Bacterial ligands in the rehabilitation of healthcare workers after COVID-19
https://doi.org/10.18093/0869-0189-2022-32-5-716-727
Abstract
Immune defense mechanisms in survivors of the COronaVIrus Disease-19 (COVID-19) and development of their rehabilitation during the pandemic both portray a great scientific and practical interest.
The aim of the study was to explore effect of Immunovac-VP-4® (I-VP-4), a vaccine based on bacterial ligands, on the clinical and airway mucosal immunity parameters, along with systemic immune response in a group of medical workers in post-COVID period and in persons who did not develop the disease.
Methods. 82 healthcare workers aged from 18 to 65 years were included in a prospective open controlled study. The participants were divided into 4 groups: groups 1 (n = 20) and 2 (n = 27) included those with a history of COVID-19, and groups 3 (n = 18) and 4 (n = 17) included those who did not have the disease. Volunteers in groups 1 and 3 received I-VP-4. Samples of oral fluid, induced sputum, nasopharyngeal and oropharyngeal mucosa scrapings, and venous blood were examined. The levels of total secretory immunoglobulin class A (sIgA) and immunoglobulin G (IgG) were determined by enzyme immunoassay. The phagocytic index (PI) of leukocytes was assessed by flow cytometry.
Results. The group of patients who did not have COVID-19 and received IVP-4 (Group 3) showed a tendency to a smaller number of COVID-19 cases, as well as some reduction in days of incapacity for work due to the acute respiratory infections (ARI). The vaccine improved airway mucosal immunity parameters and innate immune response. sIgA increased in the induced sputum (p < 0.005) and unchanged in the oropharyngeal mucosa samples in Group 1. The PI of macrophages in oral fluid doubled (p < 0.05) in this group. At the same time, those parameters decreased in Group 2. In non-infected vaccinated patients (Group 3), a significant increase of PI of blood monocytes was found on the day 90 of the study (p < 0.05). Also, a four-fold increase of PI of macrophages in oral fluid in comparison with Group 4 (p < 0.05) was noted.
Conclusion. I-VP-4 improved airway mucosal immunity mechanisms and the systemic immune response. The vaccine can be recommended for rehabilitation programs for COVID-19 survivors and for prevention of ARIs.
Keywords
About the Authors
N. O. KryukovaRussian Federation
Nadezhda O. Kryukova, Assistant, Post-Graduate Student, Department of Hospital Therapy, Pediatrics Faculty
ul. Ostrovityanova 1, Moscow, 117997
Competing Interests:
Отсутствие конфликта интересов
N. D. Abramova
Russian Federation
Natalia D. Abramova, Post-Graduate Student, Junior Researcher, Laboratory of Molecular Immunology
Maly Kazenny per. 5A, Moscow, 105064
Competing Interests:
Отсутствие конфликта интересов
E. A. Khromova
Russian Federation
Ekaterina A. Khromova, Candidate of Medicine, Research Associate, Laboratory for Vaccine Prevention and Immunotherapy of Allergic Diseases
Maly Kazenny per. 5A, Moscow, 105064
Competing Interests:
Отсутствие конфликта интересов
A. A. Khasanova
Russian Federation
Al’bina A. Khasanova, Post-Graduate Student, Department of Infectious Diseases
ul. L’va Tolstogo 42, Ulyanovsk, 432017
Competing Interests:
Отсутствие конфликта интересов
I. V. Bisheva
Russian Federation
Irina V. Bisheva, Research Associate, Laboratory of Mechanisms of Regulation of Immunity
Maly Kazenny per. 5A, Moscow, 105064
Competing Interests:
Отсутствие конфликта интересов
S. A. Skhodova
Russian Federation
Svetlana A. Skhodova – Candidate of Biological sciences, Leading Researcher, Laboratory of Mechanisms of Regulation of Immunity
Maly Kazenny per. 5A, Moscow, 105064
Competing Interests:
Отсутствие конфликта интересов
M. P. Kostinov
Russian Federation
