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      The COVID‐19 pandemic: A rapid global response for children with cancer from SIOP, COG, SIOP‐E, SIOP‐PODC, IPSO, PROS, CCI, and St Jude Global

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          Abstract

          The COVID‐19 pandemic is one of the most serious global challenges to delivering affordable and equitable treatment to children with cancer we have witnessed in the last few decades. This Special Report aims to summarize general principles for continuing multidisciplinary care during the SARS‐CoV‐2 (COVID‐19) pandemic. With contributions from the leadership of the International Society for Pediatric Oncology (SIOP), Children's Oncology Group (COG), St Jude Global program, and Childhood Cancer International, we have sought to provide a framework for healthcare teams caring for children with cancer during the pandemic. We anticipate the burden will fall particularly heavily on children, their families, and cancer services in low‐ and middle‐income countries. Therefore, we have brought together the relevant clinical leads from SIOP Europe, COG, and SIOP‐PODC (Pediatric Oncology in Developing Countries) to focus on the six most curable cancers that are part of the WHO Global Initiative in Childhood Cancer. We provide some practical advice for adapting diagnostic and treatment protocols for children with cancer during the pandemic, the measures taken to contain it (e.g., extreme social distancing), and how to prepare for the anticipated recovery period.

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          Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China

          China and the rest of the world are experiencing an outbreak of a novel betacoronavirus known as severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). 1 By Feb 12, 2020, the rapid spread of the virus had caused 42 747 cases and 1017 deaths in China and cases have been reported in 25 countries, including the USA, Japan, and Spain. WHO has declared 2019 novel coronavirus disease (COVID-19), caused by SARS-CoV-2, a public health emergency of international concern. In contrast to severe acute respiratory system coronavirus and Middle East respiratory syndrome coronavirus, more deaths from COVID-19 have been caused by multiple organ dysfunction syndrome rather than respiratory failure, 2 which might be attributable to the widespread distribution of angiotensin converting enzyme 2—the functional receptor for SARS-CoV-2—in multiple organs.3, 4 Patients with cancer are more susceptible to infection than individuals without cancer because of their systemic immunosuppressive state caused by the malignancy and anticancer treatments, such as chemotherapy or surgery.5, 6, 7, 8 Therefore, these patients might be at increased risk of COVID-19 and have a poorer prognosis. On behalf of the National Clinical Research Center for Respiratory Disease, we worked together with the National Health Commission of the People's Republic of China to establish a prospective cohort to monitor COVID-19 cases throughout China. As of the data cutoff on Jan 31, 2020, we have collected and analysed 2007 cases from 575 hospitals (appendix pp 4–9 for a full list) in 31 provincial administrative regions. All cases were diagnosed with laboratory-confirmed COVID-19 acute respiratory disease and were admitted to hospital. We excluded 417 cases because of insufficient records of previous disease history. 