Detection rates and high concentration of herpesvirus (Orthoherpesviridae) DNA in autopsy materials from patients with COVID-19 fatal outcome

Cover Image

Cite item

Full Text

Abstract

Introduction. SARS-CoV-2 infection causes immune disorders that create conditions for the reactivation of human herpesviruses (HHVs). However, the estimates of the HHVs effect on the course and outcome of COVID-19 are ambiguous.

Аim – to study the possible relationship between the HHV reactivation and the adverse outcome of COVID-19.

Materials and methods. Postmortem samples from the brain, liver, spleen, lymph nodes and lungs were obtained from 59 patients treated at the Moscow Infectious Diseases Hospital No.1 in 2021–2023. The group 1 comprised 39 patients with fatal COVID-19; group 2 (comparison group) included 20 patients not infected with SARS-CoV-2 who died from various somatic diseases. HHV DNA and SARS-CoV-2 RNA were determined by PCR.

Results. HHV DNA was found in autopsy samples from all patients. In group 1, EBV was most often detected in lymph nodes (94%), HHV-6 in liver (68%), CMV in lymph nodes (18%), HSV in brain (16%), VZV in lung and spleen (3% each). The detection rates of HHVs in both groups was similar. Important differences were found in viral load. In patients with COVID-19, the number of samples containing more than 1,000 copies of HHV DNA per 100,000 cells was 52.4%, in the comparison group – 16.6% (p < 0.002). An association has been established between the reactivation of HSV and HHV-6 and the severity of lung damage. Reactivation of EBV correlated with increased levels of liver enzymes.

Conclusion. Reactivation of HHVs in patients with fatal COVID-19 was associated with severe lung and liver damages, which indicates a link between HHV reactivation and COVID-19 deaths.

About the authors

Kirill I. Yurlov

National Research Center for Epidemiology and Microbiology, Ministry of Health of the Russian Federation

Email: kir34292@yandex.ru
ORCID iD: 0000-0002-4694-2445
SPIN-code: 1767-5652

Researcher

Russian Federation, 123098, Moscow

Sofia A. Yakushina

National Research Center for Epidemiology and Microbiology, Ministry of Health of the Russian Federation; Department of Health, Moscow Infectious Clinical Hospital No. 1

Email: sofia.iakushina@gmail.com
ORCID iD: 0000-0003-0507-0174
SPIN-code: 9585-8019

junior researcher, infectious disease physician

Russian Federation, 125367, Moscow; 123098, Moscow

Natalya E. Fedorova

National Research Center for Epidemiology and Microbiology, Ministry of Health of the Russian Federation

Email: ninani@mail.ru
ORCID iD: 0000-0001-8466-7993
SPIN-code: 1090-2763

Senior Researcher

Russian Federation, 123098, Moscow

Lidiia B. Kisteneva

National Research Center for Epidemiology and Microbiology, Ministry of Health of the Russian Federation; Department of Health, Moscow Infectious Clinical Hospital No. 1

Email: lidia.kisteneva@gmail.com
ORCID iD: 0000-0001-7336-409X
SPIN-code: 9205-3670

Dr. Sci. (Medicine), Leading Researcher

Russian Federation, 125367, Moscow; 123098, Moscow

Elena I. Kelly

Department of Health, Moscow Infectious Clinical Hospital No. 1

Email: ekelly@yandex.ru
ORCID iD: 0009-0000-2718-9462

specialist in pathological anatomy

Russian Federation, 125367, Moscow

Alexander A. Kanibolotsky

Sklifosovsky Research Institute For Emergency Medicine, «Sklifosovsky Institute»; Research Institute for Healthcare and Medical Management of Moscow Healthcare Department

Email: dr.kaa@mail.ru
ORCID iD: 0000-0001-6123-8387
SPIN-code: 3976-1662
Scopus Author ID: 57223849355
ResearcherId: HLG-3242-2023