Mikhail P. Kostinov, Doctor of Medicine, Professor, Department of Epidemiology and Modern Vaccination Technologies, Federal State Autonomous Educational Institution of Higher Education I.M.Sechenov First Moscow State Medical University of the Ministry of Healthcare of the Russian Federation (Sechenovskiy University), Head of the Laboratory for Vaccine Prevention and Immunotherapy of Allergic Diseases, Federal State Budgetary Scientific Institution “I.Mechnikov Research Institute of Vaccines and Sera”
Maly Kazenny per. 5A, Moscow, 105064,
ul. Trubetskaya 8, build. 2, Moscow, 119991
Competing Interests:
Отсутствие конфликта интересов
I. A. Baranova
Russian Federation
Irina A. Baranova, Doctor of Medicine, Professor, Department of Hospital Therapy, Pediatrics Faculty
ul. Ostrovityanova 1, Moscow, 117997
Competing Interests:
Отсутствие конфликта интересов
O. A. Svitich
Oxana А. Svitich, Doctor of Medicine, Professor, Corresponding Member of Russian Academy of Sciences, Director, Federal State Budgetary Scientific Institution “I.Mechnikov Research Institute of Vaccines and Sera”; Professor, Department of Immunology, Faculty of Medicine and Biology, Pirogov Russian National Research Medical University (Pirogov Medical University), Healthcare Ministry of Russia
ul. Ostrovityanova 1, Moscow, 117997,
Maly Kazenny per. 5A, Moscow, 105064
Competing Interests:
Отсутствие конфликта интересов
A. G. Chuchalin
Alexander G. Chuchalin, Doctor of Medicine, Professor, Academician of Russian Academy of Sciences, Head of Department of Hospital Internal Medicine, Pediatric Faculty
ul. Ostrovityanova 1, Moscow, 117997
References
1. World Health Organization. Russian Federation Coronavirus (COVID-19) statistics. Available at: https://covid19.who.int/region/euro/country/ru
2. Shah W., Hillman T., Playford E.D., Hishmeh L. Managing the long term effects of covid-19: summary of NICE, SIGN, and RCGP rapid guideline. BMJ. 2021; 372: n136. DOI: 10.1136/bmj.n136.
3. Greenhalgh T., Knight M., A’Court C. et al. Management of postacute COVID-19 in primary care. BMJ. 2020; 370: m3026. DOI: 10.1136/bmj.m3026.
4. World Health Organization. A clinical case definition of post COVID-19 condition by a Delphi consensus, 6 October 2021. Available at: https://apps.who.int/iris/handle/10665/345824
5. Terpos E., Ntanasis-Stathopoulos I., Elalamy I. et al. Hematological findings and complications of COVID-19. Am. J. Hematol. 2020; 95 (7): 834–847. DOI: 10.1002/ajh.25829.
6. Dzinamarira T., Murewanhema G., Mhango M. et al. COVID-19 prevalence among healthcare workers: а systematic review and meta-analysis. Int. J. Environ. Res. Public Health. 2021; 19 (1): 146. DOI: 10.3390/ijerph19010146.
7. Egorova N.B., Akhmatova N.K., Semenova I.B. et al. [Molecular and cellular bases of the immune regulation, immunodiagnostics and immunotheraphy (experemental models)]. Meditsinskaya immunologiya. 2006, 8 (2–3): 137–138. DOI: 10.15789/1563-0625-2006-2-3-113-194 (in Russian).
8. Pashchenkov M.V., Pinegin B.V. [Cell physiology of innate immune system: dendritic cells]. Immunologiya. 2006; 27 (6): 368–378. Available at: https://elibrary.ru/item.asp?id=9432023 (in Russian).
9. Grifoni A., Weiskopf D., Ramirez S.I. et al. Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals. Cell. 2020; 181 (7): 1489–1501.e15. DOI: 10.1016/j.cell.2020.05.015.
10. Egorova N.B., Kurbatova Ye.A. [An immunotherapeutic concept of microbial antigen application in atopy and disorders associated with facultative microflora, as exemplified by a polycomponent Immunovac-VP-4 vaccine]. Meditsinskaya immunologiya. 2008; 10 (1): 13–20. DOI: 10.15789/1563-0625-2008-1-13-20 (in Russian).
11. Ministry of Health of the Russian Federation. [The Temporary Guidelines: Prevention, diagnosis and treatment of novel coronavirus infection (COVID-19)]. 2020. Available at: http://profilaktika.su/vremennye-metodicheskie-rekomendatsii-koronavirus-2019-ncov (in Russian).
