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ORIGINAL RESEARCH

Epstein-Barr Virus Infection in Children Following Acute SARS-CoV-2 Infection
Irine Korinteli,1 Irma Korinteli,1 Leli Shanidze,2 Mzia Khalvashi,3 Eliso Turkadze4
Received: 29 May 2023; Accepted: 4 June 2023; Available online: 5 June 2023
References
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ABSTRACT
Background: Epstein–Barr virus (EBV), a human herpesvirus with potent B cell growth transforming ability, induces multiple cellular immune responses in the infected host. According to the most recent evidence, the Epstein-Barr virus is characterized by lifetime latency in B cells and intermittent recrudescence of lytic infection triggered by stresses. Furthermore, several investigations have hypothesized that autoimmune mechanisms and the persistence of SARS-CoV-2 virus fragments induce the development of long-term COVID-19. Therefore, other latent host viruses, such as Epstein-Barr virus, play an important role.

Objectives: The present study aimed to provide insight into clinical-laboratory aspects in pediatric patients with EBV after COVID-19.

Methods: This prospective study was conducted from November 2021 to November 2022 at the Tbilisi state medical university G. Zhvania Pediatric Academic Clinic. 1-3 years old, 81 outpatients with EBV infection (male 42 [51,8%] and female 66 [48,1%]) were distributed into basic (42 patients after acute SARS-CoV-2 infection) and control groups (32 patients without a history of COVDI-19). All study subjects had EBV infection markers, and conventional clinical/laboratory indices evaluated.

Results: The incidence of EBV infection is high (60.4%) in the post-COVID-19 period. Tonsil enlargement, cough, and splenomegaly were more prevalent in the basic group than in the control group: 85,7% vs. 40,6%, 81,6%, 85,7% vs. 20,5%, and 79,5% vs. 25,6%, respectively.

Conclusions: The increased incidence of EBV infection in children after the COVID-19 pandemic is a challenge requiring optimized clinical care strategies.

Keywords: COVID-19; EBV infection; SARS-CoV-2 infection.


DOI: 10.52340/GBMN.2023.01.01.32
INTRODUCTION
Epstein–Barr virus (EBV), a human double-stranded DNA herpesvirus with potent B cell growth transforming ability, induces multiple cellular immune responses in the infected host. (1-3)

According to the latest data, the Epstein–Barr virus is characterized by lifelong latency in B cells and intermittent recrudescence of lytic infection caused by stressors. (4) Some studies have suggested that autoimmune factors and the persistence of viral fragments of the SARS-CoV-2 virus cause the development of long‐term COVID-19. (5) The role of other latent host viruses, such as Epstein–Barr virus, is significant

The COVID-19 pandemic is one of the biggest challenges that has emerged concerning the health of children. As of February 7, 2023, there have been 754,816,715 confirmed cases and 830,232 deaths globally. (6) Since the beginning of the epidemic until February 2023, about 15.4 million children in the United States have tested positive for COVID-19. (7)

The first case of COVID-19 in Georgia was confirmed on February 26, 2020. (8) COVID-19 was the leading cause of morbidity in children under 15 in 2021 (1025.6 per 100,000) with high hospitalization and mortality rate (1%). (9)

According to accessible data, acute SARS-CoV-2 infection can contribute to the development of other diseases, including Epstein-Barr virus infection. (5)

In the present study, we aimed to provide insight into clinical-laboratory aspects in pediatric patients with EBV after COVID-19.
METHODS
This study was conducted from November 2021 to November 2022 at the Tbilisi state medical university G. Zhvania Pediatric Academic Clinic. 1- 3 years old, 81 outpatients with EBV infection (male 42 [51,8%] and female 66 [48,1%]) were distributed into basic (42 [60.4%] patients after acute SARS-CoV-2 infection) and control groups (32 [39.5%] patients without a history of COVDI-19).

The following investigations were performed in all study patients: full blood count (FBC), C-reactive protein (CRP), EBV serology (anti-viral capsid antigen IgM and IgG [anti-VCA IgM and anti-VCA IgG]), heterophile antibodies IgM [HA-IgM], anti-EBV nuclear antigen IgG [anti-EBNA IgG], and anti-early antigen IgG [anti-EA IgG]), and abdominal ultrasound.

Descriptive statistics and T-tests were used for statistical analysis of data. A p-value under 0.05 was considered statistically significant
RESULTS
The clinical characteristics of study patients are represented in Table 1.

TABLE 1. Clinicall characteristics of all study patients
Epstein-Barr Virus Infection in Children Following Acute SARS-CoV-2 Infection
Table 2 presents the laboratory test results in the comparator groups.

