Risk factors for severe SARS-Cov-2 infection course are poorly described in children following hematopoietic cell transplantation (HCT). In this international study, we analyzed factors associated with a severe course (intensive care unit (ICU) admission and/or mortality) in post-HCT children. Eighty-nine children (58% male; median age 9 years (min-max 1-18)) who received an allogeneic (85; 96%) or an autologous (4; 4%) HCT were reported from 28 centers (18 countries). Median time from HCT to SARS-Cov-2 infection was 7 months (min-max 0-181). The most common clinical manifestations included fever (37; 42%) and cough (26; 29%); 37 (42%) were asymptomatic. Nine (10%) children following allo-HCT required ICU care. Seven children (8%) following allo-HCT, died at a median of 22 days after SARS-Cov-2 diagnosis. In a univariate analysis, the probability of a severe disease course was higher in allo-HCT children with chronic GVHD, non-malignant disease, immune suppressive treatment (specifically, mycophenolate), moderate immunodeficiency score, low Lansky score, fever, cough, coinfection, pulmonary radiological findings, and high C-reactive protein. In conclusion, SARS-Cov-2 infection in children following HCT was frequently asymptomatic. Despite this, 10% needed ICU admission and 8% died in our cohort. Certain HCT, underlying disease, and SARS-Cov-2 related factors were associated with a severe disease course.

BMT Unit Bristol Royal Hospital for Children Bristol UK

Bone Marrow Transplantation Unit National Institute of Children's Diseases Bratislava Slovakia

Department of Cellular Therapy and Allogeneic Stem Cell Transplantation Karolinska Comprehensive Cancer Center Karolinska University Hospital Huddinge Division of Hematology Department of Medicine Huddinge Karolinska Institutet Stockholm Sweden

Department of Children and Adolescents Medicine Stem Cell Transplant Unit Rigshospitalet Copenhagen University Hospital Copenhagen Denmark

Department of Haematology Birmingham Children's Hospital Birmingham UK

Department of Haematology Royal Hospital for Children Glasgow UK

Department of Pediatric Hematology and Oncology Comenius University Bratislava Slovakia

Department of Pediatric Hematology and Oncology Hospital Universitario La Paz Madrid Spain

Department of Pediatric Hematology and Oncology St Anna Children's Hospital Department of Pediatrics and Adolescent Medicine Medical University of Vienna Vienna Austria

Department of Pediatric Hematology Oncology and Stem Cell Transplantation University of Regensburg Regensburg Germany

Department of Stem Cell Transplantation University Hospital Eppendorf Hamburg Germany

Division of Infectious Diseases University of Genova Ospedale Policlinco San Martino Genova Italy

EBMT Leiden Study Unit Leiden Netherlands

Faculty of Medicine Hebrew University of Jerusalem Pediatric Infectious Diseases Hadassah Medical Center Jerusalem Israel

Hematology Department Hospital Universitario de La Princesa Madrid Spain

Hospital Clinico Universitario de Valencia Fundación de investigación INCLIVA Hospital Clinico Universitario de Valencia Valencia Spain

HSCT Unit Department of Paediatric Haematology and Oncology University Hospital Motol Prague Czech Republic

Pediatric BMT Unit Hospital Santa Creu i Sant Pau Universitat Autonoma de Barcelona Barcelona Spain

Pediatric Cell and Gene Therapy Research Center Gene Cell and Tissue Research Institute Tehran University of Medical Sciences Tehran Iran

Pediatric Hematology and Oncology University Hospital Collegium Medicum Nicolaus Copernicus University Torun Bydgoszcz Poland

Pediatric Hematology Oncology Department of Mother and Child Azienda Ospedaliera Universitaria Integrata Verona Italy

Pediatric Hematology Oncology Hautepierre Hospital Strasbourg University Strasbourg France

Pediatric Hematology Oncology King Faisal Specialist Hospital and Research Centre Riyadh Saudi Arabia

RM Gorbacheva Research Institute Pavlov University St Petersburg Russia

Sahlgrenska University Hospital Goeteborg Sweden

Section of Pediatric Hematology Immunology and HCT Astrid Lindgren Children's Hospital Karolinska University Hospital and Division of Pediatrics CLINTEC Karolinska Institutet Stockholm Sweden

Universitaetsklinikum Frankfurt Goethe Universitaet Frankfurt Main Germany

Zobrazit více v PubMed

Pediatrics AAo. Children and COVID-19: State-Level Data Report, 2022. https://www.aap.org/en/pages/2019-novel-coronavirus-covid-19-infections/children-and-covid-19-state-level-data-report/

Leidman E, Duca LM, Omura JD, Proia K, Stephens JW, Sauber-Schatz EK. COVID-19 trends among persons aged 0-24 years—United States, March 1–December 12, 2020. Morb Mortal Wkly Rep. 2021;70:88–94. doi: 10.15585/mmwr.mm7003e1. PubMed DOI PMC

