INTERLEUKIN-15 IN THE BLOOD OF PREGNANT WOMEN DEPENDING ON THE CLINICAL COURSE OF COVID-19 AT DIFFERENT TIMES OF PREGNANCY

The aim of the study was to evaluate the relationship between the concentration of interleukin-15 (IL-15) in the blood and coagulation and biochemical parameters in women with COVID-19 at different times of pregnancy and depending on the clinical course of COVID-19.
Materials and methods. The study included 60 pregnant women with COVID-19: 14 women in the first trimester, 17 in the second trimester and 29 in the third trimester. The comparison group consisted of 20 pregnant women without clinical and laboratory signs of acute respiratory viral infections. The concentration of IL-15 in the blood serum was determined by enzyme immunoassay. Statistica 10.0 (StatSoft, USA) was used for statistical data processing. The statistically significant error level was considered to be p < 0.05.
Results. The main clinical manifestations of COVID-19 in pregnant women are catarrhal respiratory syndrome (93.3 ± 3.23 % of cases), intoxication syndrome (86.7 ± 4.38 % of cases) and neurological manifestations (66.7 ± 6.08 % of cases). Pregnant women with COVID-19 had higher blood levels of IL-15 (p = 0.003). COVID-19 is characterized by a decrease in the level of IL-15 in the blood in the third trimester of gestation compared to the first and second trimesters (p = 0.001; p = 0.013). IL-15 in the blood of SARS-CoV-2-infected pregnant women had a direct correlation with prothrombin time (p = 0.017), thrombin time (p = 0.027) and international normalized ratio (p = 0.039), and an inverse correlation with the level of lymphocytes in the blood (p = 0.009), fibrinogen (p = 0.005), serum iron (p = 0.012) and direct bilirubin (p = 0.008 in mild COVID-19). Factors associated with IL-15 in the blood of pregnant women with COVID-19 are impaired sense of smell and taste (p = 0.043), cough (p = 0.014) and vomiting (p = 0.005).
Conclusion. The relationship of IL-15 concentration in the blood with coagulation and biochemical parameters in women with COVID-19 at different stages of pregnancy and depending on the clinical course of COVID-19 was evaluated.

1. Number of COVID-19 deaths reported to WHO (cumulative total). – Available at: https://data.who.int/dashboards/covid19/deaths (accessed 13 January 2025).

2. Kumar, R. SARS-CoV-2 infection during pregnancy and pregnancy-related conditions: Concerns, challenges, management and mitigation strategies-a narrative review / R. Kumar, C. M. Yeni, N. A. Utami [et al.] // J. Infect. Public. Health. – 2021. – Vol. 14, № 7. – P. 863–875. – doi: 10.1016/j.jiph.2021.04.005.

3. Aghaeepour, N. An immune clock of human pregnancy / N. Aghaeepour, E. A. Ganio, D. Mcilwain et al. // Sci Immunol. – 2017. – Vol. 2, № 15, eaan2946. – doi: 10.1126/sciimmunol.aan2946.

4. Liu, H. Why are pregnant women susceptible to COVID-19? An immunological viewpoint / H. Liu, L. L. Wang, S. J. Zhao [et al.] // J. Reprod. Immunol. – 2020. – Vol. 139. – P. 103122. – doi: 10.1016/j.jri.2020.103122.

5. Amin, M. N. Inflammatory cytokines in the pathogenesis of cardiovascular disease and cancer / M. N. Amin, S. A. Siddiqui, M. Ibrahim [et al.] // SAGE Open Med. – 2020. – Vol. 8. – P. 205031212096575. – doi: 10.1177/2050312120965752.

6. Wang, X. Transcription factors associated with IL-15 cytokine signaling during NK cell development / X. Wang, X. Y. Zhao // Front Immunol. – 2021. – Vol. 12. – P. 610789. – doi: 10.3389/fimmu.2021.610789.

7. Lodolce, J. P. Regulation of lymphoid homeostasis by interleukin-15 / J. P. Lodolce, P. R. Burkett, R. M. Koka [et al.] // Cytokine Growth Factor Rev. – 2002. – Vol. 13, № 6. – P. 429–439. – doi: 10.1016/S1359-6101(02)00029-1.

