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Global characteristics and outcomes of SARS-CoV-2 infection in children and adolescents with cancer (GRCCC): a cohort study - 28/09/21

Doi : 10.1016/S1470-2045(21)00454-X 
Sheena Mukkada, MD a, , Nickhill Bhakta, MD a, Guillermo L Chantada, MD b, Yichen Chen, PhD a, Yuvanesh Vedaraju, MS a, Lane Faughnan, BSN a, Maysam R Homsi, MPH a, Hilmarie Muniz-Talavera, PhD a, Radhikesh Ranadive, MS a, Monika Metzger, ProfMD a, Paola Friedrich, MD a, Asya Agulnik, MD a, Sima Jeha, ProfMD a, Catherine Lam, MD a, Rashmi Dalvi, ProfMD c, Laila Hessissen, ProfMD d, Daniel C Moreira, MD a, Victor M Santana, ProfMD a, Michael Sullivan, ProfMD e, Eric Bouffet, ProfMD f, Miguela A Caniza, ProfMD a, Meenakshi Devidas, ProfPhD a, Kathy Pritchard-Jones, ProfMD g, Carlos Rodriguez-Galindo, ProfMD a
on behalf of the

Global Registry of COVID-19 in Childhood Cancer1

  Members listed in the Supplementary Material
A Juan Ribelles, Adriana Balduzzi, Alaa Elhaddad, Alejandra Casanovas, Alejandra Garcia Velazquez, Aliaksandra Laptsevich, Alicia Chang, Alessandra Lamenha F. Sampaio, Almudena González Prieto, Alvaro Lassaletta, Amaranto Suarez M, Ana Patricia Alcasabas, Anca Colita, Andres Morales La Madrid, Angélica Samudio, Annalisa Tondo, Antonella Colombini, Antonis Kattamis, N Araceli Lopez Facundo, Arpita Bhattacharyya, Aurélia Alimi, Aurélie Phulpin, Barbora Vakrmanova, Basak A Aksoy, Benoit Brethon, Jator Brian Kobuin, Carla Nolasco Monteiro, Catherine Paillard, Catherine Vezina, Bozkurt Ceyhun, Cristiana Hentea, Cristina Meazza, Daniel Ortiz-Morales, Roque Daniel Solorzano, Daniela Arce Cabrera, Daniele Zama, Debjani Ghosh, Diana Ramírez-Rivera, Doris A Calle Jara, Dragana Janic, Elianneth Rey Helo, Elodie Gouache, Enmanuel Guerrero Quiroz, Enrique Lopez, Eric Thebault, Essy Maradiegue, Eva de Berranger, Fatma S E Ebeid, Federica Galaverna, Federico Antillon-Klussmann, Felipe Espinoza Chacur, Fernando Daniel Negro, Francesca Carraro, Francesca Compagno, Francisco Barriga, Gabriela Tamayo Pedraza, Gissela Sanchez Fernandez, Gita Naidu, Gülnur Tokuc, Hamidah Alias, Hannah Grace B Segocio, Houda Boudiaf, Imelda Asetre Luna, Iris Maia, Itziar Astigarraga, Ivan Maza, Jacqueline E Montoya Vásquez, Janez Jazbec, Jelena Lazic, Jeniffer Beck Dean, Jeremie Rouger-Gaudichon, Johanny Carolina Contreras González, Jorge Huerta Aragonés, José L Fuster, Juan Quintana, Julia Palma, Karel Svojgr, Karina Quintero, Karolina Malic Tudor, Kleopatra Georgantzi, Kris Ann P Schultz, Laura Ureña Horno, Lidia Fraquelli, Linda Meneghello, Lobna Shalaby, Lola L Macias Mora, Lorna A Renner, Luciana Nunes Silva, Luisa Sisinni, Mahmoud Hammad, M Fernández Sanmartín, C Marcela Zubieta A, María Constanza Drozdowski, Maria Kourti, Marcela María Palladino, Maria R Miranda Madrazo, Marilyne Poiree, Marina Popova, Mario Melgar, Marta Baragaño, Martha J Avilés-Robles, Massimo Provenzi, Mecneide Mendes Lins, Mehmet Fatih Orhan, Milena Villarroel, Mónica Jerónimo, Mónica Varas Palma, Muhammad Rafie Raza, Mulindwa M Justin, Najma Shaheen, Nerea Domínguez-Pinilla, Nicholas S Whipple, Nicolas André, Ondrej Hrusak, Pablo Velasco Puyó, Pamela Zacasa Vargas, Paola Olate Mellado, Pascale Yola Gassant, Paulina Diaz Romero, Raffaella De Santis, Rejin Kebudi, Riza Boranbayeva, Roberto Vasquez, Romel A. Segura, Roy Enrique Rosado, Sandra Gómez, Sandra Raimbault, Sanjeeva Gunasekera, Sara M Makkeyah, Sema Buyukkapu Bay, Sergio M Gómez, Séverine Bouttefroy, Shahnoor Islam, Sherif Abouelnaga, Silvio Fabio Torres, Simone Cesaro, Sofia Nunes, Soraia Rouxinol, Sucharita Bhaumik, Symbat Saliyeva, Tamara Inostroza, Thelma Velasquez, Tint Myo Hnin, Ulrika Norén-Nyström, Valentina Baretta, Yajaira Valentine Jimenez-Antolinez, Vanesa Pérez Alonso, Vanessa Ayer Miller, Virginie Gandemer, Viviana Lotero, Volha Mishkova, Wendy Gómez-García, Yeva Margaryan, Yumna Syed

