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      Flash Survey on SARS-CoV-2 Infections in Pediatric Patients on anti-Cancer Treatment

      research-article
      a , b , , a , b , c , d , e , f , g , h , h , i , j , k , l , m , n , o , p , q , q , r , s , t , u , v , w , x , y , z , aa , ab , ac , ad , ae , af , ag , ah , ai , aj , d , b , ak
      European Journal of Cancer
      Published by Elsevier Ltd.
      COVID-19, anti-cancer chemotherapy, immunosuppression, children

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          Abstract

          Introduction

          Since the beginning of COVID-19 pandemics, it is known that the severe course of the disease occurs mostly among elderly, whereas it is rare among children and young adults. Comorbidities, in particular diabetes and hypertension, clearly associated with age, besides obesity and smoke are strongly associated with the need of intensive treatment and a dismal outcome. A weaker immunity of the elderly has been proposed as a possible explanation of this uneven age distribution. Along the same line, anecdotal information from Wuhan, China mentioned a severe course of COVID-19 in a child treated for leukemia.

          Aim and methods

          We made a flash survey on COVID19 incidence and severity among children on anticancer treatment. Respondents were asked by email to fill in a short web based survey.

          Results

          We received reports from 25 countries, where approximately 10,000 patients at risk are followed. At the time of the survey, over 200 of these children were tested, nine of whom were positive for COVID-19. Eight of the nine cases had asymptomatic to mild disease and one was just diagnosed with COVID-19. We also discuss preventive measures that are in place or should be taken as well as treatment options in immunocompromised children with COVID-19.

          Conclusion

          Thus, even children receiving anti-cancer chemotherapy may have a mild or asymptomatic course of COVID-19. While we should not underestimate the risk of developing a more severe course of COVID-19 than observed here, the intensity of preventive measures should not cause delays or obstructions in oncological treatment.

          Highlights

          • Flash survey was used to get data on COVID-19 incidence and severity.

          • Pediatric Hem/Onc departments of 25 countries responded.

          • COVID-19 may have a mild course in these immunocompromised children.

          • Precautions should be taken to prevent any infections including COVID-19.

          • Malignancy is a primary danger; preventive measures should not hinder its treatment.

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          Most cited references10

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          SARS-CoV-2 Infection in Children

          To the Editor: As of March 10, 2020, the 2019 novel coronavirus (SARS-CoV-2) has been responsible for more than 110,000 infections and 4000 deaths worldwide, but data regarding the epidemiologic characteristics and clinical features of infected children are limited. 1-3 A recent review of 72,314 cases by the Chinese Center for Disease Control and Prevention showed that less than 1% of the cases were in children younger than 10 years of age. 2 In order to determine the spectrum of disease in children, we evaluated children infected with SARS-CoV-2 and treated at the Wuhan Children’s Hospital, the only center assigned by the central government for treating infected children under 16 years of age in Wuhan. Both symptomatic and asymptomatic children with known contact with persons having confirmed or suspected SARS-CoV-2 infection were evaluated. Nasopharyngeal or throat swabs were obtained for detection of SARS-CoV-2 RNA by established methods. 4 The clinical outcomes were monitored up to March 8, 2020. Of the 1391 children assessed and tested from January 28 through February 26, 2020, a total of 171 (12.3%) were confirmed to have SARS-CoV-2 infection. Demographic data and clinical features are summarized in Table 1. (Details of the laboratory and radiologic findings are provided in the Supplementary Appendix, available with the full text of this letter at NEJM.org.) The median age of the infected children was 6.7 years. Fever was present in 41.5% of the children at any time during the illness. Other common signs and symptoms included cough and pharyngeal erythema. A total of 27 patients (15.8%) did not have any symptoms of infection or radiologic features of pneumonia. A total of 12 patients had radiologic features of pneumonia but did not have any symptoms of infection. During the course of hospitalization, 3 patients required intensive care support and invasive mechanical ventilation; all had coexisting conditions (hydronephrosis, leukemia [for which the patient was receiving maintenance chemotherapy], and intussusception). Lymphopenia (lymphocyte count, <1.2×109 per liter) was present in 6 patients (3.5%). The most common radiologic finding was bilateral ground-glass opacity (32.7%). As of March 8, 2020, there was one death. A 10-month-old child with intussusception had multiorgan failure and died 4 weeks after admission. A total of 21 patients were in stable condition in the general wards, and 149 have been discharged from the hospital. This report describes a spectrum of illness from SARS-CoV-2 infection in children. In contrast with infected adults, most infected children appear to have a milder clinical course. Asymptomatic infections were not uncommon. 2 Determination of the transmission potential of these asymptomatic patients is important for guiding the development of measures to control the ongoing pandemic.
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            Detection of Covid-19 in Children in Early January 2020 in Wuhan, China

