The clinical significance of determining viral load and genotype in children with congenital cytomegalovirus infection

The article presents the results of genotyping and determination of viral load in newborns with various forms of congenital cytomegalovirus infection. A retrospective analysis of clinical manifestations and results of laboratory examination of 50 children with congenital CMVI was carried out. The regions UL55, UL73, UL75 of glycoproteins B, N, H of CMV isolated from children with congenital CMVI were sequenced. The analysis showed the absence of a reliable association of viral load with the severity of the disease: in children with a mild course, the replicative activity of the virus was 9 times higher than in children with a moderate form of congenital CMVI (p = 0.011). Sequencing of the nucleotide sequences of the UL55 (gB) gene revealed 5 genotypes with a predominance of gB7 (60.0%). In the region of the UL73 gene, 6 genotypes were identified (gN1, gN2, gN3a, gN3b, gN4b, gN4c), gN4c was dominant (33.3%). 2 genotypes were found in the UL75 region: gH1 and gH2 (50.0%). When comparing the results of genotyping and clinical manifestations of the disease, a significant predominance of gB7 and gH2 genotypes (p = 0.049 and p = 0.027, respectively) was found in central nervous system pathology, including the development of meningoencephalitis.

1. Kravchenko EN, Kuklina LV, Shevlyukova TP. Vnutriutrobnaya infektsiya: faktory riska i problemy diagnostiki vo vremya beremennosti [Intrauterine infection: risk factors and diagnostic problems during pregnancy]. Akusherstvo i ginekologiya: Novosti. Mneniya. Obucheniya. 2023; 11(4):35—44. (In Russ.)

2. Belozerov ES, Bulankov YuI, Vasil'ev VV, et al. Rukovodstvo po infektsionnym boleznyam [Guide to Infectious Diseases]. Book 1. 4th ed., revised and updated. Saint Petersburg: OOO «Izdatel'stvo Foliant»; 2011:720. (In Russ.)

3. Pesch MH, Schleiss MR. Emerging Concepts in Congenital Cytomegalovirus. Pediatrics. 2022; 150(2):e2021055896. doi:10.1542/peds.2021-055896

4. Salomè S, Corrado FR, Mazzarelli LL, Maruotti GM, Capasso L, Blazquez- Gamero D, et al. Congenital cytomegalovirus infection: the state of the art and future perspectives. Front Pediatr. 2023; 11:1276912. doi:10.3389/fped.2023.1276912

5. Rogozina NV, Vasil'ev VV, Grineva AA, et al. Ante- i postnatal'naya diagnostika i kompleksnoe lechenie vrozhdennoi tsitomegalovirusnoi infektsii [Ante- and postnatal diagnosis and complex treatment of congenital cytomegalovirus infection]. Rossiiskii vestnik perinatologii i pediatrii. 2019; 64(6):89—93. (In Russ.)

6. Liberati C, Sturniolo G, Brigadoi G, Cavinato S, Visentin S, Cosmi E, et al. Burden of Congenital CMV Infection: A Narrative Review and Implications for Public Health Interventions. Viruses. 2024;16(8):1311. doi:10.3390/v16081311

7. Rogozina NV, Vasil'ev VV, Ivanova RA, Ushakova GM, Bezverkhaya NS. Porazheniya organov i sistem u detei, rodivshikhsya ot materei s ostroi tsitomegalovirusnoi infektsiei [Damage to organs and systems in children born to mothers with acute cytomegalovirus infection]. Infektsionnye bolezni: novosti, mneniya, obuchenie. 2023;12(2):57—64. (In Russ.)

8. Agafonova AV, Vasil'ev VV, Rogozina NV. Morfologicheskaya kharakteristika platsenty pri infektsionnom porazhenii [Morphological characteristics of the placenta in infectious lesions]. Prakticheskaya meditsina. 2021; 19(1):8—14. (In Russ.)

