Serum anti-EBV and anti-CMV antibodies in children with Sudden Sensorineural Hearing Loss: the important role of universal screening for cCMV

INTRODUCTION Sudden sensorineural hearing loss (SSNHL) is exceedingly rare in children, and the etiology is often considered idiopathic, although the Herpesviridae family might play an important role [1]. We reported 5 children who developed SSNHL without hearing recovery between September 1, 2017 and August 31, 2020 [2]. METHODS The retrospective study was conducted in the third-level referral audiological center of the "Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico" in Milan (Italy). All children who were referred with suspicion of SSNHL had undergone brain magnetic resonance imaging, serological testing, genetic evaluation, thrombophilia and autoimmunity screening, in order to find possible causes of SSNHL [2]. RESULTS Anti-VCA (viral capsid antigen) IgM, anti-VCA IgG, anti-CMV (Cytomegalovirus) IgM and anti-CMV IgG antibodies were detected in all 5 patients by chemiluminescent immunoassay (CLIA), immediately after the diagnosis of SSNHL, which occurred from 2 to 4 weeks after the onset of symptoms attributable to primary EBV infection. No significant abnormalities were identified by the other diagnostic evaluations. In 4 of the 5 cases, hearing loss was unilateral, ranging from moderate (n=2) to severe (n=2). One child experienced bilateral SSNHL of severe grade [2]. CONCLUSIONS On the basis of these preliminary results, a routine audiological examination should be recommended for young patients with virologically confirmed primary Epstein-Barr virus (EBV) infection at approximately 3-4 weeks after onset of symptoms and then repeated with periodic follow-up [2]. Despite previous evidence of possible false positivity [3], the clinical significance of the dual positivity of serum anti-EBV IgM and anti-CMV IgM antibodies is still unclear. The presence of serum anti-CMV IgM and anti-CMV IgG (with high avidity) in children with SSNHL might indicate reactivation of latent CMV, and therefore polymerase chain reaction (PCR) analysis of dried blood spot (DBS) samples on the Guthrie card (if still stored) should be performed to rule out congenital Cytomegolovirus (cCMV) infection. However, a universal cCMV screening realized by CMV PCR testing on urine within the first three weeks of life may help clarify the significance of the dual positivity of serum anti-EBV and anti-CMV antibodies in children with SSNHL. A deeper understanding of these findings might enhance the development of new treatment modalities, minimizing the negative consequences not only on global costs but also on children’s language, attention, emotions and behavior that might result from unaddressed hearing loss. References 1) Qian Y, Zhong S, Hu G, Kang H, Wang L, Lei Y. Sudden Sensorineural Hearing Loss in Children: A Report of 75 Cases. Otol Neurotol. 2018;39(8):1018-1024. doi:10.1097/MAO.0000000000001891 2) Aldè M, DI Berardino F, Marchisio P, et al. Sudden sensorineural hearing loss in children with dual positivity of serum anti-EBV IgM and anti-CMV IgM antibodies: a preliminary study [published online ahead of print, 2021 Jun 21]. Minerva Pediatr (Torino). 2021;10.23736/S2724-5276.21.06314-X. doi:10.23736/S2724-5276.21.06314-X 3) Sohn MJ, Cho JM, Moon JS, Ko JS, Yang HR. 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. Medicine (Baltimore). 2018;97(38):e12380. doi:10.1097/MD.0000000000012380