Evaluation of the dynamics of detection of viable SARS-CoV-2 (Coronaviridae: Betacoronavirus: Sarbecovirus) in biological samples obtained from patients with COVID-19 in a health care setting, as one of the indicators of the infectivity of the virus

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Abstract

Introduction. The study of the mechanisms of transmission of the SARS-CoV-2 virus is the basis for building a strategy for anti-epidemic measures in the context of the COVID-19 pandemic. Understanding in what time frame a patient can spread SARS-CoV-2 is just as important as knowing the transmission mechanisms themselves. This information is necessary to develop effective measures to prevent infection by breaking the chains of transmission of the virus.

The aim of the work – is to identify the infectious SARS-CoV-2 virus in patient samples in the course of the disease and to determine the duration of virus shedding in patients with varying severity of COVID-19.

Materials and methods. In patients included in the study, biomaterial (nasopharyngeal swabs) was subjected to analysis by quantitative RT-PCR and virological determination of infectivity of the virus.

Results. We have determined the timeframe of maintaining the infectivity of the virus in patients hospitalized with severe and moderate COVID-19. Based on the results of the study, we made an analysis of the relationship between the amount of detected SARS-CoV-2 RNA and the infectivity of the virus in vitro in patients with COVID-19. The median time of the infectious virus shedding was 8 days. In addition, a comparative analysis of different protocols for the detection of the viral RNA in relation to the identification of the infectious virus was carried out.

Conclusion. The obtained data make it possible to assess the dynamics of SARS-CoV-2 detection and viral load in patients with COVID-19 and indicate the significance of these parameters for the subsequent spread of the virus and the organization of preventive measures.

About the authors

Nadezhda A. Kuznetsova

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

Email: nadyakuznetsova0@gmail.com
ORCID iD: 0000-0002-7399-7628

PhD in Biology, Senior Researcher

Russian Federation, 123098, Moscow

Darya A. Ogarkova

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

Email: DashaDv1993@gmail.com
ORCID iD: 0000-0002-1152-4120

Junior Researcher

Russian Federation, 123098, Moscow

Vladimir A. Gushchin

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

Author for correspondence.
Email: wowaniada@gmail.com
ORCID iD: 0000-0002-9397-3762

PhD in Biology, Leading Researcher

Russian Federation, 123098, Moscow

Natalya A. Antipyat

Infectious Clinical Hospital No. 1 of the Department of Health of the Moscow

Email: natadoc70@bk.ru
ORCID iD: 0000-0001-8578-2838

Deputy Chief Physician, doctor of infectious diseases

Russian Federation, 125367, Moscow

Valeria V. Bacalin

Peoples’ Friendship University of Russia

Email: bacalinmed@gmail.com
ORCID iD: 0000-0002-0491-9925

Resident of the Department of Infectious Diseases with courses in Epidemiology and Phthisiology