Candidate of Medical Sciences, Associate Professor, Head of the Pathoanatomical Department, Head of the Department of Medical Education for Pathological Anatomy of the Research Institute of Healthcare Organization and Medical Management of the Moscow Department of Health

Russian Federation, 129090, Moscow; 115184, Moscow

Yevgeniy N. Ivkin

Sklifosovsky Research Institute For Emergency Medicine, «Sklifosovsky Institute»; Research Institute for Healthcare and Medical Management of Moscow Healthcare Department

Email: evgenuivkin@rambler.ru
ORCID iD: 0009-0004-2609-1788

pathologist doctor Research Institute of Emergency Medicine, specialist in pathological anatomy Department of Medical Education for Pathological Anatomy

Russian Federation, 129090, Moscow; 115184, Moscow

Natalia A. Antipiat

Department of Health, Moscow Infectious Clinical Hospital No. 1

Author for correspondence.
Email: natadog70@bk.ru
ORCID iD: 0000-0001-8578-2838

deputy chief physician Infectious Diseases

Russian Federation, 125367, Moscow

Igor N. Turin

Department of Health, Moscow Infectious Clinical Hospital No. 1

Email: tyurin.dti@yandex.ru
ORCID iD: 0000-0002-5696-1586
SPIN-code: 6755-0576

chief physician Infectious Diseases

Russian Federation, 125367, Moscow

Victor F. Larichev

National Research Center for Epidemiology and Microbiology, Ministry of Health of the Russian Federation

Email: vlaritchev@mail.ru
ORCID iD: 0000-0001-8262-5650
SPIN-code: 5826-1430

Dr. Sci. (Medicine), Leading Researcher

Russian Federation, 123098, Moscow

Natalia A. Demidova

National Research Center for Epidemiology and Microbiology, Ministry of Health of the Russian Federation

Email: ailande@yandex.ru
ORCID iD: 0000-0003-1961-9789
SPIN-code: 8759-0277

Researcher

Russian Federation, 123098, Moscow

Ekaterina I. Lesnova

National Research Center for Epidemiology and Microbiology, Ministry of Health of the Russian Federation

Email: wolf252006@yandex.ru
ORCID iD: 0000-0002-2801-6843
SPIN-code: 9901-8607

Senior Researcher

Russian Federation, 123098, Moscow

Regina R. Klimova

National Research Center for Epidemiology and Microbiology, Ministry of Health of the Russian Federation

Email: rklimova@yandex.ru
ORCID iD: 0000-0002-4147-8444
SPIN-code: 8286-6108

Researcher, Gamaleya NRC of Epidemiology and Microbiology

Russian Federation, 123098, Moscow

Olga V. Masalova

National Research Center for Epidemiology and Microbiology, Ministry of Health of the Russian Federation

Email: ol.mas@mail.ru
ORCID iD: 0000-0001-5571-5669
SPIN-code: 7210-0870

Dr. Sci. (Biology), Leading Researcher, Head of the Laboratory

Russian Federation, 123098, Moscow

Alla A. Kushch

National Research Center for Epidemiology and Microbiology, Ministry of Health of the Russian Federation

