Preventive effectiveness of nasal interferon-gamma among adult volunteers against acute respiratory viral infections, including COVID-19

Abstract

Background. In vitro studies showed effective viral infection block in case of pretreatment with exogenous interferons. Interferon-gamma is a unique immune interferon, actively expressed in patients with acute respiratory viral infections (ARVI) and defending the body from severe infection course.

Aim – to evaluate the safety and preventive effectiveness of nasal interferon-gamma protecting against ARVI, including COVID-19.

Material and methods. The study enrolled 630 adult volunteers with a negative PCR test result for SARS-CoV-2, without respiratory symptoms and contraindications to interferon-gamma. Participants were randomized (1 : 1) into 2 groups: the study group – with the use of a prophylactic course of nasal interferon-gamma, and the group of comparison – without a course of prophylaxis. All participants were given a diary for daily monitor respiratory symptoms, adverse events, and record the use of pharmacotherapy.

Results. Safety analysis found no differences between groups. During 28 days period a higher incidence of ARVI, including COVID-19, was observed in the group of comparison (13 vs 3 cases in the study group). The odd ratio was 0.224 (95 % CI: 0.040–0.826), p = 0.020. The total number of ARVI cases, including COVID-19, in the group of comparison during 2 months of research was 26 vs 6 in the study group. The odd ratio was 0.233 (95 % CI: 0.077–0.594), p = 0,001. The longest period of persistence of respiratory symptoms was obtained in the group of comparison (7 vs 4 days in the study group, р = 0.034).

Conclusion. Nasal interferon-gamma as a preventive measure contributes to a decrease of infection incidence of ARVI, including COVID-19.

Keywords:infection prevention; respiratory infection; interferon-gamma; healthy volunteers; ARVI; COVID-19

For citation: Talyzin P.A., Myasnikov A.L., Berns S.A., Ilyina M.A., Komazov A.A., Lynyov V.S., Ekusheva E.V. Preventive effectiveness of nasal interferon-gamma among adult volunteers against acute respiratory viral infections, including COVID-19. 2022; 43 (3): 301–11. DOI: https://doi.org/10.33029/0206-4952-2022-43-3-301-311 (in Russian)

Funding. The RAIN-2020 study was supported by the SPP «Pharmaclon» Ltd.

Conflict of interests. The authors declare no conflict of interests.

Authors’ contribution. Collection and processing of material – Ilyina M.A., Komazov A.A., Lynyov V.S.; writing text – Ilyina M.A., Komazov A.A., Berns S.A.; material editing – Talyzin P.A., Ilyina M.A., Lynyov V.S., Myasnikov A.L., Berns S.A., Komazov A.A.; approval of the final version of the article – Talyzin P.A., Myasnikov A.L., Lynyov V.S., Ekusheva E.V.; responsibility for the integrity of all parts of the article – Berns S.A., Myasnikov A.L., Talyzin P.A.

References

1. Boulware D.R., Pullen M.F., Bangdiwala A.S., Pastick K.A., Lofgren S.M., Okafor E.C., Skipper C.P., Nascene A.A., Nicol M.R., Abassi M., Engen N.W., Cheng M.P., LaBar D., Lother S.A., MacKenzie L.J., Drobot G., Marten N., Zarychanski R., Kelly L.E., Schwartz I.S., McDonald E.G., Rajasingham R., Lee T.C., Hullsiek K.H. A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19. N Engl J Med. 2020; 383 (6): 517–25. DOI: https://doi.org/10.1056/NEJMoa2016638

2. Barnabas R.V., Brown E.R., Bershteyn A., Stankiewicz Karita H.C., Johnston C., Thorpe L.E., Kottkamp A., Neuzil K.M., Laufer M.K., Deming M., Paasche-Orlow M.K., Kissinger P.J., Luk A., Paolino K., Landovitz R.J., Hoffman R., Schaafsma T.T., Krows M.L., Thomas K.K., Morrison S., Haugen H.S., Kidoguchi L., Wener M., Greninger A.L., Huang M.L., Jerome K.R., Wald A., Celum C., Chu H.Y., Baeten J.M.; Hydroxychloroquine COVID-19 PEP Study Team. Hydroxychloroquine as Postexposure Prophylaxis to Prevent Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Randomized Trial. Ann. Intern. Med. 2021; 174 (3): 344–52. DOI: https://doi.org/10.7326/M20-6519

