One hundred and fifty-eight critically ill adults with 167 respiratory specimens (NPS 154, TS 2, and BAL 11) were included during the study period. All patients were tested by the FilmArray® panel, while one and seven patients did not underwent nucleic acid amplification for influenza viruses and viral cell cultures, respectively. The first specimen collection was obtained at a median of one day (0–1 day) after ICU admission.
Respiratory viruses were detected in 64 (40.5%) patients, i.e., 64 patients with VRTIs. The comparisons of clinical data between patients with or without detection of respiratory virus are demonstrated in Table 1. Patients with VRTIs were younger (median age: 62.5 vs. 69.0 years, p = 0.003), but there were no differences in terms of chronic illness, disease severity, and clinical outcomes, including mortality rate and length of ICU or hospital stay between the two groups.
Table 1
Clinical characteristics of patients with and without viral respiratory tract infections (VRTIs).
|
All
(n = 158)
|
With VRTIs
(n = 64)
|
Without VRTIs
(n = 94)
|
p value
|
Demographic
|
|
|
|
|
Age
|
68 (56.25–77)
|
62.5 (49.25–75)
|
69 (60.25–79)
|
0.003
|
Male sex
|
87 (55%)
|
29 (45.3%)
|
58 (61.7%)
|
0.268
|
Hospital stay
|
16 (10–28)
|
16 (10–25.25)
|
16 (10–29.75)
|
0.980
|
Comorbidity
|
|
|
|
|
Hypertension
|
72 (45.6%)
|
29 (45.3%)
|
43 (45.7%)
|
0.974
|
Diabetes mellitus
|
47 (29.7%)
|
19 (29.7%)
|
28 (29.8%)
|
0.992
|
Chronic kidney disease
|
45 (28.5%)
|
19 (29.7%)
|
24 (27.7%)
|
0.836
|
Heart failure
|
37 (23.4%)
|
16 (25.0%)
|
21 (22.3%)
|
0.761
|
Coronary artery disease
|
28 (17.7%)
|
14 (21.9%)
|
14 (14.9%)
|
0.348
|
COPD
|
25 (15.8%)
|
8 (12.5%)
|
17 (18.1%)
|
0.419
|
Malignancies
|
24 (15.2%)
|
8 (12.5%)
|
16 (17.0%)
|
0.503
|
Autoimmune diseases
|
11 (7.0%)
|
3 (4.5%)
|
8 (8.7%)
|
0.529
|
Bronchiectasis
|
8 (5.0%)
|
5 (7.8%)
|
3 (3.2%)
|
0.279
|
Asthma
|
4 (2.5%)
|
2 (3.1%)
|
2 (2.1%)
|
1.000
|
Hepatic cirrhosis
|
2 (1.3%)
|
0 (0%)
|
2 (2.1%)
|
0.517
|
Severity & outcomes
|
|
|
|
|
Vasopressor use
|
64 (40.5%)
|
26 (40.6%)
|
38 (40.4%)
|
1.000
|
Septic shock
|
32 (20.3%)
|
15 (23.4%)
|
17 (18.1%)
|
0.638
|
Mechanical ventilation
|
128 (81.0%)
|
52 (81.3%)
|
76 (80.9%)
|
0.984
|
ARDS
|
60 (38.0%)
|
29 (45.3%)
|
31 (33.0%)
|
0.297
|
Moderate-to-severe
|
46 (29.1%)
|
21 (32.8%)
|
25 (26.6%)
|
0.533
|
APACHE IIa
|
21.23 ± 7.66
|
19.98 ± 6.98
|
22.09 ± 8.10
|
0.083
|
SOFA scoreb
|
7.25 ± 3.71
|
7.44 ± 3.56
|
7.12 ± 3.81
|
0.590
|
MV days
|
4 (2–10)
|
4.5 (2–9.25)
|
4 (2–12)
|
0.892
|
ICU stay
|
8 (5–14)
|
8 (5–13)
|
8 (5–14)
|
0.691
|
Hospital stay
|
16 (10–28)
|
16 (10–25.25)
|
16 (10–29.75)
|
0.980
|
ICU mortality
|
24 (15.2%)
|
7 (10.9%)
|
17 (18.1%)
|
0.289
|
28-day mortality
|
23/152 (15.1%)
|
8/62 (12.9%)
|
15/90 (16.7%)
|
0.584
|
VRTI viral respiratory tract infection, COPD chronic obstructive pulmonary disease, ARDS acute respiratory disease syndrome, APACHE II Acute Physiologic Assessment and Chronic Health Evaluation II, SOFA Sequential Organ Failure Assessment, MV mechanical ventilation, ICU intensive care unit. |
a on the ICU admission day. |
b on the day obtaining the first respiratory specimen. |
The most commonly detected virus was influenza virus (20 patients: A/H1 6, A/H3 13, B 1), followed by RV/EV (11), RSV (9), HMPV (9), HPIVs (8), HAdV (7), and HCoVs (2) (Fig. 1). To be noted, 57 adults admitted to medical ICUs with confirmed influenza were not included in the study, usually due to positive results in rapid antigen tests. The FilmArray® respiratory panel detected respiratory viruses in 54 patients and M. pneumoniae in one patient. Nine patients with negative results of the FilmArray® respiratory panel, but had VRTIs due to respiratory viruses detected by other tests, including influenza A/H3 (7), influenza A/H1 (1) and HAdV (1). Among eight patients with both NPS and BAL tested by the panel, two had discordant results: one HCoV-NL63 only in NPS and the other HAdV only in BAL. The remaining six patients had concordant NPS and BAL results, including one with influenza A/H3, one with hMPV, and four without viral pathogen. Viral cell cultures revealed respiratory viruses in 12 patients (influenza A: 3, HAdV: 3, RSV: 3, HPIV-3: 2, RV/EV: 1), accounting for 20.3% of 59 patients with VRTIs having viral cultures.
