3.1 Demographical of study participants
Among the total of 603 pediatric cases, male accounted for 55.7%(336 cases) and female accounted for 44.3% (267 cases). The average age of the patients was 41.1 months ranging from 30 days to 16.5 years old. More than a quarter of infected children were under 12 months of age, and 61.9% were under 3 years of age. Among which 24.7% (149 cases) of the whole cohort were reported with underlying disease, including asthma, allergic rhinitis, eczema, recurrent respiratory tract infections and other serious diseases such as congenital heart disease, tumors, surgery and so on. 17.9% (108 cases)of the population were allergic to food, drugs or other contacts. As for the vaccination, only 12 cases received one dose and 69 cases received two doses due to the younger age. The average vaccination rate of families with one dose or more was 55.8%, which was lower than the average level in Shanghai and even lower than the vaccination rate of the elderly over 60 years old[5]. Detailed demographical information are available in Table 1.
3.2 Clinical characteristics of children with COVID-19
Among the whole cohort, 24 cases remained asymptomatic while the other 579 cases emerged a wide range symptom which included respiratory system, digestive system, nervous system, body temperature, sensation and so on. The proportion of children with fever symptoms was 87.2% (526 cases). Since fever might precede RT-PCR positive and the electronic cases did not provide a detailed record of pre-admission temperature, there was no specific grading of the body temperature of febrile children. From another point of view, the occurrence of fever symptoms prompt parents to take their children to medical treatment in time, which is beneficial to facilitate the treatment and reduce the spread of the virus. Children with respiratory symptoms accounted over 57.4% (346 cases), among which, cough, sputum production and running nose were the main symptoms, accounting for 53.3% (321 cases), 17.6% (106 cases) and 11.6% (70 cases) respectively. More than 40.3% (243 cases) of the children had different gastrointestinal symptoms, such as abnormal defecation(163 cases,27.0%) , loss of appetite (93 cases,15.4%). As for nervous system,1 case cleared his throat frequently without sore throat or sputum production, 1 case kept reticence all the time, 2 cases were irritability, 3 cases experienced somnolence during the course of the disease. Unlike adults, only 4 cases had fatigue and none had a decrease or loss of smell or taste. According the Trial Version 9 [11] , the total of 603 pediatric cases was divided into four different degrees of disease-24 cases were the asymptomatic, 399 cases were mild, 179 cases were moderate, only 1 case was severe. All children received symptomatic and supportive care according to guidelines. Oral or intravenous antibiotics are prescribed only when laboratory tests suggested a risk of bacterial infection or when the children had symptoms of bacterial infection. 26.2% of the children (158 cases) received interferon α2b therapy, which had a certain effect on improving symptoms and shortening the time of negative conversion. Only 5 children tried a new oral small-molecule drug called Paxlovid which was Manufactured by Pfizer and approved by WHO for adults with mild to moderate COVID-19 and children aged 12 and over. There was no way to assess its efficacy.Detailed demographical information are available in Table 1.
Table 1 Negative conversion of viral RNA among 603 cases with Univariate analysis
Factors
|
Count
(%)
|
Negative conversion rate(%)
|
X2
|
P
|
7days
|
14days
|
21days
|
Sex
|
|
|
|
|
|
|
Male
|
336(55.7)
|
9.5
|
76.8
|
97.3
|
2.335
|
0.126
|
Female
|
267(44.3)
|
9.0
|
76.4
|
98.3
|
Age
|
|
|
|
|
|
|
<3
|
373(61.9)
|
3.5
|
73.2
|
98.7
|
32.054
|
0.000*
|
3-5
|
107(17.7)
|
14.0
|
83.2
|
97.2
|
6-11
|
96(15.9)
|
25
|
86.5
|
99.0
|
12-17
|
27(4.8)
|
30.0
|
85.2
|
88.9
|
BMI
|
|
|
|
|
|
|
Underweight
|
91(15.1)
|
18.7
|
73.6
|
95.6
|
2.485
|
0.478
|
Normalweight
|
277(45.9)
|
9.4
|
77.6
|
97.8
|
Overweight
|
121(20.1)
|
9.9
|
78.5
|
99.2
|
Obesity
|
114(18.9)
|
10.7
|
79.8
|
99.1
|
Underlying conditions
|
|
|
|
|
|
|
No
|
454(75.3)
|
11.5
|
79.7
|
98.5
|
2.530
|
0.112
|
Yes
|
149(24.7)
|
10.7
|
71.1
|
95.6
|
Allergic history
|
|
|
|
|
|
|
No
|
495(82.1)
|
11.1
|
77.4
|
98.0
|
0.000
|
0.990
|
Yes
|
108(17.9)
|
12.0
|
78.7
|
97.2
|
The severity of clinical outcome
|
|
|
|
|
|
|
Asymptomatic
|
24(4.0)
|
54.2
|
95.8
|
100
|
30.425
|
0.000*
|
Mild
|
399(66.2)
|
9.8
|
78.4
|
98.7
|
Moderate
|
179(29.7)
|
8.9
|
73.7
|
96.6
|
Severe
|
1(0.2)
|
0
|
0
|
0
|
Fever
|
|
|
|
|
|
|
No
|
77(12.8)
|
37.8
|
