Demographic and Epidemiological Characteristics
From November 1, 2017 to March 31, 2018, a total of 4,297 cases of laboratory-confirmed human influenza A and B viral infection were reported in our hospital. Of these, 2335 cases were human influenza A (about 85% were pH1N1 and 15% were H3N2), 1880 cases were influenza B, and 82 cases were infected with both viruses. Finally, 138 cases of hospitalized human influenza A-related viral pneumonia and 59 cases of hospitalized influenza B-related viral pneumonia were included in this study. From January 1 ,2017 to May 3, 2017, a total of 18 cases of hospitalized H7N9 -related viral pneumonia were also included in the current study. The median age of hospitalized human influenza A-related viral pneumonia patients was lower than those with B pneumonia (57 years (interquartile range (IQR), 45.8–66.3) vs. 62 years (IQR, 53–74); p = 0.034). In the 35–49-year-old age group, the proportion of hospitalized human influenza A-related viral pneumonia patients was 23.9%, which was higher than B pneumonia patients (10.2%; p = 0.027). In the ≥ 65-year-old group, the proportion of hospitalized human influenza A-related viral pneumonia patients was 32.6%, which was relatively lower than B pneumonia patients (45.8%; p = 0.079;Table 1). The proportion of comorbid conditions in hospitalized human influenza A-related viral pneumonia patients was 58%, which was lower than the B pneumonia patients and hospitalized H7N9 pneumonia patients (78% vs. 77.8%; p = 0.013). In the hospitalized patients with influenza B-related viral pneumonia, the proportion of patients with the concomitant hematological disease was 16.9%, relatively higher than those with human influenza A pneumonia and H7N9 pneumonia (8.7% vs. 0%; p = 0.085). One hospitalized pregnant patient had human influenza A-related viral pneumonia, and none of the patients presented influenza B-related viral pneumonia and H7N9-related viral pneumonia in pregnancy. The proportion of obesity to the three types of hospitalized influenza-related viral pneumonia patients was similar. Interestingly, 66.7% of hospitalized H7N9-related viral pneumonia patients were exposed to live poultry.
Clinical Characteristics and Diagnostic Findings
The most common symptoms of the three types of hospital influenza-related viral pneumonia patients were fever, cough, sputum production, shortness of breath, and fatigue. Compared to hospitalized influenza B-related viral pneumonia patients, the proportion of low-grade fever to human influenza A pneumonia patients was low (10.6% vs. 20.4%; p = 0.046; Table 2).
At the time of admission, the median value of hemoglobin in hospitalized human influenza A-related viral pneumonia patients was 124 g/dL (IQR: 104–139), higher than B pneumonia patients 117 g/dL (IQR, 95–130) (p = 0.018). The proportion of lymphocytopenia in hospitalized human influenza A-related viral pneumonia patients was 83.3%, higher than B pneumonia patients (69.5%; p = 0.028). The proportion of elevated aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and d-dimer (DD) in hospitalized human influenza A-related viral pneumonia patients was higher than that of B pneumonia patients (46.7% vs. 25.9%, p = 0.007; 67.9% vs. 51%, p = 0.033; 76.5% vs. 62.5%, p = 0.049). The proportion of pulmonary ground-glass opacities in hospitalized human influenza A-related viral pneumonia patients was 35.5%, higher than B pneumonia patients 20.3% (p = 0.035). The median value of white blood cell counts in hospitalized H7N9-related viral pneumonia patients was 4400/mm3 (IQR: 3475–5625), lower than human influenza A pneumonia patients and B pneumonia patients (7000/mm3 (IQR: 4300–9550) vs. 6900/mm3 (IQR: 4300–12600); p = 0.008). The median value of lymphocyte count in hospitalized H7N9-related viral pneumonia patients was 425/mm3 (IQR: 375 − 625), lower than human influenza A and B pneumonia patients (745/mm3 (IQR: 448–1208) vs. 1020/mm3 (IQR: 550–1690); p = .001). The proportion of lymphocytopenia in hospitalized H7N9-related viral pneumonia patients was 100.0%, higher than human influenza A and B pneumonia patients (83.3% vs. 69.5%; p = 0.006). The proportion of elevated AST, creatine kinase (CK), DD, and LDH in hospitalized H7N9-related viral pneumonia patients was higher than human influenza A and B pneumonia patients (77.8% vs. 46.7% vs. 25.9%, p < 0.001; 76.5% vs. 17.9% vs. 9.8%, p < 0.001; 94.4% vs. 76.5% vs. 62.5%, p = 0.016; 100% vs. 67.9% vs. 51%, p = 0.001). The proportion of positive culture (blood or sputum) on presentation or during hospitalization in the hospitalized H7N9-related viral pneumonia patients (bacterial and fungal) was 61.1% and 33.3%, respectively, higher than the human influenza A and B pneumonia patients (21.1% vs. 21.3%; p = 0.002) (15.8% vs. 6.4%; p = 0.028). The proportion of pulmonary ground-glass opacities and pulmonary consolidation in hospitalized H7N9-related viral pneumonia patients was 55.6% and 100.0% respectively, higher than the human influenza A and B pneumonia patients (35.5% vs. 20.3%; p = 0.012), (63.8% vs. 49.2%; p < 0.001).
