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A single centre study of viral community-acquired pneumonia in children: No evidence of SARS-CoV-2 from October 2019 to March 2020

Pneumonia is an important cause of morbidity and mortality in children. We described viral aetiologies, with particular interest in detecting SARS-CoV-2, in hospitalized pneumonia children. Human rhinovirus was the most frequently detected agent. No children tested positive for SARS-CoV-2. Our findings suggest that SARS-CoV-2 infection is rare in children and it was not circulating in Rome before COVID-19 outbreak.

rhinovirus was the most frequently detected agent. No children tested positive for SARS-CoV-2. Our findings suggest that SARS-CoV-2 infection is rare in children and it was not circulating in Rome before COVID-19 outbreak.

Abbreviated title: Virus infections in community-acquired pneumonia
Key words: Community Acquired Pneumonia, SARS-CoV-2, COVID-19, virus Community Acquired Pneumonia (CAP) remains the leading cause of mortality and morbidity in children worldwide [1]. CAP aetiology is difficult to establish and it is often multifactorial: viral and bacterial. A considerable number of childhood pneumonias is caused by viruses; in particular, viral infections appear to occur mostly in younger patients [1]. Commonly identified viruses in children with CAP include respiratory syncytial virus (RSV), influenza (Flu) A and B, parainfluenza viruses (PIV), adenovirus (ADV), human rhinovirus (hRV), human Metapneumovirus (hMPV) and human Coronavirus (hCoV) [2]. Ample evidence describes that RSV is the most commonly detected virus in hospitalized children less than 5 years old, both as single virus and as coinfection [2]. Varghese L. et al. characterized epidemiology and clinical features of hCoVs (HCoV 229E, HKU1, NL63, and OC43) in children and they found that the proportion of all identified hCoVs was highest among 1-5 years old. They detected hCoVs both in a community cohort and in hospitalized children and they reported an increased clinical severity in hospitalized children with young age and comorbidity; however, the clinical severity was not associated with hCoVs type [3].
Several papers demonstrated that the spread of pneumococcal and Haemophilus influenzae type B vaccinations reduced the global incidence of children pneumonia [4]. However, Mycoplasma J o u r n a l P r e -p r o o f pneumoniae and other atypical bacterial associated pneumonias showed a significant increment, even among pre-school children [5].
In December 2019, a novel coronavirus (SARS-CoV-2) was identified as the cause of a new infectious disease, the coronavirus disease 2019 (COVID-19). COVID-19 became a pandemic and it has affected hundreds of thousands of people worldwide. Surprisingly, only a small number of cases of COVID-19 has been described in children, suggesting that SARS-CoV-2 infection in the paediatric population is unusual [6]. Analysing clinical features of COVID-19 hospitalized paediatric patients, Chinese preliminary studies reported polypnea, fever and cough as the most common symptoms; a high rate of these patients presented unilateral or bilateral pulmonary lesions on chest computed tomography [7]. Streptococcus pneumoniae and Haemophilus influenza type B. The aim of the present study was to examine viral aetiologies in children less than 14 years old hospitalized with pneumonia from October 1, 2019 to March 31, 2020. In particular, the most interesting aspect was to test the SARS-CoV-2 presence and its diffusion among our paediatric population. hMPV and human Bocavirus (hBoV), as described [8]. Real-Time PCR reactions targeting the RdRp and the E-genes of SARS-CoV-2 were developed in-house following the protocols described by Corman et al [9]. Mycoplasma pneumoniae was detected by Real-Time PCR reactions on DNA extracted from oropharyngeal swabs, as described [10]. Demographic, epidemiological, clinical and laboratory data were systematically collected. On hospital admission, we assigned each child a clinical severity score (from 0 to 8) according to respiratory rate, oxygen saturation in room air, presence of retractions and ability to feed [8]. A chest X ray was obtained in all children and radiological findings were classified as single pulmonary consolidation, multiple pulmonary consolidations or interstitial findings.  Table 1).

DISCUSSION
Our aim was to describe viral aetiologies, with particular interest in detecting SARS-CoV-2, in hospitalized pneumonia children under 14 years of age. In contrast to a plenty of papers declaring RSV the main cause of children's CAP [2], in our study hRV was more frequently associated with pneumonia.
However, the clinical severity score was higher in RSV patients and hRV was found in 9/17 cases (53%) in coinfection, consistent with the notion that hRV is very frequently detected in respiratory infections J o u r n a l P r e -p r o o f during childhood. According to previous studies, no significant laboratory and radiological differences between children hospitalized for pneumonia were observed. Since the enrollment period partially overlapped with COVID-19 peak infection in Italy, we investigated also SARS-CoV-2 distribution in children hospitalized with CAP in a tertiary University Hospital in Rome. Kelvin AA et al. suggest that children are susceptible to SARS-CoV-2 infection, but frequently they do not have notable disease, raising the possibility that they could be facilitators of viral transmission [11]. In our population, we detected two cases of HKU1, an HCoV belonging to the same genus beta of SARS-CoV-2, but no children with CAP tested positive for the novel CoV. These results seem consistent with several recent papers who have demonstrated that children appear to be less susceptible to severe SARS-CoV-2 infection [6,12]. Reasons remain unclear [12]. Despite some evidences describing pneumonia as the most frequent clinical manifestation among COVID-19 hospitalized children [7], in our population, in Rome, no children tested positive for COVID-19, even PICU admitted ones.
Another interesting aspect was the hospitalization rate, spanning from 13 (31%) in February to 3 (7%) in March. Environmental risk factors such as household crowding and air pollution, as well as virulence factors, play a fundamental role in developing lower respiratory infection [13] and particularly pneumonia [14]. Accordingly, the lockdown that Italian authorities established to confine COVID-19 and the resulting decrease in social interactions (schools and day nurseries closure) were likely determinant in reducing CAP which required hospitalization.
The major limitation of our study was the small size of the sample. However, to our knowledge, no reports about SARS-CoV-2 detection in children admitted for CAP before and during COVID-19 outbreak are available. In conclusion, in this small study, we demonstrated that no children tested positive for SARS-CoV-2 over October 2019-March 2020 period, confirming SARS-CoV-2 is very rare in children and it was not circulating in Rome the months before the Italian COVID-19 outbreak. We