Background
Methods
Study design
Patients
Definitions
Data collection
RSV | RV | hMPV | HCoV | FLU | HAdV | HBoV | PIV |
p-value | |
---|---|---|---|---|---|---|---|---|---|
N = 331 single pathogens | 200 | 30 | 23 | 24 | 21 | 14 | 10 | 9 | |
Age in months mean (SD) |
5.8 (6.4)
|
5.4(8.5)
| 10.2(11.45) |
5.1(6.7)
|
15.1(23.2)
| 11.8(11.7) |
18.6(12.4)
| 6.8(8.4) | 0.001b
|
Median (IQR) |
3.75 (5.56)
|
2.75(5.4)
| 4.69(11.84) |
2.67(5.62)
|
2.13(23.53)
| 6.4(19.79) |
15.59(24.58)
| 5.67(4.87) | |
Male, n(%)
| 113(56.5) | 18(60.0) | 11(47.8) | 9(37.5) | 11(52.4) | 8(57.1) | 5(50.0) | 4(44.4) | 0.638a,c
|
DSS | |||||||||
mean (SD) |
14.9 (6.9)
| 12.6(7.9) | 12.2(7.6) |
8.3(6.6)
|
7.9(7.2)
| 11.9(8.6) |
19.1(3.4)
| 13.9(8.1) | 0.000b
|
median (IQR) |
17.0(10.0)
| 13.0(15.8) | 13.0(16.0) |
7.0,
|
4.0(9.5)
| 9.0(18.2) |
19.0(6.5)
| 13(16.0) | |
DSS ≤6, n(%) |
27(13.5)
| 7(23.6) | 7(30.4) |
10 (41.7)
|
12(57.1)
| 5(35.7) | 0(0.0) | 2(22.2) | 0.000a,c
|
DSS 7–13,n(%) | 51(25.5) | 10(33.3) | 7(30.4) | 10(41.7) | 5(23.8) | 3(21.4) | 0(0.0) | 3(33.3) | |
DSS 14–19, n(%) | 78(39.0) | 5(16.7) | 6(26.1) | 3(12.5) |
2(9.5)
| 2(14.3) |
7 (70.0)
| 2(22.2) | |
DSS ≥20, n(%) | 44(22.0) | 8(26.7) | 3(13.0) | 1(4.2) | 2(9.5) | 4(28.6) | 3(30.0) | 2(22.2) |
RSV | RV | hMPV | HCoV | FLU | HAdV | HBoV | PIV |
p-value | |
---|---|---|---|---|---|---|---|---|---|
N = 331 single pathogens | 200 | 30 | 23 | 24 | 21 | 14 | 10 | 9 | |
Fever, n(%)
| 108(54.3) |
9(30.0)
| 12(52.2) | 9(37.5) |
17(81.0)
| 7(50.0) | 6(60.0) | 5(55.6) | 0.030a
|
Cough, n(%)
|
187(94.5)
| 24(80.0) | 22(95.7) |
13(54.2)
|
14(66.7)
|
10(71.4)
| 9(90.0) | 8(88.9) | 0.000a
|
Rhinorrhea, n(%)
| 190(95.0) | 28(93.3) | 22(95.7) | 22(91.7) | 20(95.2) | 12(85.7) | 10(100.0) | 8(88.9) | 0.819a
|
Illness > 4 days, n(%)
|
180(90.0)
|
19(63.3)
| 16(69.6) |
13(54.2)
|
10(47.6)
| 9(64.3) | 8(80.0) | 8(100.0) | 0.000a
|
Apnea, n(%)
| 7(3.5) | 1(3.3) | 0(0.0) | 1(4.2) | 0(0.0) | 1(7.1) | 1(10.0) | 0(0.0) | 0.789a,b
|
Wheezing, n(%)
|
95(47.5)
| 13(43.3) | 6(26.1) | 6(25.0) |
3(14.3)
| 6(42.9) | 7(70.0) | 3(33.3) | 0.013a,b
|
Hypoxia, n(%)
|
105(52.5)
| 9(30.0) | 9(39.1) |
3(12.5)
| 6 (28.6) | 5(35.7) | 6(60.0) | 5(55.6) | 0.003a,b
|
Dyspnea, n(%)
|
136(68.0)
| 16(53.3) | 15(65.2) |
7(29.2)
|
5(23.8)
| 7(50.0) |
8(80.0)
| 6(66.7) | 0.000a
|
Tachypnea, n(%)
| 123(61.5) | 21(70.0) | 12(52.2) | 12(50.0) |
7(33.3)
| 7(50.0) |
10(100.0)
| 5(55.6) | 0.021a
|
RSV | RV | hMPV | HCoV | FLU | HAdV | HBoV | PIV |
p-value | |
---|---|---|---|---|---|---|---|---|---|
N = 331 single pathogens | 200 | 30 | 23 | 24 | 21 | 14 | 10 | 9 | |
Hospitalization | |||||||||
admission, n(%)
|
162(81.0)
| 22(73.3) | 16(69.6) |
10(41.7)
| 16(76.2) | 10(71.4) | 9(90.0) | 7(77.8) | 0.004a
|
days, mean (SD) | 4.4(2.8) | 3.3(3.1) | 3.2(1.5) | 3.9(3.4) | 2.9(2.7) | 2.9(2.1) | 3.2(1.9) | 5.3(2.7) | 0.014b
|
median (IQR) | 4.0 (4.0) | 2.0(3.75) | 3.0(2.0) | 3.0(3.75) | 2.0(1.75) | 2.0(1.5) | 3.0(1.5) | 4.0(5.0) | |
Therapy | |||||||||
AB initiated, n(%)
| 75(37.5) | 7(23.3) | 7(30.4) | 4(16.7) | 7(33.3) | 1(7.1) | 4(40.0) | 6(66.7) | 0.029a,c
|
AB no of days, mean (SD) | 2.4(3.3) | 1.4(2.7) | 2.4(3.9) | 1.5(3.6) | 2.0(3.0) | 0.5(1.9) | 2.8(3.6) | 3.7(3.3) | 0.091b
|
