Purine nucleoside phosphorylase (PNP) deficiency causes inadequate purine metabolite detoxification, which leads to combined immunodeficiency and variable neurologic symptoms. Hematopoietic stem cell transplantation (HSCT) cures the immunodeficiency, but large studies on the long-term outcomes are lacking. In a retrospective study of the European Society for Blood and Marrow Transplantation, we investigated 46 patients with PNP deficiency from 21 centers. We analyzed the presenting clinical signs and outcomes after HSCT. Cognition (0-3), hearing (0-3), interaction (0-4), movement (0-4), and occupation (0-3) (CHIMO) were scored at the last follow-up (FU) visit (no impairment, 17; mild, 15-16; moderate, 12-14; and severe impairment, <12). The median age at initial presentation was 7.5 (1-48) months. The patients presented with infections (41%), neurological dysfunction (39%), both (15%), or autoimmune disease (5%). At the time of HSCT (median age, 26 [2-192] months), neurological abnormalities were observed in 88% of patients. After a median FU of 7.9 (1.0-22.3) years, 40 patients were alive with a 3-year overall survival (OS)/event-free survival (EFS) probabilities of 86% (confidence interval [CI], 77%-97%)/75% (CI, 64%-89%), respectively. High-level (>50%-100%)/low-level donor chimerism (11%-50%) was observed in 85%/15% of patients, respectively, leading to resolution of T lymphopenia. The median overall CHIMO score was 14 (6-17), while the median scores for each component were 3 (0-3), 3 (1-3), 4 (1-4), 3 (1-4), and 2 (0-3), respectively. Patients who underwent HSCT before 24 months after the initial presentation demonstrated superior OS (P = .049). Neurological symptoms that occurred before 11 months of age were associated with reduced OS (P = .027). While the overall results were satisfactory, earlier diagnosis could further improve outcomes.

We investigated the outcomes of 179 pediatric patients with severe aplastic anemia (SAA) transplanted upfront (n=87) or after failure of immunosuppressive therapy (IST) (n=92). With a median follow-up of 4.0 years (range 0.2-10.7) after HSCT, 161 patients were alive at last follow-up. The cumulative incidence of graft failure, grade II-IV acute and chronic graft-versus-host-disease (GVHD) was 10%, 18%, and 8%, respectively. Five-year overall survival (OS) and GVHD-free, relapse/rejection-free survival (GRFS) were 89% and 79%, respectively. Patients transplanted upfront from a matched sibling donor (MSD) or ≥9/10 HLA-matched unrelated donor (MUD) both achieved an OS of 95%. OS was superior in patients transplanted upfront compared with those transplanted after failure of IST (upfront 95% [89-100] vs. post-IST failure 83% [75-91], p<0.01). However, OS in the post-IST failure group improved over time, resulting in comparable OS of upfront and post-IST failure HSCT from 2015 (97% vs. 89%, p=0.09). Subgroup analysis of patients transplanted from an MSD revealed no difference in GRFS with different conditioning regimens, including cyclophosphamide (Cy), Cy/anti-thymocyte globulin (ATG), and fludarabine/Cy/ATG (Cy 80% vs. Cy/ATG 84% vs. Flu/Cy/ATG 90%, p=n.s.). Moreover, there was no difference in GRFS of MUD-HSCT comparing patients transplanted upfront or post-IST failure (upfront 77% vs. post-IST failure 76%, p=n.s.). Our data highlight the good transplant outcomes of a consecutive pediatric SAA cohort. While upfront HSCT from a readily available MUD is a viable option if an MSD is not available, HSCT after IST failure from a well-matched unrelated donor also yields favorable outcomes.