Email: vitallku@mail.ru
ORCID iD: 0000-0002-3396-5533
SPIN-code: 6964-1715

Professor, Dr. Sci. (Biology), Leading Researcher

Russian Federation, 123098, Moscow

References

  1. Carvalho J.L., Silva-Carvalho A.E., Garcez E.M., Saldanha-Araujo F. Commentary: mesenchymal stem cells: a new piece in the puzzle of COVID-19 treatment. Front. Immunol. 2021; 12: 682195. https://doi.org/10.3389/fimmu.2021.682195
  2. Rabi F.A., Al Zoubi M.S., Kasasbeh G.A., Salameh D.M., Al-Nasser A.D. SARS-CoV-2 and coronavirus disease 2019: what we know so far. Pathogens. 2020; 9(3): 231. https://doi.org/10.3390/pathogens9030231
  3. Blanco-Melo D., Nilsson-Payant B.E., Liu W.C., Uhl S., Hoagland D., Møller R., et al. Imbalanced host response to SARS-CoV-2 drives development of COVID-19. Cell. 2020; 181(5): 1036–45.e9. https://doi.org/10.1016/j.cell.2020.04.026
  4. Montazersaheb S., Hosseiniyan Khatibi S.M., Hejazi M.S., Tarhriz V., Farjami A., Ghasemian Sorbeni F., et al. COVID-19 infection: an overview on cytokine storm and related interventions. Virol. J. 2022; 19(1): 92. https://doi.org/10.1186/s12985-022-01814-1
  5. Lowery S.A., Sariol A., Perlman S. Innate immune and inflammatory responses to SARS-CoV-2: Implications for COVID-19. Cell Host Microbe. 2021; 29(7): 1052–62. https://doi.org/10.1016/j.chom.2021.05.004
  6. Liu L., Wei Q., Lin Q., Fang J., Wang H., Kwok H., et al. Anti-spike IgG causes severe acute lung injury by skewing macrophage responses during acute SARS-CoV infection. JCI Insight. 2019; 4(4): e123158. https://doi.org/10.1172/jci.insight.123158
  7. Zheng M., Gao Y., Wang G., Song G., Liu S., Sun D., et al. Functional exhaustion of antiviral lymphocytes in COVID-19 patients. Cell Mol. Immunol. 2020; 17(5): 533–5. https://doi.org/10.1038/s41423-020-0402-2
  8. Wang Y., Zheng J., Islam M.S., Yang Y., Hu Y., Chen X. The role of CD4+FoxP3+ regulatory T cells in the immunopathogenesis of COVID-19: implications for treatment. Int. J. Biol. Sci. 2021; 17(6): 1507–20. https://doi.org/10.7150/ijbs.59534
  9. Thorne L.G., Reuschl A.K., Zuliani-Alvarez L., Whelan M.V.X., Turner J., Noursadeghi M., et al. SARS-CoV-2 sensing by RIG-I and MDA5 links epithelial infection to macrophage inflammation. EMBO J. 2021; 40(15): e107826. https://doi.org/10.15252/embj.2021107826
  10. Cantan B., Luyt C.E., Martin-Loeches I. Influenza infections and emergent viral infections in intensive care unit. Semin. Respir. Crit. Care Med. 2019; 40(4): 488–97. https://doi.org/10.1055/s-0039-1693497
  11. Talan L., Akdemir Kalkan İ., Altıntaş N.D., Yörük F. Cytomegalovirus reactivation in critically-ill COVID-19 patients. Balkan Med. J. 2022; 39(4): 301–2. https://doi.org/10.4274/balkanmedj.galenos.2022.2022-2-2
  12. Amaral P.H., Ferreira B.M., Roll S., Neves P.D., Pivetta L.G., Mohrbacher S., et al. COVID-19 and cytomegalovirus co-infection: a challenging case of a critically ill patient with gastrointestinal symptoms. Eur. J. Case Rep. Intern. Med. 2020; 7(10): 001911. https://doi.org/10.12890/2020_001911
  13. Bernal K.D.E., Whitehurst C.B. Incidence of Epstein-Barr virus reactivation is elevated in COVID-19 patients. Virus Res. 2023; 334: 199157. https://doi.org/10.1016/j.virusres.2023.199157
  14. Manoharan S., Ying L.Y. Epstein Barr virus reactivation during COVID-19 hospitalization significantly increased mortality/death in SARS-CoV-2(+)/EBV(+) than SARS-CoV-2(+)/EBV(-) patients: a comparative meta-analysis. Int. J. Clin. Pract. 2023; 2023: 1068000. https://doi.org/10.1155/2023/1068000
  15. Berzero G., Campanini G., Vegezzi E., Paoletti M., Pichiecchio A., Simoncelli A.M., et al. Human herpesvirus 6 encephalitis in immunocompetent and immunocompromised hosts. Neurol. Neuroimmunol. Neuroinflamm. 2021; 8(2): e942. https://doi.org/10.1212/NXI.0000000000000942
  16. Di Nora A., Pizzo F., Costanza G., Ruggieri M., Falsaperla R. Human herpes 6 encephalitis in co-infection with COVID-19. Acta Neurol. Belg. 2023; 123(2): 687–8. https://doi.org/10.1007/s13760-022-01961-w