Russian Federation, 117198, Moscow

Olga A. Burgasova

Peoples’ Friendship University of Russia

Email: olgaburgasova@mail.ru
ORCID iD: 0000-0002-5486-0837

Dr. Sci. (Med.), professor

Russian Federation, 117198, Moscow

Lyudmila A. Vasilchenko

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

Email: milavasilchenko97@gmail.com
ORCID iD: 0000-0003-0780-7782

Junior Researcher

Russian Federation, 123098, Moscow

Alexey A. Samkov

Infectious Clinical Hospital No. 1 of the Department of Health of the Moscow

Email: a.a.samkov@yandex.ru
ORCID iD: 0000-0002-0365-3096

Deputy Chief Medical Officer, doctor of infectious diseases

Russian Federation, 125367, Moscow

Yana V. Simakova

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

Email: nadyakuznetsova0@gmail.com
ORCID iD: 0000-0002-5033-6931

Researcher

Russian Federation, 123098, Moscow

Elizaveta V. Divisenko

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

Email: elizaveta.divisenko@yandex.ru

Junior Researcher

Russian Federation, 123098, Moscow

Andrei E. Siniavin

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

Email: andreysi93@ya.ru
ORCID iD: 0000-0001-7576-2059

Researcher

Russian Federation, 123098, Moscow

Artem P. Tkachuk

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

Email: artem.p.tkachuk@gmail.com
ORCID iD: 0000-0003-3262-4873

PhD in Biology, Leading Researcher

Russian Federation, 123098, Moscow

Liudmila V. Kolobukhina

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

Email: lkolobuchina@yandex.ru
ORCID iD: 0000-0001-5775-3343

MD, Dr. Sci. (Med.), professor

Russian Federation, 123098, Moscow

Elena V. Shidlovskaya

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

Email: lenitsa@gmail.com
ORCID iD: 0000-0001-8199-6417

Researcher

Russian Federation, 123098, Moscow

Igor N. Tyurin

Infectious Clinical Hospital No. 1 of the Department of Health of the Moscow

Email: ikb1@zdrav.mos.ru
ORCID iD: 0000-0002-5696-1586

Candidate of Medical Sciences, Chief physician, doctor of the highest qualification category, anesthesiologist-resuscitator

Russian Federation, 125367, Moscow

Irina S. Kruzhkova

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

Email: irina-kru@yandex.ru
ORCID iD: 0000-0002-1983-481X

Researcher

Russian Federation, 123098, Moscow

Vladimir I. Zlobin

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

Email: vizlobin@mail.ru
ORCID iD: 0000-0002-0164-5113

Dr. Sci. (Med.), professor, Academician of the RAS, Chief Researcher

Russian Federation, 123098, Moscow

Maria A. Nikiforova

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

Email: marianikiforova@inbox.ru
ORCID iD: 0000-0001-5823-6508

Researcher

Russian Federation, 123098, Moscow

Mikhail A. Odnoralov

Infectious Clinical Hospital No. 1 of the Department of Health of the Moscow

Email: nadyakuznetsova0@gmail.com
ORCID iD: 0000-0003-0525-6075

Resident

Russian Federation, 125367, Moscow

Alexander L. Gintsburg

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

Email: gintsburg@gamaleya.org
ORCID iD: 0000-0003-1769-5059

Dr. Sci. (Biol.), professor, Academician of the RAS, Director

Russian Federation, 123098, Moscow

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Supplementary files

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3. Fig. 1. Viral load in samples with infectious and non-infectious virus. p < 0.0001 when calculated using the Wilcoxon signed rank test (W); p < 0.001* when calculated using the Mann–Whitney test.

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4. Fig. 2. The percent of infectious virus depending on the time after the onset of symptoms.

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5. Fig. 3. Analysis of the persistence of an infectious virus in the nasopharyngeal swabs of patients depending on the time of onset of symptoms. The vertical line shows the median virus persistence time (8 days).

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6. Fig. 4. Comparison of the Ct values for different protocols of the viral RNA identification in samples with an infectious and non-infectious virus.

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7. Fig. 5. ROC-analysis curves for different RNA detection protocols relative to identification of the infectious virus.

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8. Fig. 6. Comparison of the specificity and sensitivity of different RNA detection protocols in relation to the identification of an infectious virus.

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9. Fig. S1. Sensitivity and specificity for various cut-off values: A – HKU-ORF1; B – HKU-N; C – E_Sarbeco; D – N_Sarbeco; E – RdRp; F – NSP1.

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Copyright (c) 2023 Kuznetsova N.A., Ogarkova D.A., Gushchin V.A., Antipyat N.А., Bacalin V.V., Burgasova O.A., Vasilchenko L.A., Samkov A.A., Simakova Y.V., Divisenko E.V., Siniavin A.E., Tkachuk A.P., Kolobukhina L.V., Shidlovskaya E.V., Tyurin I.N., Kruzhkova I.S., Zlobin V.I., Nikiforova M.A., Odnoralov M.A., Gintsburg A.L.

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