a Department of Global Pediatric Medicine, St Jude Children’s Research Hospital, Memphis, TN, USA 
b Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Déu, Barcelona, Spain 
c Department of Pediatrics, Bombay Hospital Institute of Medical Sciences, Mumbai, India 
d Department of Pediatric Hematology and Oncology, Mohammed V University, Rabat, Morocco 
e Children’s Cancer Centre, Royal Children’s Hospital, Department of Paediatrics, University of Melbourne, Melbourne, VIC, Australia 
f Division of Haematology/Oncology, Hospital for Sick Children, Toronto, ON, Canada 
g Developmental Biology and Cancer Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, London, UK 

* Correspondence to: Dr Sheena Mukkada, Department of Global Pediatric Medicine, St Jude Children’s Research Hospital, Memphis, TN 38105, USA Department of Global Pediatric Medicine St Jude Children’s Research Hospital Memphis TN 38105 USA

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Summary

Background

Previous studies have shown that children and adolescents with COVID-19 generally have mild disease. Children and adolescents with cancer, however, can have severe disease when infected with respiratory viruses. In this study, we aimed to understand the clinical course and outcomes of SARS-CoV-2 infection in children and adolescents with cancer.

Methods

We did a cohort study with data from 131 institutions in 45 countries. We created the Global Registry of COVID-19 in Childhood Cancer to capture de-identified data pertaining to laboratory-confirmed SARS-CoV-2 infections in children and adolescents (<19 years) with cancer or having received a haematopoietic stem-cell transplantation. There were no centre-specific exclusion criteria. The registry was disseminated through professional networks through email and conferences and health-care providers were invited to submit all qualifying cases. Data for demographics, oncological diagnosis, clinical course, and cancer therapy details were collected. Primary outcomes were disease severity and modification to cancer-directed therapy. The registry remains open to data collection.

Findings

Of 1520 submitted episodes, 1500 patients were included in the study between April 15, 2020, and Feb 1, 2021. 1319 patients had complete 30-day follow-up. 259 (19·9%) of 1301 patients had a severe or critical infection, and 50 (3·8%) of 1319 died with the cause attributed to COVID-19 infection. Modifications to cancer-directed therapy occurred in 609 (55·8%) of 1092 patients receiving active oncological treatment. Multivariable analysis revealed several factors associated with severe or critical illness, including World Bank low-income or lower-middle-income (odds ratio [OR] 5·8 [95% CI 3·8–8·8]; p<0·0001) and upper-middle-income (1·6 [1·2–2·2]; p=0·0024) country status; age 15–18 years (1·6 [1·1–2·2]; p=0·013); absolute lymphocyte count of 300 or less cells per mm3 (2·5 [1·8–3·4]; p<0·0001), absolute neutrophil count of 500 or less cells per mm3 (1·8 [1·3–2·4]; p=0·0001), and intensive treatment (1·8 [1·3–2·3]; p=0·0005). Factors associated with treatment modification included upper-middle-income country status (OR 0·5 [95% CI 0·3–0·7]; p=0·0004), primary diagnosis of other haematological malignancies (0·5 [0·3–0·8]; p=0·0088), the presence of one of more COVID-19 symptoms at the time of presentation (1·8 [1·3–2·4]; p=0·0002), and the presence of one or more comorbidities (1·6 [1·1–2·3]; p=0·020).

Interpretation

In this global cohort of children and adolescents with cancer and COVID-19, severe and critical illness occurred in one fifth of patients and deaths occurred in a higher proportion than is reported in the literature in the general paediatric population. Additionally, we found that variables associated with treatment modification were not the same as those associated with greater disease severity. These data could inform clinical practice guidelines and raise awareness globally that children and adolescents with cancer are at high-risk of developing severe COVID-19 illness.

Funding

American Lebanese Syrian Associated Charities and the National Cancer Institute.

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