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Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children is characterized by a wide variety of expressions ranging from asymptomatic to, rarely, critical illness. The basis of this variability is not yet fully understood. The aim of this study was to identify clinical and genetic risk factors predisposing to disease susceptibility and progression in children., Methods: We enrolled 181 consecutive children aged less than 18 years hospitalized with or for SARS-CoV-2 infection during a period of 24 months. Demographic, clinical, laboratory, and microbiological data were collected. The development of coronavirus disease 2019 (COVID-19)-related complications and their specific therapies were assessed. In a subset of 79 children, a genetic analysis was carried out to evaluate the role of common COVID-19 genetic risk factors (chromosome 3 cluster; ABO -blood group system; FUT2 , IFNAR2 , OAS1/2/3 , and DPP9 loci)., Results: The mean age of hospitalized children was 5.7 years, 30.9% of them being under 1 year of age. The majority of children (63%) were hospitalized for reasons different than COVID-19 and incidentally tested positive for SARS-CoV-2, while 37% were admitted for SARS-CoV-2 infection. Chronic underlying diseases were reported in 29.8% of children. The majority of children were asymptomatic or mildly symptomatic; only 12.7% developed a moderate to critical disease. A concomitant pathogen, mainly respiratory viruses, was isolated in 53.3%. Complications were reported in 7% of children admitted for other reasons and in 28.3% of those hospitalized for COVID-19. The respiratory system was most frequently involved, and the C-reactive protein was the laboratory test most related to the development of critical clinical complications. The main risk factors for complication development were prematurity [relative risk (RR) 3.8, 95% confidence interval (CI) 2.4-6.1], comorbidities (RR 4.5, 95% CI 3.3-5.6), and the presence of coinfections (RR 2.5, 95% CI 1.1-5.75). The OAS1/2/3 risk variant was the main genetic risk factor for pneumonia development [Odds ratio (OR) 3.28, 95% CI 1-10.7; p value 0.049]., Conclusion: Our study confirmed that COVID-19 is generally less severe in children, although complications can develop, especially in those with comorbidities (chronic diseases or prematurity) and coinfections. Variation at the OAS1/2/3 genes cluster is the main genetic risk factor predisposing to COVID-19 pneumonia in children., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Di Pietro, Ronzoni, Meschia, Tagliabue, Lombardi, Pinzani, Bosis, Marchisio and Valenti.)

Background: The containment measures adopted during COVID-19 pandemic have influenced the epidemiology of other respiratory viruses. Aim: We analyzed the modification of the incidence and etiology of lower respiratory tract infections (LRTIs) in young children during COVID-19 pandemic. Methods: Case series of all children under 2 years old hospitalized at a tertiary care Hospital in the Center of Milan, Italy diagnosed with LRTIs in three consecutive winter seasons (from the 1st of November to the last day of February in 2018/2019, 2019/2020 and 2020/2021). We compared the number of hospitalizations and viral detections in the 2020/2021 with the average of 2018/2019 and 2019/2020 (pre-COVID-19) using the Poisson distribution. Results: we enrolled 178 patients (66 from 2018/2019, 96 from 2019/2020, 16 from 2020/2021) 94 males (53%) and 84 females (47%), with a median (IQR) age of 5 (2-13) months. The number of hospitalizations during the 2020/2021 season was 80% lower than the average of the pre-COVID-19 seasons (16 vs. 81, p < 0 .001). Overall, 171 (96%) patient's nasopharyngeal aspirate (NPA) detected at least one virus (110, 64%, single-detection, 61, 36%, co-detections). In 2020/2021 we observed the disappearance of Respiratory Syncytial virus (0 vs. 54, p < 0.001), Influenza virus (0 vs. 6.5, p = 0.002), Metapneumovirus (0 vs. 8, p < 0.001), Parainfluenza viruses (0 vs. 3.5, p = 0.03) and a significant reduction of Adenovirus (2 vs. 7, p = 0.03), Bocavirus (2 vs. 7.5, p = 0.02) and Enterovirus (1 vs. 5, p = 0.04). No significant difference was found for Rhinoviruses (14 cases vs. 17, p = 0.2), other Coronaviruses (0 vs. 2, p = 0.1), and Cytomegalovirus (1 vs. 1, p = 0.7). Conclusions: We observed a striking reduction in hospitalizations due to LRTIs and a modification of the etiology, with enveloped viruses mainly affected., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ippolito, La Vecchia, Umbrello, Di Pietro, Bono, Scalia, Pinzani, Tagliabue, Bosis, Agostoni and Marchisio.)