Regarding the Model of a Disease X Pandemic Requiring a Higher Priority in Ensuring Biological Safety

The aim of the work was to create an analytical model of a test disease X pandemic that requires a priority approach to ensuring biological safety, using COVID-19 and influenza as an example. The created pandemic model consists of 2 elements: the pandemic phenomenon itself using COVID-19 as a case study and the post-pandemic period using the Spanish flu as an example. The formalized structure, signs, parameters, properties and negative consequences of the COVID-19 pandemic as a phenomenon with an extraordinary scale of epidemic spread, socio-economic and other critical consequences that disorganize society, comparable with threats to national and international security, the readiness for which is a part of ensuring biological safety in a broad format, have been determined using the epidemiological method, the law of large numbers (LLN in probability theory), and the global application of digital and genomic technologies. An in-depth study of the COVID-19 pandemic has revealed the value of a certain structure of the clinical and epidemiological content of the epidemic phase of the pandemic, which determined the high quantitative parameters of spread and mortality. A 10-fold range of change in the key criterion, both upward and downward, has been established, which is incompatible with the emergence and existence of a pandemic as a phenomenon. The proof of the effectiveness, efficiency, scientific and practical significance of the COVID-19-based disease X pandemic model is the full implementation of the epidemiological forecast of COVID-19 pandemic duration in 2024 that we have developed for all its elements and parameters. The imitation of the post-pandemic period of disease X is represented by data on the circulation of the H1N1 influenza virus for more than 100 years, seasonal outbreaks and epidemics between 1920 and 1957, four moderate pandemics relative to the “Spanish flu” after 1957, and the production of particularly pathogenic potentially epidemic variants of the influenza virus. In general, the model is proposed to be used to monitor and assess preparedness for future pandemics in the format of biological disasters when forming state policy in the field of biological safety, as well as to prevent the occurrence of emergencies within the framework of the implementation of the International Health Regulations (2005).

1. [Address by the WHO Director-General at the World Governments Summit – 12 February 2024]. (Cited 07 March 2024). [Internet]. Available from: https://www.who.int/ru/director-general/speeches/detail/who-director-general-s-speech-at-the-world-governments-summit---12-february-2024.

2. International Health Regulations (2005). Third edition. 2016. 82 p.

3. Kiselev O.I. [Pandemics of the early 21st century. Avian influenza and the 2009 H1N1 “swine” flu pandemic]. St. Petersburg: “Foliant”; 2016. 368 p.

4. L’vov D.K., Al’khovsky S.V., Kolobukhina L.V., Burtseva E.I. [Etiology of the COVID-19 epidemic outbreak in Wuhan (Hubei Province, People’s Republic of China) associated with the 2019-nCoV virus (Nidovirales, Coronaviridae, Coronavirinae, Betacoronavirus, subgenus Sarbecovirus): lessons learned from the SARS-CoV epidemic]. Voprosy Virusologii [Problems of Virology]. 2020; 65(1):6–15. DOI: 10.36233/0507-4088-2020-65-1-6-15.

5. Toporkov V.P. [COVID-19 pandemic: duration and epidemiological forecast]. Problemy Osobo Opasnykh Infektsii [Problems of Particularly Dangerous Infections]. 2023; (4):141–8. DOI: 10.21055/0370-1069-2023-4-141-148.

6. COVID – Coronavirus Statistics – Worldometer. (Cited 13 Apr 2024). [Internet]. Available from: https://www.worldometers.info/coronavirus/.

7. Taubenberger J.K., Morens D.M. 1918 influenza: the mo­ ther of all pandemics. Emerg. Infect. Dis. 2006; 12(1):15–22. DOI: 10.3201/eid1201.050979.

8. Supotnitsky M.V. [The Spanish flu pandemic of 1918– 1920 in the context of other influenza pandemics and avian flu]. Meditsinskaya Kartoteka [Medical Catalogue]. 2006; (11):31–4; (12):15–25, 28–30; 2007; (1):16–22.

9. Briko N.I. [100 years after the Spanish flu pandemic. Evolution of the influenza virus and development of influenza vaccines]. Epidemiologiya i Vaktsinoprofilaktika [Epidemiology and Vaccinal Prevention]. 2018; 17(4):68–97. DOI: 10.31631/2073-3046-2018-17-4-68-97

10. Morozova O.M., Troshina T.I., Morozova E.N., Morozov A.N. [The 1918 Spanish flu pandemic in Russia. Issues one hundred years onward]. Zhurnal Mikrobiologii, Epidemiologii i Immunobiologii [Journal of Microbiology, Epidemiology and Immunobiology]. 2021; 98(1):113–24 DOI: 10.36233/0372-9311-98.

