Pochtovyi Andrei A, Kustova Daria D, Siniavin Andrei E, Dolzhikova Inna V, Shidlovskaya Elena V, Shpakova Olga G, Vasilchenko Lyudmila A, Glavatskaya Arina A, Kuznetsova Nadezhda A, Iliukhina Anna A, Shelkov Artem Y, Grinkevich Olesia M, Komarov Andrei G, Logunov Denis Y, Gushchin Vladimir A, Gintsburg Alexander L
Federal State Budget Institution "National Research Centre for Epidemiology and Microbiology Named after Honorary Academician N. F. Gamaleya" of the Ministry of Health of the Russian Federation, 123098 Moscow, Russia.
Department of Virology, Biological Faculty, Lomonosov Moscow State University, 119991 Moscow, Russia.
Vaccines (Basel). 2023 Sep 28;11(10):1533. doi: 10.3390/vaccines11101533.
The spread of COVID-19 continues, expressed by periodic wave-like increases in morbidity and mortality. The reason for the periodic increases in morbidity is the emergence and spread of novel genetic variants of SARS-CoV-2. A decrease in the efficacy of monoclonal antibodies (mAbs) has been reported, especially against Omicron subvariants. There have been reports of a decrease in the efficacy of specific antiviral drugs as a result of mutations in the genes of non-structural proteins. This indicates the urgent need for practical healthcare to constantly monitor pathogen variability and its effect on the efficacy of preventive and therapeutic drugs. As part of this study, we report the results of the continuous monitoring of COVID-19 in Moscow using genetic and virological methods. As a result of this monitoring, we determined the dominant genetic variants and identified the variants that are most widespread, not only in Moscow, but also in other countries. A collection of viruses from more than 500 SARS-CoV-2 isolates has been obtained and characterized. The genetic lines XBB.1.9.1, XBB.1.9.3, XBB.1.5, XBB.1.16, XBB.2.4, BQ.1.1.45, CH.1.1, and CL.1, representing the greatest concern, were identified among the dominant variants. We studied the in vitro efficacy of mAbs Tixagevimab + Cilgavimab (Evusheld), Sotrovimab, Regdanvimab, Casirivimab + Imdevimab (Ronapreve), and Bebtelovimab, as well as the specific antiviral drugs Remdesivir, Molnupiravir, and Nirmatrelvir, against these genetic lines. At the current stage of the COVID-19 pandemic, the use of mAbs developed against early SARS-CoV-2 variants has little prospect. Specific antiviral drugs retain their activity, but further monitoring is needed to assess the risk of their efficacy being reduced and adjust recommendations for their use.
新冠病毒肺炎（COVID-19）的传播仍在继续，表现为发病率和死亡率呈周期性的波浪式上升。发病率周期性上升的原因是严重急性呼吸综合征冠状病毒2（SARS-CoV-2）新基因变体的出现和传播。已有报道称单克隆抗体（mAbs）的效力下降，尤其是针对奥密克戎亚变体。也有报道称，由于非结构蛋白基因突变，特定抗病毒药物的效力降低。这表明实际医疗保健迫切需要持续监测病原体的变异性及其对预防和治疗药物效力的影响。作为本研究的一部分，我们报告了使用基因和病毒学方法对莫斯科的COVID-19进行持续监测的结果。通过这种监测，我们确定了主要的基因变体，并识别出不仅在莫斯科，而且在其他国家也最为广泛传播的变体。已获得并表征了来自500多个SARS-CoV-2分离株的病毒库。在主要变体中，确定了最受关注的基因谱系XBB.1.9.1、XBB.1.9.3、XBB.1.5、XBB.1.16、XBB.2.4、BQ.1.1.45、CH.1.1和CL.1。我们研究了mAbs替沙格韦单抗+西加韦单抗（恩适得）、索托维单抗、雷吉丹维单抗、卡西瑞维单抗+因德维单抗（罗钠普瑞韦）和贝替洛维单抗，以及特定抗病毒药物瑞德西韦、莫努匹拉韦和奈玛特韦对这些基因谱系的体外效力。在COVID-19大流行的现阶段，使用针对早期SARS-CoV-2变体开发的mAbs前景渺茫。特定抗病毒药物仍保持其活性，但需要进一步监测以评估其效力降低的风险并调整其使用建议。
