Epidemiological characteristics of Cytomegalovirus infection in children before and after the COVID-19 pandemic in Henan, China, 2016–2022

Dear editor,

We read with interest the publication by Li et al. and Zhou et al. in the journal of infection, which showed that a decreasing trend of the infection in children with Acinetobacter baumannii and Haemophilus influenzae under the impact of the coronavirus disease 2019 (COVID-19) pandemic in Henan, China.^,  In particular, the publication by Yu and colleagues in this journal, which showed that the Cytomegalovirus (CMV) infection cases and the incidence rates of CMV infection in neonates (0–28 days after birth) decreased during the COVID-19 pandemic. However, few studies have examined the impact of the COVID-19 pandemic on CMV infection in children (0–18 years old). Therefore, we hope to provide additional information to support these conclusions by sharing the results of one of our studies, which analyzed changes of CMV infection in children before and after the COVID-19 pandemic in Henan, China, 2016–2022.

Human CMV (human herpes virus-5), a member of the Betaherpesvirinae subfamily of the family Herpesviridae that causes significant morbidity and mortality in immunosuppressed children, can be found in 80–100% of healthy adults in various population. Following the initial infection, CMV can set up lifelong latent infection in undifferentiated CD34⁺ stem cells, CD33⁺ myeloid progenitor cells, the CD14⁺ monocytes and dendritic cells that they mature into, regretfully.^,  In immunocompetent children, primary CMV infection commonly causes a mild illness, such as lymphopenia, lymphadenopathy, fever and hepatosplenomegaly. However, CMV has significant implications for children who are or become immunodeficient. CMV can be transmitted to the neonate by various ways (transplacentally, through maternal genital secretions during delivery and postnatally via maternal oral secretions, breast milk, objects contaminated with body fluids and via blood products). Congenital CMV infection is the leading infectious cause of developmental and neurological disabilities and sensorineural hearing loss in children. Overall, 10% of congenital CMV cases are symptomatic at birth, with a broad range of clinical presentations at birth, from a single isolated symptom to multiorgan involvement and a mortality rate of up to 3–4%. Unfortunately, there is no effective vaccine to prevent the infection of CMV. Therefore, CMV 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. It is urgent to take precise prevention strategies for controlling the infection of CMV by understanding the situation of children CMV infection in different countries or regions. In response to COVID-19, China has implemented strict interventions, such as 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. These control measures not only seriously affect people’s lifestyle but also may also affect the epidemiology characteristics of pathogens. Hence, analyzing the impact of children CMV infection before and after the COVID-19 pandemic will provide efficient clinical management strategies.

In this study, the laboratory-based surveillance data of CMV infection in children under 18 years old were collected from January 2016 to December 2022 at Henan Children’s Hospital (National Children’s Regional Medical Center, Henan Children’s Medical Center), 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. The number of CMV infections as well as the age characteristics of infected persons in seven years before and after the COVID-19 pandemic was analyzed to explore the impact of the COVID-19 pandemic on epidemiological characteristics of CMV infection in children. The positive number of CMV DNA and CMV IgM before the COVID-19 epidemic (2016–2019) was significantly higher than that after the COVID-19 epidemic (2020–2022), with P values of 0.000 and 0.001, respectively (Figs. 1A and 2A). However, there was no significant difference in the number of positive CMV IgG before and after the COVID-19 epidemic, with P values of 0.272 (Fig. 1C). As shown in Figs. 1A and 2A, the positive number of CMV DNA (n = 2163 in 2016, n = 2151 in 2017, n = 2376 in 2018, n = 2076 in 2019, n = 1514 in 2020, n = 1835 in 2021, n = 1234 in 2022) and CMV IgM (n = 788 in 2016, n = 758 in 2017, n = 1083 in 2018, n = 756 in 2019, n = 740 in 2020, n = 739 in 2021, n = 412 in 2022) decreased significantly in January 2020, July 2021 and November 2022, which reflected the three COVID-19 outbreaks in Henan. Although there was a modest increase of the number of positive CMV DNA and CMV IgM 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 CMV DNA and CMV IgM persisted for several months after the end of the second COVID-19 pandemic, which may have suppressed rise trend in CMV infection due to the policies adopted by the government during the COVID-19 pandemic. However, the positive number of CMV IgG (n = 5523 in 2016, n = 4842 in 2017, n = 4063 in 2018, n = 7729 in 2019, n = 5505 in 2020, n = 5789 in 2021, n = 4103 in 2022) before the COVID-19 epidemic was slightly lower than that after the epidemic (P > 0.05) (Fig. 3A). Therefore, epidemiological trend of the infection of CMV in children had indeed changed before and after the COVID-19 pandemic in Henan.

Furthermore, the total number of CMV DNA, CMV IgM and CMV IgG positive patients under 1 year old accounted for 86.5%, 96.4% and 94%.1, respectively (Figs. 1B, 2B, and 3B). In addition, after COVID-19 pandemic, the positive number of CMV DNA, CMV IgM and CMV IgG decreased in<2 w, 3–12 w, 12 w–1 y, 1–3 y, 3–5 y and 5–18 y age groups (Figs. 1C, 2C, and 3D), indicating that the COVID-19 pandemic reduced the infection of CMV in children. More importantly, the COVID-19 pandemic had little effect on the positive rate of CMV DNA, but increased the positive rate of CMV IgG and CMV IgM (Figs. 1D, 2D, and 3D). Those changes may be mainly related to a series of strict measures taken during the COVID-19 pandemic, such as suspension of classes, paying attention to hand hygiene.

In conclusion, CMV infections have declined in children of all ages during the COVID-19 pandemic. Close monitoring of epidemiological trends can help prevent CMV infection in children, especially those under 1 years of age.