Supplementary Material 4 shows that 34.0% (367/1079) of Flu-p patients were coinfected with other community-aquired pathogens. The most common coinfected pathogens were Klebsiella pneumoniae (31.6%, 116/367), Streptococcus pneumoniae (29.7%, 109/367) and Staphylococcus aureus (19.3%, 71/1079), respectively.
All Flu-p patients were administrated antibiotics after admission and NAI during disease course, with early NAI administrated to 35.7% (385/1079) of patients. In total, 24.3% (262/1079) of Flu-p patients received systemic corticosteroids during hospitalization. Regarding adverse outcomes, 23.1% (249/1079) developed respiratory failure, 24.6% (265/1079) experienced heart failure, and 8.2% (89/1079) developed septic shock, respectively. In total, 17.9% (193/1079) of Flu-p patients received invasive ventilation and 22.4% (242/1079) were admitted to the ICU. The 30-day mortality rate for Flu-p patients was 19.3% (208/1079) (Table 1).
In total, 59.1% (75/127) of RSV-p patients were male, and 96.9% (123/127) were age 50 years or older. Underlying medical conditions affected 65.4% (83/127) of RSV-p patients, and the top three conditions were cardiovascular disease (34.6%, 44/127), chronic pulmonary disease (23.6%, 30/127) and cerebrovascular disease (15.7%, 20/127). Cough (96.1%, 122/127) was the most common symptom, with sputum production (11.0%, 14/127) occurring significantly less often . Dyspnea and fever were present in 71.7% (91/127) and 55.9% (71/127) of RSV-p patients, respectively.
Coinfections were isolated in 30.7% (39/127) of RSV-p patients. The top three coinfected pathogens were Klebsiella pneumoniae (48.7%, 19/39), Staphylococcus aureus (20.5%, 8/39), and Streptococcus spp. (7.7%, 3/39), respectively (see Supplementary Material 4).
All RSV-p patients received antibiotics, and 7.9% (10/127) were administered systemic corticosteroids during hospitalization. Noninvasive and invasive ventilation were performed in 25.2% (32/127) and 11.0% (14/127) of RSV-p patients, respectively. Heart failure (33.1%, 42/127) was the most frequent complication, followed by respiratory failure (29.1%, 37/127) and acute renal failure (6.3%, 8/127). In total, 11.0% (14/127) of RSV-p patients were admitted to the ICU, and the 30-day mortality rate was 14.2% (18/127) (Table 1).
Table 2
Comparison of clinical management and outcomes between patients with Flu-p and RSV-p
Variable
|
Flu-p
(n=1079)
|
FluA-p
(n=693)
|
FluB-p
(n=386)
|
RSV-p
(n=127)
|
p value†
|
Early NAI therapy
|
385 (35.7)
|
232 (33.5)
|
153 (39.6)
|
0 (0.0)
|
< 0.001
|
Systemic corticosteroids use (n, %)
|
262 (24.3)
|
132 (19.0)
|
130 (33.7)
|
10 (7.9)
|
< 0.001
|
Noninvasive ventilation (n, %)
|
279 (25.9)
|
159 (22.9)
|
120 (31.1)
|
32 (25.2)
|
0.872
|
Invasive ventilation (n, %)
|
193 (17.9)
|
158 (22.8)
|
35 (9.1)
|
14 (11.0)
|
0.052
|
Vasopressor use (n, %)
|
40 (3.7)
|
27 (3.9)
|
13 (3.4)
|
6 (4.7)
|
0.748
|
Complications (n, %)
|
|
|
|
|
|
Respiratory failure
|
249 (23.1)
|
167 (24.1)
|
82 (21.2)
|
37 (29.1)
|
0.129
|
Heart failure
|
265 (24.6)
|
147 (21.2)
|
118 (30.6)
|
42 (33.1)
|
< 0.001
|
Septic shock
|
89 (8.2)
|
53 (4.9)
|
36 (5.2)
|
7 (5.5)
|
0.281
|
Acute renal failure
|
66 (6.1)
|
39 (5.6)
|
27 (7.0)
|
8 (6.3)
|
0.935
|
gastrointestinal bleeding
|
48 (4.4)
|
40 (5.8)
|
8 (2.1)
|
3 (2.4)
|
0.269
|
Admittance to ICU (n, %)
|
242 (22.4)
|
176 (25.4)
|
66 (17.1)
|
14 (11.0)
|
0.003
|
Length of stay in hospital
(days, median, IQR)
|
10.0 (8.0-14.0)
|
12.0 (7.0-14.5)
|
10.0 (8.0-17.0)
|
14.0 (10.0-23.0)
|
< 0.001
|
30-day mortality (n, %)
|
208 (19.3)
|
136 (19.6)
|
72 (18.7)
|
18 (14.2)
|
0.163
|
NAI: neuraminidase inhibitor; ICU: intensive care unit. †: Comparisons were made between patients with Flu-p and RSV-p. The bolded values are p-values < 0.05, which represented significant differences between patients with Flu-p and RSV-p.