  17. Katz J., Yue S., Xue W. Herpes simplex and herpes zoster viruses in COVID-19 patients. Ir. J. Med. Sci. 2022; 191(3): 1093–7. https://doi.org/10.1007/s11845-021-02714-z
  18. Shafiee A., Teymouri Athar M.M., Amini M.J., Hajishah H., Siahvoshi S., Jalali M., et al. Reactivation of herpesviruses during COVID-19: A systematic review and meta-analysis. Rev. Med. Virol. 2023; 33(3): e2437. https://doi.org/10.1002/rmv.2437
  19. Nakashima J., Kadomatsu Y., Itagaki S., Otani T., Kiriu T., Matsunaga A., et al. A case-series of six autopsy cases of COVID-19 including three cases of cytomegalovirus coinfection. Pathol. Int. 2022; 72(6): 358–60. https://doi.org/10.1111/pin.13230
  20. Haslbauer J.D., Zinner C., Stalder A.K., Schneeberger J., Menter T., Bassetti S., et al. Vascular damage, thromboinflammation, plasmablast activation, T-cell dysregulation and pathological histiocytic response in pulmonary draining lymph nodes of COVID-19. Front. Immunol. 2021; 12: 763098. https://doi.org/10.3389/fimmu.2021.763098
  21. Iqbal B., Rahman N.M., Hallifax R.J. COVID-19-related pleural diseases. Semin. Respir. Crit. Care Med. 2023; 44(4): 437–46. https://doi.org/10.1055/s-0043-1769616
  22. Paolucci S., Cassaniti I., Novazzi F., Fiorina L., Piralla A., Comolli G., et al. EBV DNA increase in COVID-19 patients with impaired lymphocyte subpopulation count. Int. J. Infect. Dis. 2021; 104: 315–9. https://doi.org/10.1016/j.ijid.2020.12.051
  23. Simonnet A., Engelmann I., Moreau A.S., Garcia B., Six S., El Kalioubie A., et al. High incidence of Epstein-Barr virus, cytomegalovirus, and human-herpes virus-6 reactivations in critically ill patients with COVID-19. Infect. Dis. Now. 2021; 51(3): 296–9. https://doi.org/10.1016/j.idnow.2021.01.005
  24. Chen T., Song J., Liu H., Zheng H., Chen C. Positive Epstein-Barr virus detection in coronavirus disease 2019 (COVID-19) patients. Sci. Rep. 2021; 11(1): 10902. https://doi.org/10.1038/s41598-021-90351-y
  25. Meng M., Zhang S., Dong X., Sun W., Deng Y., Li W., et al. COVID-19 associated EBV reactivation and effects of ganciclovir treatment. Immun. Inflamm. Dis. 2022; 10(4): e597. https://doi.org/10.1002/iid3.597
  26. Giacconi R., Cardelli M., Piacenza F., Pierpaoli E., Farnocchia E., Di Rosa M., et al. Effect of cytomegalovirus reactivation on inflammatory status and mortality of older COVID-19 patients. Int. J. Mol. Sci. 2023; 24(7): 6832. https://doi.org/10.3390/ijms24076832
  27. Pérez-Granda M.J., Catalán P., Muñoz P., Aldámiz T., Barrios J.C., Ramírez C., et al. Cytomegalovirus reactivation in patients diagnosed with severe COVID-19: A point prevalence study in a general hospital. Rev. Esp. Quimioter. 2023; 36(1): 45–51. https://doi.org/10.37201/req/068.2022
  28. Pérez-Pedrero Sánchez-Belmonte M.J., Sánchez-Casado M., Moran Gallego F.J., Piza Pinilla R., Gomez Hernando C., Paredes Borrachero I. Herpes simplex virus type 1 (HSV-1) over-infection in patients with acute respiratory distress syndrome secondary to COVID-19 pneumonia: Impact on mortality. Med. Clin. (Engl. Ed). 2023; 160(2): 66–70. https://doi.org/10.1016/j.medcle.2022.04.019
  29. Yang X., Yu Y., Xu J., Shu H., Xia J., Liu H., et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir. Med. 2020; 8(5): 475–81. https://doi.org/10.1016/S2213-2600(20)30079-5
  30. Li Q., Chen Z., Zhou X., Li G., Zhang C., Yang Y. Ferroptosis and multi-organ complications in COVID-19: mechanisms and potential therapies. Front. Genet. 2023; 14: 1187985. https://doi.org/10.3389/fgene.2023.1187985
  31. Gabrielli L., Balboni A., Borgatti E.C., Virgili G., Petrisli E., Cantiani A., et al. Inherited chromosomally integrated human herpesvirus 6: laboratory and clinical features. Microorganisms. 2023; 11(3): 548. https://doi.org/10.3390/microorganisms11030548