3. Mitjà O., Corbacho-Monné M., Ubals M., Alemany A., Suñer C., Tebé C., Tobias A., Peñafiel J., Ballana E., Pérez C.A., Admella P., Riera-Martí N., Laporte P., Mitjà J., Clua M., Bertran L., Sarquella M., Gavilán S., Ara J., Argimon J.M., Cuatrecasas G., Cañadas P., Elizalde-Torrent A., Fabregat R., Farré M., Forcada A., Flores-Mateo G., López C., Muntada E., Nadal N., Narejos S., Nieto A., Prat N., Puig J., Quiñones C., Ramírez-Viaplana F., Reyes-Urueña J., Riveira-Muñoz E., Ruiz L., Sanz S., Sentís A., Sierra A., Velasco C., Vivanco-Hidalgo RM., Zamora J., Casabona J., Vall-Mayans M., González-Beiras C., Clotet B.; BCN-PEP-CoV2 Research Group. A Cluster-Randomized Trial of Hydroxychloroquine for Prevention of Covid-19. N Engl J Med. 2021; 384 (5): 417–27. DOI: https://doi.org/10.1056/NEJMoa2021801

4. Abella B.S., Jolkovsky E.L., Biney B.T., Uspal J.E., Hyman M.C., Frank I., Hensley S.E., Gill S., Vogl D.T., Maillard I., Babushok D.V., Huang A.C., Nasta S.D., Walsh J.C., Wiletyo E.P., Gimotty P.A., Milone M.C., Amaravadi R.K; Prevention and Treatment of COVID-19 With Hydroxychloroquine (PATCH) Investigators. Efficacy and Safety of Hydroxychloroquine vs Placebo for Pre-exposure SARS-CoV-2 Prophylaxis Among Health Care Workers: A Randomized Clinical Trial. JAMA Intern. Med. 2021; 181 (2): 195–202. DOI: https://doi.org/10.1001/jamainternmed.2020.6319

5. Akhtar S., Das J.K., Ismail T., Wahid M., Saeed W., Bhutta Z.A. Nutritional perspectives for the prevention and mitigation of COVID-19. Nutr. Rev. 2021; 79 (3): 289–300. DOI: https://doi.org/10.1093/nutrit/nuaa063

6. Zakurskaya V.Ya., Sizyakina L.P., Kharitonova M.V., Shlyk S.V. Dynamics of specific humoral response in COVID-19 patients. Immunologiya. 2022; 43 (1): 71–7. DOI: https://doi.org/10.33029/0206-4952-2022-43-1-71-77 (in Russian)

7. Semenova E.V., Pavliuk V.V., Uvarova M.A., Ivanov A.V. Features of humoral immunity after COVID-19. Medical Immunology (Russia). 2022; 24 (2): 337–50. DOI: https://doi.org/10.15789/1563-0625-FOH-2452 (in Russian)

8. Andreev I.V., Nechay K.O., Andreev A.I., Zubaryova A.P., Esaulova D.R., Alenova A.M., Nikolaeva I.A., Chernyavskaya O.P., Lomonosov K.S., Shulzhenko A.E., Kurbacheva O.M., Latysheva E.A., Shartanova N.V., Nazarova E.V., Romanova L.V., Cherchenko N.G., Smirnov V.V., Averkov O.V., Martynov A.I., Vechorko V.I., Gudima G.O., Kudlay D.A., Khaitov M.R., Khaitov R.M. Post-vaccination and post-infection humoral immune response to the SARS-CoV-2 infection. Immunologiya. 2022; 43 (1): 18–32. DOI: https://doi.org/10.33029/0206-4952-2022-43-1-18-32 (in Russian)

9. Sungnak W., Huang N., Bécavin C., Berg M., Queen R., Litvinukova M., Talavera-López C., Maatz H., Reichart D., Sampaziotis F., Worlock K.B., Yoshida M., Barnes J.L.; HCA Lung Biological Network. SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes. Nat Med. 2020; 26 (5): 681–7. DOI: https://doi.org/10.1038/s41591-020-0868-6

10. Rockx B., Kuiken T., Herfst S., Bestebroer T., Lamers M.M., Oude Munnink B.B., de Meulder D., van Amerongen G., van den Brand J., Okba N.M.A., Schipper D., van Run P., Leijten L., Sikkema R., Verschoor E., Verstrepen B., Bogers W., Langermans J., Drosten C., Fentener van Vlissingen M., Fouchier R., de Swart R., Koopmans M., Haagmans B.L. Comparative pathogenesis of COVID-19, MERS, and SARS in a nonhuman primate model. Science. 2020; 368 (6494): 1012–5. DOI: https://doi.org/10.1126/science.abb7314

11. Zou L., Ruan F., Huang M., Liang L., Huang H., Hong Z., Yu J., Kang M., Song Y., Xia J., Guo Q., Song T., He J., Yen H.L., Peiris M., Wu J. SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients. N Engl J Med. 2020; 382 (12): 1177–9. DOI: https://doi.org/10.1056/NEJMc2001737