11. Toporkov V.P. [COVID-19 pandemic and prerequisites for developing a pandemic model of acute respiratory viral zoonotic infectious disease]. In: Popova A.Yu., Kutyrev V.V., editors. [Collection of Materials of the IV International Scientific and Practical Conference “Counteracting the New Coronavirus Infection and Other Infectious Diseases” and the International Conference “Results and Prospects for Cooperation of Joint Research Centers for the Study and Prevention of Infectious Diseases in Africa, Asia and South America” (December 7–9, 2023, St. Petersburg)]. Saratov: Amirit; 2023. P. 315–9.

12. Coronavirus (COVID-19) Cases. (Cited 10 May 2024). [Internet]. Available from: https://ourworldindata.org/covid-cases.

13. WHO. Epidemic and Pandemic Alert and Response. Cumulative Number of Confirmed SARS Cases, 31 Desember 2003. Geneva; 2004.

14. Onishchenko G.G., Fedorov Yu.M., Toporkov V.P., Kulichenko A.N., Karavaeva T.B., Shiyanova A.E., Kuklev E.V., Kutyrev V.V. [Atypical pneumonia (SARS) and sanitary protection of the territory]. Problemy Osobo Opasnykh Infektsii [Problems of Particularly Dangerous Infections]. 2003; (1):3–19.

15. Cherkassky B.L. [SARS and avian influenza: comparative epidemiological analysis]. Epidemiologiya i Infektsionnye Bolezni [Epidemiology and Infectious Diseases]. 2007; (2):1–8

16. WHO. MERS-CoV – United Arab Emirates. (Cited 10 May 2024). [Internet]. Available from: https://www.who.int/csr/don/31-january-2020-mers-united-arab-emirates/en/.

17. Smolensky V.Yu., Udovichenko S.K., Toporkov V.P., Kutyrev V.V. [Regarding the risks of occurrence of emergency situations in the sphere of biological safety of international concern and their predictors]. Problemy Osobo Opasnykh Infektsii [Problems of Particularly Dangerous Infections]. 2017;(3):5–11. DOI: 10.21055/0370-1069-2017-3-5-11.

18. Ebola Disease Basics. (Cited 06 Oct 2024). [Internet]. Available from: https://www.cdc.gov/ebola/about/index.html?CDC_AAref_Val=https://www.cdc.gov/vhf/ebola/resources/outbreaktable.html.

19. WHO. 10th Ebola outbreak in the Democratic Republic of the Congo declared over; vigilance against flare-ups and support for survivors must continue. (Cited 06 Feb 2024). [Internet]. Available from: https://www.who.int/ru/news/item/25-06-2020-10thebola-outbreak-in-the-democratic-republic-of-the-congo-declaredover-vigilance-against-flare-ups-and-support-for-survivors-mustcontinue.

20. WHO. Ebola virus disease. (Cited 06 Oct 2024). [Internet]. Available from: https://www.who.int/ru/news-room/fact-sheets/detail/ebola-virus-disease.

21. WHO. Marburg virus disease. (Cited 06 Oct 2024). [Internet]. Available from: https://www.who.int/ru/news-room/factsheets/detail/marburg-virus-disease.

22. Adam D. 15 million people have died in the pandemic, WHO says. The World Health Organization’s long-awaited estimate of excess COVID deaths is in line with other studies. Nature. 2022; 605:206. DOI: 10.1038/d41586-022-01245-6.

23. [The IMF estimates the global economy’s losses since the start of the COVID pandemic at $3.7 trillion]. (Cited 28 Feb 2024). [Internet]. Available from: https://www.rbc.ru/economics/06/10/2023/651f4cdf9a7947124f5ea79b.

24. [The WHO stated that the world economy has lost $13.8 trillion due to COVID-19]. (Cited 28 Feb 2024). [Internet]. Available from: https://ren.tv/news/v-mire/1113233-predstavitel-voz-v-rfrasskazala-ob-ekonomicheskom-ushcherbe-ot-covid-19.