  32. Qiu M.Z., He C.Y., Lu S.X., Guan W.L., Wang F., Wang X.J., et al. Prospective observation: Clinical utility of plasma Epstein-Barr virus DNA load in EBV-associated gastric carcinoma patients. Int. J. Cancer. 2020; 146(1): 272–80. https://doi.org/10.1002/ijc.32490
  33. Solomay T.V., Semenenko T.A., Filatov N.N., Vedunova S.L., Lavrov V.F., Smirnova D.I., et al. Reactivation of Epstein-Barr virus (Herpesviridae: Lymphocryptovirus, HHV-4) infection during Covid-19: epidemiological features. Voprosy virusologii. 2021; 66(2): 152–61. https://doi.org/10.36233/0507-4088-40 https://elibrary.ru/nhbzyr (in Russian)
  34. Roncati L., Manenti A., Fabbiani L., Malagoli C., Nasillo V., Lusenti B., et al. HSV1 viremia with fulminant hepatitis as opportunistic sequela in severe COVID-19. Ann. Hematol. 2022; 101(1): 229–31. https://doi.org/10.1007/s00277-021-04417-y
  35. Silaghi-Dumitrescu R., Patrascu I., Lehene M., Bercea I. Comorbidities of COVID-19 patients. Medicina (Kaunas). 2023; 59(8): 1393. https://doi.org/10.3390/medicina59081393
  36. Nikitskaya E., Lebedeva A., Ivanova O., Maryukhnich E., Shpektor A., Grivel J.C., et al. Cytomegalovirus-productive infection is associated with acute coronary syndrome. J. Am. Heart Assoc. 2016; 5(8): e003759. https://doi.org/10.1161/JAHA.116.003759
  37. Chimenti C., Verardo R., Grande C., Francone M., Frustaci A. Infarct-like myocarditis with coronary vasculitis and aneurysm formation caused by Epstein-Barr virus infection. ESC Heart Fail. 2020; 7(3): 938–41. https://doi.org/10.1002/ehf2.12611
  38. Chen X., Li Y., Deng L., Wang L., Zhong W., Hong J., et al. Cardiovascular involvement in Epstein-Barr virus infection. Front. Immunol. 2023; 14: 1188330. https://doi.org/10.3389/fimmu.2023.1188330
  39. Prasoppokakorn T., Assanasen T., Chantranuwatana P., Suankratay C. EBV-associated lymphoid interstitial pneumonia in IBD patient: Case report and literature review. Respir. Med. Case Rep. 2020; 30: 101059. https://doi.org/10.1016/j.rmcr.2020.101059
  40. Yurlov K.I., Masalova O.V., Kisteneva L.B., Khlopova I.N., Samokhvalov E.I., Malinovskaya V.V., et al. Human herpesviruses increase the severity of hepatitis. Biology (Basel). 2021; 10(6): 483. https://doi.org/10.3390/biology10060483
  41. Lin J., Zheng Y., Zhao N., Cui F., Wu S. Herpesvirus latent infection promotes stroke via activating the OTUD1/NF-κB signaling pathway. Aging (Albany NY). 2023; 15(17): 8976–92. https://doi.org/10.18632/aging.205011.
  42. Verma D., Church T.M., Swaminathan S. Epstein-Barr virus lytic replication induces ACE2 expression and enhances SARS-CoV-2 pseudotyped virus entry in epithelial cells. J. Virol. 2021; 95(13): e0019221. https://doi.org/10.1128/JVI.00192-21
  43. Perera M.R., Greenwood E.J.D., Crozier T.W.M., Elder E.G., Schmitt J., Crump C.M., et al. Human cytomegalovirus infection of epithelial cells increases SARS-CoV-2 superinfection by upregulating the ACE2 receptor. J. Infect. Dis. 2023; 227(4): 543–53. https://doi.org/10.1093/infdis/jiac452
  44. Yu X., Li L., Chan M.T.V., Wu W.K.K. Bioinformatic analyses suggest augmented interleukin-17 signaling as the mechanism of COVID-19-associated herpes zoster. Environ. Sci. Pollut. Res. Int. 2021; 28(46): 65769–75. https://doi.org/10.1007/s11356-021-15567-x
  45. Naendrup J.H., Garcia Borrega J., Eichenauer D.A., Shimabukuro-Vornhagen A., Kochanek M., Böll B. Reactivation of EBV and CMV in severe COVID-19-epiphenomena or trigger of hyperinflammation in need of treatment? A large case series of critically ill patients. J. Intensive Care Med. 2022; 37(9): 1152–8. https://doi.org/10.1177/08850666211053990
  46. Yang E.V., Webster Marketon J.I., Chen M., Lo K.W., Kim S.J., Glaser R. Glucocorticoids activate Epstein Barr virus lytic replication through the upregulation of immediate early BZLF1 gene expression. Brain Behav. Immun. 2010; 24(7): 1089–96. https://doi.org/10.1016/j.bbi.2010.04.013