12. De Vries J., Michielsen H.J., Van Heck G.L. Assessment of fatigue among working people: a comparison of six questionnaires. Occup. Environ. Med. 2003; 60 (Suppl. 1): i10–15. DOI: 10.1136/oem.60.suppl_1.i10.
13. Guiot J., Demarche S., Henket M. et al. Methodology for sputum induction and laboratory processing. J. Vis. Exp. 2017; (130): 56612. DOI: 10.3791/56612.
14. Oliferuk N.S., Arshinova S.S., Martynov А.I., Pinegin B.V. [Normative parameters of the human phagocytе system determined by flow cytometry: manual for doctors of clinical laboratory diagnostics]. Moscow: MBK Konsalting, 2009. Available at: https://www.elibrary.ru/item.asp?id=22684680 (in Russian).
15. Nesterova I.V., Chudilova G.A., Kovaleva S.V. et al. [Methods for a comprehensive assessment of the functional activity of neutrophilic granulocytes in normal and pathological conditions: Guidelines for immunologists-allergists, doctors and biologists of clinical laboratory diagnostics]. Krasnodar: Publishing House of the Kuban State Medical University; 2017. Available at: https://www.ksma.ru/cms/files/metodicheskie%20rekomendacii%20po%20ng_2017.pdf (in Russian).
16. Egorova N.B., Kurbatova E.A., Gruber I.M., Semenova I.B. [Immunovac-VP-4 in the prevention of acute respiratory diseases in children’s organized groups]. Zhurnal mikrobiologii, epidemiologii i immunobiologii. 2010; (6): 35–40. Anailable at: https://elibrary.ru/item.asp?id=31267700 (in Russian).
17. Janeczek K., Kaczyńska A., Emeryk A., Cingi C. Perspectives for the use of bacterial lysates for the treatment of allergic rhinitis: A systematic review. J. Asthma Allergy. 2022; 15: 839–850. DOI: 10.2147/JAA.S360828.
18. Varadhachary A., Chatterjee D., Garza J. et al. Salivary anti-SARSCoV-2 IgA as an accessible biomarker of mucosal immunity against COVID-19. medRxiv. 2020. DOI: 10.1101/2020.08.07.20170258.
19. Isho B., Abe K.T., Zuo M. et al. Persistence of serum and saliva antibody responses to SARS-CoV-2 spike antigens in COVID-19 patients. Sci. Immunol. 2020; 5 (52): eabe5511. DOI: 10.1126/sciimmunol.abe5511.
20. Fang L., Zhou L., Tamm M., Roth M. OM-85 Broncho-Vaxom®, a bacterial lysate, reduces SARS-CoV-2 binding proteins on human bronchial epithelial cells. Biomedicines. 2021; 9 (11). DOI: 10.3390/biomedicines9111544.
21. Cirauqui C., Benito-Villalvilla C., Sánchez-Ramón S. et al. Human dendritic cells activated with MV130 induce Th1, Th17 and IL-10 responses via RIPK2 and MyD88 signalling pathways. Eur. J. Immunol. 2018; 48 (1): 180–193. DOI: 10.1002/eji.201747024.
22. Benito-Villalvilla C., Cirauqui C., Diez-Rivero C.M. et al. MV140, a sublingual polyvalent bacterial preparation to treat recurrent urinary tract infections, licenses human dendritic cells for generating Th1, Th17, and IL-10 responses via Syk and MyD88. Mucosal Immunol. 2017; 10 (4): 924–935. DOI: 10.1038/mi.2016.112.
23. Mitroulis I., Ruppova K., Wang B. et al. Modulation of myelopoiesis progenitors is an integral component of trained immunity. Cell. 2018; 172 (1–2): 147–161.e12. DOI: 10.1016/j.cell.2017.11.034.
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For citations:
Kryukova N.O., Abramova N.D., Khromova E.A., Khasanova A.A., Bisheva I.V., Skhodova S.A., Kostinov M.P., Baranova I.A., Svitich O.A., Chuchalin A.G. Bacterial ligands in the rehabilitation of healthcare workers after COVID-19. PULMONOLOGIYA. 2022;32(5):716-727. (In Russ.) https://doi.org/10.18093/0869-0189-2022-32-5-716-727