The Molecular and Biological Patterns Underlying Sustained SARS-CoV-2 Circulation in the Human Population

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Abstract

Introduction. 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.

Materials and methods. 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.

Results. 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.

Conclusion. 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.

About the authors

Daria D. Kustova

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

Email: kustovadaria@yandex.ru
ORCID iD: 0000-0002-8382-275X

junior researcher, Laboratory of mechanisms of population variability of pathogenic microorganisms; PhD student, Department of Virology, Faculty of Biology

Russian Federation, 123098, Moscow; 119991, Moscow

Andrei A. Pochtovyi

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; I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)

Author for correspondence.
Email: a.pochtovyy@gamaleya.org
ORCID iD: 0000-0003-1107-9351

Cand. Sci. (Biol.), senior researcher, Laboratory of mechanisms of population variability of pathogenic microorganisms

Russian Federation, 123098, Moscow; 119991, Moscow; 119435, Moscow

Olga G. Shpakova

Moscow Healthcare Department

Email: shpakovaog@dcli.ru

Head of the laboratory of the Moscow Scientific and Practical Center for Laboratory Research

Russian Federation, 127006, Moscow

Irina A. Shtinova

Moscow Healthcare Department

Email: shtinovaia@dcli.ru

Head of Laboratory Center of the Moscow Scientific and Practical Center for Laboratory Research

Russian Federation, 127006, Moscow

Nadezhda A. Kuznetsova

National Research Centre for Epidemiology and Microbiology Named after Honorary Academician N.F. Gamaleya of the Ministry of Health of the Russian Federation

Email: nadyakuznetsova0@yandex.ru
ORCID iD: 0000-0002-7399-7628

Cand. Sci. (Biol.), senior researcher, Laboratory of mechanisms of population variability of pathogenic microorganisms

Russian Federation, 123098, Moscow

Denis A. Kleimenov

National Research Centre for Epidemiology and Microbiology Named after Honorary Academician N.F. Gamaleya of the Ministry of Health of the Russian Federation

Email: mne10000let@yandex.ru
ORCID iD: 0000-0001-9422-7238

Cand. Sci. (Med.), Head, Laboratory of translational biomedicine

Russian Federation, 123098, Moscow

Andrey G. Komarov

Moscow Healthcare Department

Email: komarovag@zdrav.mos.ru
ORCID iD: 0009-0000-8597-7125

Cand. Sci. (Med.), Head of the Moscow Scientific and Practical Center for Laboratory Research

Russian Federation, 127006, Moscow

Vladimir A. Gushchin

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; I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)

Email: wowaniada@yandex.ru
ORCID iD: 0000-0002-9397-3762

Dr. Sci. (Biology), Head, Laboratory of mechanisms of population variability of pathogenic microorganisms, Reference center for coronavirus infection; senior researcher, Department of virology, Biological faculty

Russian Federation, 123098, Moscow; 119991, Moscow; 119435, Moscow

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Supplementary files

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2. Fig. 1. Genetic variants of SARS-CoV-2 circulating in Moscow since the start of the COVID-19 pandemic. a – dynamics of genetic variants of SARS-CoV-2 circulating in Moscow. The left Y-axis indicates the proportion of genetic lineages, while the right axis represents the number of new COVID-19 cases per 100,000 population; b – changes in the number of mutations in the predominant circulating variants of SARS-CoV-2. The ordinate axis displays the mutation count. The periods (months) are indicated on the abscissa axis.

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3. Fig. 2. Mutations in the RBD of the spike protein of the predominant SARS-CoV-2 variants. The Y-axis represents SARS-CoV-2 variants, and the X-axis represents amino acid substitutions. Zero values reflect the proportion of mutations tending to zero; empty cells represent the absence of mutations at a specific position.

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4. Fig. 3. Comparative analysis of viral load in predominant SARS-CoV-2 variants in Moscow. a – viral load in Wuhan (B.1.X), Delta (B.1.617.2 + AY.X), and Omicron (BA.1/BA.2.X) variants; b – viral load in Omicron BA.1.X, BA.2.X, and BA.5.X variants; c – viral load in BA.5.X, CL.X, XBB.1.X, and XBB.1.9.X variants. The Y-axis denotes Ct values, while the X-axis represents SARS-CoV-2 variants and the number of samples.

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5. The Molecular and Biological Patterns Underlying Sustained SARS-CoV-2 Circulation in the Human Population
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Copyright (c) 2024 Kustova D.D., Pochtovyi A.A., Shpakova O.G., Shtinova I.A., Kuznetsova N.A., Kleimenov D.A., Komarov A.G., Gushchin V.A.

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Согласие на обработку персональных данных с помощью сервиса «Яндекс.Метрика»

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2. Категории обрабатываемых данных: файлы «cookies» (куки-файлы). Файлы «cookie» – это небольшой текстовый файл, который веб-сервер может хранить в браузере Пользователя. Данные файлы веб-сервер загружает на устройство Пользователя при посещении им Сайта. При каждом следующем посещении Пользователем Сайта «cookie» файлы отправляются на Сайт Оператора. Данные файлы позволяют Сайту распознавать устройство Пользователя. Содержимое такого файла может как относиться, так и не относиться к персональным данным, в зависимости от того, содержит ли такой файл персональные данные или содержит обезличенные технические данные.

3. Цель обработки персональных данных: анализ пользовательской активности с помощью сервиса «Яндекс.Метрика».

4. Категории субъектов персональных данных: все Пользователи Сайта, которые дали согласие на обработку файлов «cookie».

5. Способы обработки: сбор, запись, систематизация, накопление, хранение, уточнение (обновление, изменение), извлечение, использование, передача (доступ, предоставление), блокирование, удаление, уничтожение персональных данных.

6. Срок обработки и хранения: до получения от Субъекта персональных данных требования о прекращении обработки/отзыва согласия.

7. Способ отзыва: заявление об отзыве в письменном виде путём его направления на адрес электронной почты Оператора: info@rcsi.science или путем письменного обращения по юридическому адресу: 119991, г. Москва, Ленинский просп., д.32А

8. Субъект персональных данных вправе запретить своему оборудованию прием этих данных или ограничить прием этих данных. При отказе от получения таких данных или при ограничении приема данных некоторые функции Сайта могут работать некорректно. Субъект персональных данных обязуется сам настроить свое оборудование таким способом, чтобы оно обеспечивало адекватный его желаниям режим работы и уровень защиты данных файлов «cookie», Оператор не предоставляет технологических и правовых консультаций на темы подобного характера.

9. Порядок уничтожения персональных данных при достижении цели их обработки или при наступлении иных законных оснований определяется Оператором в соответствии с законодательством Российской Федерации.

10. Я согласен/согласна квалифицировать в качестве своей простой электронной подписи под настоящим Согласием и под Политикой обработки персональных данных выполнение мною следующего действия на сайте: https://journals.rcsi.science/ нажатие мною на интерфейсе с текстом: «Сайт использует сервис «Яндекс.Метрика» (который использует файлы «cookie») на элемент с текстом «Принять и продолжить».