TABLE 2. . Laboratory test results of studi patients
Epstein-Barr Virus Infection in Children Following Acute SARS-CoV-2 Infection
Abbreviations: CRP, C-reactive protein; M±SD, mean ± standard deviation; WBC, white blood cells.

Table 3 contains the results of EBV serological testing.

TABLE 3. EBV serological tests in study groups
Epstein-Barr Virus Infection in Children Following Acute SARS-CoV-2 Infection
Abbreviations: anti-VCA IgG, anti-viral capsid antigen IgG; anti-VCA IgM, anti-viral capsid antigen IgM; HA IgM, heterophile antibodies IgM.
DISCUSSION
According to the existing evidence, the incidence of EBV is high after the resolution of acute SARS-CoV-2 infection.4 The results of the present study corroborate the trend mentioned above; we found that EBV exposure is 60.4% in patients after acute COVID-19 disease (p<0.05).

The distribution and frequency of clinical symptoms and signs of EBV infection in our study subjects follow the previously reported evidence. (1) Tonsil enlargement, cough, and splenomegaly were more prevalent in the basic group than in the control group: 85,7% vs. 40,6%, 81,6%, 85,7% vs. 20,5%, and 79,5% vs. 25,6%, respectively.

All laboratory test (hemoglobin, total white blood cells and their subtypes, and C-reactive protein) results were significantly higher in EBV-infected patients following the acute COVID-19, except platelet count. These findings back up the findings of Yanming Wu et al. (3)

EBV serological testing results were also different between comparators. The positive heterophile antibodies IgM (HA IgM) cases were significantly higher in EBV-infected patients after acute SARS-CoV-2 infection (p<0.05). There is no relevant literature data concerning EBV serology in children after COVID-19.
CONCLUSIONS

The increased prevalence of EBV infection in children after the COVID-19 pandemic is an issue that requires enhanced treatment measures.

AUTHOR AFFILIATION

1 Department of Child and Adolescent Medicine, Tbilisi State Medical University (TSMU), Tbilisi, Georgia

2 Department of Laboratory and Diagnostic, G. Zhvania Pediatric Academic Clinic, Tbilisi State Medical University (TSMU), Tbilisi, Georgia

3 Department of Obstetrics and Gynecology, “Brothers” International Hospital of Batumi, Batumi, Georgia

4 Department of Neonatology, The First University Clinic of Tbilisi State Medical University (TSMU), Tbilisi, Georgia

REFERENCES

  1. Alan B. Rickinson, Heather M. Long, Umaimainthan Palendira. Cellular immune controls over Epstein–Barr virus infection: new lessons from the clinic and the laboratory/Trends in Immunology Volume 35, Issue 4, April 2014, Pages 159-169, https://doi.org/10.1016/j.it.2014.01.003.

  2. Ankesh Gupta, Surbhi Khurana, Rojaleen Das …, Rapid chromatographic immunoassay-based evaluation of COVID-19. A cross-sectional, diagnostic test accuracy study & its implications for COVID-19 management in India, Indian Journal of Medical Research 153(1-2):p 126-131, Jan–Feb 2021. doi: 10.4103/ijmr.IJMR_3305_20.

  3. Yanming Wu, Suli Ma, Lingjun Zhang…, Clinical manifestations and laboratory results of 61 children with infectious mononucleosis, J Int Med Res. 2020 Oct; 48(10):300060520924550. doi: 10.1177/0300060520924550.

  4. Ying Liang, Ligong Hou, Guangjun Hou…, The influences of the COVID-19 pandemic on Epstein-Barr virus infection in children, Henan, China, J Infect. 2023 May; 86(5): 525–528. Published online 2023 Jan 20. doi: 10.1016/j.jinf.2023.01.021.

  5. Ralf D. Hess, Routine Epstein-Barr Virus Diagnostics from the Laboratory Perspective: Still Challenging after 35 Years, J Clin Microbiol, 2004 Aug; 42(8): 3381–3387, https://doi.org/10.1128/jcm.42.8.3381-3387.2004.

  6. WHO Coronavirus (COVID-19) Dashboard, https://covid19.who.int/

  7. Children and COVID-19: State-Level Data Report, American Academy of Pediatrics, https://www.aap.org/en/pages/2019-novel-coronavirus-covid-19-infections/children-and-covid-19-state-level-data-report/

  8. COVID-19 statistic in Georgia, https://www.ncdc.ge/#/pages/file/ea1784b5-d3d0-4dd9-b29f-1369f5d6bbec.

  9. Gold JE, Okyay RA, Licht WE, Hurley DJ. Investigation of long COVID 19 prevalence and its relationship to Epstein–Barr virus reactivation, Pathogens, 2021;10(6):763, https://doi.org/10.3390/pathogens10060763/

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