BACKGROUND: Early diagnosis of congenital CMV infection (cCMVI) allows for early intervention and follow-up to detect delayed hearing loss. While CMV PCR in urine is the gold standard for cCMVI diagnosis, saliva testing is often performed.
OBJECTIVE: Our aim was to determine (i) if swab saliva sampling needed standardization, (ii) if a threshold value in \"virus copies per million cells (Mc)\" in saliva samples could improve clinical specificity, and (iii) to establish a correlation between viral load in saliva and symptomatology/outcome of cCMVI.
METHODS: In our institution, universal newborn screening is performed on saliva swabs at delivery or until day 3 of life. If positive, CMV PCR in urine is done within 2 weeks to confirm or exclude cCMVI.
RESULTS: Cell quantification showed that saliva swab sampling was well performed as 95.4 % samples had more than 100 cells/10 µL. There was a good correlation between saliva viral load in copies/mL and in copies/Mc (Pearson\'s r = 0.96, p < 0.0001). However, threshold values, established to determine a viral load level at which we could confidently identify infected newborns, did not improve positive predictive value (21.8 % for copies/mL and 21 % for copies/Mc vs 25.4 % without threshold) but instead reduced sensitivity (88 % and 85% vs 100 % without threshold). Samples collected on day 2 or 3 had better positive predictive value (38.7 %) compared to those collected on day 1 (23.8 %). Symptomatology at birth was not significantly associated with viral load in saliva at diagnosis. However, sequelae occurrence was associated with viral load in saliva (copies/Mc).
CONCLUSIONS: Our results confirm that saliva swab is a suitable sample for universal neonatal screening. However, identifying newborns that will develop sequelae remains an issue in the management of cCMVI.

Background: Human cytomegalovirus (hCMV) is the most common etiological agent of congenital infections seen in newborns. Among the most commonly observed complications in children with congenital human cytomegalovirus infection are those affecting the visual system. Ocular complications of congenital CMV (cCMV) are a topic rarely addressed in the literature, which prompted the authors to update the available knowledge with the latest data. Methodology: English-language literature published between April 2000 and November 2023 (PubMed, NIH, Google Scholar) was analyzed for ocular complications of cCMV. The data obtained were categorized according to the ocular area involved and the incidence. A compilation of criteria for the symptomatic form of cCMV was also created. Results: The cCMV complications described in the literature affect all parts of the visual system: the anterior segment, the posterior segment, the posterior visual pathways, and the visual cortex. The most commonly described ocular complication of cCMV is choroidal and retinal scarring. Conclusions: Ophthalmic complications of cCMV can cause severe visual disturbances. Ophthalmic diagnosis in newborns should include hCMV PCR testing, which has the highest sensitivity and specificity. In the symptomatic form of cCMV, treatment should be instituted according to recommendations. A consensus should be established for screening of primary hCMV infection in pregnant women, the way in which to define the symptomatic form of cCMV, and the appropriateness and standards of treatment for primary hCMV infection in pregnant women.

Plant viruses such as brome mosaic virus and cowpea chlorotic mottle virus are effectively purified through PEG precipitation and sucrose cushion ultracentrifugation. Increasing ionic strength and an alkaline pH cause the viruses to swell and disassemble into coat protein subunits. The coat proteins can be reassembled into stable virus-like particles (VLPs) that carry anionic molecules at low ionic strength and through two-step dialysis from neutral pH to acidic buffer. VLPs have been extensively studied due to their ability to protect and deliver cargo, particularly RNA, while avoiding degradation under physiological conditions. Furthermore, chemical functionalization of the surface of VLPs allows for the targeted drug delivery. VLPs derived from plants have demonstrated great potential in nanomedicine by offering a versatile platform for drug delivery, imaging, and therapeutic applications.

BACKGROUND: This phase 1 trial evaluated the safety, reactogenicity, and immunogenicity of mRNA-1647, an mRNA-based cytomegalovirus (CMV) vaccine, in CMV-seronegative and -seropositive adults.
METHODS: Participants were randomly assigned to receive 30, 90, 180, or 300 µg of mRNA-1647 or placebo on a 0-, 2-, and 6-month schedule and followed for 12 months after the last dose.
RESULTS: A total of 154 (80 CMV-seronegative and 74 CMV-seropositive) participants were enrolled; 118 participants were randomized to mRNA-1647 and 36 to placebo. Mean (SD) age was 32.5 (8.6) and 35.1 (8.9) years in the placebo and mRNA-1647 groups, respectively, in phase B (63% and 64% female) and 42.5 (6.2) and 33.3 (8.7) years, respectively, in phase C (2% and 16% female). No deaths, related serious adverse events, or adverse events of special interest were reported. Most adverse reactions were grade ≤2 severity. Increased neutralizing antibody, binding antibody, and antigen-specific cell-mediated responses were observed across mRNA-1647 treatment groups, regardless of CMV serostatus.
CONCLUSIONS: This phase 1, first-in-human trial demonstrated mRNA-1647 has an acceptable safety profile in adults and elicits humoral and cellular immune responses.
BACKGROUND: NCT03382405; https://clinicaltrials.gov/ct2/show/NCT03382405.