|
Predictors of RSV-p
Bivariate analyses indicated that RSV-p was associated with age ≥ 50 years, cardiovascular disease, cerebrovascular disease, chronic pulmonary disease, chronic kidney disease, solid malignant tumor, fever, myalgia, sputum production, respiratory rates ≥ 30 beats/min, lymphocytes < 0.8×109/L and blood albumin < 35 g/L (Table 1).
A multivariate logistic regression model indicated that age ≥ 50 years [odds ratio (OR) 11.207 , 95% confidence interval (CI) 3.266 - 38.456, p < 0.001], cerebrovascular disease (OR 4.189, 95% CI 1.473 - 11.918, p = 0.007), chronic kidney disease (OR 8.934, 95% CI 2.114 - 37.760, p = 0.003), solid malignant tumor (OR 3.407, 95% CI 1.102 - 10.533, p = 0.033), nasal congestion (OR 4.088, 95% CI 1.857-8.999, p < 0.001), myalgia (OR 0.126, 95% CI 0.056 - 0.285, p < 0.001), sputum production (OR 0.006, 95% CI 0.003 - 0.014, p < 0.001), respiratory rates ≥ 30 beats/min (OR 2.612, 95% CI 1.105 - 6.173, p = 0.029), lymphocytes < 0.8×109/L (OR 0.145, 95% CI 0.053 - 0.398, p < 0.001) and blood albumin < 35 g/L (OR 6.454, 95% CI 2.842 - 14.661, p < 0.001) were all statistically significant, independent predictors of RSV-p (Fig. 3).
Impact of virus type on severity of outcomes
The effects of virus type on the severity of outcomes are presented in Table 3. Univariate logistic regression analyses indicated that, relative to RSV-p, FluA-p was associated with an increased risk for severe outcomes (OR 1.931, 95% CI 1.241 - 3.005, p = 0.004), including invasive ventilation (OR 2.384, 95% CI 1.331 - 4.271, p = 0.003) and ICU admission (OR 2.748, 95% CI 1.537 - 4.913, p = 0.001). In contrast, the 30-day mortality rate was not significant for FluA-p (OR 1.479, 95% CI 0.868 - 2.519, p = 0.150). Regarding FluB-p and RSV-p, the risks were similar for all of the following: general risk for severe outcomes (OR 1.506, 95% CI 0.944 - 2.403, p = 0.086 ), invasive ventilation (OR 0.805, 95% CI 0.418 - 1.550, p = 0.516 ), ICU admission (OR 1.665, 95% CI 0.900 - 3.080, p = 0.104), and 30-day mortality rate (OR 1.389, 95% CI 0.793 - 2.432, p = 0.251).
A multivariate logistic regression analysis adjusting for age, sex, duration of illness onset to admission, comorbidities (cardiovascular disease, cerebrovascular disease, diabetes mellitus, chronic pulmonary disease, asthma, chronic kidney disease and solid malignant tumor), obesity, pregnancy, smoking history, administration of early NAI, systemic corticosteroid use during hospitalization, and coinfections, indicated that, relative to RSV-p, FluA-p was associated with an increased risk for severe outcomes [adjusted OR (aOR) 2.313, 95% CI 1.377 - 3.885, p = 0.002), including invasive ventilation (aOR 2.680, 95% CI 1.393 - 5.154, p = 0.003), ICU admission (aOR 2.067, 95% CI 1.064 - 4.015, p = 0.032) and 30-day mortality (aOR 2.503, 95% CI 1.229 - 5.101, p = 0.012). Regarding FluB-p and RSV-p, the risks were similar for all of the following: invasive ventilation (aOR 0.683, 95% CI 0.333 - 1.400, p = 0.297 ), ICU admission (aOR 1.994, 95% CI 0.993 - 4.005, p = 0.052), 30-day mortality (aOR 1.898, 95% CI 0.937 - 3.846, p = 0.075), and total number of severe outcomes (aOR 1.630, 95% CI 0.958 - 2.741, p = 0.071) (Table 3 and Fig. 3).
