Clinical and immunological correlations in COVID-19: experience of immunomodulatory therapy

Abstract

Introduction. Attempts to influence the interaction between SARS-CoV-2 and immune system provide additional opportunities to prevent both COVID-19 development and progression of its complications.

Aim of the study - to evaluate the reasonability of immunomodulatory therapy in the complex treatment of hospitalized COVID-19 patients.

Material and methods. 43 hospitalized patients with COVID-19 were included in the study: comparison group (n = 21) and the main group (n = 22), in which on the 7-14th day of hospitalization after standard complex treatment was additionally used a protease inhibitor with virocidal properties, aprotinin, aminodihydrophthalazinedione sodium (Galavit®), normal human immunoglobulin (IgG, IgA, IgM), interferon alpha-2b.

The following indicators were assessed at 1-3, 5-7 and 9-15 days from the start of the immunomodulatory therapy: level of interleukin(IL)-6, T cells (T-helpers and cytotoxic T-lymphocytes), immunoregulatory index (СD4+/СD8+ ratio). The indices were measured by EIA, cytofluorimetric and immunochemiluminescent methods.

Results. In the main group pro-inflammatory cytokine IL-6 level significantly decreased against the background of immunomodulatory therapy, IL-6 level changes directly correlated with the use of immunomodulators. In the main group, the level of T-cell subpopulations began to recover starting from the 3rd day of observation, reaching the lower normal limit by the 14th day of treatment with immunomodulators. After 7 days of observation, in 18 (81.8 %) patients with SARS-CoV-2 in the main group CD4+/CD8+ ratio was ≥ 1.4. In the comparison group, 15 (71.4 %) patients with moderate disease course had a CD4+/CD8+ ratio ≤ 1.4 and 2 (9.5 %) patients had CD4+/CD8+ ratio of ≥ 1.4. Viral load decreased significantly faster in the main group (p ≤ 0.005). According to PCR tests, SARS-CoV-2 elimination occurred in the main group at day 11 in all patients, and in the comparison group, the PCR test was negative only in 4 out of 20 patients (25 %) on the 21st day of the disease. АП patients in the main group showed positive clinical dynamics. In the comparison group, despite the standard treatment carried out, no significant positive dynamics was achieved; noted the addition of a secondary bacterial infection on the 21st day of the disease.

Conclusion. Thus, immunomodulatory therapy may improve the effectiveness of treatment of patients with COVID-19.

Keywords:immunity; cytokines; IL-6; T-lymphocytes; lymphopenia; COVID-19; SARS-CoV-2; immunomodulators; aminodihydrophthalazinedione sodium; Galavit®; aprotinin

For citation: Khorobryh T.V., Makhnach G.K., Volgin M.V., Khorobryh V.V., Mishchenko N.P., Ivashchenko A.A., Loginov V.G., Yakubova E.V. Clinical and immunological correlations in COVID-19: experience of immunomodulatory therapy. Immunologiya. 2021; 42 (4): 376-84. DOI: https://doi.org/10.33029/0206-4952-2021-42-4-376-384 (in Russian)

Funding. The study had no sponsor support.

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

References

1. Tang N., Li D., Wang X., Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J. Thromb. Haemost. 2020; 18 (4): 844–7. DOI: https://doi.org/10.1111/jth.14768

2. Bottcher-Friebertshauser E., Klenk H. D., Garten W. Activation of influenzа viruses by proteases from host cells and bacteria in the human airway epithelium. Pathog. Dis. 2013; 69 (2): 87–100. DOI: https://doi.org/10.1111/2049-632X.12053

3. Moore J.B., June C.H. Cytokine release syndrome in severe COVID-19. Science. 2020; 368 (6490): 473–4. DOI: https://doi.org/10.1126/science.abb8925

4. Blanco-Melo D., Nilsson-Payant B.E., Liu W.-C., Lim J.K., Albrecht R.A., ten Oever B.R. Imbalanced host response to SARS-CoV-2 drives development of COVID-19. Cell. 2020; 181 (5): 1036–45.e9. DOI: https://doi.org/10.1016/j.cell.2020.04.026