Gotzinger F, Santiago-Garcia B, Noguera-Julian A, Lanaspa M, Lancella L, Calo Carducci FI, et al. COVID-19 in children and adolescents in Europe: a multinational, multicentre cohort study. Lancet Child Adolesc Health. 2020;4:653–61. doi: 10.1016/S2352-4642(20)30177-2. PubMed DOI PMC

Shekerdemian LS, Mahmood NR, Wolfe KK, Riggs BJ, Ross CE, McKiernan CA, et al. Characteristics and outcomes of children with coronavirus disease 2019 (COVID-19) infection admitted to US and Canadian pediatric intensive care units. JAMA Pediatr. 2020;174:868–73. doi: 10.1001/jamapediatrics.2020.1948. PubMed DOI PMC

Akcay N, Kihtir HS, Durak C, Kendirli T, Havan M, Kockuzu E, et al. Mortality risk factors among critically Ill children with acute COVID-19 in PICUs: a multicenter study from turkish pediatric critical COVID-19 and MIS-C Study Group. Pediatr Infect Dis J. 2022;41:742–50. doi: 10.1097/INF.0000000000003592. PubMed DOI PMC

Ljungman P, de la Camara R, Mikulska M, Tridello G, Aguado B, Zahrani MA, et al. COVID-19 and stem cell transplantation; results from an EBMT and GETH multicenter prospective survey. Leukemia. 2021;35:2885–94. doi: 10.1038/s41375-021-01302-5. PubMed DOI PMC

Shah DP, Ghantoji SS, Ariza-Heredia EJ, Shah JN, El Taoum KK, Shah PK, et al. Immunodeficiency scoring index to predict poor outcomes in hematopoietic cell transplant recipients with RSV infections. Blood. 2014;123:3263–8. doi: 10.1182/blood-2013-12-541359. PubMed DOI PMC

Marks KJ, Whitaker M, Agathis NT, Anglin O, Milucky J, Patel K, et al. Hospitalization of infants and children aged 0-4 years with laboratory-confirmed COVID-19 - COVID-NET, 14 states, March 2020-February 2022. Morb Mortal Wkly Rep. 2022;71:429–36. doi: 10.15585/mmwr.mm7111e2. PubMed DOI PMC

Shem-Tov N, Yerushalmi R, Danylesko I, Litachevsky V, Levy I, Olmer L, et al. Immunogenicity and safety of the BNT162b2 mRNA COVID-19 vaccine in haematopoietic stem cell transplantation recipients. Br J Haematol. 2022;196:884–91. doi: 10.1111/bjh.17918. PubMed DOI PMC

Tixagevimab and Cilgavimab (Evusheld) for pre-exposure prophylaxis of COVID-19. JAMA 2022; 327: 384–5. PubMed

FDA. FDA takes actions to expand use of treatment for outpatients with mild-to-moderate COVID-19, 2022. https://www.fda.gov/news-events/press-announcements/fda-takes-actions-expand-use-treatment-outpatients-mild-moderate-covid-19.

Health AowotNIo. NIH. COVID-19 Treatment Guidelines. 2022. An official website of the National Institutes of Health. https://www.covid19treatmentguidelines.nih.gov/tables/therapeutic-management-of-hospitalized-children/

Sharma A, Bhatt NS, St Martin A, Abid MB, Bloomquist J, Chemaly RF, et al. Clinical characteristics and outcomes of COVID-19 in haematopoietic stem-cell transplantation recipients: an observational cohort study. Lancet Haematol. 2021;8:e185–e193. doi: 10.1016/S2352-3026(20)30429-4. PubMed DOI PMC

Bhatt NS, Sharma A, Martin AS, Abid MB, Brown VI, Diaz MA, et al. Clinical characteristics and outcomes of COVID-19 in pediatric and early adolescent and young adult haematopoietic stem cell transplant recipients: a cohort study. Transplant Cell Ther. 2022;28:696.e1–696.e7. doi: 10.1016/j.jtct.2022.06.026. PubMed DOI PMC

Daudt LE, Corso MCM, Kerbauy MN, de Assis L, Rechenmacher C, Colturato I, et al. COVID-19 in HSCT recipients: a collaborative study of the Brazilian Society of Marrow Transplantation (SBTMO) Bone Marrow Transplant. 2022;57:453–9. doi: 10.1038/s41409-021-01561-x. PubMed DOI PMC

Bailey AJM, Kirkham AM, Monaghan M, Shorr R, Buchan CA, Bredeson C, et al. A portrait of SARS-CoV-2 infection in patients undergoing hematopoietic cell transplantation: a systematic review of the literature. Curr Oncol. 2022;29:337–49. doi: 10.3390/curroncol29010030. PubMed DOI PMC