Table 3
Impact of viruses types on severe outcomes
Clinical outcomes
|
Viruses types
(reference: RSV)
|
Univariate logistic analysis
|
Multivariate logistic analysis
|
OR (95% CI)
|
p-value
|
*aOR (95% CI)
|
p-value
|
Severe outcomes
|
Influenza A
|
1.931 (1.241-3.005)
|
0.004
|
2.313 (1.377-3.885)
|
0.002
|
Influenza B
|
1.506 (0.944-2.403)
|
0.086
|
1.630 (0.958-2.741)
|
0.071
|
Invasive ventilation
|
Influenza A
|
2.384 (1.331-4.271)
|
0.003
|
2.680 (1.393-5.154)
|
0.003
|
Influenza B
|
0.805 (0.418-1.550)
|
0.516
|
0.683 (0.333-1.400)
|
0.297
|
Admittance to ICU
|
Influenza A
|
2.748 (1.537-4.913)
|
0.001
|
2.067 (1.064-4.015)
|
0.032
|
Influenza B
|
1.665 (0.900-3.080)
|
0.104
|
1.994 (0.993-4.005)
|
0.052
|
30-day mortality
|
Influenza A
|
1.479 (0.868-2.519)
|
0.150
|
2.503 (1.229-5.101)
|
0.012
|
Influenza B
|
1.389 (0.793-2.432)
|
0.251
|
1.898 (0.937-3.846)
|
0.075
|
OR: odd ratio; CI: confidence interval; aOR: adjusted odd ratio. *: adjusted for age, sex, duration from illness onset to admisssion, comorbidities (cardiovascular disease, cerebrovascular disease, diabetes mellitus, chronic pulmonary disease, asthma, chronic kidney disease and solid malignant tumor), obesity, pregancy, smoking history, systemic corticosteroid use and coinfections.
|
Figure 4 shows that after adjusting for confounders, the 30-day mortality rate for FluA-p patients was significantly lower than that of RSV-p patients [adjusted hazard ratio (aHR) 2.280, 95% CI 1.203 - 4.312, p = 0.011]. In contrast, the 30-day mortality rates for patients with FluB-p and RSV-p were similar (aHR 1.208, 95% CI .650 - 2.246, p = 0.549).
Risk factors for severe outcomes in RSV-p patients
Compared to RSV-p patients without severe outcomes, RSV-p patients with severe outcomes were older and were more likely to present with chronic pulmonary disease. The proportions of lymphocytes < 0.8×109/L, haemoglobin < 100 g/, blood urea nitrogen > 7 mmol/L, and PO2/FiO2 < 250 mmHg at admission, and the use of systemic corticosteroids during hospitalization, were higher in RSV-p patients with severe outcomes than in RSV-p patients without severe outcomes (Supplementary Material 5).
To explore the risk factors for severe outcomes in RSV-p patients, the following variables were entered into a logistic regression model: age, chronic pulmonary disease, smoking history, confusion, leukocytes > 10×109/L, lymphocytes < 0.8×109/L, haemoglobin < 100 g/, blood urea nitrogen > 7 mmol/L, PO2/FiO2 < 250 mmHg, and systemic corticosteroid use. Results indicated that age (OR 1.084, 95% CI 1.010 - 1.164, p = 0.026), chronic pulmonary disease (OR 5.512, 95% CI 1.721 - 17.652, p = 0.004), confusion (OR 8.293, 95% CI 2.022 - 34.016, p = 0.003), lymphocytes < 0.8×109/L (OR 6.011, 95% CI 1.376 - 26.249, p = 0.017), and blood urea nitrogen > 7 mmol/L (OR 3.588, 95% CI 1.161 - 11.088, p = 0.026) at admission were statistically significant, independent risk factors for severe outcomes in RSV-p patients (Table 4).
Table 4
Risk factor for severe outcomes in RSV-p patients
Risk factors
|
OR (95% CI)
|
p value
|
Age
|
1.084 (1.010-1.164)
|
0.026
|
COPD
|
5.512 (1.721-17.652)
|
0.004
|
Confusion
|
8.293 (2.022-34.016)
|
0.003
|
Lymphocytes < 0.8×109/L
|
6.011(1.376-26.249)
|
0.017
|
BUN > 7 mmol/L
|
3.588 (1.161-11.088)
|
0.026
|