Blood cancer in children infected with COVID-19: A comprehensive systematic review
Authors: Alhumaid Saad , Noaim Khalid Al , Almuslim Anwar A , Turkistani Jamela A. , Alqurini Zainab Sabri , Alshakhs Abdullah Mohammed , Dossary Nourah Al , Alabdulqader Muneera , Majzoub Rabab Abbas , Alnaim Abdulrahman A. , Alahmari Abdulaziz A. , Ghamdi Mohammed A. Al , Alabdulmohsen Wafa , Alsharidah Zakaria Ali , Alkhamees Munther Saleh , AlAithan Laith Abbas , Almurayhil Abdulaziz Ahmed , Almurayhil Yousuf Ahmed , Aljubran Hassan Abdullah , Alhamdan Zahra Salman , Shabib Maitham Abdullah , Aldandan Ali Wasel , Allowaim Abduljaleel Ahmed , Al-Rasasi Ali Younis , Albahrani Ahlam Ayesh , Salem Btol Ali Al , Bukhamseen Mugdad Saleem , Ayeyd Jinan Sadiq Al , Mutair Abbas Al , Alhumaid Hesham , Alawi Zainab Al , Rabaan Ali A. 
Published: May 2023

Abstract
Background: Blood cancer is the most common type of cancer and the leading cause of death by disease past infancy among children. Children with blood cancer are vulnerable population to viral infections such as coronavirus disease 2019 (COVID-19).
Objectives: To estimate the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in blood cancer children and analyse the demographic parameters, clinical characteristics and treatment outcomes in blood cancer children with COVID-19 illness.
Methods: For this systematic review, we searched ProQuest, Medline, Embase, PubMed, CINAHL, Wiley online library, Scopus and Nature through the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guideline for studies on the development of COVID-19 in children with blood cancer, published from December 1, 2019 to April 30, 2023, with English language restriction.
Results: Of the 3077 papers that were identified, 155 articles were included in the systematic review (83 case report, 54 cohort and 18 case-series studies). Studies involving 1289 blood cancer children with confirmed COVID-19 were analysed. Leukaemias (1141 cases) were the most frequent types of blood cancer observed in children who developed COVID-19, followed by non-Hodgkin’s lymphomas (59 cases), Hodgkin’s lymphomas (36 cases), Langerhans cell histiocytosis (7 cases), myelodysplastic syndrome (7 cases) and myeloid neoplasm (1 case). Among all 1289 blood cancer paediatric cases who transmitted SARS-CoV-2, some children were documented to be admitted to the intensive care unit (ICU) (n = 175, 13.6%), intubated and placed on mechanical ventilation (n = 111, 8.6%), suffered acute respiratory distress syndrome (n = 144, 11.2%) or died (n = 111, 8.6%). Overall, COVID-19 in children with different types of blood cancer resulted in no or low severity of disease in more than 78.6% of all included cases (COVID-19 severity: asymptomatic = 239, mild = 603, or moderate = 171). Treatment for COVID-19 was not necessary in a high number of blood cancer children (n = 94, 7.3%). Fatality in blood cancer children with COVID-19 was reported in any of the included blood cancer categories for leukaemias (n = 99, 8.7%), non-Hodgkin’s lymphomas (n = 7, 11.9%), Hodgkin’s lymphomas (n = 2, 5.5%), myelodysplastic syndrome (n = 1, 14.3%) or myeloid neoplasm (n = 1, 100%). Fatality rate in blood cancer children infected with SARS-CoV-2 was the highest in patients with Hispanic ethnicity (n = 44/111, 39.6%) and COVID-19–related fatality was highest in male patients (76.5% of deceased patients). Most studies reported to alter the intensity and regimen of anticancer treatment in blood cancer children during course of SARS-CoV-2 infection, however, many studies have reported to successfully treat COVID-19 without any changes to the anticancer treatment.
Conclusion: Globally, leukaemias were the most prevalent and myeloid neoplasms were the least prevalent blood cancer types in children who developed SARS-CoV-2 infection. Children with blood cancer tend to have milder COVID-19 symptoms and are less likely to be hospitalized and have better prognosis when compared to adults. Continuation of anticancer treatment in individual paediatric blood cancer patients with COVID-19 seems to be possible.