Discussion
In this retrospective study we described a numerous cohort of 316 pediatric patients with SARS-CoV2 infection, admitted to our Pediatric Emergency Department from March 17th, 2020 to December 1st, 2020.
For the first time, we described changes in trend of infection during the principal Lockdown phases identified by the Italian Government during the pandemic and we evaluated epidemiological links and main clinical features among these historical periods, in order to demonstrate the efficacy of Italian Containment Measures before the introduction of the first COVID-19 vaccine in Italy on December 27th, 2020.
Over the period starting from March 17th, 2020 until December 1st, 2020 on a total of 13.703 admissions to our PED, 5001 children have been tested for SARS-CoV2 (36.5%). During the phase 4 we performed the highest percentage of NST 49.7%, and the highest percentage of positive NST on total NST performed 7.9%.
As already pointed out in Northern Italy and other country’s EDs and PEDs [
16,
20‐
22], also our PED showed a marked decrease in the total number of accesses, due probably to Government recommendation to avoid direct access to ED and the general fear of becoming infected by accessing hospital facilities (
https://flunewseurope.org/SeasonOverview).
Moreover, the introduction of preventing measures for the diffusion of SARS-CoV2 contributed to the decrease of other viruses circulation, as showed for influenza virus [
23].
The age group with the highest number of positive NST is the group between 0 and 6 years. The group of 16–18 years old, including young adults, has the lowest finding of positive NST, but as a pediatric hospital, the majority of admissions are under 11 years old.
Interestingly, the high percentage of NST performed during the phase 4 could be attributed to the increased request of NST for the readmission at school or after a contact with a positive case of a family member, as registered in our electronic database.
Previously published studies have not shown complete concordance on the most common epidemiological link. Parri et al. described a large Italian cohort of 170 patients with SARS-CoV2 infection [
3]. .They reported a 41% of patients with a familial relative positive at NST for SARS-CoV2, 42% reported a suspected extrafamilial contact, 12% travelled in endemic areas and 4% were symptomatic without a clear contact with a positive or suspect case. According to the author this finding is different from what has been observed in previous Chinese cohorts [
2,
24,
25].
Garazzino et al., reported, in a cohort of 759 Italian patients, that 70.5% of children had at least one infected parent and 10% had an infected household [
4].
In our study familial link was predominant during all phases of Lockdown in all age categories with 214 children on the total of 316 (68%), with a predominance during the first lockdown and phase 2. It is noteworthy how the familial link is predominant also after the reduction of containment measures during the summer period, which coincided with the reopening of schools, most work activities and public or private meeting places.
As reported by Romani et al. [
26] in their cohort 38 out of 43 children belonged to a family cluster. Noteworthy in 37% of cases, they found that the family member was a healthcare worker.
We observed an increase of Extra-Familial and Unknown Link during the last phases, especially among older children and adolescents. The extra-familial link accounted for the highest percentage in the 11–15 years group (40%) and in the phase 4, coherent with the hypothesis that adolescents were infected mostly by peers during the summer.
About the intra-scholastic link, places where social distancing and the correct use of personal protective equipment (PPE) are observed, such as primary schools, the risk of being infected seems to be low, at least starting from 6 years of age [
27]. In Italy more than 65,000 schools reopened in September, but only 1212 had experienced outbreaks about 4 weeks later and only one secondary school had a cluster of more than 10 infected people [
28].
A prospective study on the prevalence of SARS-CoV2 infection among students and the association between the increase in transmissibility and the dates of reopening of schools in different regions, did not find a significant association between the reopening of schools and the increase of infection in the general population [
29]. These findings have been supported by other case series in other states, all supporting a low risk in transmitting the infection in schools in Germany, Australia and England [
30‐
32]. A common limit in these studies is the impossibility of distinguishing transmissions in schools and those attributable to the use of public transport, leisure time activities or sports [
33].
In our cohort we found 17 (5.3% of the total cohort) patients with a clear intra scholastic exposure, detected from October 8th, 2020 to December 1st, 2020. Eight of them belonged to the 0–6 years age group 0–6 years, 5 to the 7–10 years age group, 3 to the 11–15 years age group, 1 to the 16–18 years age group. We remember nevertheless that high school and university remained closed since the Phase 1 of National Lockdown. Additionally, 29.5% referred to be infected by their teacher and were all aged 0–7 years, while the other 79.5% declared to be infected by classmates. These preliminary data about the intra-scholastic link suggest the need of further studies.
Parri et al. [
3] observed that children were frequently categorized as asymptomatic (17%) or mild (63%), according to the classification of disease made by Dong et al. [
2], differently from the previous Chinese cohorts [
24,
25], in which it was reported a majority of moderate cases. Garazzino et al. observed a 12% of asymptomatic children and the majority showed mild symptoms such as cough or rhinitis [
4]. Gotzinger et al. reported in a multicenter multinational cohort study involving 582 individuals, a 16% of asymptomatic patients [
34].
In our study we have found a milder clinical presentation of children admitted to PED according to different age groups.
Previous studies reported fever respectively in 48% of children according to Parri et al. [
3]; 41% according to Lu et al. [
24] and 36% according to Qiu et al. [
25] while Garazzino et al. reported fever as the most common symptom among their pediatric cohort (81.9%), especially among infants [
4].