Cowpea chlorotic mottle virus (CCMV) and brome mosaic virus (BMV) are naked plant viruses with similar characteristics; both form a T = 3 icosahedral protein capsid and are members of the bromoviridae family. It is well known that these viruses completely disassemble and liberate their genome at a pH around 7.2 and 1 M ionic strength. However, the 1 M ionic strength condition is not present inside cells, so an important question is how these viruses deliver their genome inside cells for their viral replication. There are some studies reporting the swelling of the CCMV virus using different techniques. For example, it is reported that at a pH~7.2 and low ionic strength, the swelling observed is about 10% of the initial diameter of the virus. Furthermore, different regions within the cell are known to have different pH levels and ionic strengths. In this work, we performed several experiments at low ionic strengths of 0.1, 0.2, and 0.3 and systematically increased the pH in 0.2 increments from 4.6 to 7.4. To determine the change in virus size at the different pHs and ionic strengths, we first used dynamic light scattering (DLS). Most of the experiments agree with a 10% capsid swelling under the conditions reported in previous works, but surprisingly, we found that at some particular conditions, the virus capsid swelling could be as big as 20 to 35% of the original size. These measurements were corroborated by atomic force microscopy (AFM) and transmission electron microscopy (TEM) around the conditions where the big swelling was determined by DLS. Therefore, this big swelling could be an easier mechanism that viruses use inside the cell to deliver their genome to the cell machinery for viral replication.

A universal screening research study was conducted in six hospitals to identify the clinical sensitivity of polymerase chain reaction (PCR) testing on newborn dried blood spots (DBSs) versus saliva specimens for the diagnosis of congenital cytomegalovirus (cCMV). CMV DNA positive results from DBSs or saliva were confirmed with urine testing. Findings of several false-positive (FP) saliva PCR results prompted an examination of a possible association with donor milk. Documentation of the frequency of positive saliva results, including both true-positive (TP) and FP status from clinical confirmation, occurred. The frequency of donor milk use was compared for TP and FP cases. Of 22,079 participants tested between 2016 and 2022, 96 had positive saliva results, 15 were determined to be FP, 79 TP, and 2 were excluded for incomplete clinical evaluation. Newborn donor milk use was identified for 18 (19.14%) of all the positive saliva screens. Among the 15 FPs, 11 (73.33%) consumed donor milk compared to 7 of the 79 TPs (8.8%) (OR 28.29, 95% CI 7.10-112.73, p < 0.001). While milk bank Holder pasteurization inactivates CMV infectivity, CMV DNA may still be detectable. Due to this possible association, screening programs that undertake testing saliva for CMV DNA may benefit from documenting donor milk use as a potential increased risk for FP results.

BACKGROUND: Cytomegalovirus (CMV) is the most common agent of congenital infection in humans. It is a main cause of neurodevelopmental delay and sensorineural hearing loss in infancy. Since the 2000s, a number of studies have used Valganciclovir as a therapy for children with congenital CMV infection.
METHODS: In order to evaluate the efficacy of Valganciclovir in preventing clinical sequelae and its possible side effects, we performed a review of the published literature. This search was completed via PubMed for manuscripts published from January 2007 to December 2021, combining the MeSH words \"Valganciclovir\", \"Congenital\", and \"Cytomegalovirus\".
RESULTS: A total of 27 articles were included (12 retrospective studies, 4 prospective studies, 1 randomized controlled trial, and 10 case reports). The clinical features were similar to those already described in the literature. The therapeutic protocols used were very different between the various studies included and neonatal antiviral treatments were only moderately effective. The therapy proved to be well-tolerated.
CONCLUSIONS: The quality of the included studies and the sample size were limited due to the rarity of the disease. The use of different therapeutic protocols in terms of starting dates, doses, and durations made it impossible to compare and correctly evaluate the efficacy of the treatments. Randomized controlled trials are needed to establish the correct effective dose with the fewest side effects and the most efficient duration of therapy.