BACKGROUND:Vancomycin is widely used to treat serious Gram-positive infections but is difficult to dose given its narrow therapeutic index and risk of acute kidney injury at high doses. We aimed to study whether model-informed precision dosing (MIPD) of vancomycin, compared with standard-of-care therapeutic drug monitoring (TDM), increases pharmacokinetic and pharmacodynamic target attainment, is safe, and reduces vancomycin-associated acute kidney injury in children with severe illness. METHODS:The BENEFICIAL trial is a pragmatic, individually randomised, controlled superiority trial done in 14 paediatric or neonatal intensive care and haemato-oncology units in seven hospitals in Belgium. Critically ill patients younger than 18 years initiating intravenous vancomycin for suspected or confirmed Gram-positive infection were eligible. Key exclusion criteria were extracorporeal support, severe acute kidney injury, chronic kidney disease, and imminent death. The intervention combined the use of an MIPD dosing calculator for starting and follow-up doses, with extra sampling for TDM in the first hours of treatment compared with standard-of-care TDM. Patients were randomly assigned (1:1) to MIPD or standard-of-care TDM of vancomycin using stratified permuted blocks by ward type. Allocation occurred via a secure web interface; patients, families, and the biostatistician were masked, but treating physicians and pharmacist staff were not. The intervention used Bayesian software with early sampling to estimate AUC. The primary outcome was the proportion of patients with a 24-h AUC-to-MIC ratio of 400-600 mg·h/L, assuming a minimum inhibitory concentration of 1 mg/L, 24-48 h after treatment initiation. A key secondary outcome was the proportion of patients with new or worsening acute kidney injury or death. These outcomes were assessed in the intention-to-treat (ITT) population (all randomly assigned patients who provided informed consent). Safety was evaluated in all patients who received at least one dose of vancomycin. This trial is registered with ClinicalTrials.gov (NCT04666948) and the EU Clinical Trials register (EudraCT 2019-004538-40), and is closed to recruitment. FINDINGS:Between Dec 28, 2020, and Dec 14, 2023, 332 patients aged between 1 day and 18 years were randomly assigned, 165 to the standard-of-care group and 167 to the intervention group. 18 participants were excluded from the analysis when their deferred consent was not followed by informed consent; therefore 314 patients (179 male and 135 female) were included in the analysis. Target AUC-to-MIC ratio attainment at 24-48 h was found in 82 (53·9%) of 152 patients with available data in the standard-of-care group and 112 (71·8%) of 156 in the MIPD group (absolute difference 18·9% [1·7 to 34·7]). The proportion of patients with acute kidney injury or all-cause mortality was numerically but not significantly lower in the intervention group (26 [16·9%] of 154 vs 19 [12·4%] of 153; absolute difference -4·5% [95% CI -11·6 to 3·5]). Serious adverse events occurred in eight (5%) of 158 patients in the standard-of-care group and eight (5%) of 156 patients in the intervention group. One patient in the intervention group died due to a serious adverse event at least possibly related to the vancomycin administration method. INTERPRETATION:AUC-based MIPD improves AUC-to-MIC ratio-based target attainment and has a low risk of harm. Given that elevated vancomycin AUC is a well established driver of acute kidney injury, the lower cumulative exposure observed in this trial support the use of MIPD in severely ill children, particularly in those who require long treatment durations or present with additional acute kidney injury risk factors. FUNDING:Belgian Federal Knowledge Centre Trials Programme.

BACKGROUND:Antimicrobial management in pediatric transplantation lacks standardized international guidelines, and current practices across European transplant centers remain poorly described. This study aimed to evaluate microbiological screening and peri-transplant antimicrobial strategies among centers participating in the European Reference Network on Transplantation in Children (ERN TransplantChild), including both solid organ transplantation (SOT) and hematopoietic stem cell transplantation (HSCT) programs. METHODS:Between December 2022 and February 2023, healthcare professionals within the network completed a structured survey addressing microbiological screening practices and peri-transplant antimicrobial strategies in pediatric transplant recipients. RESULTS:Of 127 transplant programs invited, 76 (59.8%) responded, including 62 SOT and 14 HSCT programs from 36 centers across 16 European countries. Pre-transplant screening strategies, microbiological methods, and decolonization practices varied substantially between centers. Reported prevalence of methicillin-resistant Staphylococcus aureus and extended-spectrum β-lactamase-producing organisms was below 10% in most programs. In SOT, perioperative prophylaxis varied according to transplanted organ type. Cephalosporins were most commonly used in kidney and heart transplantation, whereas broader-spectrum regimens, including piperacillin-tazobactam and vancomycin, were more frequently adopted in liver, intestinal, and lung transplantation. Postoperative prophylaxis was continued beyond 24 h in most SOT programs. Antifungal prophylaxis was more commonly adopted in liver, intestinal, and lung transplant recipients. In HSCT, antibacterial peri-transplant use was not routinely prescribed in a substantial proportion of programs, particularly in autologous transplantation, whereas antifungals were widely used in allogeneic HSCT. CONCLUSIONS:Marked heterogeneity in microbiological screening and peri-transplant antimicrobial strategies across European pediatric transplant centers underscores the need for transplant-specific, evidence-based guidelines distinguishing between SOT and HSCT settings. These findings provide a foundation for the development of shared clinical pathways and harmonized recommendations.

