From January 1, 2015 to December 31, 2019, a total of the 67,842 respiratory samples were tested; 58,253 from KINRESS and 9,589 from SNUCH. One or more respiratory viruses were detected from 35,459 (52.3%) samples and 2,854 (4.2%) samples were positive for HCoVs (HCoV-OC43 2.1%, HCoV-NL63 1.7%, and HCoV-229E 0.4% by type).
By the data source, a total of 58,253 respiratory samples were collected by KINRESS. 30,442 (52.3%) samples were positive for any respiratory viruses and HCoVs were detected in 2,391 (4.1%) samples (Figure 1). The number of samples and occurrence rate by type were as follows; HCoV-229E, 203 (0.3%); HCoV-NL63, 1,032 (1.8%); and HCoV-OC43, 1,156 (2.0%) [see Additional file 1].
During the same period, a total of 9,589 respiratory samples tested in SNUCH, and one or more respiratory viruses were detected from 5,017 (52.3%) samples. Of 463 (4.8%) samples positive for HCoVs (Figure 1), 67 (0.7%) were positive for HCoV-229E, 139 (1.4%) for HCoV-NL63, 268 (2.8%) for HCoV-OC43 [see Additional file 1].
Demographics
The median age of patients sampled by KINRESS was 13 years (IQR 3-48 years) and 45.3% were male. In 2,391 samples with HCoV detection, the median patient age was 13 years (IQR 2-54 years) and 43.1% were male. The pattern of HCoV positive rate by age group showed two peaks in HCoV prevalence among children less than 2 years of age (5.4%) and older adults aged over 70 years (5.5%) (Figure 2).
In SHUCH, the median age of patients tested was 2 years (IQR 0-7 years) and 57.5% were male. In 463 children with HCoV detection, the median age was 2 years (IQR 0-4 years) and 54.9% were male. HCoV was most prevalent in 2 – 4 years olds with percent positive of 6.4%, followed by 5.2% in 0 – 1 year olds and 3.4% in 5 – 19 years olds.
Annual and seasonal distribution of HCoVs
In KINRESS data, the detection rates of HCoV by one epidemic year ranged from 4.1% in 2015/16 to 5.2% in 2016/17. Seasonal detection rates of HCoV in SNUCH were ranged from 4.9% in 2018/2019 to 5.8% in 2017/18.
Both KINRESS and SNUCH data demonstrated high detection rate of HCoV during winter season (November to February) each year, showing the highest monthly detection rates up to 11.9% in December 2016 and 16.1% in November 2018, in KINRESS and SNUCH respectively (Figure 3). Both data showed similar circulation pattern of three types with minimal differences. HCoV-OC43 was most prevalent among three types and mostly peaked during winter season in KINRESS and SNUCH. In 2018/19 winter season, HCoV-OC43 was predominant in SNUCH while KINRESS data showed similar detection rates of HCoV-OC43 and HCoV-NL63. HCoV-NL63 was identified with alternate peaks occurring late winter (from January to March) or early winter (from November to January) from both data sources. Meanwhile, HCoV-229E had smaller peaks every other winter in 2015/16 and 2017/18 (Figure 3).
Co-detection with respiratory viruses
The proportion positive for each virus of the test-positive viruses from KINRESS and SNUCH during the study period was shown in Figure 4. The average proportion of HCoVs of the test-positive viruses in KINRESS and SNUCH were 7.2% and 7.6%, respectively. Human rhinovirus was the most commonly detected in both institutions (17.1% in KINRESS, 22.2% in SNUCH). The second most prevalent virus was respiratory syncytial virus (10.1%) in SNUCH and influenza virus (14.4%) in KINRESS.
Among 2,391 HCoV-positive samples obtained in KINRESS, 436 (18.2%) samples were co-detected with other respiratory viruses. Co-detections with non-HCoV viruses were observed in 374 (28.9%) of HCoV-positive samples from patients younger than 20 years old. In this age group, human rhinovirus (8.3%) and adenovirus (7.8%) were most frequently co-detected [see Additional file 2]. Figure 2 showed a higher co-detection rate in the younger age groups with the highest rate of 33.7% in infants <2 years of age and the lowest rate (3.6%) in those ≥70 years of age.
Of the 463 HCoV-positive samples in SNUCH, 189 (40.8%) samples were co-detected with one or more respiratory viruses other than HCoVs. Frequently detected viruses with HCoVs were human rhinovirus (13.2%), respiratory syncytial virus (13.0%), and adenovirus (10.4%). Influenza virus (4.3%) was less commonly detected with HCoVs. Co-detections with two different types of HCoVs were seen in 11 samples [see Additional file 2].
Clinical diagnosis
The clinical diagnosis of the 135 previously healthy children with a single detection of HCoVs are summarized in Table 1. The median age was 1 year old (IQR 0-2.5 years) and 54.1% were male. There was no significant differences in the median age and age distribution by type (p= 0.444, p= 0.46). Upper respiratory infection was the most common clinical diagnosis throughout all 3 types. HCoV-NL63 was frequently associated with croup (17.0% in HCoV-NL63 vs. 3.9% in remainder, p=0.029) Febrile illness was more prevalent in HCoV-229E and HCoV-OC43 than HCoV-NL63 (p= 0.044).
Table 1. Clinical features of previously healthy children with a single HCoV detection in SNUCH, 2015-2019
|
HCoV-229E (n=12)
|
HCoV-NL63 (n=47)
|
HCoV-OC43 (n=76)
|
P-value
|
Age
|
|
|
|
|
Median months [IQR]
|
28.0 [ 5.5;81.5]
|
11.0 [ 4.0;35.0]
|
13.5 [ 2.0;34.0]
|
0.444
|
0 – <2 years
|
6 (50.0)
|
32 (68.1)
|
49 (64.5)
|
0.46
|
2 – <5 years
|
3 (25.0)
|
12 (25.5)
|
19 (25.0)
|
5 – 19 years
|
3 (25.0)
|
3 (6.4)
|
8 (10.5)
|
Sex
|
|
|
|
|
Male
|
9 (75.0)
|
24 (51.1)
|
40 (52.6)
|
0.309
|
Female
|
3 (25.0)
|
23 (48.9)
|
36 (47.4)
|
Clinical diagnosis
|
|
|
|
|
Upper respiratory infection
|
7 (58.3)
|
29 (61.7)
|
45 (59.2)
|
0.965
|
Croup
|
0 (0.0)
|
8 (17.0)
|
3 (3.9)
|
0.029
|
Pneumonia
|
2 (16.7)
|
6 (12.8)
|
12 (15.8)
|
0.875
|
Bronchiolitis
|
1 (8.3)
|
3 (6.4)
|
5 (6.6)
|
1.000
|
Febrile illness#
|
2 (16.7)
|
1 (2.1)
|
11 (14.5)
|
0.044
|
Note, HCoV-positive cases with other co-detected viruses were excluded from this analysis.
*Data are numbers (percentages) of patients unless otherwise indicated.
#Febrile illness did not accompany any respiratory symptoms.