            To the Editor: A small number of cases of coronavirus disease 2019 (Covid-19) have been described in children, 1,2 and our understanding of the spectrum of illness is limited. 3 We conducted a retrospective analysis involving hospitalized children in Wuhan, China. From January 7 to January 15, 2020, a total of 366 hospitalized children (≤16 years of age) were enrolled in a retrospective study of respiratory infections at three branches of Tongji Hospital, which are located 14 km to 34 km from one another in central Wuhan (Fig. S1 in the Supplementary Appendix, available with the full text of this letter at NEJM.org). The study was approved by the ethics committee of Tongji Hospital. Among the 366 children, the most frequently detected pathogens were influenza A virus (in 23 patients [6.3%]) and influenza B virus (in 20 [5.5%]). SARS-CoV-2, the virus that causes Covid-19, was detected in 6 patients (1.6%). Informed consent was obtained from the parents or guardians of the patients with Covid-19 for the publication of their clinical data. The dates of illness onset in the six patients with Covid-19 were between January 2 and January 8, 2020, and the patients were hospitalized between January 7 and January 13 (Fig. S2). Details of the study methods are provided in the Supplementary Appendix. The median age of the six patients was 3 years (range, 1 to 7) (Table 1). All six children had previously been completely healthy. Common clinical characteristics included high fever (>39°C) (in all six patients), cough (in all six), and vomiting (in four). Laboratory investigations showed that the levels of lymphocytes, white cells, and neutrophils were below the normal range in six, four, and three patients, respectively. Four of the six patients had pneumonia, as assessed radiographically, with computed tomographic scans of the chest showing typical viral pneumonia patterns (Fig. S3). One child was admitted to the pediatric intensive care unit (ICU) and received pooled immune globulin from healthy donors. All the patients were treated empirically with antiviral agents, antibiotic agents, and supportive therapies. All the patients recovered after hospitalization for a median of 7.5 days (range, 5 to 13). This study showed that Covid-19 occurred in children, causing moderate-to-severe respiratory illness, in the early phase of the SARS-CoV-2 outbreak in Wuhan and was associated with ICU admission in one patient. None of the patients or their family members had had direct exposure to Huanan Seafood Wholesale Market (the initial location to which cases of Covid-19 were linked) or to one another. It is worth mentioning that we unexpectedly found a case of Covid-19 in one patient (Patient 3) who resided outside Wuhan; this patient had illness onset on January 2, 2020. The patient and her family were residents of the Yangxin area of Huangshi and had not traveled outside the city in the month before illness onset. We have not identified the source of infection for this patient. Our findings indicate that SARS-CoV-2 infections in children were occurring early in the epidemic. 4
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              Novel Coronavirus Infection in Hospitalized Infants Under 1 Year of Age in China

              This study characterizes the demographic, epidemiologic, and clinical characteristics of hospitalized infants diagnosed with coronavirus disease 2019 infection between December 8, 2019, and February 6, 2020, in China.
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                Author and article information

