Our study confirms that COVID-19 is generally less severe in children, as indicated by lower rate of hospitalization and need of oxygen therapy. However, in a minority of children (~ 4% of our series) it may present with a severe phenotype, including MIS-C and MAS.

In our population, asymptomatic infections were more frequent in the paediatric age group than in adults: 56% of children, in fact, had no symptoms related to SARS-CoV-2 infection as compared to 18% in the young/middle-aged group and 10% in the older group. The rate of asymptomatic infection so far reported in children is quite variable, ranging from 15.5 to 65% [12,13,14,15,16]: this wide variability may be due to differences in the time of data collection, in geographical regions and in the different attitude towards screening diagnosis for contact tracing.

In agreement with previous reports, fever and respiratory symptoms were the most common clinical features both in the paediatric and adult population [17, 18], though symptoms in the paediatric age group were generally milder and limited to the upper airways. Anosmia/dysgeusia were reported almost exclusively in adult subjects [19,20,21].

The use of a diagnostic algorithm applied to the whole paediatric cohort enabled to assess the role of coinfections. Although documented only in a minority of patients exclusively belonging to the paediatric age, viral coinfections were associated with a greater burden of disease, including the need for hospitalization and oxygen supplementation. Though limited, data from our series suggest that coinfections may be associated with a more severe disease course also in children, and thus should be investigated in all patients with a diagnosis of SARS-CoV-2 infection.

Comorbidities, particularly diabetes, obesity and hypertension, are known risk factors for severe COVID-19 in adults [3, 4]. In our study population, comorbidities were, as expected, more frequent in the young/middle-aged and in the older age groups and this may likely explain the greater COVID-19 severity among adults. The eight children with comorbidities identified in our series, however, had a more severe disease course, as opposed to paediatric patients with no underlying disease. Recent meta-analyses have highlighted that the presence of comorbidities increases the risk of severe COVID-19 and associated mortality also in children, and further prospective studies are needed to better characterize the impact of underlying conditions on the clinical course of paediatric COVID-19 [22,23,24].

The length of hospital stay was significantly lower in the paediatric group, as compared to the young/middle aged and older groups; this finding is consistent with a retrospective analysis of subjects from the early phase of the pandemic conducted in China, which documented significantly shorter hospital stay for COVID-19 in children than in adults [25]. None of the children included in our study, required intensive care or died because of SARS-CoV2 infection, confirming previous reports of low requirement for intensive treatments and low mortality rate in the paediatric population [26, 27]. A meta-analysis of paediatric COVID-19 cases (0 – 17 years), occurring over the period from August 2020 to August 2021 in the United States, identified a low percentage of patients requiring invasive mechanical ventilation (0 to 3%) and a death rate of 0.4% among hospitalized children [28].

None of our paediatric patients suffered from long-COVID, according to the National Institute for Healthcare Excellence definition, which includes both ongoing (4 to 12 weeks) and post-COVID-19 (≥ 12 weeks) symptoms [29]. However, the actual risk of persistent symptoms following acute COVID-19 in children is uncertain, in addition features of long-COVID are poorly characterized in this age group [30]. Long-term sequelae related to COVID-19 were described more rarely in children than in adults, although recent systematic reviews have reported a consistent number of paediatric long-COVID cases (with a highly variable prevalence depending on the considered case series, ranging from 4 up to 66%), highlighting how the presence of long-lasting COVID-19 manifestations should be investigated also in the paediatric population [29,30,31,32]. Case series reported by Brackel emphasize the nonspecific and broad clinical manifestations seen in post‐COVID complaints [30]. Notably, neuropsychiatric symptoms are the most frequent long-term complications in paediatric patients with a history of SARS-CoV-2 infection, particularly among pre-adolescents and adolescents, with mood and sleep disorders and fatigue being the most frequent complaints [32]. However, it is often difficult to assess whether these symptoms are a direct consequence of COVID-19 or should be more appropriately attributed to pandemic-induced stress and its related restrictions [33, 34].

MIS-C is a multisystem inflammatory syndrome affecting patients aged 0 to 19 years and related to SARS -CoV-2 infection either at the time of diagnosis or in the preceding 2 to 6 weeks. The most frequent clinical features of MIS-C include fever, mucocutaneous findings, cardiac involvement (myocardial dysfunction, cardiac conduction abnormalities and shock), gastrointestinal symptoms, lymphadenopathy, and neurological manifestations. The exact incidence of this condition is unknown, and at present it is considered a rare complication of SARS-CoV-2 infection [35]. Due to its possible cardiac involvement, MIS-C is a potentially life-threatening condition in the absence of a timely treatment with immunosuppressant agents (IVIG and high dose IV steroid pulses represent the first line therapeutic approach) [36,37,38]. Our study identified a total of 3 cases of MIS-C (all younger than 10 years) out of 84 paediatric patients with proven SARS-CoV-2 infection. All patients were successfully treated with IVIG and high dose IV steroids and none required intensive care, probably as a result of a timely diagnosis and early treatment initiation in tertiary care paediatric centers.

The main limitation of our study is the relatively small size of the enrolled population. This is mainly due to the fact that the present analysis was conducted in the context of a wider project, sponsored by the Italian Ministry of Health. Patients with cystic fibrosis, bronchiectasis and lung transplantation with acute SARS-CoV-2 infection were enrolled over a short period of time and their severity of disease and outcome was compared with the general population. In addition, since the study population was enrolled before the onset or at the earliest stage of the vaccination campaign in our country, we could not evaluate the impact of SARS-CoV-2 vaccination on disease severity and outcome. Finally, data were collected in the pre-Omicron phase of the pandemic, when circulating variants caused a more severe disease than the one secondary to Omicron.

However, the fact that we considered only RT-PCR confirmed cases, the search for coinfection and the evaluation of their impact on the severity of disease, the use of objective parameters to assess disease severity and the availability of a 6-month follow up for all the included patients represent significant strengths of our study.