median (IQR) | 0.0(7.0) | 0.0(0.8) | 0.0(7.0) | 0.0(0.0) | 0.0(5.0) | 0.0(0.0) | 0.0(7.0) | 3.0(7.0) | |
Oxygen initiated,n(%) | 106(53) | 9(30) | 9(39.1) | 3(12.5) | 6(28.6) | 5(35.7) | 7(60) | 5(55.6) | 0.062a,c
|
Oxygen no of days, mean (SD) | 2.4(2.7) | 1.2(2.2) | 1.5(1.7) | 1.0(1.8) | 0.9(1.5) | 1.4(2.1) | 1.6(1.3) | 2.9(2.9) | 0.052b
|
median (IQR) | 2.35(4.0) | 0.0(2.5) | 1.0(3.0) | 0.0(2.3) | 0.0(1.8) | 0.5(2.5) | 2.0(2.0) | 3.0(5.0) | |
Nebulizationd initiated n(%) | 63(31.5) | 6(20) | 6(26.1) | 0(0) | 3(14.3) | 4(28.6) | 6(60) | 3(33.3) | 0.086a,c
|
Nebulizationd, no of days, mean (SD) | 1.2(2.0) | 0.7(1.5) | 0.8(1.3) | 0.0(0.0) | 0.4(0.9) | 1.4(2.1) | 2.2(2.2) | 1.3(1.6) | 0.050b
|
median (IQR) | 0.0(2.0) | 0.0(1.0) | 0.0(1.75) | 0.0(0.0) | 0.0(0.0) | 0.0(2.75) | 2.0(3.0) | 0.0(3.0) | |
Laboratory | |||||||||
CRP performed, n(%) | 111(55.5) | 16(33.0) | 9(39.1) | 14(58.3) | 15(71.4) | 7(50.0) | 4(40.0) | 2(22.2) | 0.401a,c
|
CRP max level, mean (SD), mg/L | 23.1(25.4) | 13.8(19.9) | 71.0(117.7) | 19.0(44.4) | 16.6(18.8) | 27.3(36.7) | 23.7(26.3) | 26.0(31.1) | 0.440b
|
median (IQR) | 14.0(37.0) | 5.0(25.5) | 14.0(112.0) | 0.0(14.5) | 9.0(25.0) | 7.0(63.0) | 21.0(48) | 26.0(44.0) | |
CRP > 40, n(%), mg/L | 27(13.5) | 2(6.7) | 3(13.0) | 2(8.3) | 2(9.5) | 2(14.3) | 2(20.0) | 1(11.1) | 0.706a,c
|
WBC performed, n(%) | 26(13.0) | 3(10.0) | 1(4.3) | 0(0.0) | 8(38.1) | 1(7.1) | 1(10.0) | 1(11.1) | 0.028a,c
|
WBC max level, mean (SD), 109/L | 11.6 (4.5) | 9.5 (2.4) | 7.6 | . | 8.1 (2.9) | 12.7 | 13.6 (0.3) | 27.0 | 0.065b
|
median (IQR) | 11.1(6.1) | 9.4 | 7.6(0) | . | 8.8(5.6) | 12.7(0.0) | 13.6(0.0) | 27.0(0) |
Disease severity score (DSS)
Respiratory pathogens
Other diagnostic procedures
Statistical analysis
Results
Patient enrollment
Demographics
Viral results
RT-PCR results | N | Proportion out of total (n = 560 cases) | Detection in single infections | Proportion out of total single infections (n = 331) | Detection in multiple infections | Proportion out of total multiple infections (n = 126) |
---|---|---|---|---|---|---|
Negative | 103 | 18.4% | ||||
Single | 331 | 59.1% | ||||
Dual | 106 | 18.9% | ||||
Triple | 18 | 3.2% | ||||
Quadruple | 2 | 0.4% | ||||
RSV | 291 | 52.0% | 200 | 60.4% | 91 | 72.2% |
RV | 72 | 12.9% | 30 | 9.1% | 42 | 33.3% |
HCoV | 71 | 12.7% | 24 | 7.3% | 47 | 37.3% |
HAdV | 45 | 8.0% | 14 | 4.2% | 31 | 24.6% |
hMPV | 42 | 7.5% | 23 | 6.9% | 19 | 15.1% |
FLU | 33 | 5.9% | 21 | 6.3% | 12 | 9.5% |
PIV | 29 | 5.2% | 9 | 2.7% | 20 | 15.9% |
HBoV | 22 | 3.9% | 10 | 3.0% | 12 | 9.5% |
Clinical symptoms and management of single viral infections
Univariate | Multivariate | |||
---|---|---|---|---|
Variable | Spearman’s ρ |
p-valuea
| Regression coefficient | Adjusted p-value |
Age | −0.096 | .128 | −0.019 | 0.165 |
DSS | 0.371 | <0.01 | −0.038 | 0.052 |
AB initiated | 0.334 | <0.01 | 0.352 | 0.571 |
AB no of days | 0.336 | <0.01 | 0.026 | 0.769 |
FiO2 no of days | 0.671 | <0.01 | 0.885 | <0.01 |
Nebulizer | 0.120 | <0.01 | 0.293 | 0.005 |
RSV | <0.01 | 0.306 | 0.226 | |
RV | 0.022 | 0.409 | 0.324 | |
hMPV | 0.446 | |||
HCoV | 0.623 | |||
FLU | 0.024 | |||
HAdV | 0.125 | |||
HboV | 0.470 | |||
PIV | 0.128 |
-