BACKGROUND: Sensorineural hearing loss (SNHL) is the most common birth disorder. The cause of SNHL is heterogeneous and varies in different populations. Understanding the causes of a hearing loss (HL) predict the outcome of cochlear implantation and is of great importance in understanding the mechanism of the disease and in providing the best treatment. Undiagnosed and untreated HL has a profound effect on the acquisition of early communication skills, speech, language, academic, emotional, and psychosocial development in children.
OBJECTIVE: To determine the cause of HL and implantation age in pediatric cochlear implant (CI) users in a Danish population.
METHODS: Data of 100 children (54 females and 46 males), age 0-17 years, was analyzed. All of the children were implanted during 2020-2022.
RESULTS: Hereditary HL was diagnosed in 44 cases (44%), with pathogenic variants in the SLC26A4 gene found in 14 cases (14%). Syndromic HL was diagnosed in 23 children (23%). Non-syndromic HL was diagnosed in 21 children (21%), where the most common genetic variation was found in the GJB2 gene. Acquired prenatal and postnatal sensory disorders TORCH risk factors were associated with HL in 25 cases (25%). Congenital CMV DNA was diagnosed in 23 samples (23%). The cause of the HL remained unknown for 31 (31%) children. In 70 (70%) of the participants the HL was diagnosed at time of newborn hearing screening (NHS). Twenty-three of the children were diagnosed with congenital severe to profound bilateral HL and were simultaneously implanted between 8 and 14 months (mean age 10.5 months). In the remaining 47 cases, the HL was progressive and the children were implanted when the HL reached the criteria for implantation.
CONCLUSIONS: In the current study, the major causes of HL were alterations in the SLC26A4 gene: 13% with Pendred syndrome and 1% non-syndromic. Thirty-one (31%) had HL of unknown origin and almost half of these cases had inner ear malformations (n = 16).

Cytomegalovirus (CMV) can infect individuals at any age, including infants, who may contract it from infected mothers (congenital CMV [cCMV]). Whereas CMV infection is typically asymptomatic or causes mild illness in healthy individuals, infection can result in severe outcomes in immunocompromised individuals and in infants with cCMV. This systematic review aims to characterize the economic impact of CMV and cCMV infections.
Medline, Embase, and LILACS databases were searched for publications reporting the economic impact of cCMV and CMV infections across all age groups. Manuscripts published between 2010 and 2020 from Australia, Latin America, Canada, Europe, Israel, Japan, the United States, and global (international, worldwide) studies were included; congress materials were excluded. Outcomes of interest included cCMV- and CMV-attributable direct costs/charges, resource utilization, and indirect/societal costs.
Of 751 records identified, 518 were excluded based on duplication, population, outcome, study design, or country. Overall, 55 articles were eligible for full-text review; 25 were further excluded due to population, outcome, study design, or congress abstract. Two publications were additionally identified, resulting in economic impact data compiled from 32 publications. Of these, 24 publications reported cost studies of cCMV or CMV, including evaluation of direct costs/charges, healthcare resource utilization, and indirect/societal costs, and 7 publications reported economic evaluations of interventions. The populations, methods and outcomes used across these studies varied widely.
CMV and cCMV infections impose a considerable economic impact on different countries, populations, and outcomes. There are substantial evidence gaps where further research is warranted.

Congenital cytomegalovirus (cCMV) is the most common perinatal infection, the leading cause of nongenetic sensorineural hearing loss, and one of the leading causes of neurodevelopmental impairment in the developed world. Early identification via newborn screening (NBS) would benefit the many undiagnosed infants who are either asymptomatic or mildly to moderately symptomatic, of whom 20% develop sequelae. The sensitivity of a recently developed PCR-based method to detect CMV in dried blood spots (DBS) is less than 80% and requires significantly more specimen than any other NBS test. We sought to improve the analytical sensitivity of the screening method by using droplet digital PCR and direct PCR and decreasing the amount of specimen utilized. The methods were tested with CMV-spiked filters, DBS from CMV-spiked cord blood, and DBS from neonates with cCMV. The results showed that the analytical sensitivity of all modified methods was equivalent to that of the reference method, with consistent CMV detection at high viral loads and inconsistent detection at low viral loads. IMPORTANCE Implementation of screening for cCMV in public health programs is hindered by feasibility challenges, including limited specimen availability and an insufficiently sensitive DBS-based screening assay. We report on efforts to improve the currently available DBS-based molecular assay to increase its feasibility of implementation in newborn screening programs. Although the analytical sensitivity of the modified methods was similar at the lower IU, equivalent CMV detection was achieved using one punch instead of the required three punches for the reference method. This reduction in sample size has the potential to substantially improve feasibility of NBS for cCMV. A population-based study is needed to further evaluate the clinical sensitivity of the improved assay.