Abstract： Objective:To explore the clinical characteristics, risk factors and possible inflammatory response mechanisms in critically ill patients with influenza and invasive pulmonary aspergillosis co-infection.Methods:Sixty-four patients with severe influenza virus pneumonia were included in the RICU of the China-Japanese Friendship Hospital from November 1 st, 2017 to March 31 th, 2018. There were 33 males and 31 females, with an average age of (55±14) years. T-tests or χ 2 test were applied for comparisons between the two groups. Fifteen patients were complicated with IPA and were classified as the IPA group, while the other 49 served as the control group. The clinical characteristics, laboratory examinations, and endoscopic manifestations were compared between the two groups and the risk factors for severe influenza virus pneumonia with IPA were analyzed by multivariate logistic regression. The possible mechanisms of inflammatory response were explored by comparing the differences of plasma inflammatory factors between the two groups. Results:Seven patients (7/15, 47.7%) in the IPA group died. The percentage of wheezing in the IPA group ( n=13) was significantly higher than that in the control group ( n=25) ( P<0.05). The values of WBC [(11.0±2.7)×10 9/L], and the levels of blood GM [(2.46±0.80) μg/L] and BALF GM [(5.30±0.98) μg/L] in the IPA group were significantly higher than those in the control group, while PCT was lower than that in the control group[(6.1±3.3)×10 9/L, (0.33±0.07) μg/L and (0.73±0.17) μg/L, respectively] ( P<0.01). Compared with the control group, the chest CT of the IPA group showed more nodules along the bronchial bundle ( n=11), massive consolidation shadow ( n=9), halo sign ( n=3) and cavity/air crescent sign ( n=5) (control group: 8, 11, 0 and 4, respectively) ( P<0.05). Airway mucosal pseudomembrane formation ( n=12) and airway stenosis ( n=10) were significantly higher in the IPA group than in the control group (2 and 17) ( P<0.05). Multivariate logistic regression analysis suggested that the history of glucocorticoid use after ICU admission, normal PCT, multiple nodules, halo signs and pseudomembrane formation under endoscopy were risk factors for severe influenza virus pneumonia with IPA. The plasma pro-inflammatory factors IFN-γ [IPA group: 34.9 (20.6-64.0) μg/L] and IL-2 [16.2 (8.9-20.7) μg/L] were significantly lower than in patients without IPA [control group: 65.2 (43.8-124.5) μg/L and 20.4 (14.6-28.8) μg/L, respectively] ( P<0.05); while the inflammatory inhibitors IL-4 [51.6 (32.7-69.7) μg/L) and IL-10 [15.7 (11.8-92.5) μg/L] were higher in IPA group [control group 8.9 (6.1-15.0) μg/L and 7.8 (3.6-21.8) μg/L] ( P<0.05). SOFA scores showed a negative correlation with IFN-γ ( r=-0.658, P=0.02) and IL-6 ( r=-0.602, P=0.038), but a positive correlation with IL-10 ( r=0.641, P=0.025) by Spearman correlation analysis. Conclusions:Some relatively specific clinical characteristics could be found in severe influenza pneumonia complicated with IPA. IPA should be highly suspected when a patient had a history of glucocorticoid use after ICU admission, high WBCs in the course of treatment without significant increase of PCT,multiple nodules along the airway distribution and the characteristic pseudomembrane formation under bronchoscopy. Influenza virus caused imbalance of immune responses, leading to a weakened pro-inflammatory response and a strengthened inflammatory suppression, which might be a possible mechanism for IPA development.