Risk factors for a severe disease course in children with SARS-COV-2 infection following hematopoietic cell transplantation in the pre-Omicron period: a prospective multinational Infectious Disease Working Party from the European Society for Blood and Marrow Transplantation group (EBMT) and the Spanish Group of Hematopoietic Stem Cell Transplantation (GETH) study

Abstract

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.

COVID‐19 disease in children and adolescents following allogeneic hematopoietic stem cell transplantation: A report from the Turkish pediatric bone marrow transplantation study group

“…29 Overall organ impairment caused by treatment-related toxicities as well as comorbidities among HSCT recipients could be the causes for the survival difference between the healthy pediatric population versus pediatric HSCT recipients. 26,28 The clinical features of the patients with COVID were similar to other studies, fever being the most common clinical presentation followed by cough. Characteristics of the patients in our cohort in comparison to other pediatric studies are summarized in Table 5.…”

“…25 The causes of this higher OS in pediatric HSCT recipients compared to adults are not well understood. The longer median time to COVID-19 infection (median 15 months) after HSCT in CIBMTR study including pediatric and young adult HSCT patients was suggested as one of the factors of the high survival in their cohort, 26 but we also found similar high survival rates in our cohort despite a shorter median time from HSCT to COVID infection (median 7 months). Age-related differences in immune function, expression and distribution of angiotensin-converting enzyme 2 receptor in pediatric population, which is a receptor used by the virus to gain entry into cells, endothelial and clotting function were suggested as other cause of better survival rates in children.…”

“…Characteristics of the patients in our cohort in comparison to other pediatric studies are summarized in Table 5. 23,26,30,31 In univariate analysis transplantation involving donors other than an HLA well-matched donor, lymphopenia HSCT recipients. 32,33 The main changes in hemocytometry markers are characterized by neutrophilia, lymphopenia, and thrombocytopenia in COVID-19.…”

“…The Centers for Disease Control and Prevention 2021 Morbidity and Mortality Weekly Report data reported an ICU requirement rate of 0.8%, with COVID‐19‐related mortality less than 0.1% in the 0‐ to 17‐year‐old pediatric population 29 . Overall organ impairment caused by treatment‐related toxicities as well as comorbidities among HSCT recipients could be the causes for the survival difference between the healthy pediatric population versus pediatric HSCT recipients 26,28 …”

COVID‐19 after hematopoietic cell transplantation and chimeric antigen receptor (CAR)‐T‐cell therapy

“…The course of disease is less severe in pediatric HCT recipients compared to adults. 16 Multicenter studies in children and young adults receiving HCT report a mortality rate of 6%-9% [24][25][26] (occasionally higher at 21%), 27 and ICU admission in 9%-26%. 24,26,28 Despite the relative "mildness" of disease, [24][25][26] unfavorable outcomes such as ICU admissions and death are substantially more frequent in immunocompromised children compared to those with intact immunity who experience mostly asymptomatic disease, rarely leading to ICU admission (<1%) and death (<0.1%).…”