5. Mareev V.Y., Orlova Y.A., Pavlikova E.P., et al. Proactive anti-inflammatory and anticoagulant therapy in the treatment of advanced stages of new coronavirus infection (COVID-19). Clinical case review and study design: COVICIN vs ruxolitinib AND secukinumab in an open-label, prospective, randomised trial in patients with COVID-19 (COVID). Cardiology. 2020; 60 (9). DOI: https://doi.org/10.18087/cardio.2020.9.n1338

6. Pillay T.S. Gene of the month: the 2019-nCoV/SARS-CoV-2 novel coronavirus spike protein. J. Clin. Pathol. 2020; 73 (7): 366–9. DOI: https://doi.org/10.1136/jclinpath-2020-206658

7. Zhirnov O.P., Klenk H.D., Wright P.F. Aprotinin and similar protease inhibitors as drugs against influenza. Antiviral Res. 2011; 92 (1): 27–36.

8. Zhirnov O. P., Malyshev N. A.. New developments in the treatment of influenza and acute respiratory viral infections with aprotinin using a metered dose mini-propellant hand-held inhaler [Electronic resource]. The attending physician. 2014; (1): 57–62. DOI: https://www.lvrach.ru/2014/01/15435873/ (date of access July 17, 2020) (in Russian)

9. Sologub T.V., Osinovets O.Yu. Use of the immunomodulatory drug Galavit in the treatment of influenza. Clinician. 2012; (2): 1–5. (in Russian)

10. Latysheva T.V., Setdikova N.H., Man’ko K.S. Secondary immunodeficiencies. Potential use of the domestic immunomodulator galavit. Cytokines and inflammation. 2005; 4 (3): 95–9. (in Russian)

11. Korsunsky V.N., Bruskin A.B., Denisov L.A., Ivanov R.A. Comparative study of the pharmacokinetics of different dosage forms of interferon alfa-2b. Effective pharmacotherapy in obstetrics and gynecology. 2007; (1): 24–9. (in Russian)

12. Provisional methodological recommendations «Prevention, diagnosis and treatment of new coronavirus infection (2019-nCoV)» RF Ministry of Health of the Russia, Version 4 (27.03.2020) [Electronic resource]. URL: https://static3.rosminzdrav.ru/system/attachments/attaches/000/049/877/original/COVID19_recomend_v4.pdf (date of access July 17, 2020) (in Russian)

13. Provisional methodological recommendations «Prevention, diagnosis and treatment of new coronavirus infection (2019-nCoV)» RF Ministry of Health of the Russia, Version 6 (28.04.2020) [Electronic resource]. URL: https://static1.rosminzdrav.ru/system/attachments/attaches/000/050/122/original/28042020_%D0%9CR_COVID-19_v6.pdf (date of access July 17, 2020) (in Russian)

14. Order of the Ministry of Health of the Russian Federation No. 198n of 19.03.2020 «On temporary procedure for the organization of work of medical organizations in order to implement measures to prevent and reduce the risks of spread of new coronavirus infection COVID 19)». As amended by Order of the Ministry of Health of Russia of 27.03.2020 No. 246n, of 02.04.2020 No. 264n, of 29.04.2020 No. 385n, of 18.05.2020 No. 459n) [Electronic resource]. URL: https://minjust.consultant.ru/documents/45802 (date of access July 17, 2020) (in Russian)

15. Rospotrebnadzor letter No. 02/6509-2020-32 of 9 April 2020 on recommendations to prevent the spread of new coronavirus infection in healthcare organisations [Electronic resource]. URL: https://www.rospotrebnadzor.ru/region/korono_virus/rek_ros.php (date of access July 17, 2020) (in Russian)

16. Tay M.Z., Poh C.M., Rnia L., MacAry P.A., Ng L.F.P. The trinity of COVID-19: immunity, inflammation and intervention. Nat. Rev. Immunol. 2020; 20 (6): 363–74. DOI: https://doi.org/10.1038/s41577-020-0311-8

All articles in our journal are distributed under the Creative Commons Attribution 4.0 International License (CC BY 4.0 license)


JOURNALS of «GEOTAR-Media»