Impact of cytomegalovirus DNAemia detected by next-generation sequencing on short-term prognosis after lung transplantation

Background

Cytomegalovirus (CMV) is a common opportunistic pathogen following lung transplantation, associated with post-transplant complications and adverse outcomes. This study aims to evaluate the incidence of CMV DNAemia identified through metagenomic next-generation sequencing (mNGS) during the early postoperative phase of lung transplantation and assess its effects on the short-term outcomes for recipients.

Methods

We conducted a retrospective analysis of clinical data from 115 patients who received lung transplants at the Affiliated Wuxi People's Hospital of Nanjing Medical University between May 2020 and November 2023. Based on mNGS-detected CMV DNAemia status, patients were stratified into DNAemia group and normal group. Nonparametric tests (Mann-Whitney U/Wilcoxon signed-rank) and mixed-effects models for intergroup comparisons. Kaplan-Meier survival analysis with log-rank testing for overall survival differences. Univariate logistic regression to identify risk factors for ICU mortality and 90-day mortality. Multivariate logistic regression adjusting for confounders. Propensity score matching (1∶1 optimal nearest neighbor, caliper = 0.25) was implemented to address covariate imbalance, followed by univariate logistic regression analyses in the matched cohort.

Results

In the early postoperative period following lung transplantation, CMV DNAemia was detected via mNGS with an incidence rate of 15.7%. The CMV DNAemia group demonstrated a significantly lower 90-day overall survival rate compared to the normal group, with the Log-rank test revealing statistically significant survival differences between groups (p < 0.001). Univariate and multivariate logistic regression analyses identified CMV DNAemia as an independent risk factor for ICU all-cause mortality (OR = 5.00, 95% CI: 1.37–18.27, p = 0.015), while with other pathogens infections independently predicted 90-day all-cause mortality (OR = 3.40, 95% CI: 1.10–10.44, p = 0.033). After propensity score matching, baseline characteristics were well-balanced between the CMV DNAemia and normal groups. In the matched cohort, univariate logistic regression further confirmed CMV DNAemia as an independent risk factor for ICU mortality (OR = 7.43, 95% CI: 1.23–45.00, p = 0.029). Mediation analysis demonstrated that co-pathogen infections mediated the relationship between CMV DNAemia and 90-day all-cause mortality, with a proportion mediated of 20.6% (95% CI: 1.7%–138.5%, p < 0.001).

Conclusions

mNGS revealed a higher incidence of early CMV DNAemia post-lung transplantation than previously reported. CMV DNAemia significantly correlates with poor prognosis. Despite limitations in sample size and retrospective design, this study provides novel insights into CMV monitoring and management post-transplantation. Future research should determine optimal timing for preemptive antiviral strategies guided by mNGS.