Allogeneic hematopoietic cell transplantation (HCT) has represented a curative therapy for transfusion-dependent thalassemia (TDT) for over four decades. Despite major advances in conditioning regimens, graft-versus-host disease (GVHD) prophylaxis, and supportive care, substantial heterogeneity persists in patient preparation strategies and transplant protocols across centers. To address these practice variations and provide harmonized guidance, the European Society for Blood and Marrow Transplantation (EBMT) Practice Harmonization and Guidelines Committee convened an international expert workshop in Berlin (Germany) on September 29–30, 2025. A structured literature review was conducted in advance. Evidence was presented, critically appraised, and discussed in consensus-based sessions. Recommendations were formulated using the GRADE framework and approved by panel members and external reviewers. These guidelines summarize contemporary evidence regarding pre-transplant optimization, conditioning regimens according to age and donor type, management of iron overload and ineffective erythropoiesis, and approaches for alternative donor transplantation and gene therapy. The aim of this document is to provide practical, evidence-informed recommendations to standardize HCT practice and optimize outcomes for children and adults with TDT globally, including in resource-limited settings.

Genetic defects in one of the DNA double strand break (DSB) repair proteins lead to distinct human syndromes with severe clinical manifestations, including impaired neurological and immunological development, cancer proneness and sensitivity to ionizing radiation. Since diagnostic and therapeutic procedures frequently use DNA damaging agents, identification of radiosensitive individuals is imperative to optimize patient management. However, patients with a (severe) combined immunodeficiency (S)CID are often ineligible for lymphocyte-based radiosensitivity testing. Therefore, this study investigated the suitability of two fibroblast-based assays as alternative methods. DSB repair was evaluated following X-ray irradiation by an optimized cytokinesis-block micronucleus (MN) assay and the γH2AX focus test in fibroblasts from patients with a confirmed or suspected diagnosis of radiosensitive (S)CID. Using both assays, patients with a defect in Artemis were identified as radiosensitive while those with a RAG1/2 deficiency were not considered as radiosensitive. Although MN scoring was not feasible in irradiated fibroblasts deficient in XLF, LIG4 or NBS1, radiosensitivity could be readily demonstrated through impaired DNA DSB repair kinetics with the γH2AX focus assay in fibroblasts deficient in XLF or LIG4, but not in those deficient in NBS1. While both ATM defective fibroblasts clearly showed increased radiation-induced MN yields, one of the two fibroblast cell lines could not be identified as radiosensitive based on residual γH2AX focus levels. This study suggests that combining the fibroblast MN assay and γH2AX focus test can effectively exclude in vitro radiosensitivity in patients with a suspicion of radiosensitive (S)CID, particularly when lymphocyte-based radiosensitivity testing is not feasible.

