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      Coronavirus Disease 2019 in Children

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          Abstract

          Since its appearance in Wuhan in mid-December 2019, acute respiratory syndrome coronavirus 2 (SARS-CoV-2) related 19 coronavirus disease (COVID-19) has spread dramatically worldwide. It soon became apparent that the incidence of pediatric COVID-19 was much lower than the adult form. Morbidity in children is characterized by a variable clinical presentation and course. Symptoms are similar to those of other acute respiratory viral infections, the upper airways being more affected than the lower airways. Thus far, over 90% of children who tested positive for the virus presented mild or moderate symptoms and signs. Most children were asymptomatic, and only a few cases were severe, unlike in the adult population. Deaths have been rare and occurred mainly in children with underlying morbidity. Factors as reduced angiotensin-converting enzyme receptor expression, increased activation of the interferon-related innate immune response, and trained immunity have been implicated in the relative resistance to COVID-19 in children, however the underlying pathogenesis and mechanism of action remain to be established. While at the pandemic outbreak, mild respiratory manifestations were the most frequently described symptoms in children, subsequent reports suggested that the clinical course of COVID-19 is more complex than initially thought. Thanks to the experience acquired in adults, the diagnosis of pediatric SARS-CoV-2 infection has improved with time. Data on the treatment of children are sparse, however, several antiviral trials are ongoing. The purpose of this narrative review is to summarize current understanding of pediatric SARS-CoV-2 infection and provide more accurate information for healthcare workers and improve the care of patients.

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          Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

          Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
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            SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

            Summary The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency. Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases. Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets. Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry. Our results reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention.
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              Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention

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                Author and article information

                Contributors
                Journal
                Front Pediatr
                Front Pediatr
                Front. Pediatr.
                Frontiers in Pediatrics
                Frontiers Media S.A.
                2296-2360
                28 May 2021
                2021
                28 May 2021
                : 9
                : 668484
                Affiliations
                Section of Pediatrics, Pediatric Pulmonology Unit, Department of Translational Medical Sciences, Università di Napoli Federico II , Naples, Italy
                Author notes

                Edited by: Milos Jesenak, Comenius University, Slovakia

                Reviewed by: Ilaria Corsini, Sant'Orsola-Malpighi Polyclinic, Italy; Zuzana Rennerova, Slovak Medical University, Slovakia; Guerrino Macori, University College Dublin, Ireland

                *Correspondence: Francesca Santamaria santamar@ 123456unina.it

                This article was submitted to Pediatric Pulmonology, a section of the journal Frontiers in Pediatrics

                †These authors share first authorship

                Article
                10.3389/fped.2021.668484
                8193095
                34123972
                98f656cc-7fef-4fc6-b249-546d44074f88
                Copyright © 2021 Borrelli, Corcione, Castellano, Fiori Nastro and Santamaria.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 16 February 2021
                : 28 April 2021
                Page count
                Figures: 4, Tables: 5, Equations: 0, References: 190, Pages: 20, Words: 16420
                Categories
                Pediatrics
                Review

                covid-19,novel coronavirus,sars-cov-2,children,adolescents,chest imaging,drugs,therapy

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