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2. Fig. 1. The frequency of herpesvirus detection in autopsy materials in patients with COVID-19 fatal outcome (group 1) and without COVID-19 (group 2). Horizontally – the designation of herpesviruses; vertically – the frequency of detection of herpesvirus DNA, in %. COVID-19(+) – 1st group patients with fatal COVID-19; COVID-19(−) – 2nd group patients who died without COVID-19. * – p < 0.05.

Download (278KB)
Indexing metadata
3. Fig. 2. Concentrations of herpesvirus DNA in the organs from patients who died with a confirmed diagnosis of COVID-19 (COVID +) or as a result of somatic non-infectious diseases (COVID−). On X-axis – the designations of the organs from which autopsy materials were obtained; on Y-axis – the amount of HHV DNA in copies per 100 thousand cells. The minimum and maximum values of DNA concentration are presented, the lines indicate the medians. * – p < 0.05..

Download (757KB)
Indexing metadata

Copyright (c) 2024 Yurlov K.I., Yakushina S.A., Fedorova N.E., Kisteneva L.B., Kelly E.I., Kanibolotsky A.A., Ivkin Y.N., Antipiat N.A., Turin I.N., Larichev V.F., Demidova N.A., Lesnova E.I., Klimova R.R., Masalova O.V., Kushch A.A.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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

1. Я (далее – «Пользователь» или «Субъект персональных данных»), осуществляя использование сайта https://journals.rcsi.science/ (далее – «Сайт»), подтверждая свою полную дееспособность даю согласие на обработку персональных данных с использованием средств автоматизации Оператору - федеральному государственному бюджетному учреждению «Российский центр научной информации» (РЦНИ), далее – «Оператор», расположенному по адресу: 119991, г. Москва, Ленинский просп., д.32А, со следующими условиями.

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».