Human inborn errors of immunity (IEI) represent a diverse group of genetic disorders affecting the innate and/or adaptive immune system. Some IEI entities comprise defects in DNA repair factors, resulting in (severe) combined immunodeficiencies, bone marrow failure, predisposition to malignancies, and potentially resulting in radiosensitivity (RS). While other IEI subcategories such as common variable immunodeficiency (CVID) and immune dysregulation disorders also associate with lymphoproliferative and malignant complications, the occurrence of RS phenotypes in the broader IEI population is not well characterized. Nonetheless, identifying RS in IEI patients through functional testing is crucial to reconsider radiation-related therapeutic protocols and to improve overall patient management. This study aimed to investigate chromosomal RS in a diverse cohort of 107 IEI patients using the G0 cytokinesis-block micronucleus (MN) assay. Our findings indicate significant variability in RS across specific genetic and phenotypical subgroups. Severe RS was detected in all ataxia-telangiectasia (AT) patients, a FANCI deficient and ERCC6L2 deficient patient, but not in any other IEI patient included in this cohort. Age emerged as an influencing factor for both spontaneous and radiation-induced MN yields, while the manifestation of additional clinical features, including infection susceptibility, immune dysregulation, or malignancies did not associate with increased MN levels. Our extensive analysis of RS in the IEI population underscores the clinical importance of RS assessment in AT patients and supports RS testing in all IEI patients suspected of having a DNA repair disorder associated with RS.

Previous research has explored the experiences of sibling pediatric stem cell donors; gaps remain, particularly regarding children and adolescents in Belgium who donate to severely ill siblings. This study examines their personal and relational experiences through qualitative analysis. Semi-structured interviews with 13 donors revealed a mix of eagerness and obligation—while they were willing to help, many felt they had no choice and were often overlooked. Findings highlight a lack of post-donation support and the need for greater recognition of donors’ experiences. Despite improvements in pre-donation care, enhanced post-donation support remains crucial. A structured, personalized approach is recommended. Conclusion: Enhanced post-donation support is essential to address the emotional and psychological impact on sibling donors. Further research should explore how donor age and recipient outcomes shape the donation experience.

Congenital amegakaryocytic thrombocytopenia is a rare, inherited bone marrow failure syndrome. Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is currently the only curative treatment. In this retrospective study, we analysed 66 patients with allo-HSCT, reported in the European Society for Blood and Marrow Transplantation (EBMT) registry. Bone marrow (BM) was the most widely used stem cell source (n = 40; 61%) followed by peripheral blood (PB) (n = 18; 27%), and unrelated umbilical cord blood (UCB) (n = 8; 12%). Most frequently was a HLA-matched graft from related (n = 26; 39%) and unrelated (n = 15; 23%) donors after a myeloablative busulfan-based conditioning regimen. GvHD prophylaxis was mostly cyclosporine and methotrexate (53%). The 6-year cumulative incidence of graft-failure and second transplant were 25% and 17%, respectively. The 6-year disease-free survival (DFS) and overall survival (OS) were 66.9% and 85.6%, respectively. The 6-year transplant-related mortality (TRM) was 8.0%. In conclusion, most patients with CAMT benefit from allo-HSCT, but with many graft failures.

Pathogenic variants in SUFU (suppressor of fused homolog) are regularly identified in tumor samples and are linked with malignancy by disinhibition of the sonic hedgehog (SHH) signaling pathway. 1 Carballo G.B. Honorato J.R. de Lopes G.P.F. Spohr T. A highlight on Sonic hedgehog pathway. Cell Commun Signal. 2018; 16: 11 Crossref PubMed Scopus (253) Google Scholar In rare cases heterozygous germline variants in SUFU are identified. This heterozygous state is associated with predisposition for various malignancies. The overall risk for tumor development (of any type) in heterozygous individuals is around 68%. 2 Guerrini-Rousseau L. Masliah-Planchon J. Waszak S.M. et al. Cancer risk and tumour spectrum in 172 patients with a germline SUFU pathogenic variation: a collaborative study of the SIOPE Host Genome Working Group. J Med Genet. 