3.1 Active CMV infection
During the study period, a total of 4,261 patients were admitted to the ICU. Among them, 4,022 patients were initially excluded for reasons that included: i. Not meeting the ARDS diagnostic criteria (n=3,987); ii. Survived for less than 72 h (n=23); iii. Pregnant or lactating women (n=7), and iv. Younger than 18 years (n=5). Preliminarily, 239 ARDS patients were screened, however, 71 were excluded for; i. Lacking CMV detection (n=69) and ii. Receiving antiviral therapy before entering the ICU (n=2). Finally, a total of 168 ARDS patients were enrolled (Figure 1)
Among the 168 enrolled ARDS patients, there were 31 (18.5%) cases of active CMV infections within the 28-day ICU hospitalization period (Figure 1). A total of 25 (80.7%) of the 31 cases with active CMV infection exhibited positive results at ICU admission, moreover, 4 cases at day 14 and 2 cases at day 21.
3.2 Clinical features
We recruited 168 patients with complete data, among whom 111 were male (66.1%). The mean age for all study participants was 58 ± 15 years. Based on the median scores for APACHE Ⅱ (20) and SOFA (9), the disease was very severe. Patients with mild, moderate, and severe ARDS were 32 (19.0%), 66 (39.3%), and 70 (41.7%), respectively. The main cause of ARDS was pneumonia (91.7%). Patients' heart and respiratory rates were higher. The main comorbidities were hypertension (n=47, 28.0%), cardiovascular diseases (n=47, 28.0%), and connective tissue diseases (n=31, 18.5%). Except for connective tissue disease [35.5% vs. 14.6% (n), p=0.011], differences in these clinical characteristics between the two groups were not significant (Table 1).
Moreover, the active CMV infection group exhibited low monocyte counts (median: 0.2 vs. 0.5 (109/L), p=0.006), hemoglobin levels (median: 82 vs. 97 (g/L), p=0.009), platelet counts (median: 102 vs. 145 (109/L), p=0.012), and T-helper lymphocytes/T-suppressor lymphocytes (Th/Ts) counts (median: 0.98 vs. 1.32, p=0.030). There were no significant differences for other laboratory findings between the two groups (Table 2).
3.3 Risk factors
In the multivariate regression model, monocytes [OR: 0.182, 95% CI: 0.054-0.617, p=0.006], hemoglobin [OR: 0.974, 95% CI: 0.953-0.996, p=0.020], blood transfusion [OR: 3.790, 95% CI: 1.407-10.210, p=0.008], and septic shock [OR: 4.889, 95% CI: 1.018-23.478, p=0.047] were independently associated with active CMV infection in ARDS patients. Based on the regression coefficient (β), monocytes [β: -1.702] and hemoglobin [β: -0.026] were inhibitory factors for active CMV infection. However, blood transfusion [β: 1.332] and septic shock [β: 1.587] were found to facilitate active CMV infection (Table 3).
3.4 Treatments, complications, and clinical outcomes
Most of the patients (96.8%) with active CMV infection were administered with antiviral therapy [96.8% vs. 0% (n), p<0.01] after ICU admission. Moreover, compared to the group without active CMV infection, immunosuppressive drugs [29.0% vs. 9.5% (n), p=0.007] and blood transfusion [38.7% vs. 13.1% (n), p=0.003] were found to have been highly administered in the group with active CMV infection before ICU admission. Other therapeutic measures were not significantly different between the two groups (Table 4).
Severe pneumonia with a prevalence of 91.7% was found to be a major complication in ARDS patients. Compared to the non-active CMV infection group, the number of ARDS patients diagnosed with septic shock [90.3% vs. 71.5% (n), p=0.037] in the active CMV infection group was higher. Although statistical significance was not reached, the rate of AECOPD was low in cases without (11.7%) than in cases with (22.6%) active CMV infection (Table 4).
Length of invasive mechanical ventilation (IMV) [median: 42 vs. 29 (d), p=0.045], 28-day ventilator-free days (VFD) [median: 0 vs. 0 (d), p=0.039], ICU length of stay [median: 32 vs. 22 (d), p=0.047], and the 28-day all-cause mortality rate [51.6% vs. 26.3% (n), p=0.009] in the active CMV infection group were significantly higher than in the non-active CMV infection group (Table 4).
3.5 Oxygenation influence
Continuous observation of arterial oxygenation over 7 days of active infection with CMV revealed that the CMV group exhibited worse outcomes in oxygenation within 5-day hospitalization in ICU than the non-active CMV infection group. On day 5, oxygenation was significantly worse in the active CMV group than in the non-active CMV infection group [median: 179 vs. 193 (P/F), p=0.046] (Figure 2).