RSV: RSV was the most frequently detected virus and was found in 200 out of 331 (60.4%) single infections. The mean age of children with RSV was 5.8 months and they were significantly younger than children with FLU or HBoV. RSV positive children were significantly more often hospitalized than HCoV positive children. The DSS for children with RSV and HBoV was significantly higher than for those with HCoV and FLU. The mean DSS for RSV was 14.9, the second highest after HBoV (DSS 19.1). This was significantly higher than for instance FLU (DSS 7.9). Apneas occurred in 7/200 (3.5%) of RSV single infections. One child was RT-PCR positive for RSV as single pathogen, despite a first vaccination with palivizumab. It was a 2 month old boy born after 32 weeks of gestation with a mild disease course (DSS 13, LOS 4). None of the children in the study were treated with the antiviral drug ribavirin.
-
Rhinovirus: RV was the second most commonly identified single virus infection (30/331, 9.1%). The mean age of children with RV was young; 5.4 months. The DSS was not significantly different compared to those of other viruses.
-
Human metapneumovirus: For hMPV, there were no significant differences compared to the other viruses with regard to age, DSS and admission rate.
-
Coronavirus: Children with HCoV had the lowest mean age (5.1 months) of all virus groups. The mean DSS was 8.6, which was significantly lower than for RSV or HBoV. The admission rate was 10/24 (41.7%), the lowest of all virus groups.
-
Influenzavirus: The mean age at onset of disease for FLU was 15.1 months, which was significantly higher than for RSV and some other viruses. The mean DSS was 7.9, lowest of all virus groups and significantly lower than for RSV. None of the patients was treated with antiviral drugs like oseltamivir.
-
Adenovirus: For HAdV, there were no significant differences compared to the other viruses with regard to DSS and admission rate.
-
Bocavirus: The mean age of children with HBoV was 18.6 months, which was significantly higher than for RSV, RV and HCoV. The mean DSS was also highest (19.1), which was significantly higher than for FLU. The admission rate was 9/10 (90.0%). Although the admission rate was the highest of all virus groups, this difference was not significant. The mean number of days of nebulization therapy with salbutamol and ipratropium bromide was 2.2 (SD 2.2) days, highest of all, although this was not significant compared to the other viruses.
-
Parainfluenzavirus: The mean DSS for children with PIV was 13.9, third highest after HBoV and RSV. The number of times that antibiotics were initiated was highest for PIV (6/9, 66.7%).
Clinical symptoms and management of multiple viral infections
RT-PCR negative | RT-PCR positive |
p-valuea
| Single ARI | Multiple ARI |
p-value | |
---|---|---|---|---|---|---|
DSS, mean | 8.83 | 13.83 |
0.000
| 13.57 | 14.51 | 0.243 |
Fever n/total (%) | 37/103 (35.9) | 243/457 (53.2) |
0.002
| 173/331 (52.3) | 70/126 (55.6) | 0.529 |
Admission n/total, (%) | 74/103 (71.8) | 342/457 (74.8) | 0.530 | 252/331 (76.1) | 90/126 (71.4) | 0.300 |
LOS (days) | 2.99 | 3.95 |
0.003
| 4.02 | 3.76 | 0.432 |
Oxygen supply (days) | 0.85 | 1.98 |
0.000
| 1.99 | 1.96 | 0.912 |
Nebulizer therapy (days) | 1.03 | 1.19 | 0.227 | 1.10 | 1.46 | 0.140 |
Antibiotics (days) | 1.56 | 2.32 |
0.041
| 2.19 | 2.67 | 0.190 |