2022; 59: 1123-1132 Crossref PubMed Scopus (3) Google Scholar Early-onset medulloblastoma is the most common tumor type found in 50% of the patients with a median age of 18 months at diagnosis. 2 Guerrini-Rousseau L. Masliah-Planchon J. Waszak S.M. et al. Cancer risk and tumour spectrum in 172 patients with a germline SUFU pathogenic variation: a collaborative study of the SIOPE Host Genome Working Group. J Med Genet. 2022; 59: 1123-1132 Crossref PubMed Scopus (3) Google Scholar In addition to predisposition to malignancies, SUFU haploinsufficiency has also been associated with macrocephaly 3 Guerrini-Rousseau L. Dufour C. Varlet P. et al. Germline SUFU mutation carriers and medulloblastoma: clinical characteristics, cancer risk, and prognosis. Neuro Oncol. 2018; 20: 1122-1132 Crossref PubMed Scopus (46) Google Scholar ,4 Klein S.D. Nguyen D.C. Bhakta V. et al. Mutations in the sonic hedgehog pathway cause macrocephaly-associated conditions due to crosstalk to the PI3K/AKT/mTOR pathway. Am J Med Genet. 2019; 179: 2517-2531 Crossref PubMed Scopus (17) Google Scholar and Gorlin syndrome, 5 Alvarez-Salafranca M. Garcia-Garcia M. Montes-Torres A. Rivera-Fuertes I. Lopez-Gimenez M.T. Ara M. SUFU-associated Gorlin syndrome: expanding the spectrum between classic nevoid basal cell carcinoma syndrome and multiple hereditary infundibulocystic basal cell carcinoma. Australas J Dermatol. 2023; 64: 249-254 Crossref PubMed Scopus (1) Google Scholar , 6 Ogden T. Higgins S. Elbaum D. Wysong A. The relevance of a suppressor of fused (SUFU) mutation in the diagnosis and treatment of Gorlin syndrome. JAAD Case Rep. 2018; 4: 196-199 Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar , 7 Smith M.J. Beetz C. Williams S.G. et al. Germline mutations in SUFU cause Gorlin syndrome-associated childhood medulloblastoma and redefine the risk associated with PTCH1 mutations. J Clin Oncol. 2014; 32: 4155-4161 Crossref PubMed Scopus (206) Google Scholar as well as with a recognizable neurodevelopmental phenotype at the mild end of the Joubert syndrome spectrum. 8 De Mori R. Romani M. D'Arrigo S. et al. Hypomorphic recessive variants in SUFU impair the sonic hedgehog pathway and cause Joubert syndrome with cranio-facial and skeletal defects. Am J Hum Genet. 2017; 101: 552-563 Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar , 9 Schroder S. Li Y. Yigit G. et al. Heterozygous truncating variants in SUFU cause congenital ocular motor apraxia. Genet Med. 2021; 23: 341-351 Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar , 10 Schroder S. Yigit G. Li Y. et al. The genetic spectrum of congenital ocular motor apraxia type cogan: an observational study, continued. Orphanet J Rare Dis. 2023; 18: 101 Crossref PubMed Scopus (1) Google Scholar , 11 Serpieri V. D'Abrusco F. Dempsey J.C. et al. SUFU haploinsufficiency causes a recognisable neurodevelopmental phenotype at the mild end of the Joubert syndrome spectrum. J Med Genet. 2022; 59: 888-894 Crossref PubMed Scopus (19) Google Scholar

Invasive aspergillosis (IA) and mucormycosis (IM) cause significant morbidity and mortality in immunocompromised and/or hospitalized patients. Isavuconazonium sulfate, a prodrug of the antifungal triazole isavuconazole, has been approved for treatment of IA and IM in adults; and was recently approved in children. This study describes the outcomes, safety, and pharmacokinetics of isavuconazole for the treatment of proven, probable, or possible IA or IM in children. In this phase 2, open-label, non- comparative study, patients aged 1 to <18 years with at least possible invasive mold disease were enrolled across 10 centers in the US, Spain, and Belgium from 2019 to 2022. Patients received 10 mg/kg isavuconazonium sulfate daily (maximum 372 mg; equivalent to 5.4 mg/kg or 200 mg isavuconazole) for up to 84 (IA) or 180 days (IM). Outcomes included rates of all-cause case fatality, overall response, treatment-emergent adverse events (TEAEs), and pharmacokinetics. Of 31 patients enrolled, 61.3% were 1-<12 years old; 58.1% had underlying hematologic malignancies. The successful overall response rate at the end of treatment was 54.8%. Day 42 all-cause case fatality was 6.5%; 93.5% experienced TEAEs, and two patients discontinued treatment due to drug-related TEAEs. Dosing at 10 mg/kg (maximum dose: 372 mg) met the pre-defined exposure threshold of above the 25th percentile for the area under the concentration-time curve (>= 60 mgh/L). Simulated doses of 15 mg/kg improved drug exposures in patients aged 1-<3 years. Isavuconazole was well tolerated in children, with exposure consistent with adult studies. Successful response was documented in 54.8% of patients.