18 (1%; 95% CI 0·61–1·65) of 1590 COVID-19 cases had a history of cancer, which seems to be higher than the incidence of cancer in the overall Chinese population (285·83 [0·29%] per 100 000 people, according to 2015 cancer epidemiology statistics 9 ). Detailed information about the 18 patients with cancer with COVID-19 is summarised in the appendix (p 1). Lung cancer was the most frequent type (five [28%] of 18 patients). Four (25%) of 16 patients (two of the 18 patients had unknown treatment status) with cancer with COVID-19 had received chemotherapy or surgery within the past month, and the other 12 (25%) patients were cancer survivors in routine follow-up after primary resection. Compared with patients without cancer, patients with cancer were older (mean age 63·1 years [SD 12·1] vs 48·7 years [16·2]), more likely to have a history of smoking (four [22%] of 18 patients vs 107 [7%] of 1572 patients), had more polypnea (eight [47%] of 17 patients vs 323 [23%] of 1377 patients; some data were missing on polypnea), and more severe baseline CT manifestation (17 [94%] of 18 patients vs 1113 [71%] of 1572 patients), but had no significant differences in sex, other baseline symptoms, other comorbidities, or baseline severity of x-ray (appendix p 2). Most importantly, patients with cancer were observed to have a higher risk of severe events (a composite endpoint defined as the percentage of patients being admitted to the intensive care unit requiring invasive ventilation, or death) compared with patients without cancer (seven [39%] of 18 patients vs 124 [8%] of 1572 patients; Fisher's exact p=0·0003). We observed similar results when the severe events were defined both by the above objective events and physician evaluation (nine [50%] of 18 patients vs 245 [16%] of 1572 patients; Fisher's exact p=0·0008). Moreover, patients who underwent chemotherapy or surgery in the past month had a numerically higher risk (three [75%] of four patients) of clinically severe events than did those not receiving chemotherapy or surgery (six [43%] of 14 patients; figure ). These odds were further confirmed by logistic regression (odds ratio [OR] 5·34, 95% CI 1·80–16·18; p=0·0026) after adjusting for other risk factors, including age, smoking history, and other comorbidities. Cancer history represented the highest risk for severe events (appendix p 3). Among patients with cancer, older age was the only risk factor for severe events (OR 1·43, 95% CI 0·97–2·12; p=0·072). Patients with lung cancer did not have a higher probability of severe events compared with patients with other cancer types (one [20%] of five patients with lung cancer vs eight [62%] of 13 patients with other types of cancer; p=0·294). Additionally, we used a Cox regression model to evaluate the time-dependent hazards of developing severe events, and found that patients with cancer deteriorated more rapidly than those without cancer (median time to severe events 13 days [IQR 6–15] vs 43 days [20–not reached]; p<0·0001; hazard ratio 3·56, 95% CI 1·65–7·69, after adjusting for age; figure). Figure Severe events in patients without cancer, cancer survivors, and patients with cancer (A) and risks of developing severe events for patients with cancer and patients without cancer (B) ICU=intensive care unit. In this study, we analysed the risk for severe COVID-19 in patients with cancer for the first time, to our knowledge; only by nationwide analysis can we follow up patients with rare but important comorbidities, such as cancer. We found that patients with cancer might have a higher risk of COVID-19 than individuals without cancer. Additionally, we showed that patients with cancer had poorer outcomes from COVID-19, providing a timely reminder to physicians that more intensive attention should be paid to patients with cancer, in case of rapid deterioration. Therefore, we propose three major strategies for patients with cancer in this COVID-19 crisis, and in future attacks of severe infectious diseases. First, an intentional postponing of adjuvant chemotherapy or elective surgery for stable cancer should be considered in endemic areas. Second, stronger personal protection provisions should be made for patients with cancer or cancer survivors. Third, more intensive surveillance or treatment should be considered when patients with cancer are infected with SARS-CoV-2, especially in older patients or those with other comorbidities.
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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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              Is Open Access

