EBV VCA IgM and cytomegalovirus IgM dual positivity is a false positive finding related to age and hepatic involvement of primary Epstein–Barr virus infection in children

Abstract Primary Epstein–Barr virus (EBV) infection is common in childhood, and dual positivity of serum EBV IgM and cytomegalovirus (CMV) IgM antibodies occur in some cases. This study aimed to evaluate the cause of EBV and CMV IgM dual positivity to determine whether it represents a false-positive finding or a true coinfection. A total of 494 children diagnosed with primary EBV infection, manifesting as infectious mononucleosis, were recruited. The diagnosis was based on positive EBV viral capsid antigen (VCA) IgM antibodies, and serum CMV IgM antibodies and liver enzymes were also evaluated in 149 subjects. Of 149 children with primary EBV infection, 40 (26.8%) had serum EBV VCA IgM and CMV IgM dual positivity. However, true CMV infection was confirmed only in 1 child of 40 (2.5%) who was positive for both serum CMV Ag and urine CMV polymerase chain reaction (PCR) and negative for serum CMV IgG antibody. Among the children with primary EBV infection, the rate of dual positivity was higher in infants and lower in adolescents (P = .013). Liver enzymes were more significantly elevated in children with dual positivity than in those with negative results for CMV IgM antibodies (P = .026), which correlated with the serum EBV and CMV IgM titers. Serum EBV and CMV IgM dual positivity are more prevalent in children with primary EBV infection than what was previously reported. Our results indicate that serum EBV and CMV IgM dual positivity represents a false-positive finding, as opposed to an actual CMV coinfection, possibly due to antigenic cross-reactivity.