Clinical and biological features of CMV reactivation in ARDS: a prospective cohort study

BACKGROUND: Cytomegalovirus (CMV) can be reactivated in patients with acute respiratory distress syndrome (ARDS), a condition associated with poor prognosis. However, the biological characteristics and bio-clinical connection of CMV reactivation remain unclear. METHODS: CMV reactivation was assessed in ARDS patients upon ICU admission. Clinical characteristics and outcomes were analysed. The primary outcome was 90-day mortality. Multivariate and time-dependent Cox regression analyses were performed. Plasma and bronchoalveolar lavage fluid (BALF) samples were collected for proteomic and metabolomic analyses to explore underlying associations. RESULTS: In total, 151 ARDS patients were included; 151 plasma and 48 BALF samples were analysed. During 90-day follow-up, CMV reactivation was observed in 31.1% (47/151) of patients. Patients with CMV reactivation exhibited significantly higher mortality (38.3% vs. 21.2%; hazard ratio [HR] 2.09, 95% confidence interval [CI] 1.12–3.90, P = 0.018). This result remained significant after multivariate regression (adjusted HR 1.97, 95% CI 1.04–3.74, P = 0.037) and time-dependent Cox regression (time-adjusted HR 2.61, 95% CI 1.38–4.94, P = 0.003). Fewer ventilator-free days (mean difference [MD] − 12.48, 95% CI − 17.75 to − 7.22, P < 0.001) and longer ICU stays (MD 16.22, 95% CI 8.36 − 24.09, P = 0.006) were observed in patients with CMV reactivation, which remained significant after regression adjustment, and experienced multiple adverse clinical outcomes. Subgroup analysis of the primary outcome indicated that patients with pulmonary reactivation had a higher risk of mortality. Proteomic analyses revealed suppression of immune, complement, and ribosomal subunit biogenesis pathways in BALF, along with activation of immune responses in plasma in patients with CMV reactivation. Metabolomic analyses revealed significant upregulation of tryptophan metabolism in plasma and pyrimidine metabolism in BALF in the CMV reactivation group. Several biomarkers linked to host immune responses and viral replication, including CXCL5 (correlation coefficient [Corr.] 0.301, P = 0.038), DERPC (Corr. −0.314, P = 0.030) in BALF and PTX3 in blood (Corr. 0.291, P < 0.001) etc. were correlated with increased mortality. CONCLUSIONS: Patients with CMV reactivation exhibited a significantly poor clinical prognosis. Distinct host protein expression and metabolic alterations in different sample types were observed in the CMV reactivation group. These findings provide new insights into the impact of CMV reactivation in ARDS patients.