The impact of passive immunoprophylaxis against respiratory syncytial virus infection on the frequency and severity of acute respiratory diseases and proteolytic enzyme levels in children aged 1–3 years

Preventing respiratory diseases in young children remains a primary focus in pediatric healthcare.

Purpose. To evaluate the impact of passive immunization against respiratory syncytial virus (RSV) in children at high risk of severe RSV infection on the incidence of respiratory illnesses and the levels of proteolytic enzyme biomarkers in children aged 1–3 years.

Material and methods. The study included 216 children aged 0–3 years, divided into three groups: Main Group 1 (children who received RSV immunization), Main Group 2 (children without immunization), and a control group (health groups I and II). Health assessments were conducted during the newborn period and at ages 1–3 years. Biomarkers of pulmonary proteolytic enzymes were measured, including matrix metalloproteinases 2 (MMP-2) and 9 (MMP-9), tissue inhibitor of matrix metalloproteinase-2 (TIMMP-2), and vascular endothelial growth factor (VEGF-D).

Results. The absence of RSV immunoprophylaxis in the first year of life significantly contributed to the development of recurrent obstructive bronchitis (AP = 46%) and pneumonia (AP = 49.7%) in early childhood. An association was identified between MMP-9 and TIMMP-2 levels in serum and the frequency of recurrent obstructive bronchitis at ages 1–3 years. The lack of passive RSV immunization during the first year of life increased the likelihood of VEGF-D levels reaching very high values (≥97‰) by a factor of 10. An increased risk of recurrent obstructive bronchitis was also observed at elevated VEGF-D levels (≥90‰). Completing the RSV immunization cycle was associated with a significant reduction in respiratory disease cases and decreased VEGF-D levels.

Conclusion. Passive immunization against RSV in children at risk for severe RSV infection is associated with a reduction in respiratory disease incidence, recurrent obstructive bronchitis, and pneumonia, as well as an impact on fibrosis markers in children aged 1–3 years.

1. Baranov A.A., Namazova-Baranova L.S., Davydova I.V., Bokeriya E.L., Vishnyova E.A., Fedoseyenko M.V., Selimzyanova L.R. Immunoprophylaxis of Respiratory Syncytial Virus Infection in Children. Pediatricheskaya farmakologiya 2015; 12(5): 543–549. (in Russ.) DOI: 10.15690/pf.v12i5.1456

2. Namazova-Baranova L.S., Turti T.V., Keshishyan E.S., Davydova I.V., Galustyan A.V., Harris B. et al. Safety and Efficacy of Palivizumab in Children at High Risk of Severe Respiratory Syncytial Virus Infection in the Russian Federation. Farmateka 2016; 1: 43–50. (in Russ.)

3. Karampatsas К., Kong J. Bronchiolitis: an update on management and prophylaxis. Br J Hospital Med 2019; 80(5): 278– 284. DOI: 10.12968/hmed.2019.80.5.278

4. Tavares V.B., E Souza J.S., Affonso M.V.G. Factors associated with 5-min APGAR score, death and survival in neonatal intensive care: a case-control study. BMC Pediatr 2022; 22(1): 560. DOI: 10.1186/s12887–022–03592–9

5. Wang X.-.Y, Wang B., Wen Y.-M. From therapeutic antibodies to immune complex vaccines. npj Vaccines 2019; 4: 2. DOI: 10.1038/s41541–018–0095-z

6. Soto J.A., Gálvez N.M.S., Pacheco G.A., Bueno S.M., Kalergis A.M. Antibody development for preventing the human respiratory syncytial virus pathology. Molr Med 2020; 26(1): 35. DOI:10.1186/s10020–020–00162–6

7. Krsheminskaya I.V., Ovsyannikov D.Yu., Degtyarev D.N., Degtyareva E.A. Respiratory syncytial viral bronchiolitis in nedonoshennykh children and predictors of its severe course. Neonatologiya: novosti, mneniya, obuchenie 2016; 2(12): 67–80. (in Russ.)

8. Simões M.C.R.D.S., Inoue Y., Matsunaga N.Y., Carvalho M.R.V., Ribeiro G.L.T., Morais E.O. et al. Recurrent wheezing in preterm infants: Prevalence and risk factors. J Pediatr (RioJ) 2019; 95(6): 720–727. DOI: 10.1016/j.jped.2018.06.007

9. Kuryanova Sh.M., Khudainazarovа S.R., Ilkhomova Kh.A. Features of the spread of respiratory diseases in children and some immunological indicators. V International Scientific Conference «Medicine and Health Care» 2020; 45–47. DOI:10.26787/nydha-2618–8783–2021–6–4–45–51

10. Cui N., Hu M., Khalil R.A. Biochemical and Biological Attributes of Matrix Metalloproteinases. Progress Mol Biol Translat Scie 2017; 147: 1–73. DOI: 10.1016/bs.pmbts.2017.02.005

11. Bronchopulmonary dysplasia. In: Avery’s Neonatology. 6th. Ed. Editors M.G. MacDonald, M.M. Seshia, M.D. N.-Y. Mullert: Lippincott Williams & Wilkins, 2015; 578–599.

12. Yeoh D.K., Foley D.A. , Minney-Smith C.A., Martin A.C., Mace A.O., Sikazwe C.T. et al. Impact of Coronavirus Disease 2019 Public Health Measures on Detections of Influenza and Respiratory Syncytial Virus in Children During the 2020 Australian Winter. Clin Infect Dis 2021; 72(12): 2199–2202. DOI: 10.1093/cid/ciaa1475

13. Zhang S., Akmar L.Z., Bailey F., Rath B.A., Alchikh M., Schweiger B. et al. Cost of respiratory syncytial virus-associated acute lower respiratory infection management in young children at the regional and global level: a systematic review and meta-analysis. J Infect Dis 2020; 222: 680–687. DOI: 10.1093/infdis/jiz683

14. Hirono J., Sanaki H. Expretion of tissue inhibitor of metalloproteinases and matrix metalloproteinases in the ischemic brain of photothrombosis model mice. NeuroReport 2018; 29: 174–180. DOI: 10.1097/wnr.0000000000000946

15. Cui N., Hu M., Khalil R.A. Biochemical and Biological Attributes of Matrix Metalloproteinases. Progress Mol Biol Translat Scie 2017; 147: 1–73. DOI: 10.1016/bs.pmbts.2017.02.005

16. Kelmanson I.A. Principles of evidence-based pediatrics. St. Petersburg: Foliant, 2004; 240. (in Russ.)