                Contributors
                Journal
                Eur J Cancer
                Eur. J. Cancer
                European Journal of Cancer
                Published by Elsevier Ltd.
                0959-8049
                1879-0852
                7 April 2020
                7 April 2020
                Affiliations
                [a ]CLIP - Childhood Leukemia Investigation Prague
                [b ]Department of Pediatric Hematology, Charles University and Univ. Hospital Motol, Prague, Czechia
                [c ]Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN, USA
                [d ]Clinica Pediatrica Universita degli Studi di Milano Bicocca, Monza, Italy
                [e ]Oncologia Pediatrica, Ospedale Papa Giovanni XXIII, Bergamo, Italy
                [f ]Pediatric Hematology Oncology Unit, Department of Pediatrics, University of Milano-Bicocca, MBBM Foundation, ASST Monza
                [g ]Hospital Sant Joan de Déu de Barcelona, Spain
                [h ]Hospital General Universitario de Albacete, Spain
                [i ]Hospital Virgen de la Salud, Spain
                [j ]Department of Oncology and Children’s Research Center, University Children’s Hospital Zurich, Zurich, Switzerland
                [k ]Department of Peadiatrics and Adolescent Medicine, Rigshospitalet University Hospital, Copenhagen, Denmark
                [l ]Department of Pediatric Hematology and Oncology, St. Anna Children's Hospital, Medical University of Vienna, Vienna, Austria
                [m ]Pediatric Oncology, Karolinska University Hospital, Sweden
                [n ]Department of Pediatric Haematology and Oncology, Sahlgrenska University Hospital, Gothenberg, Sweden
                [o ]UZ Brussels, Belgium
                [p ]Princess Maxima Center for Pediatric Oncology, Utrecht, Netherlands
                [q ]Department of Pediatric Oncology Hematology and Clinical Immunology Heinrich Heine University Dusseldorf
                [r ]Klinik für Pädiatrische Hämatologie und Onkologie Universtitätsklinikum Eppendorf, Hamburg, Germany
                [s ]University Hospital Schleswig-Holstein, Campus Lübeck, Germany
                [t ]Department of Pediatric Haematology and Oncology, Hannover Medical School, Hannover, Germany
                [u ]National Children’s Cancer Service, Children’s Health Ireland at Crumlin, Dublin, Ireland
                [v ]Yong Loo Lin School of Medicine and Cancer Science Institute, National University of Singapore, and Viva-University Children's Cancer Centre, National University Hospital, Singapore
                [w ]Schneider Children's Medical Center of Israel
                [x ]Great Ormond Street Hospital, London, UK
                [y ]Department of Paediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
                [z ]University of Malaya Medical Centre, Kuala Lumpur, Malaysia
                [aa ]Department of Pediatric Hematology and Oncology, Comenius University, Bratislava, Slovakia
                [ab ]The Cancer Centre for Children, The Children's Hospital at Westmead, Australia
                [ac ]LAUMC-Rizk Hospital, Beirut, Lebanon
                [ad ]University Children`s Hospital, Belgrade, Serbia
                [ae ]Hokkaido University in Sapporo, Japan
                [af ]Department of Pediatric Hematology and Oncology, Nicolaus Copernicus University, Bydgoszcz, Poland
                [ag ]2nd Department of Paediatrics, Semmelweis University, Budapest, Hungary
                [ah ]Oncohematology Unit, Dep. of Ped., University of Pécs, Hungary
                [ai ]Hospital de Pediatría, "Prof. Dr. Juan P. Garrahan", Argentina
                [aj ]Onco Hematology Unit, Dept. Salute della Donna e del Bambino, Università degli Studi di Padova, Italy
                [ak ]Childrens Hospital Medical Center Schleswig-Holstein, Kiel, Germany
                Author notes
                [] Corresponding author. CLIP - Childhood Leukemia Investigation Prague. Ondrej.Hrusak@ 123456gmail.com
                Article
                S0959-8049(20)30162-3
                10.1016/j.ejca.2020.03.021
                7141482
                32305831
                091c14e4-deba-4767-9715-52c7aa6a3cd6
                © 2020 Published by Elsevier Ltd.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 27 March 2020
                : 28 March 2020
                Categories
                Article

                Oncology & Radiotherapy
                covid-19,anti-cancer chemotherapy,immunosuppression,children
                Oncology & Radiotherapy
                covid-19, anti-cancer chemotherapy, immunosuppression, children

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