9. Marsico C, Aban I, Kuo H, James SH, Sanchez PJ, Ahmed A, et al.; Collaborative Antiviral Study Group (CASG). Blood Viral Load in Symptomatic Congenital Cytomegalovirus Infection. J Infect Dis. 2019; 219(9):1398— 1406. doi:10.1093/infdis/jiy695

10. De Cuyper E, Acke F, Keymeulen A, De Leenheer E, Van Hoecke H, Padalko E, et al. Risk Factors for Natural Hearing Evolution in Newborns With Congenital Cytomegalovirus Infection. JAMA Otolaryngol Head Neck Surg. 2024;150(1):30—38. doi:10.1001/jamaoto.2023.3507

11. Smiljkovic M, Le Meur JB, Malette B, Boucoiran I, Minsart AF, Lamarre V, et al. Blood viral load in the diagnostic workup of congenital cytomegalovirus infection. J Clin Virol. 2020;122:104231. doi:10.1016/j.jcv.2019.104231

12. Boppana SB, Fowler KB, Pass RF, Rivera LB, Bradford RD, Lakeman FD, Britt WJ. Congenital cytomegalovirus infection: association between virus burden in infancy and hearing loss. J Pediatr. 2005;146(6):817—823. doi:10.1016/j.jpeds.2005.01.059

13. Lanari M, Lazzarotto T, Venturi V, Papa I, Gabrielli L, Guerra B, et al. Neonatal cytomegalovirus blood load and risk of sequelae in symptomatic and asymptomatic congenitally infected newborns. Pediatrics. 2006; 117(1): e76—e83. doi:10.1542/peds.2005-0629.

14. Kabani N, Pinninti S, Boppana S, Fowler K, Ross S. Urine and Saliva Viral Load in Children with Congenital Cytomegalovirus Infection. J Pediatric Infect Dis Soc. 2023;12(4):230—233. doi:10.1093/jpids/piad013

15. Puhakka L, Pati S, Lappalainen M, Lönnqvist T, Niemensivu R, Lindahl P, et al. Viral shedding, and distribution of cytomegalovirus glycoprotein H (UL75), glycoprotein B (UL55), and glycoprotein N (UL73) genotypes in congenital cytomegalovirus infection. J Clin Virol. 2020;125:104287. doi:10.1016/j.jcv.2020.104287

16. Vasil'ev VV, Rogozina NV, Markin IV. Sovremennye predstavleniya o mekhanizmakh razvitiya vrozhdennoi tsitomegalovirusnoi infektsii [Modern concepts of the mechanisms of development of congenital cytomegalovirus infection]. Zhurnal infektologii. 2023;15(2):35—46. (In Russ.)

17. Rossiiskoe obshchestvo neonatologov, Rossiiskaya assotsiatsiya spetsialistov perinatal'noi meditsiny. Klinicheskie rekomendatsii «Vrozhdennaya tsitomegalovirusnaya infektsiya» [Clinical guidelines "Congenital cytomegalovirus infection"]. Moscow; 2023:62. (In Russ.)

18. Dong N, Cao L, Zheng D, Su L, Lu L, Dong Z, et al. Distribution of CMV envelope glycoprotein B, H and N genotypes in infants with congenital cytomegalovirus symptomatic infection. Front Pediatr. 2023;11:1112645. doi:10.3389/fped.2023.1112645

19. Sarkar A, Das D, Ansari S, Chatterjee RP, Mishra L, Basu B, et al. Genotypes of glycoprotein B gene among the Indian symptomatic neonates with congenital CMV infection. BMC Pediatr. 2019;19(1):291. doi:10.1186/s12887-019-1666-5

20. Pati SK, Pinninti S, Novak Z, Chowdhury N, Patro RK, Fowler K, et al.; NIDCD CHIMES Study Investigators. Genotypic diversity and mixed infection in newborn disease and hearing loss in congenital cytomegalovirus infection. Pediatr Infect Dis J. 2013; 32(10):1050—1054. doi:10.1097/INF.0b013e31829bb0b9

21. Ross SA, Pati P, Jensen TL, Goll JB, Gelber CE, Singh A, et al. Cytomegalovirus Genetic Diversity Following Primary Infection. J Infect Dis. 2020; 221(5):715—720. doi:10.1093/infdis/jiz507

22. Dong, N., Cao, L., Zheng, D., Su, L., Lu, L., Dong, Z., Xu, M., & Xu, J. Distribution of CMV envelope glycoprotein B, H and N genotypes in infants with congenital cytomegalovirus symptomatic infection. Front Pediatr. 2023; 11:1112645. doi:10.3389/fped.2023.1112645