以来的三年多时间里，对SARS-CoV-2进行了分子遗传监测，包括从感染个体采集鼻咽拭子、评估病毒载量以及随后的全基因组测序。
我们识别出与疾病发病率上升相关的主要遗传谱系。我们仔细研究了SARS-CoV-2蛋白的氨基酸替换情况，并对感染新出现的新冠肺炎变体患者的拭子样本中的病毒载量进行了量化。我们的研究结果表明，病毒持续存在的模式具有以下特点：1）周期性血清型转变导致血清病毒中和活性大幅降低（>10倍）；2）受体结合域（RBD）中血清型特异性点突变的积累，以适度规避中和抗体并增强受体亲和力；3）在单一血清型内，黏膜表面释放的病毒量逐渐增加。
该模型恰当地解释了莫斯科新冠肺炎发病率的动态变化。为全面理解这些动态变化，获取有关免疫张力和相对于遗传谱系组成的抗体中和作用的人群水平数据至关重要。
