Deciphering the implications of CMV DNA in BALF detected by PCR poses a challenge for pediatric practitioners, and standardized clinical criteria for immunocompetent patients are lacking. In the present study, immunocompetent pediatric patients under 2 years old, who were admitted with CAP and tested positive for CMV DNA in BALF, were further categorized according to the results of CMV serological testing. It was surprising that 64.5% of the patients had CMV active infection. Consequently, pediatricians should exercise vigilance regarding the possibility of active CMV infection when managing young patients hospitalized for CAP who have tested positive for CMV DNA in BALF.
In the present study, a secondary pathogen was identified more frequently among cases categorized as CMV replication compared with those categorized as active CMV infection. This observation might not necessarily suggest a causative role for CMV in patients with CMV replication. Furthermore, the active CMV infection group had a lower rate of the presence of wheezing than the CMV replication group. This could be attributed to the finding that the most commonly detected pathogens were respiratory syncytial virus and M. pneumoniae, both of which are known to contribute to wheezing susceptibility in young children [18, 19].
In our study, the active CMV infection group had a lower frequency of requiring supplemental oxygen in comparison with the CMV replication group. The reason might be that CMV infection in immunocompetent individuals rarely leads to severe illness [20]. Furthermore, patients with active CMV infection had a lower hemoglobin lever than patients with CMV replication, which may be linked to physiologic anemia. Additionally, patients with active CMV infection had higher ALT and AST levels than patients with CMV replication, indicating that active CMV infection is more commonly associated with the elevation of hepatic aminotransferases. However, the ALT and AST levels were not significantly elevated, aligning with the findings from a previous study [21]. The levels of hepatic aminotransferases in cases of CMV infection are generally lower than those in cases of hepatitis caused by hepatitis viruses.
Our results showed that the median BALF CMV DNA copy number did not differ significantly between patients with active CMV infection and CMV replication. This suggests that the BALF CMV DNA copy number might not be a discriminatory marker for active CMV infection versus CMV replication. However, the median CMV DNA copy numbers in blood and urine were higher in patients with active CMV infection, compared with those in patients with CMV replication. These results indicate that the BALF CMV DNA copy numbers in blood and in urine could serve as discriminators between active CMV infection and CMV replication. In addition, the median CMV DNA copy number was higher in BALF than in blood and urine samples, which might support the concept of a compartmentalization and spill-over effect in the pathogenic response. Thus, having CMV disease in the lungs should theoretically lead to higher CMV loads within the respiratory system, with a spill-over effect extending into the bloodstream when CMV replication cannot be effectively controlled within the lungs [22, 23].
Our results revealed a positive correlation between blood CMV DNA copy number and the ALT level, similar to the results of a previous study [24]. This suggests that the level of blood CMV DNA could potentially serve as a monitoring parameter for CMV-associated infantile hepatitis. Notably, this study shows for the first time that the CMV DNA copy number in urine also was positively correlated with the ALT level, which has not been discussed before. Given that urine is a noninvasive specimen, analysis of urine might be more convenient than blood specimen analysis for monitoring CMV infection-related diseases.
The present study has several limitations. Firstly, we did not conduct dynamic detection of the CMV loads in blood, urine, and BALF samples; such dynamic monitoring could provide a more comprehensive understanding of the correlation between CMV load and clinical characteristics, and thus, warrants further investigation. Secondly, our study categorized CMV-infected patients into two groups according to the presence of CMV serum-specific antibody; however, it is important to note that serological tests might have limitations for accurately diagnosing CMV infection [25]. Hence, the exploration of more sensitive markers of active CMV infection should be a focus for future research. Lastly, our findings were derived from a single medical center, potentially limiting their generalizability to patients in different regions.