Abstract Background Invasive aspergillosis (IA) and invasive mucormycosis (IM) are life-threatening invasive fungal diseases (IFDs) that occur in critically ill and/or immunocompromised patients. Approved treatment options have significant limitations in pediatric patients. This study assessed the safety and outcomes of isavuconazonium sulfate (ISAV) for the treatment of IFD in this patient population. Methods This phase 2, open-label, non-comparative study enrolled patients at 10 centers in Belgium, Spain, and the US between 2019 and 2022. Patients aged 1 to < 18 years with possible, probable or proven IA or IM per the 2008 (EORTC/MSG) criteria received ISAV 10 mg/kg (max. 372 mg) every 8 h on days 1 and 2, and once-daily thereafter (intravenous or oral), for ≤ 84 days (IA) or ≤ 180 days (IM). Primary objectives were safety, including treatment-emergent adverse events (TEAEs), drug-related TEAEs, vital signs, electrocardiograms and laboratory parameters. Other key outcomes included all-cause case fatality through Day 42, overall response as assessed by an independent committee, and plasma ISAV levels. Data were summarized descriptively. Results Overall, 31 patients aged 1–17 years were enrolled; 80.6% were female and 61.3% were White (Table 1). The most common primary underlying condition was hematologic malignancy (58.1%). Patients received ISAV for a median (range) duration of 55 (2–181) days. Plasma ISAV levels were consistent with those seen in adults receiving the standard dose (Table 2). TEAEs occurred in 29 (93.5%) patients for a total of 415 events. Nine (29.0%) patients experienced drug-related TEAEs, and treatment was withdrawn in 2 patients due to TEAEs. Serious TEAEs occurred in 18 (58.1%) patients and were assessed as drug-related by the investigator in 1 patient (3.2%). All-cause case fatality through Day 42 was 6.5%. Overall, successful response rates were 54.8% at the end of treatment (EOT, Table 3). Table 1: Demographics and baseline characteristics (FAS) ALL, acute lymphocytic leukemia; AML, acute myelogenous leukemia (includes relapsed disease); B-LL, B-cell lymphoblastic leukemia/lymphoma; EORTC/MSG, European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and Mycoses Study Group; FAS, full analysis set; IA, invasive aspergillosis; IFD, invasive fungal disease; IM, invasive mucormycosis; MDS to AML, myelodysplastic syndrome transformed to AML; NHL, non-Hodgkin lymphoma; SD, standard deviation. An investigator assessment of IFD diagnosis was used. The FAS included all patients who are enrolled and receive at least one dose of study drug. Patients with possible IFD were eligible for enrollment; diagnostic tests to confirm the disease as ‘probable’ or ‘proven’ according to EORTC/MSG 2008 criteria were completed within 10 days after first dose of study drug. Other IFDs were defined as IFDs confirmed not to be IA or IM.Table 2:Overview of study drug exposure (SAF) and pharmacokinetic evaluation (PKAS) EORTC/MSG, European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the Mycoses Study Group; IA, invasive aspergillosis; IFD: invasive fungal disease; IM, invasive mucormycosis; IV, intravenous; PKAS, pharmacokinetic analysis set; SAF, safety analysis set; SD, standard deviation. An investigator assessment of IFD diagnosis was used. Possible IFD was defined according to EORTC/MSG 2008 mycological criteria. Other IFDs were defined as IFDs confirmed not to be either IA or IM. The FAS included all patients who are enrolled and receive at least one dose of study drug. The PKAS consisted of all patients who took at least 1 dose of study drug and recorded least 1 plasma concentration measurement.Table 3:Overview of adverse events (SAF), all-cause case fatalities and clinical response outcomes (FAS) AC, adjudication committee; FAS, full analysis set; IA, invasive aspergillosis; IFD: invasive fungal disease; IM, invasive mucormycosis; EOT, end of treatment; SAF, safety analysis set; TEAE, treatment-emergent adverse