Results of 5-year monitoring of the circulation of seasonal Сoronaviruses in hospitalized children in the pre-pandemic period

Coronaviruses can cause damage to various parts of the respiratory system, gastrointestinal tract, and other organs and systems.The aim of the study: to monitor the circulation of seasonal coronaviruses in hospitalized children in the pre-pandemic period.

Materials and methods: real-time multiplex PCR was used to test samples of nasopharyngeal mucus from 2188 patients aged 1 monthto 17 years, hospitalized with acute respiratory infection in 2014—2018. The results are presented with the indication of the fractions (%) and the calculation of the 95% confidence interval according to Klopper-Pearson. The differences between the groups were evaluated using the Pearson χ2 test. The differences in the groups were considered statistically significant at the level of the criterion p< 0.05.

Results: monitoring of the circulation of pathogens of acute respiratory viral infection (ARVI) during 5 epidemic seasons showed that the appearance of a new subtype of coronavirus in 2019 was preceded by a gradual displacement of influenza, RS-and bocavirus infections from the circulation due to a statistically significant increase in the proportion of seasonal coronaviruses from 3.6% in 2014—2015 to 10.8% in the prepandemic season 2018—2019 (p= 0.007). The circulation of seasonal coronaviruses had a distinct seasonality (november-april)with the peak of registration in february (28.4%) and march (36.7%). Seasonal coronaviruses were detected in 7.3% of hospitalized children with ARVI, with a predominance in the age groups under 2 years (58.2%) and 3—6 years (25.4%). Hospitalization was more often required for patients with lower respiratory tract lesions (58.2%), a fifth of which was pneumonia (21.8%). In most children, ARVI caused by coronaviruses occurred as a monoinfection (79.9%), combined infection with other pathogens was observed in 20.1% of cases with fluctuations from 18.2% to 28.6% in different epidemic seasons. Viral associations are most common in young children (85.2%).

1. Monto AS, DeJonge PM, Callear AP, Bazzi LA, Capriola SB, Malosh RE, Martin ET, Petrie JG. Coronavirus Occurrence and Transmission Over 8 Years in the HIVE Cohort of Households in Michigan. The Journal of Infectious Diseases.2020:1—8. https://doi.org/10.1093/infdis/jiaa161

2. Timchenko V.N., Sukhovetskaya V.F., Chernova T.M, Barakina E.V.,Pochinyaeva L.M., Malinovskaya V.V., Semenenko T.A., Shuvalov A.N. The role of early etiological decoding of acute respiratory viral infections in antiviral therapy choice for children in a hospital setting. Pediatriya=Pediatrics.2020; 99(1):101—106. (In Russ.) DOI: 10.24110/0031-403X-2020-99-1-100-106

3. Heimdal I, Moe N, Krokstad S, Christensen А., Skanke L.H., Nordbø S.A., Døllner Н. Human coronavirus in hospitalized children with respiratory tract infections: a 9-year population-based study from Norway. J Infect Dis. 2019; 219:1198—1206. DOI: 10.1093/infdis/jiy646

4. Lau SK, Woo PC, Yip CC, Tse H, Tsoi HW, Cheng VC, Lee P, Tang BS, Cheung CH, Lee RA, So LY, Lau YL, Chan KH, Yuen K. Coronavirus HKU1 and other coronavirus infections in Hong Kong. Journal of Clinical Microbiology. 2006; 44(6):2063—2071. DOI: 10.1128/JCM.02614-05

5. Ivanov D.O., Chernova T.M., Pavlova E.B., Timchenko V.N., Barakina E.V. Coronaviral infection. Pediatr=Pediatrician. 2020; 11(3): 109—117. (In Russ.) https://doi.org/10.17816/PED113109-117

6. Pene F, Merlat A, Vabret A, Rozenberg F, Buzyn A, Dreyfus F, Cariou A, Freymuth F., Lebon P. Coronavirus 229E-related pneumonia in immunocompromised patients. Clin Infect Dis.2003; 37(7):929—932. https://doi.org/10.1086/377612

7. Kuypers J, Martin ET, Heugel J, Wright N, Morrow R, Englund JA. Clinical disease in children associated with newly described coronavirus subtypes. Pediatrics.2007; 119(1):e70—6. DOI: 10.1542 / peds.2006-1406

8. Risku M., Lappalainen S., Räsänen S., Vesikari T. Detection of human coronaviruses in children with acute gastroenteritis. Journal of Сlinical Virology.2010; 48(1):27—30. DOI: 10.1016/j.jcv.2010.02.013

9. Paloniemi M., Lappalainen S., Vesikari T. Commonly circulating human coronaviruses do not have a significant role in the etiology of gastrointestinal infections in hospitalized children. Journal of Clinical Virology.2014; 62:114—117. DOI: 10.1016/j.jcv.2014.10.017

10. Jevšnik М., Steyer А., Pokorn М., Mrvič Т., Grosek Š., Strle F., Lusa L., Petrovec М. The Role of Human Coronaviruses in Children Hospitalized for Acute Bronchiolitis, Acute Gastroenteritis, and Febrile Seizures: A 2-Year Prospective Study. Plos One.2016. https://doi.org/10.1371/journal.pone.0155555

11. Stewart JN, Mounir S, Talbot PJ. Human coronavirus gene expression in the brains of multiple sclerosis patients. Virology.1992; 191(1):502—505. DOI: 10.1016/0042-6822(92)90220-j

12. Yeh EA, Collins A, Cohen ME, Duffner PK, Faden H. Detection of coronavirus in the central nervous system of a child with acute disseminated encephalomyelitis. Pediatrics.2004; 113(1Pt1): 73—76. DOI:10.1542/peds.113.1e73

13. Esper F., Shapiro E.D., Weibel C., Ferguson D., Landry M L., Kahn J.S. Association between a Novel Human Coronavirus and Kawasaki Disease. The Journal of Infectious Diseases.2005; 191(4):499—502. https://doi.org/10.1086/428291

14. Principi N., Bosis S., Esposito S. Effects of Coronavirus Infections in Children. Emerg Infect Dis.2010 Feb; 16(2):183—188. DOI: 10.3201/eid1602.090469

15. Dokhov M.A., Tikhomirova A.A., Vaulin G.F. Nonparametric criteria in the program "Statistica": Study guide. Sankt-Peterburg:SPbGPMU. 2019:40. (In Russ.).

16. Varghese L, Zachariah P, Vargas C, LaRussa Ph., Demmer R.T., Furuya Yo.E, Whittier S., Reed C., Stockwell M.S., Saiman L. Epidemiology and clinical features of human coronaviruses in the pediatric population. J Pediatric Infect Dis. 2018; 7:151—158. DOI: 10.1093/jpids/