12. Peiris J.S., Chu C.M., Cheng V.C., Chan K.S., Hung I.F., Poon L.L., Law K.I., Tang B.S., Hon T.Y., Chan C.S., Chan K.H., Ng J.S., Zheng B.J., Ng W.L., Lai R.W., Guan Y., Yuen KY; HKU/UCH SARS Study Group. Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study. Lancet. 2003; 361 (9371): 1767–72. DOI: https://doi.org/10.1016/s0140-6736(03)13412-5

13. Ziegler C.G.K., Miao V.N., Owings A.H., Navia A.W., Tang Y., Bromley J.D., Lotfy P., Sloan M., Laird H., Williams H.B., George M., Drake R.S., Christian T., Parker A., Sindel C.B., Burger M.W., Pride Y., Hasan M., Abraham G.E. 3rd, Senitko M., Robinson T.O., Shalek A.K., Glover S.C., Horwitz B.H., Ordovas-Montanes J. Impaired local intrinsic immunity to SARS-CoV-2 infection in severe COVID-19. Cell. 2021; 184 (18): 4713–4733.e22. DOI: https://doi.org/10.1016/j.cell.2021.07.023

14. Mateus J., Grifoni A., Tarke A., Sidney J., Ramirez S.I., Dan J.M., Burger Z.C., Rawlings S.A., Smith D.M., Phillips E., Mallal S., Lammers M., Rubiro P., Quiambao L., Sutherland A., Yu E.D., da Silva Antunes R., Greenbaum J., Frazier A., Markmann A.J., Premkumar L., de Silva A., Peters B., Crotty S., Sette A., Weiskopf D. Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans. Science. 2020; 370 (6512): 89–94. DOI: https://doi.org/10.1126/science.abd3871

15. Chen G., Wu D., Guo W., Cao Y., Huang D., Wang H., Wang T., Zhang X., Chen H., Yu H., Zhang X., Zhang M., Wu S., Song J., Chen T., Han M., Li S., Luo X., Zhao J., Ning Q. Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest. 2020; 130 (5): 2620–9. DOI: https://doi.org/10.1172/JCI137244

16. Zheng M., Gao Y., Wang G., Song G., Liu S., Sun D., Xu Y., Tian Z. Functional exhaustion of antiviral lymphocytes in COVID-19 patients. Cell. Mol. Immunol. 2020; 17 (5): 533–5. DOI: https://doi.org/10.1038/s41423-020-0402-2

17. Ricke D.O. Two Different Antibody-Dependent Enhancement (ADE) Risks for SARS-CoV-2 Antibodies. Front Immunol. 2021; 12: 640093. DOI: https://doi.org/10.3389/fimmu.2021.640093

18. Wen J., Cheng Y., Ling R., Dai Y., Huang B., Huang W., Zhang S., Jiang Y. Antibody-dependent enhancement of coronavirus. Int J Infect Dis. 2020; 100: 483–9. DOI: https://doi.org/10.1016/j.ijid.2020.09.015

19. COVID-19: Developing Drugs and Biological Products for Treatment or Prevention. Guidance for Industry. FDA (February, 2021). URL: http://resource.nlm.nih.gov/9918231202706676

20. Rock K.L., Reits E., Neefjes J. Present Yourself! By MHC Class I and MHC Class II Molecules. Trends Immunol. 2016; 37 (11): 724–37. DOI: https://doi.org/10.1016/j.it.2016.08.010

21. Bruchez A., Sha K., Johnson J., Chen L., Stefani C., McConnell H., Gaucherand L., Prins R., Matreyek K.A., Hume A.J., Mühlberger E., Schmidt E.V., Olinger G.G., Stuart L.M., Lacy-Hulbert A. MHC class II transactivator CIITA induces cell resistance to Ebola virus and SARS-like coronaviruses. Science. 2020; 370 (6513): 241–7. DOI: https://doi.org/10.1126/science.abb3753

22. Kimball A., Hatfield K.M., Arons M., James A., Taylor J., Spicer K., Bardossy A.C., Oakley L.P., Tanwar S., Chisty Z., Bell J.M., Methner M., Harney J., Jacobs J.R., Carlson CM., McLaughlin H.P., Stone N., Clark S., Brostrom-Smith C., Page L.C., Kay M., Lewis J., Russell D., Hiatt B., Gant J., Duchin J.S., Clark T.A., Honein M.A., Reddy S.C., Jernigan J.A; Public Health – Seattle & King County; CDC COVID-19 Investigation Team. Asymptomatic and Presymptomatic SARS-CoV-2 Infections in Residents of a Long-Term Care Skilled Nursing Facility – King County, Washington, March 2020. MMWR Morb Mortal Wkly Rep. 2020; 69 (13): 377–81. DOI: https://doi.org/10.15585/mmwr.mm6913e1

