Can viral load predict a symptomatic congenital CMV infection? A systematic review and meta-analysis

Cytomegalovirus (CMV) is the most common cause of congenital infection. Although only 10% of infected newborns are symptomatic at birth, a clinical disease may develop later in infancy. An early diagnosis of symptomatic congenital CMV is important for successful treatment. The aim of this study was to evaluate if a higher viral load in different biological fluids at the time of diagnosis correlates with symptomatic disease. A systematic search of Medline, Embase, and SCOPUS from 1976 to August 2024 was performed. Studies were included if the viral load was clearly identifiable as median and mean. Two independent reviewers completed screening, full-text review, data extraction, and quality assessment. Study results were reported as median and interquartile range (IQR: Q1–Q3), with group comparisons based on median differences. Pooled estimates of median differences with 95% confidence intervals were obtained using a median-based meta-analysis approach. Of 4558 studies identified, 11 were used in the meta-analysis with a total of 796 patients (376 symptomatic and 420 asymptomatic babies) for blood determinations and 919 patients for urine (331 symptomatic and 588 asymptomatic babies). Symptomatic infants showed significant higher viral load in blood (pooled difference of median = 1.77 × 104, 0.82;2.72 IU/mL) and a trend in urine (pooled difference of median = 339.7 × 104, − 22.2;701.43 IU/mL). Conclusion: In conclusions, we provide preliminary data that a high CMV load in blood and urine may be associated with symptomatic disease in newborns. Wider and more homogeneous evidence is warranted to confirm our conclusions and to identify a threshold for patients at risk of clinical disease. (Table presented.)