Correlation of cytomegalovirus viral load between whole blood and plasma of congenital cytomegalovirus infection under valganciclovir treatment

Abstract

Background Congenital cytomegalovirus (CMV) infection (cCMV) can cause sensorineural hearing loss and neurodevelopmental disabilities in children. Oral valganciclovir (VGCV) therapy has been reported to improve long-term audiological and neurodevelopmental outcomes in patients with cCMV. The levels of CMV DNA in whole blood have been monitored in previous studies. However, quantitative methods using whole blood have not been standardized. Recently, the plasma viral load has been standardized and widely used in CMV-associated diseases. Methods CMV viral loads in whole blood and plasma were serially measured in 24 patients with a confirmatory diagnosis of cCMV during oral VGCV therapy using an in-house real-time PCR assay. Plasma samples were assayed using the Cobas 6800 system (Roche Diagnostics) in addition to an in-house assay. Results Plasma CMV viral loads were remarkably decreased at the end of therapy compared to before therapy. A significant correlation of CMV levels between whole blood and plasma was observed (Spearman’s ρ = 0.566). The levels of CMV DNA before therapy were significantly correlated with the period of decreasing the viral loads to below the detection limit, not only in whole blood (Spearman’s ρ = 0.901) but also in plasma (Spearman, ρ = 0.804). Finally, CMV viral loads between the in-house assay and commercially available standardized assay in 75 plasma samples with positive PCR results for CMV were compared; a significant correlation was observed between the results of both assays. Conclusions There was a significant correlation between the two assays (Spearman, ρ = 0.882), suggesting that CMV plasma viral loads measured by the standardized assay are widely used to monitor the levels of CMV DNA in patients with cCMV during oral VGCV therapy.

Decoding human cytomegalovirus for the development of innovative diagnostics to detect congenital infection

“…Technologies used to identify HCMV have evolved over the last half-century, and nucleic acid amplification-based tests [i.e., polymerase chain reaction (PCR)] 56 have become the current standard for routine sample testing in multiple tissue matrices. 57 – 59 Technologies that incorporate NAAT-based approaches can be qualitative (detection of CMV only or yes/no answer) or quantitative (CMV detection with calculation of viral load). Quantitative approaches can be used to determine a patient’s response to antiviral therapy, the likelihood that the viral load correlates with the clinical presentation, the appropriate time to discontinue treatment, and the risks for possible relapse of infection.…”

“…Therefore, when utilizing NAAT, clinicians should consider the following when making clinical management decisions the: (1) type of specimen (i.e., urine, saliva, whole blood, or plasma), (2) limits of detection and quantification chosen by the clinical laboratory, (3) linear range of the assay, and (4) reproducibility within the institution. 57 , 59 , 81 , 82 While whole blood allows for the determination of both the cell-free and cell-associated HCMV DNA, serum or plasma is used to detect only the cell-free fraction.…”