8. Marks-Konczalik, J. IL-2-induced activation-induced cell death is inhibited in IL-15 transgenic mice / J. Marks-Konczalik, S. Dubois, J. M. Losi [et al.] // Proc Natl Acad Sci. – 2000. – Vol. 97, № 21. – P. 11445–11450. – doi: 10.1073/pnas.200363097.

9. Bamford, R. N. Interleukin (IL) 15/IL-T production by the adult T-cell leukemia cell line HuT-102 is associated with a human T-cell lymphotrophic virus type I region/IL-15 fusion message that lacks many upstream AUGs that normally attenuates IL-15 mRNA translation / R. N. Bamford, A. P. Battiata, J. D. Burton [et al.] // Proc Natl Acad Sci. – 1996. – Vol. 93, № 7. – P. 2897–2902. – doi: 10.1073/pnas.93.7.2897.

10. Budagian, V. IL-15/IL-15 receptor biology: a guided tour through an expanding universe / V. Budagian, E. Bulanova, R. Paus [et al.] // Cytokine Growth Factor Rev. – 2006. – Vol. 17, № 4. – Р. 259–280. – doi: 10.1016/j.cytogfr.2006.05.001.

11. Anguille, S. Short-term cultured, interleukin-15 differentiated dendritic cells have potent immunostimulatory properties / S. Anguille, E. L. Smits, N. Cools [et al.] // J. Transl. Med. – 2009. – Vol. 7. – Р. 109. – doi:10.1186/1479-5876-7-109.

12. Tagaya, Y. Identification of a novel receptor/signal transduction pathway for IL-15/T in mast cells / Y. Tagaya, J. D. Burton, Y. Miyamoto [et al.] // EMBO J. – 1996. – Vol. 15, № 18. – Р. 4928–4939.

13. Quinn, L. S. Interleukin-15: a novel anabolic cytokine for skeletal muscle / L. S. Quinn, K. L. Haugk, K. H. Grabstein // Endocrinology. – 1995. – Vol. 136, № 8. – Р. 3669–7362. – doi: 10.1210/endo.136.8.7628408.

14. McInnes, I. B. Interleukin-15 mediates T cell-dependent regulation of tumor necrosis factor-alpha production in rheumatoid arthritis / I. B. McInnes, B. P. Leung, R. D. Sturrock [et al.] // Nat. Med. – 1997. – Vol. 3, № 2. – Р. 189–195. – doi: 10.1038/nm0297-189.

15. Malengier-Devlies, B. Severe COVID-19 patients display hyper-activated NK cells and NK cell-platelet aggregates / B. Malengier-Devlies, J. Filtjens, K. Ahmadzadeh [et al.] // Front Immunol. – 2022. – Vol. 13. – Р. 861251. – doi: 10.3389/fimmu.2022.861251.

16. Angioni, R. Age-severity matched cytokine profiling reveals specific signatures in Covid-19 patients / R. Angioni, R. SánchezRodríguez, F. Munari [et al.] // Cell Death Dis. – 2020. – Vol. 11, № 11. – Р. 957. – doi: 10.1038/s41419-020-03151-z.

17. Amarilla-Irusta, A. CD151 identifies an NK cell subset that is enriched in COVID-19 patients and correlates with disease severity / A. Amarilla-Irusta, O. Zenarruzabeitia, A. Sevilla [et al.] // J Infect. – 2024. – Vol. 89, № 6. – Р. 106304. – doi: 10.1016/j.jinf.2024.106304.

18. Witkowski, M. Untimely TGFβ responses in COVID-19 limit antiviral functions of NK cells / M. Witkowski, C. Tizian, M. Ferreira-Gomes [et al.] // Nature. – 2021. – Vol. 600, № 7888. – Р. 295–301. – doi: 10.1038/s41586-021-04142-6.

19. Rubio, R. Maternal and neonatal immune response to SARS-CoV-2, IgG transplacental transfer and cytokine profile / R. Rubio, R. Aguilar, M. Bustamante [et al.] // Front Immunol. – 2022. – Vol. 13. – Р. 999136. – doi: 10.3389/fimmu.2022.999136.

20. Singh, A. K. Opposing roles for sMAdCAM and IL-15 in COVID-19 associated cellular immune pathology / A. K. Singh, N. Kasarpalkar, S. Bhowmick [et al.] // J. Leukoc Biol. – 2022. – Vol. 111, № 6. – Р. 1287–1295. – doi: 10.1002/JLB.3COVBCR0621-300R.