Clinical and immunological criteria for predicting the chronic course of herpesvirus infections in the outcome of infectious mononucleosis of various etiologies in children

• Olga I. Demina
• Tatyana A. Chebotareva
• Sofya A. Kuznetsova
• Andrej A. Cheburkin
• Dmitry S. Tikhomirov
• Olga S. Fedyanina
• Tatiana A. Tupoleva
• Ludmila N. Mazankova

Abstract

Establishing the prognostic significance of criteria for the chronicity of herpesvirus infections after the first episode of mononucleosis-like syndrome is an urgent task.

The aim of the study is to evaluate the criteria for predicting the chronic course of herpesvirus infections in children who have experienced the first episode of mononucleosis syndrome.

Material and methods. An observational cohort study was conducted. A total of 107 children with mononucleosis-like syndrome, admitted to the Z.A. Bashlyaeva Children’s City Clinical Hospital, Moscow City Health Department from 2013 to 2018, were randomly sampled. As part of the etiological diagnostics, laboratory markers of EBV, CMV, and HHV-6 were determined: the concentration of viral DNA in peripheral blood mononuclear cells by PCR and the determination of antiviral antibodies of the IgG and IgM classes by ELISA. Immunological parameters were assessed using a cellular biochip. The depth of follow-up observation ranged from 2 to 6 years. During statistical processing of the results, the reliability of the difference in frequencies was calculated using parametric and nonparametric methods, including determining the relative risk and odds ratios (RR and OR), and ROC analysis was used. Differences were considered statistically significant at p≤0.05.

Results. The distinctive symptom of EBV infection of the mono-etiological variant was splenomegaly (p<0.05); with mixed infection, difficulty in nasal breathing and hepatomegaly were significantly more often detected. Primary mono-EBV IM is the most unfavorable prognostic etiological variant – 21 (72.41%) patients with an outcome of clinical recovery compared to 8 (27.59%) children with an outcome of chronic infection, OR when compared with other etiologies variants of IM was 0.3000 (95% CI 0.1004–0.8964, p=0.03. It has been established that in case of IM caused by primary EBV infection, the predictor of the outcome in the chronic course of the infection is the immunoregulatory index (IRI) >1.2 and the proportion of CD8⁺ AM CD45RA lymphocytes <7.4%.

Conclusion. The first episode of EBV-, CMV- and HHV 6-associated infectious mononucleosis is characterized by minimal differences in the clinical picture, and therefore it is necessary to conduct laboratory tests for the presence of herpesvirus DNA in blood mononuclear cells, determining its concentration using the PCR method and IgM antibodies to herpes viruses using ELISA. As criteria for the outcome of the disease in the chronic course, it is advisable to use the immunoregulatory index and the proportion of CD8⁺ atypical mononuclear cells from the total number of lymphocytes, while the auxiliary innovative diagnostic method is the cellular biochip method.

Keywords: children; infectious mononucleosis; Epstein-Barr virus; cytomegalovirus; human herpes virus 6; cellular biochip; chronic course of infection

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