25. [Forbes. Experts estimate the damage to the global economy from coronavirus at $35 trillion]. (Cited 28 Feb 2024). [Internet]. Available from: https://www.forbes.ru/newsroom/finansyi-investicii/408477-eksperty-ocenili-ushcherb-mirovoy-ekonomikeot-koronavirusa-v.

26. [Prime. It has been calculated how the population of the Earth has grown in 2024]. (Cited 30 Jan 2025). [Internet]. Available from: https://1prime.ru/20241230/naselenie-853963465.html.

27. WHO. COVID-19 epidemiological update – 13 August 2024. (Cited 02 Oct 2024). [Internet]. Available from: https://www.who.int/publications/m/item/covid-19-epidemiological-updateedition-170.

28. Khalili M., Karamouzian M., Nasiri N., Javadi S., Mirzazadeh A., Sharifi H. Epidemiological characteristics of COVID19: a systematic review and meta-analysis. Epidemiol. Infect. 2020; 148:e130. DOI: 10.1017/S0950268820001430.

29. Hu B., Guo H., Zhou P., Z.L. Shi. Characteristics of SARSCoV-2 and COVID-19. Nat. Rev. Microbiol. 2021; 19:141–54. DOI: 10.1038/s41579-020-00459-7.

30. WHO. Coronavirus disease 2019 (COVID-19) Situation Report – 46. (06 March 2020). [Internet]. Available from: https://www.who.int/docs/default-source/coronaviruse/situationreports/20200306-sitrep-46-covid-19.pdf.

31. Heymann D.L., Shindo N.; WHO Scientific and Technical Advisory Group for Infectious Hazards. COVID-19: what is next for public health? Lancet. 2020; 395(10224):542–5. DOI: 10.1016/ S0140-6736(20)30374-3.

32. Emery J.C., Russell T.W., Liu Y., Hellewell J., Pearson C.A.; CMMID COVID-19 Working Group; Knight G.M., Eggo R.M., Kucharski A.J., Funk S., Flasche S., Houben R.M. The contribution of asymptomatic SARS-CoV-2 infections to transmission on the Diamond Princess cruise ship. Elife. 2020; 9:e58699. DOI: 10.7554/eLife.58699.

33. Sah P., Fitzpatrick M.C., Zimmer C.F., Abdollahi E., JudenKelly L., Moghadas S.M., Singer B.H., Galvani A.P. Asymptomatic SARS-CoV-2 infection: A systematic review and meta-analysis. Proc. Natl Acad. Sci. USA. 2021; 118(34):e2109229118. DOI: 10.1073/pnas.2109229118.

34. Yokota S., Kuroiwa E., Nishioka K. [Novel coronavirus disease (COVID-19) and the “cytokine storm”. Prospects for effective treatment from the point of view of the pathophysiology of the inflammatory process]. Infektsionnye Bolezni: Novosti, Mneniya, Obuchenie [Infectious Diseases: News, Opinions, Training]. 2020; 9(4):13–25. DOI: 10.33029/2305-3496-2020-9-4-13-25.

35. Sa Ribero M., Jouvenet N., Dreux M., Nisole S. Interplay between SARS-CoV-2 and the type I interferon response. PLoS Pathog. 2020; 16(7):e1008737. DOI: 10.1371/journal.ppat.1008737.

36. Chizhevsky A.L. [Earthly Echo of Solar Storms]. Moscow: “Mysl”; 1976. 367 p.

37. Stallibrass K.O. [Fundamentals of Epidemiology]. Moscow; Leningrad: “Biomedgiz”; 1936. 591 p.

38. [Coronavirus: statistics around the world]. (Cited 08 Nov 2022). [Internet]. Available from: https://yandex.ru/covid19/stat?geoId=225&ysclid=l81lgbxa5w326113632.

39. WHO. Coronavirus disease 2019 (COVID-19) Situation Report – 88. 2020. (Cited 28 May 2024). [Internet]. Available from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports/situation-reports-archive.