              Systematic review of COVID‐19 in children shows milder cases and a better prognosis than adults

              Abstract Aim The coronavirus disease 2019 (COVID‐19) pandemic has affected hundreds of thousands of people. Data on symptoms and prognosis in children are rare. Methods A systematic literature review was carried out to identify papers on COVID‐19, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), using the MEDLINE and Embase databases between January 1 and March 18, 2020. Results The search identified 45 relevant scientific papers and letters. The review showed that children have so far accounted for 1%‐5% of diagnosed COVID‐19 cases, they often have milder disease than adults and deaths have been extremely rare. Diagnostic findings have been similar to adults, with fever and respiratory symptoms being prevalent, but fewer children seem to have developed severe pneumonia. Elevated inflammatory markers were less common in children, and lymphocytopenia seemed rare. Newborn infants have developed symptomatic COVID‐19, but evidence of vertical intrauterine transmission was scarce. Suggested treatment included providing oxygen, inhalations, nutritional support and maintaining fluids and electrolyte balances. Conclusions The coronavirus disease 2019 has occurred in children, but they seemed to have a milder disease course and better prognosis than adults. Deaths were extremely rare.
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                Author and article information

                Contributors
                k.pritchard-jones@ucl.ac.uk
                Journal
                Pediatr Blood Cancer
                Pediatr Blood Cancer
                10.1002/(ISSN)1545-5017
                PBC
                Pediatric Blood & Cancer
                John Wiley and Sons Inc. (Hoboken )
                1545-5009
                1545-5017
                13 May 2020
                : e28409
                Affiliations
                [ 1 ] Children's Cancer Centre Royal Children's Hospital and Department of Paediatrics Faculty of Medicine Dentistry and Health Sciences University of Melbourne Melbourne Australia
                [ 2 ] Division of Haematology/Oncology Hospital for Sick Children Toronto Ontario Canada
                [ 3 ] Department of Global Pediatric Medicine St Jude Children's Research Hospital Memphis Tennessee
                [ 4 ] Hematology/Oncology/SCT Children's Hospital Colorado University of Colorado Aurora Colorado
                [ 5 ] Pediatric Hematology Oncology Tawam Hospital Al Ain Abu Dhabi United Arab Emirates
                [ 6 ] Birmingham Children's Hospital and Institute of Cancer and Genomic Sciences University of Birmingham Edgbaston Birmingham UK
                [ 7 ] Pediatric Hematology/Oncology Seattle Children's Hospital Seattle Washington
                [ 8 ] School of Nursing University of California San Francisco San Francisco California
                [ 9 ] Division of Nursing Hematology/Oncology Boston Children's Hospital Boston Massachusetts
                [ 10 ] Department of Pediatric Surgery Children's Hospital University of Tuebingen Tuebingen Germany
                [ 11 ] Dana‐Farber/Boston Children's Cancer and Blood Disorders Center Brigham and Women's Hospital Harvard Medical School, Boston, Massachusetts
                [ 12 ] Paediatric Department MBBM Foundation ASST Monza Ospedale San Gerardo University of Milano Bicocca Monza Italy
                [ 13 ] Childhood Cancer International (www.childhoodcancerinternational.org) and International representative of Fed Española de Padres de NIÑOS CON Cáncer (www.cancerinfantil.org) Madrid Spain
                [ 14 ] Departments of Global Pediatric Medicine and Infectious Diseases St Jude Children's Research Hospital Memphis Tennessee
                [ 15 ] Division of Quality of Life and Palliative Care Department of Oncology St Jude Children's Research Hospital Memphis Tennessee
                [ 16 ] Pediatric Hematology Oncology Oncology Institute Istanbul University Istanbul Turkey
                [ 17 ] Pediatric Hematology and Oncology Mohammed V University of Rabat, Rabat Morocco
                [ 18 ] School of Cancer Science King's College London, UK Institute of Cancer Policy and Conflict and Health Research Group and Research for Health Care in Conflict (https://r4hc‐mena.org/), London, UK
                [ 19 ] International Society of Paediatric Oncology (SIOP) UCL Great Ormond Street Institute of Child Health University College London London UK
                Author notes
                [*] [* ] Correspondence

                Kathy Pritchard‐Jones, Professor of Paediatric Oncology, President, International Society of Paediatric Oncology (SIOP), UCL Great Ormond Street Institute of Child Health, University College London, 30 Guilford Street, London, WC1N 1EH, UK.

                Email: k.pritchard-jones@ 123456ucl.ac.uk

                Author information
                https://orcid.org/0000-0002-8606-5889
                https://orcid.org/0000-0002-6832-6539
                https://orcid.org/0000-0002-2360-8946
                https://orcid.org/0000-0003-0713-7651
                https://orcid.org/0000-0001-5524-203X
                https://orcid.org/0000-0003-4344-8174
                https://orcid.org/0000-0002-3322-273X
                https://orcid.org/0000-0002-2384-9475
                Article
                PBC28409
                10.1002/pbc.28409
                7235469
                32400924
                5555c8c4-a539-490c-973a-ae2d1438d1b5
                © 2020 Wiley Periodicals, Inc.

                This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.

                History
                : 24 April 2020
                : 24 April 2020
                Page count
                Figures: 0, Tables: 1, Pages: 12, Words: 9481
                Funding
                Funded by: NIHR Great Ormond Street Hospital Biomedical Research Centre
                Categories
                Special Report
                Special Report
                Custom metadata
                2.0
                corrected-proof
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.2 mode:remove_FC converted:19.05.2020

                Pediatrics
                acute lymphoblastic leukemia,burkitt lymphoma,childhood cancer,covid‐19,hodgkin lymphoma,low‐grade glioma,nephroblastoma,pediatrics,retinoblastoma,sars‐cov‐2,who global initiative on childhood cancer,wilms tumor

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