event. An investigator assessment of IFD diagnosis was used. Possible IFD was defined according to EORTC/MSG 2008 mycological criteria. Other IFDs were defined as IFDs confirmed not to be either IA or IM. If patient did not reach Day 42 or Day 84 of therapy, then the AC did not perform these assessments. The frequency 'N' in a column heading represents the number of patients included in the investigator assessment of IFD diagnosis. Overall response was based on a composite of clinical, mycological, and radiological responses with success criteria assessed. Overall response was considered 'Not evaluable' when one of the composite responses was not assessed. TEAEs were defined as adverse events observed after starting the study drug through 30 days after the last dose. Drug-related events, as assessed by the investigator, were those with a reasonable possibility that the event may have been caused by the study drug; if any other relationship was missing, the event was also considered as drug-related. The FAS and SAF were equivalent, and included all patients who were enrolled and received at least one dose of study drug. Conclusion Treatment with ISAV in 31 immunocompromised pediatric patients with IFDs was well tolerated; only one (3.2%) patient had a serious drug-related TEAE. Plasma drug levels were also similar to those in adult patients. Overall favorable response was observed in > 50% of patients at EOT. All-cause case fatality rates were low (6.5%) at Day 42. Disclosures Antonio C. Arrieta, MD, FIDSA, FPIDS, Astellas Pharma Global Development, Inc.: Advisor/Consultant|Astellas Pharma Global Development, Inc.: Grant/Research Support|Astellas Pharma Global Development, Inc.: Honoraria|Cumberland Pharmaceutical: Grant/Research Support|IDbyDNA: Advisor/Consultant|IDbyDNA: Grant/Research Support|Melinta: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|Nabriva: Grant/Research Support|Paratek Pharmaceuticals: Grant/Research Support|Pfizer, Inc: Advisor/Consultant|Pfizer, Inc: Grant/Research Support|Roche/Genentech: Grant/Research Support|The Medicine Company: Grant/Research Support Heidi Segers, MD, PhD, ALLTogether Consortium: Board Member|Astellas Pharma Global Development, Inc.: Support for the present publication|Jazz Pharmaceuticals: Support for attending meetings and/or travel|Stand up against Cancer Grant /C1 KU Leuven Grant: Grant/Research Support Jaime G. Deville, MD, Astellas Pharma Global Development, Inc.: Support for the present publication William J. Muller, MD, PhD, Adagio Therapeutics: Advisor/Consultant|Ansun Biopharma: Grant/Research Support|Astellas Pharma Global Development, Inc.: Grant/Research Support|Astellas Pharma Global Development, Inc.: Support for the present publication|AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|DiaSorin Molecular LLC: Advisor/Consultant|Eli Lilly and Company: Grant/Research Support|Enanta Pharmaceuticals: Grant/Research Support|F. Hoffmann-La Roche: Grant/Research Support|Finley Law Firm, P.C: Expert Testimony|Gilead Sciences: Grant/Research Support|Janssen Biotech: Grant/Research Support|Karius, Inc.: Grant/Research Support|Melinta Therapeutics, Inc.: Grant/Research Support|Merck: Grant/Research Support|Moderna: Grant/Research Support|Nabriva Therapeutics, plc: Grant/Research Support|Paratek Pharmaceuticals, Inc.: Grant/Research Support|Pfizer: Grant/Research Support|Sanofi Pasteur LLC: Advisor/Consultant|Tetraphase Pharmaceuticals, Inc.: Grant/Research Support Angela Manzanares, MD, Astellas Pharma Global Development, Inc.: Support for the present publication|Gilead Sciences: Support for attending meetings and/or travel Michael N. Neely, MD, Astellas Pharma Global Development, Inc.: Advisor/Consultant|Astellas Pharma Global Development, Inc.: Support for the present publication Victoria Bordon, MD, PhD, Astellas Pharma Global Development, Inc.: Support for the present publication Benjamin Hanisch, MD, American Society of Transplantation: Board Member|Astellas Pharma