40. Akimkin V.G., Popova A.Yu., Khafizov K.F., Dubodelov D.V., Ugleva S.V., Semenenko T.A., Ploskireva A.A., Gorelov A.V., Pshenichnaya N.Yu., Ezhlova E.B., Letyushev A.N., Demina Yu.V., Kutyrev V.V., Maksyutov R.A., Govorun V.M., Dyatlov I.A., Totolyan A.A., Kulichenko A.N., Balakhonov S.V., Rudakov N.V., Trotsenko O.E., Noskov A.K., Zaitseva N.N., Toporkov A.V., Lioznov D.A., Andreeva E.E., Mikailova O.M., Komarov A.G., Ananyev V.Yu., Moldovanov V.V., Logunov D.Yu., Gushchin V.A., Dedkov V.G., Cherkashina A.S., Kuzin S.N., Tivanova E.V., Kondrasheva L.N., Saenko V.V., Selezov S.Yu., Gasanov G.A., Svanadze N.Kh., Glazov M.B., Ostroushko A.A., Mironov K.O., Esman A.S., Osina N.A., Bodnev S.A., Komissarov A.B., Danilenko D.M., Bogun A.G., Skryabin Yu.P., Lopatovskaya K.V., Shtrek S.V., Volynkina A.S., Gladkikh A.S., Kotova V.O., Vodopyanov A.S., Novikova N.A., Speranskaya A.S., Samoilov A.E., Neverov A.D., Shpak I.M. [COVID-19: evolution of the pandemic in Russia. Communication II: dynamics of circulation of SARS-CoV-2 virus genovariants]. Zhurnal Mikrobiologii, Epidemiologii i Immunobiologii [Journal of Microbiology, Epidemiology and Immunobiology]. 2022; 99(4):381– 96. DOI: 10.36233/0372-9311-295.

41. WHO. Classification of Omicron (B.1.1.529): SARS-CoV-2 Variant of Concern. [Internet]. Available from: https://www.who.int/news/item/26-11-2021-classification-of-omicron-(b.1.1.529)-sarscov-2-variant-of-concern.

42. Saxena S.K., Kumar S., Ansari S., Paweska J.T., Maurya V.K., Tripathi A.K., Abdel-Moneim A.S. Transmission dynamics and mutational prevalence of the novel Severe acute respiratory syndrome coronavirus-2 Omicron Variant of Concern. J. Med. Virol. 2022; 94(5):2160–6. DOI: 10.1002/jmv.27611.

43. Kutyrev V.V., Popova A.Yu., Smolensky V.Yu., Ezhlova E.B., Demina Yu.V., Safronov V.A., Karnaukhov I.G., Ivanova A.V., Shcherbakova S.A. [Epidemiological features of new coronavirus infection (COVID-19). Communication 1: Modes of implementation of preventive and anti-epidemic measures]. Problemy Osobo Opasnykh Infektsii [Problems of Particularly Dangerous Infections]. 2020;(1):6–13.DOI: 10.21055/0370-1069-2020-1-6-13.

44. Belov A.B., Kulikov P.V. [Resolved and problematic issues of influenza epidemiology one hundred years after the Spanish flu pandemic]. Epidemiologiya i Vaktsinoprofilaktika [Epidemiology and Vaccinal Prevention]. 2019; 18(5):109–20. DOI: 10.31631/2073-3046-2019-18-5-109-120.

45. Golubev D.B., Kuznetsov O.K. [Expected influenza pandemic]. Epidemiologiya i Vaktsinoprofilaktika [Epidemiology and Vaccinal Prevention]. 2009; (3):5–11.

46. WHO. Avian Influenza A(H5N1) – United States of America. (Cited 28 May 2024). [Internet]. Available from: https://www.who.int/ru/emergencies/disease-outbreak-news/item/2024-DON512.

47. Herfst S., Schrauwen E.J., Linster M., Chutinimitkul S., de Wit E., Munster V.J., Sorrell E.M., Bestebroer T.M., Burke D.F., Smith D.J., Rimmelzwaan G.F., Osterhaus A.D., Fouchier R.A. Airborne transmission of influenza A/H5N1 virus between ferrets. Science. 2012; 336(6088):1534–41. DOI: 10.1126/science.1213362.

48. Imai M., Watanabe T., Hatta M., Das S.C., Ozawa M., Shinya K., Zhong G., Hanson A., Katsura H., Watanabe S., Li C., Kawakami E., Yamada S., Kiso M., Suzuki Y., Maher E.A., Neumann G., Kawaoka Y. Experimental adaptation of influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets. Nature. 2012; 486(7403):420–8. DOI: 10.1038/nature10831.

49. Madjid M., Lillibridge S., Mirhaji P., Casscells W. Influenza as a bioweapon. J. R. Soc. Med. 2003; 96(7):345–6. DOI: 10.1177/014107680309600709.