Twelve (18.8%) of 64 patients with and 25 (26.6%) of 94 patients without VRTIs had RTIs due to other pathogens. Of 12 patients with VRTIs, coexisting pneumonia caused by bacteria was present in nine patients, including two with Klebsiella pneumoniae and two with Staphylococcus aureus infections, while three patients had concurrent pulmonary aspergillosis. Of the latter, one had concurrent fursarosis and pneumocystis, and another biopsy-proven Candida tropicalis tracheobronchitis. Of co-infections due to non-respiratory viruses, one had cytomegalovirus pneumonitis and the other human simplex virus-1 tracheobronchitis. Among seven fatal patients with VRTIs (HAdV: 2, RSV: 2, RV/EV: 2, influenza A/H3: 1), two were complicated with concurrent bacterial pneumonia.
Among all 158 patients with respiratory distress, 22 (46.8%) of 47 patients with acute decompensated heart failure had VRTIs, while the proportions of VRTIs in patients with pneumonia, tracheobronchitis, acute exacerbation of chronic obstructive pulmonary disease, and asthma were 45.8% (38/83), 36.4% (4/11), 29.2% (4/24), and 50% (2/4), respectively. None of nine patients related to metabolic acidosis (5 patients), sepsis of unknown source (3), or K. pneumoniae bacteremia complicated by liver abscess (1) had VRTI.
The multivariable logistic regression analyses revealed the risk factors associated with VRTIs in Table 2. The variables significantly associated with VRTIs in the simple regression analysis but not in the multivariable model included myalgia, rhinorrhea, neutrophil-to-lymphocyte ratio > 12.5, and specimen collected by a flock swab. None of the blood biomarkers, such as white blood cell count, serum levels of C-reactive protein or procalcitonin, were predictive of the existence of VRTIs. Age less than 65 years old (OR, 4.61; 95% CI, 1.99–11.40), household contact with someone having upper RTI (OR, 4.28; 95% CI 1.82–10.82), the presence of fever (OR, 3.16; 95% CI 1.23–8.81), productive cough (OR, 3.42; 95% CI, 1.45–8.63), or sore throat (OR, 3.82; 95% CI 1.27–12.59), were significantly associated with VRTIs. The association of the number of the above variables with probability of VRTI was shown in Fig. 2 and Additional File 1, Table S2.
Table 2
Simple and multivariable regressions for factors associated with viral respiratory tract infections.
Variables
|
Odds ratio (95% CI)
|
p value
|
Odds ratio (95% CI)
|
p value
|
Age < 65 years
|
3.23 (1.67–6.34)
|
< 0.001
|
4.61 (1.99–11.40)
|
< 0.001
|
Household contact with a person having upper RTI
|
2.76 (1.42–5.45)
|
0.003
|
4.28 (1.82–10.82)
|
0.001
|
Clinical symptoms
|
|
|
|
|
Rhinorrhea
|
3.70 (1.87–7.47)
|
< 0.001
|
2.15 (0.86–5.53)
|
0.103
|
Sore throat
|
3.68 (1.65–8.60)
|
0.002
|
3.82 (1.27–12.59)
|
0.021
|
Myalgia
|
2.95 (1.30–6.97)
|
0.011
|
2.16 (0.78–6.16)
|
0.139
|
Productive cough
|
2.87 (1.18–7.56)a
|
0.024
|
3.42 (1.45–8.63)b
|
0.007
|
Fever
|
2.29 (1.05–5.34)
|
0.044
|
3.16 (1.23–8.81)
|
0.020
|
Dyspnea
|
2.11 (0.47–14.75)
|
0.369
|
|
|
Dry cough
|
1.48 (0.55–4.21)a
|
0.442
|
|
|
Headache
|
1.35 (0.48–3.73)
|
0.561
|
|
|
Malaise
|
1.14 (0.60–2.18)
|
0.678
|
|
|
Altered mental status
|
0.64 (0.24–1.56)
|
0.347
|
|
|
Laboratory tests
|
|
|
|
|
White blood cell count
|
1.00 (1.00–1.00)
|
0.513
|
|
|
Leukocytosisc
|
0.75 (0.40–1.43)
|
0.389
|
|
|
Leukopeniad
|
1.10 (0.21–5.19)
|
0.897
|
|
|
NLR
|
1.01 (0.99–1.04)
|
0.231
|
|
|
NLR > 12.5
|
1.79 (0.90–3.55)
|
0.094
|
2.43 (1.00–6.16)
|
0.053
|
C-reactive protein (CRP)e
|
1.00 (0.99–1.01)
|
0.849
|
|
|
CRP ≥ 89 mg/L
|
2.14 (0.44–11.31)
|
0.348
|
|
|
Procalcitonin (PCT)f
|
1.01 (0.97–1.06)
|
0.601
|
|
|
PCT > 0.35 ng/mL
|
1.63 (0.58–4.62)
|
0.355
|
|
|
Flocked swab use
|
1.99 (1.04–3.84)
|
0.038
|
2.10 (0.94–4.83)
|
0.073
|
CI confidence interval, RTI respiratory infection, NLR neutrophil-to-lymphocyte ratio. |
a Compared to no cough. |
b Compared to no or dry cough. |
c White blood cell count > 11,000 /µL |
d White blood cell count < 4,000 /µL |
e Available in 27 patients |
f Available in 62 patients |