Global Development, Inc.: Support for the present publication|NIH: Site PI for International Pediatric Fungal Network- funds to institution Alvaro Lassaletta, MD, PhD, Astellas Pharma Global Development, Inc.: Support for the present publication|Gilead Sciences: Stocks/Bonds Brian T. Fisher, DO, MPH/MSCE, Allovir: Grant/Research Support|Astellas Pharma Global Development, Inc.: Support for the present publication|Merck: Grant/Research Support|Pfizer: Grant/Research Support Julie Autmizguine, MD, MHS, Astellas Pharma Global Development, Inc.: Advisor/Consultant|Astellas Pharma Global Development, Inc.: Support for the present publication Andreas H. Groll, MD, Amplyx: Advisor/Consultant|Astellas: Advisor/Consultant|Astellas: sered at the speakers’ bureau|Basilea: Advisor/Consultant|Basilea: served at the speakers’ bureau|F2G: Advisor/Consultant|F2G: served at the speakers’ bureau|Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Gilead Sciences: served at the speakers’ bureau|Merck Sharp & Dohme LLC: Advisor/Consultant|Merck Sharp & Dohme LLC: Grant/Research Support|Merck Sharp & Dohme LLC: served at the speakers’ bureau|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: served at the speakers’ bureau Shamim Sinnar, MD, PhD, Astellas Pharma Global Development, Inc.: Astellas Employee Rodney Croos-Dabrera, PhD, Astellas Pharma Global Development, Inc.: Astellas Employee Marc Engelhardt, MD, Astellas Pharma Global Development, Inc.: Support for the present publication|Basilea Pharmaceutica International Ltd: Employee of Basilea Pharmaceutica International Ltd|Basilea Pharmaceutica International Ltd: Stocks/Bonds Mark E. Jones, PhD, Astellas Pharma Global Development, Inc: Support for the present publication|Basilea Pharmaceutica International Ltd: Employee of Basilea Pharmaceutica International Ltd|Basilea Pharmaceutica International Ltd: Stocks/Bonds Laura Kovanda, PhD, Astellas Pharma Global Development Inc.: Astellas Employee

EDITORIAL article Front. Immunol., 27 March 2023Sec. Primary Immunodeficiencies Volume 14 - 2023 | https://doi.org/10.3389/fimmu.2023.1189312

Background: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is clinically diverse, and children have a low risk of developing severe coronavirus disease 2019 (COVID-19). However, children with chronic diseases have a potentially increased risk. Methods: We performed a prospective surveillance study with longitudinal serum SARS-CoV-2 anti-nucleocapsid antibody quantification and questionnaires in pediatric tertiary care patients during the first waves of the COVID-19 pandemic (November 2020-September 2021). The results were compared with those of healthy children and adults from the same geographic area. Results: We obtained 525 samples from 362 patients (M/F ratio of 1.3:1; median age of 11.1 years) comprising children with immune-suppressive or immunemodulating drugs (32.9%), inborn errors of immunity (23.5%), type 1 diabetes mellitus (15.2%), and rheumatic diseases (11.9%). A total of 51 (9.7%) samples were seropositive among 37/351 children (10.5%). Seropositivity increased from 5.8% in November-December 2020 to 21.6% in July-September 2021. Compared with adults, a longitudinal analysis revealed reduced seroprevalence but similar kinetics as in children from the same country. Demographic or social variables and disease characteristics did not correlate with seropositivity. Being obese and household contact with COVID-19-infected individuals significantly increased the odds of infection. The majority of seropositive patients had mild symptoms (21/37). One-third were asymptomatic and/or unaware of having COVID-19 (10/37). Four patients (4/37) needed hospitalization, with good clinical outcomes. Conclusions: Although harboring a chronic disease, we observed a low SARS-CoV-2 incidence in a cohort of pediatric tertiary care patients, comparable with healthy children during the first year of the pandemic. Infection was mostly associated with mild symptoms.