We also observed a high frequency of fever (66%), in particular among preschooler children aged 0–6 years (71.9%) in our study, and it could be explained by the fact that they analyzed patients in a period ranging from March 3rd to May 2nd, 2020 which coincided with our lockdown phase and initial phase 2, when the implementation of medical phone consultation, telemedicine, and tele-expertise was encouraged, especially for febrile patients. Indeed, we found the highest percentage of symptom fever in Phase 1, 79% and Phase 2.67%. We used 37.5 °C as limit value to consider febrile patients with SARS-Cov2 according to the previous literature about SARS-Cov2 infection in pediatric population [
3,
4,
24] and used this limit to perform NST in patients admitted to our PED according to the Italian Government guidelines [
11].
As mentioned above the decision to test patients for SARS-CoV2 varied frequently among the different phases of lockdown. During early phases we tested mainly children with respiratory symptoms or fever, close contacts with a proven COVID-19 subject, or recent travel to specific endemic areas listed and constantly updated by WHO [
35]. During last phases we started performing NST for SARS-CoV2 on patients with gastrointestinal symptoms, according to recent literature reporting gastrointestinal symptoms and associated complications, as symptoms associated with SARS-CoV2 infection [
4,
36,
37]. Probably for this reason we detected a progressive occurrence of gastrointestinal symptoms in infected patients during the last period of observation (Phase 3 12.5%, Phase 4 10% and New containment Measures 12.8%) with a total of 34. Six abdomen UltraSound were performed (1.9%) and all of them in the New Containment Measures phase (Table
4).
Loss of smell and the loss of taste were typical symptoms of COVID-19 that we reported only in older children in line with other previous studies. The categories of older children aged 11–18 years also resulted more frequently symptomatic than younger children with two 16-years-old patients requiring ICU admissions from the PED. The reason for this phenomenon could be that parents of asymptomatic or pauci-symptomatic older children did not bring them to our PED, preferring to manage mild clinical symptoms at home, according to the recommendations of the Italian Ministry of Health. For this reason, it’s mandatory to focus on adolescents and young adults that came to PED with moderate/severe symptoms requiring in severe cases intensive care.
Other “special categories” include children with comorbidities (the most common were respiratory, cardiac or neuromuscular chronic diseases). These categories needed frequent hospitalization and, in some cases, respiratory support, or even treatment in the Intensive Care Unit. Infants aged < 1 month represented about 12.9% of the total cohort of children (p > 0,05).
In our opinion and according to other studies [
3,
4,
34] involving pediatric cases, these “special needs” categories have to be focused on because of the risk of rapid clinical deterioration and the high rate of hospitalization.
Dong and colleagues reported that, on a sample of 2143 pediatric patients, the proportion of severe and critical cases was 10.6, 7.3, 4.2, 4.1 and 3.0% for the age group of <1, 1–5, 6–10, 11–15 and > 15 years, but they analyzed only the period from January 16, 2020, to February 8, 2020. The limit of the study was that only 731 patients (34%) were laboratory-confirmed, while the others had only a clinical diagnosis based on respiratory symptoms [
2].
While in Parri et al. study [
3] 36% performed a Chest X ray and among them 52% showed some alterations such as interstitial abnormality or consolidations, in our cohort we have performed 158 Chest X-ray (50%), with a prevalence of interstitial pattern or consolidations (
p < 0,05). We found a progressive reduction in number of Chest X-ray performed during last period, this could probably be attributed to the increase in the expertise of our practitioner in detect patients who requires an imaging, thanks to the better knowledge of respiratory complications in pediatric patients.
Blood tests (including blood cell count and chemistry routine) were performed on 32,3% of children (p > 0,05).
We observed a total of 63% of patients needing hospitalization during all phases of lockdown, in line with previous literature [
4,
34]. We reported in particular a significant decrease from the first lockdown phase, 91.7% to the phase 4, 40.7% (
p < 0,05). This data was congruent with the finding of patients more asymptomatic (19%) or pauci-symptomatic in the last phase than in the first phase (asymptomatic patients were 0%), due to the increase in the number of NST performed and to the tendency to hospitalize only patients at high risk, with comorbidities or with a moderate-severe symptom. We reported 2 patients needing ICU admission, both 16-years old. Gotzinger et al. reported 48 patients requiring ICU admission and significant risk factors were being younger than 1-month, male sex, comorbidities and lower respiratory tract infections [
34].
Pediatricians working in the PED should pay attention not only to patients with acute infection and a positive NST for SARS-CoV2 but also to those patients less than 21 years of age presenting with persistent fever > 38 °C for at least 24 h, with multisystem (
> 2) organ involvement (cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic or neurological) laboratory evidence of inflammation and the history of recent SARS-CoV-2 infection by RT-PCR, serology, or antigen test; or COVID-19 exposure within the 4 weeks prior to the onset of symptoms, possibly presenting MIS-C [
38].
We have observed 7 patients with a final diagnosis of MIS-C, they were all admitted during the last phase of New Containment Measures, the mean age of our patients was 8.5 years-old with an interquartile age of 1.8–12.8.
Limitations of the study
All patients were enrolled from a single PED, situated in Rome, Lazio, Italy, an area partially spared in the early stages of the pandemic. The Age Groups were not homogeneous in number of patients, in particular for the 16–18 years old group, because the total admissions, as a Pediatric hospital, for this specific group were normally low. Our hospital is a COVID-19 Hub for numerous peripheric hospital, so an important number of patients were hospitalized without being admitted in PED. Data have been collected by different operators, even with a standardized method. Parents and caregivers of a tested positive patients in our PED, were not routinely tested with a NST, unless the patients were hospitalized.