The influences of the COVID-19 pandemic on Epstein-Barr virus infection in children, Henan, China

We read with interest the publication by Yu and colleagues in the journal of infection, which showed that the cytomegalovirus (CMV) infection cases and the incidence rates of CMV infection in neonates decreased during the coronavirus disease 2019 (COVID-19) pandemic. Primary infection of epstein-barr virus (EBV) and CMV, two common human herpesviruses, are asymptomatic but can be associated with infectious mononucleosis (IM) syndrome, including fever, tonsillar pharyngitis, and lymphadenopathy. However, few studies have examined the impact of the COVID-19 pandemic on EBV infection in children. We hope to provide additional information to support these conclusions by sharing the results of one of our studies, which analyzed changes of EBV infection in children before and after the COVID-19 pandemic in Henan, China.

EBV, a double-stranded DNA virus of the herpes family best known as the agent responsible for a variety of diseases, such as IM, EB virus-associated hemophagocytic lymphohistiocytosis, and chronic active EB virus infection, has a ubiquitous distribution in approximately 50% of children and 90% of adults worldwide. The pathogenic mechanism of EBV is the infection of B lymphocytes after proliferation of epithelial cells in the oropharynx, and the infected cells circulate through the blood system of the body to the whole body, resulting in systemic infection. Preschoolers younger than 5 years old will show diversified clinical symptoms after infection with EBV, and patients often show fever, lymph node enlargement, and liver enlargement. However, due to the imperfect immune response system and weak response-ability of infants and young children, the body cannot produce an effective immune response to the invasion of the virus after infection, so the clinical manifestations are not obvious and often ignored by people, causing great hidden dangers. Unfortunately, there is no effective vaccine to prevent EBV infection. Therefore, EBV is a major and important pathogen in children all over the world, which is a serious threat to children's health and brings a heavy burden to patients, families, and society. In response to the COVID-19 pandemic, China have implemented strict interventions (digital technology pandemic prevention, zero-case policy, all-staff nucleic acid testing, all-staff vaccinations, the long-term quarantine system, and the official accountability system) from 2020 to 2022 to control the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)^{,  ,}  . Simultaneously, the SARS-CoV-2 infection prevention and control measures have seriously affect people's lifestyle and the transmission of many other pathogens. Therefore, analyzing the changes of EBV infection in children before and after the COVID-19 pandemic will provide efficient clinical management strategies.

In this study, laboratory-based surveillance of EBV infection in children under 18 years old were conducted from January 2019 to December 2022 at Henan Children's Hospital, a 3A pediatric hospital with more than 2.4 million outpatient service per year, accounting for approximately 10% of total number of children in Henan. In addition, Henan Children's Hospital has been approved as the National Children's Regional Medical Center, Henan Children's Medical Center, and Henan Pediatric Disease Clinical Medical Research Center. The number of EBV infections as well as the age characteristics of infected persons in four years before and after the COVID-19 pandemic was analyzed to explore the impact of the COVID-19 pandemic on the prevalence trend of EBV infection in children. As shown in Fig. 1A and Fig. 1B, the positive number of EBV IgM and EBV IgG decreased significantly in January 2020, July 2021 and November 2022, which reflected the three COVID-19 outbreaks in Henan. Although there was a modestly increase of the number of positive EBV IgM and EBV IgG in children during the recovery period of the COVID-19 pandemic from September 2020 to March 2021, it was still lower than the same period before the COVID-19 pandemic. Notably, the reduction of the number of positive EBV IgM and EBV IgG persisted for several months after the end of the second COVID-19 pandemic, which may have suppressed rise trend in EBV infection duing to the policies adopted by the government during the COVID-19 pandemic. Therefore, epidemiological trend of the infection of EBV in children had indeed changed before and after the COVID-19 pandemic in Henan.

Furthermore, the total number of EBV IgM positive patients under 5 years old accounted for 72% of the total number of EBV IgM between 0 - 18y old from 2019 to 2021 (Fig. 2A), the total number of EBV IgG positive patients under 5 years old accounted for 65% of the total number of EBV IgG between 0 - 18y old from 2019 to 2021 (Fig. 2C). In addition, after COVID-19 pandemic, the positive number of EBV IgM and EBV IgG decreased in < 1y, 1 - 3y, 3 - 5y and 5 - 18y age groups (Fig. 2B and Fig. 2D), indicating that the COVID-19 pandemic reduced the infection of EBV in children. This change may be mainly related to a series of strict measures taken during the COVID-19 pandemic, such as suspension of classes, increased awareness of wearing masks and paying attention to hand hygiene.

In summary, EBV infections in children 0 - 18 years of age declined during the COVID-19 pandemic. Despite the gradual relaxation of COVID-19 control, the situation remains serious. We should foster the vision of a community with a shared future for mankind, help each other, jointly address risks and challenges, and jointly safeguard the well-being of people of all countries. Therefore, we need to closely observe changes affecting EBV prevalence before and after the COVID-19 outbreak.

In conclusion, EBV infections have declined in children of all ages during the COVID-19 pandemic. Close monitoring of epidemiological trends can help prevent EBV infection in children, especially those under 5 years of age.