84.4
|
98.7
|
14.963
|
0.000*
|
Yes
|
526(87.2)
|
7.4
|
76.6
|
97.9
|
Cough
|
|
|
|
|
|
|
No
|
282(46.8)
|
13.8
|
75.9
|
97.5
|
1.199
|
0.549
|
Non-productive cough
|
215(35.7)
|
6.5
|
81.4
|
99.1
|
Productive cough
|
106(17.6)
|
14.2
|
74.5
|
97.2
|
Sore throat
|
|
|
|
|
|
|
No
|
554(91.9)
|
10.8
|
76.4
|
98.0
|
.215
|
0.022*
|
Yes
|
49(8.1)
|
16.3
|
91.8
|
98.0
|
Rhinobyon
|
|
|
|
|
|
|
No
|
549(91.0)
|
11.5
|
78.0
|
98.0
|
0.301
|
0.583
|
Yes
|
54(9.0)
|
9.3
|
74.1
|
98.1
|
Running nose
|
|
|
|
|
|
|
No
|
533(88.4)
|
11.8
|
77.9
|
97.9
|
0.648
|
0.421
|
Yes
|
70(11.6)
|
7.1
|
75.7
|
98.6
|
Appetite
|
|
|
|
|
|
|
Normal
|
510(84.6)
|
12.9
|
66.0
|
98.0
|
3.306
|
0.069
|
Abnormal
|
93(15.4)
|
2.2
|
75.3
|
97.8
|
Defecation
|
|
|
|
|
|
|
Normal
|
440(73.0)
|
13.0
|
81.6
|
98.6
|
13.271
|
0.000*
|
Abnormal
|
163(27.0)
|
6.7
|
66.9
|
96.3
|
Personal vaccination
|
|
|
|
|
|
|
Unvaccinated
|
522(88.6)
|
7.7
|
75.1
|
97.9
|
71.862
|
0.000*
|
1dose
|
12(1.5)
|
33.3
|
75
|
100
|
2doses
|
69(9.9)
|
34.8
|
95.7
|
98.6
|
Household vaccination rates
|
|
|
|
|
|
|
≤0.25
|
58(9.6)
|
5.2
|
56.9
|
98.3
|
36.019
|
0.000*
|
0.26-0.50
|
230(38.1)
|
5.7
|
75.2
|
99.1
|
0.51-0.75
|
219(36.3)
|
13.7
|
80.8
|
95.9
|
0.76-1
|
96(15.9)
|
22.9
|
88.5
|
100
|
Therapy method
|
|
|
|
|
|
|
Medical observation
|
145(24.0)
|
13.1
|
76.6
|
98.0
|
0.173
|
0.678
|
Symptomatic treatment
|
458(76.0)
|
10.7
|
77.9
|
98.0
|
Ct-values of N
|
|
|
|
|
|
|
<20
|
74(18.4)
|
0
|
75.7
|
97.3
|
4.083
|
0.130
|
20-30
|
305(50.6)
|
5.9
|
77.7
|
98.4
|
>30
|
224(37.1)
|
22.3
|
57.4
|
97.8
|
Ct-values of ORFab
|
|
|
|
|
|
|
<20
|
68(11.3)
|
0
|
77.9
|
97.1
|
4.609
|
0.100
|
20-30
|
292(48.4)
|
5.8
|
76.4
|
98.3
|
>30
|
243(40.3)
|
21.0
|
79.0
|
97.9
|
1.X2 value and P values were calculated by Log rank test.
2.Underlying conditions included Asthma,Eczema,Rhinitis,conjunctivitis, tic disorders, ADHD, diabetes, lung disease, kidney disease,cancer, and congenital disease.
3.3 Related factors and potential predictors of negative conversion of SARS-CoV-2 RNA
According the Trial Version 9[12], all patients were discharged from hospital or released from quarantine on the basis of two consecutive negative RT-PCR assay results at least 24 hours apart. At the time of admission, the median CT value for ORF1ab gene at was 27.35(IQR:22.94-34.72) and median Ct value for N gene was 27.18(IQR:22.86-33.12). The median duration of virus shedding in all patients was 12 days (IQR:9-14), range from 2 to 49 days. The rate of RNA negative conversion within 7 days, 14 days and 21 days among all patients were 11.3%(95%CI:8.7%-13.8%), 77.6%(95%CI:74.3%-80.9%), 98.0%(95%CI:96.9%-99.1%). We evaluated the effect of 18 factors on negative conversion of SARS-CoV-2 in 603 cases. The results were summarized in Table 1. As shown above, age, fever, the severity of clinical outcome, defecation, sore throat, personal vaccination, household vaccination rates were significantly related to RNA negative conversion. The significant factors were performed secondly by Multivariate Cox Regression method(Figure 1,Figure 2). It showed the severity of clinical outcome, personal vaccination-2doses, household vaccination rates, abnormal defecation were independently associated with negative conversion of viral RNA, suggesting that patient who had abnormal defecation or with more severe condition would delay virological clearance, while patient accepted 2 doses vaccination or with higher household vaccination rates would accelerate virological clearance.
3.4 Patients with intermittent negative Status
When analyzing the data for these 603 patients, we found that almost a quarter of the patients fell into a condition in which the SARS-CoV-2 was detected again after the first negative nucleic acid. This condition was also observed when novel coronavirus was first discovered in 2019, and researchers defined this state as intermittent negative status. We divided 603 children into two groups: with intermittent negative status (149 cases) and without intermittent negative status (454 cases) to compare the differences between the two groups. The median time of the children with intermittent negative status group was 14 days(IQR:11-15) and that in non-intermittent group was 11 days(IQR:9-13). After analyzing the variables by Mann-Whitney U test, there were three variables including Ct value of ORFab, appetite, defecation,which were significant different(P<0.05) between the two groups. Further logistic regression with the three variables indicated that loss of appetite (OR:5.343; 95%CI: 3.307-8.632) and abnormal defecation(OR:2.840; 95%CI:1.736-4.645) was positively associated with intermittent negative status (Figure 3).