23. Richard M., Kok A., de Meulder D., Bestebroer T.M., Lamers M.M., Okba N.M.A., Fentener van Vlissingen M., Rockx B., Haagmans B.L., Koopmans M.P.G., Fouchier R.A.M., Herfst S. SARS-CoV-2 is transmitted via contact and via the air between ferrets. Nat Commun. 2020; 11 (1): 3496. DOI: https://doi.org/10.1038/s41467-020-17367-2

24. Liu Y., Ning Z., Chen Y., Guo M., Liu Y., Gali NK., Sun L., Duan Y., Cai J., Westerdahl D., Liu X., Xu K., Ho KF., Kan H., Fu Q., Lan K. Aerodynamic analysis of SARS-CoV-2 in two Wuhan hospitals. Nature. 2020; 582 (7813): 557–60. DOI: https://doi.org/10.1038/s41586-020- 2271-3

25. Wölfel R., Corman V.M., Guggemos W., Seilmaier M., Zange S., Müller M.A., Niemeyer D., Jones T.C., Vollmar P., Rothe C., Hoelscher M., Bleicker T., Brünink S., Schneider J., Ehmann R., Zwirglmaier K., Drosten C., Wendtner C. Virological assessment of hospitalized patients with COVID-2019. Nature. 2020; 581 (7809): 465–9. DOI: https://doi.org/10.1038/s41586-020-2196-x

26. Zaichuk T.A., Nechipurenko Y.D., Adzhubey A.A., Onikienko S.B., Chereshnev V.A., Zainutdinov S.S., Kochneva G.V., Netesov S.V., Matveeva O.V. The Challenges of Vaccine Development Against Betacoronaviruses: Antibody Dependent Enhancement and Sendai Virus as a Possible Vaccine Vector. Mol Biol (Mosk). 2020; 54 (6): 922–38. DOI: https://doi.org/10.31857/S0026898420060154 (in Russian)

27. Yin X., Riva L., Pu Y., Martin-Sancho L., Kanamune J., Yamamoto Y., Sakai K., Gotoh S., Miorin L., De Jesus P.D., Yang C.C., Herbert K.M., Yoh S., Hultquist J.F., García-Sastre A., Chanda S.K. MDA5 Governs the Innate Immune Response to SARS-CoV-2 in Lung Epithelial Cells. Cell Rep. 2021; 34 (2): 108628. DOI: https://doi.org/10.1016/j.celrep.2020.108628

28. Hsin F., Chao T.-L., Chan Y.-R., Kao H.-C., Liu W.-D., Wang J.-T., Pang Y.-H., Lin C.-H., Tsai Y.-M., Lin J.-Y., Chang S.-Y., Liu H.M. Distinct Inductions of and Responses to Type I and Type III Interferons Promote Infections in Two SARS-CoV-2 Isolates. bioRxiv. 2020. 04.30. 071357; DOI: https://doi.org/10.1101/2020.04.30.071357

29. Rebendenne A., Valadão A.L.C., Tauziet M., Maarifi G., Bonaventure B., McKellar J., Planès R., Nisole S., Arnaud-Arnould M., Moncorgé O., Goujon C. SARS-CoV-2 triggers an MDA-5-dependent interferon response which is unable to control replication in lung epithelial cells. J Virol. 2021; 95 (8): e02415–20. DOI: https://doi.org/10.1128/JVI. 02415-20

30. Nikiforov V.V., Sologub T.V., Tokin I.I., Cvetkov V.V., Erofeeva M.K., Zarubaev V.V. The possibility of using interferon-γ for influenza infection. Epidemiology and infectious Diseases. 2015; 20 (3): 11–6. URL: https://cyberleninka.ru/article/n/vozmozhnost-ispolzovaniya-interferona-upri-grippoznoy-infektsii (in Russian)

31. Myasnikov A.L., Berns S.A., Zverev K.V., Lartseva O.A., Talyzin P.A. Efficacy of Interferon-γ in the prevention of SARS-COV-2 infection (COVID-19): results of a prospective controlled trial. International Journal of Biomedicine. 2020; 10 (3): 182–8. DOI: https://doi.org/10.21103/Article10(3)_OA1

32. Sologub Т.V., Midikari A.S., Agafonov V.N., Suzdalcev A.A., Tsvetkov V.V. Efficiency and performance of use of recombinant interferon-γ in complex therapy of patients with influenza A (H1N1) pdm09. Epidemiology and infectious Diseases. 2017; 22 (2): 58–63. DOI: http://dx.doi.org/10.18821/1560-9529-2017-22-2-58-63 (in Russian)

33. Interim Guidelines «Prevention, Diagnosis and Treatment of Novel Coronavirus Infection (COVID-19)» Version 15 dated 22.02.2022 (approved by the Ministry of Health of Russian Federation). URL: https://static-0.minzdrav.gov.ru/system/attachments/attaches/000/059/392/original/%D0%92%D0%9C%D0%A0_COVID-19_V15.pdf (date of access 01.05.2022) (in Russian)

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