Faura A, Rives S, Lassaletta A, Sebastian E, Madero L, Huerta J, et al. Initial report on Spanish pediatric oncologic, hematologic, and post stem cell transplantation patients during SARS-CoV-2 pandemic. Pediatr Blood Cancer. 2020;67:e28557. doi: 10.1002/pbc.28557. PubMed DOI PMC

Kebudi R, Kurucu N, Tugcu D, Hacisalihoglu S, Fisgin T, Ocak S, et al. COVID-19 infection in children with cancer and stem cell transplant recipients in Turkey: a nationwide study. Pediatr Blood Cancer. 2021;68:e28915. doi: 10.1002/pbc.28915. PubMed DOI PMC

Madhusoodhan PP, Pierro J, Musante J, Kothari P, Gampel B, Appel B, et al. Characterization of COVID-19 disease in pediatric oncology patients: the New York-New Jersey regional experience. Pediatr Blood Cancer. 2021;68:e28843. doi: 10.1002/pbc.28843. PubMed DOI PMC

Rouger-Gaudichon J, Thebault E, Felix A, Phulpin A, Paillard C, Alimi A, et al. Impact of the first wave of COVID-19 on pediatric oncology and hematology: a report from the French Society of Pediatric Oncology. Cancers. 2020;12:3398. doi: 10.3390/cancers12113398. PubMed DOI PMC

Haeusler GM, Ammann RA, Carlesse F, Groll AH, Averbuch D, Castagnola E, et al. SARS-CoV-2 in children with cancer or after haematopoietic stem cell transplant: an analysis of 131 patients. Eur J Cancer. 2021;159:78–86. doi: 10.1016/j.ejca.2021.09.027. PubMed DOI PMC

Mukkada S, Bhakta N, Chantada GL, Chen Y, Vedaraju Y, Faughnan L, et al. Global characteristics and outcomes of SARS-CoV-2 infection in children and adolescents with cancer (GRCCC): a cohort study. Lancet Oncol. 2021;22:1416–26. doi: 10.1016/S1470-2045(21)00454-X. PubMed DOI PMC

Meena JP, Kumar Gupta A, Tanwar P, Ram Jat K, Mohan Pandey R, Seth R. Clinical presentations and outcomes of children with cancer and COVID-19: a systematic review. Pediatr Blood Cancer. 2021;68:e29005. doi: 10.1002/pbc.29005. PubMed DOI PMC

Johnston EEMI, Davis ES, Araya B, Richman J, Brackett J, Dickens D, et al. The Pediatric Oncology COVID-19 Case (POCC) Report. April 29, 2020. https://www.uab.edu/medicine/icos/images/POCC_Report/Bi-weekly_POCC_Report/Report.1.26.22.pdf. accessed 31 Oct 2022.

Hospital SJCsR. Global Registry of COVID-19 in Childhood Cancer, 2022. https://app.powerbi.com/view?r=eyJrIjoiNGQ3NDAwZDItYjRjNi00MjNhLWE2NTMtNmFjNmU1YTgzZDMwIiwidCI6IjIyMzQwZmE4LTkyMjYtNDg3MS1iNjc3LWQzYjNlMzc3YWY3MiIsImMiOjN9. accessed 31 Oct 2022.

Ben-Shimol S, Livni G, Megged O, Greenberg D, Danino D, Youngster I, et al. COVID-19 in a subset of hospitalized children in Israel. J Pediatr Infect Dis Soc. 2021;10:757–65. doi: 10.1093/jpids/piab035. PubMed DOI PMC

Atalla E, Kalligeros M, Mylona EK, Tsikala-Vafea M, Shehadeh F, Georgakas J, et al. Impact of influenza infection among adult and pediatric populations with hematologic malignancy and hematopoietic stem cell transplant: a systematic review and meta-analysis. Clin Ther. 2021;43:e66–e85. doi: 10.1016/j.clinthera.2021.03.002. PubMed DOI

Hutspardol S, Essa M, Richardson S, Schechter T, Ali M, Krueger J, et al. Significant transplantation-related mortality from respiratory virus infections within the first one hundred days in children after hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2015;21:1802–7. doi: 10.1016/j.bbmt.2015.06.015. PubMed DOI PMC

Rowan CM, Gertz SJ, Zinter MS, Moffet J, Bajwa RPS, Barnum JL, et al. A multicenter investigation of respiratory syncytial viral infection in children with hematopoietic cell transplantation. Transpl Infect Dis. 2018;20:e12882. doi: 10.1111/tid.12882. PubMed DOI

Zama D, Baccelli F, Colombini A, Contino A, Calore E, Petris MG, et al. Favorable outcome of SARS-CoV-2 infection in pediatric hematology oncology patients during the second and third pandemic waves in Italy: a multicenter analysis from the Infectious Diseases Working Group of the Associazione Italiana di Ematologia e Oncologia Pediatrica (AIEOP) Ann Hematol. 2022;101:1843–51. doi: 10.1007/s00277-022-04884-x. PubMed DOI PMC