Complications, Treatment, and Clinical Outcomes
In the current study, the proportion of intensive care unit (ICU) admission in hospitalized human influenza A-related viral pneumonia patients was 19.6%, which higher than 6.8% of B pneumonia patients (p = 0.024). The proportion of IMV in hospitalized human influenza A-related viral pneumonia patients was 16.7%, which also higher than that in B pneumonia patients 3.4% (p = 0.01) (Table 3). The proportion of IMV and extracorporeal membrane oxygenation (ECMO) treatment in hospitalized H7N9-related viral pneumonia patients was 38.9% and 11.1%, respectively, which was higher than that in human influenza A and B pneumonia patients (16.7% vs. 3.4%; p = 0.001), (1.4% vs. 0%; p = 0.048). The median value of hospital expense of hospitalized H7N9-related viral pneumonia patients was 66095.6 Yuan (IQR, 42450.6–129574.2), which was higher than that of human influenza A and B pneumonia patients (IQR, 25642.3 Yuan (13184.5–53805.7) vs. 18316.8 Yuan (IQR, 11111.1–35750.5); p < 0.001). There was no difference in death to three types of hospitalized influenza-related viral pneumonia patients.
In the treatment, the rate of antifungal drug use for H7N9 was 72.2% and that for glucocorticoid in hospitalized H7N9-related viral pneumonia patients was 100%, which was higher than human influenza A and B pneumonia patients (30.4% vs. 37.3%; p = 0.002), (55.8% vs. 40.7%; p < 0.001). All the hospitalized human influenza A-related viral pneumonia patients and hospitalized influenza B-related viral pneumonia patients were treated with aseltamivir or peramivir or both, and all the hospitalized H7N9-related viral pneumonia patients were treated with a combination of aseltamivir with peramivir. However, the time from onset of illness to administration of antiviral therapy in hospitalized H7N9-related viral pneumonia patients was 4 days (IQR, 3–8.3), which was relatively shorter than that of human influenza A and B pneumonia patients (7 days (IQR, 5–10.8) vs. 6 days (range, 3–14); p = 0.089). The time of administration of antiviral therapy to virus-negative time of hospitalized H7N9-related viral pneumonia patients was 5.5 days (IQR, 2.8–10), shorter than human influenza A and B pneumonia patients (10 days (IQR, 6–14.5) vs. 11 days (IQR, 6–17.75); p = 0.007).
Factors associated with IMV due to Three Types Hospitalized Influenza-related Viral Pneumonia Patients
In the univariate analysis, the three types hospitalized influenza-related viral pneumonia patients with IMV had significantly higher neutrophil percentage, C-reactive protein, AST, DD, blood urea nitrogen, pro-B-type natriuretic peptides, and partial pressure arterial oxygen/fraction of inspired oxygen (PaO2:FiO2) levels than the three types hospitalized influenza-related viral pneumonia patients without IMV. Furthermore, the proportion of patients with shortness of breaths, lymphocytopenia, elevated procalcitonin, AST, CK, DD, and LDH, positive bacterial culture (sputum) on presentation or during hospitalization, positive bacterial culture (blood or sputum) on presentation or during hospitalization, CURB-65 score ≥ 2, bilateral pneumonia, and pulmonary consolidation in the three types of hospitalized influenza-related viral pneumonia patients with IMV was significantly higher than those without IMV, while the lymphocyte count in the three types of pneumonia patients with IMV was lower than those without IMV (Table S1 in the Supplementary Material). In the multivariate analysis, pulmonary consolidation (odds ratio (OR): 13.67; 95% confidence interval (CI): 1.54–121.12; p = 0.019) and positive bacterial culture (sputum) at the time of presentation or during hospitalization (OR: 7.71; 95% CI: 2.48–24.03; p < 0.001) were independently associated with IMV in the three types hospitalized influenza-related viral pneumonia patients(Table S3 in the Supplementary Material).
Factors Associated with Death due to the three Types Hospitalized Influenza-related Viral Pneumonia Patients
In the univariate analysis, the three types of hospitalized influenza-related viral pneumonia patients who die in the hospital had significantly higher neutrophil percentage, hemoglobin, blood platelet counts, C-reactive protein, DD, blood urea nitrogen, pro-B-type natriuretic peptides, and PaO2:FiO2 levels than the survivors. Also, the proportion of elevated white blood cell count and procalcitonin, positive bacterial culture (sputum) on presentation or during hospitalization, CURB-65 score ≥ 2, IMV, shock to the three types hospitalized influenza-related viral pneumonia patients who die in the hospital was significantly higher than that of the survivors (Table S2 in the Supplementary Material). In the multivariate analysis, shock (OR: 13.16; 95% CI: 2.06–84.07; p = 0.006), white blood cell count > 10,000/mm3 (OR: 7.22; 95% CI: 1.47–35.58; p = 0.015) and positive bacterial culture(blood or sputum) on presentation or during hospitalization (OR: 6.27; 95% CI: 1.36–28.85; p = 0.018) were independently associated with death in the three types hospitalized influenza-related viral pneumonia patients (Table 4).