Inflammatory responses in SARS-CoV-2 associated Multisystem Inflammatory Syndrome and Kawasaki Disease in children: An observational study.

Multisystem Inflammatory Syndrome in Children (MIS-C) is a severe inflammatory disease in children related to SARS-CoV-2 with multisystem involvement including marked cardiac dysfunction and clinical symptoms that can resemble Kawasaki Disease (KD). We hypothesized that MIS-C and KD might have commonalities as well as unique inflammatory responses and studied these responses in both diseases. In total, fourteen children with MIS-C (n=8) and KD (n=6) were included in the period of March-June 2020. Clinical and routine blood parameters, cardiac follow-up, SARS-CoV-2-specific antibodies and CD4+ T-cell responses, and cytokine-profiles were determined in both groups. In contrast to KD patients, all MIS-C patients had positive Spike protein-specific CD3+CD4+ T-cell responses. MIS-C and KD patients displayed marked hyper-inflammation with high expression of serum cytokines, including the drug-targetable interleukin (IL)-6 and IFN-γ associated chemokines CXCL9, 10 and 11, which decreased at follow-up. No statistical differences were observed between groups. Clinical outcomes were all favourable without cardiac sequelae at 6 months follow-up. In conclusion, MIS-C and KD-patients both displayed cytokine-associated hyper-inflammation with several high levels of drug-targetable cytokines.

Late endocrine effects after hematopoietic stem cell transplantation in children with nonmalignant diseases.

The number of children undergoing hematopoietic stem cell transplantation (HSCT) for nonmalignant diseases has increased in recent years. Endocrine complications are common after HSCT for malignant diseases, while little is known about long-term prevalence and risk factors in children transplanted for nonmalignant diseases. We retrospectively evaluated gonadal function, near adult height and thyroid function in 197 survivors of pediatric HSCT for hemoglobinopathies (n = 66), inborn errors of immunity/metabolism (n = 74) and bone marrow failure disorders (n = 57); median follow-up was 6.2 years (range 3.0-10.5). Gonadal dysfunction occurred in 55% of (post)pubertal females, was still present at last assessment in 43% and was more common after busulfan- than treosulfan-based conditioning (HR 10.6, CI 2.2-52.7; adjusted for HSCT indication). Gonadal dysfunction occurred in 39% of (post)pubertal males, was still present at last assessment in 32% and was less common in those who were prepubertal compared to (post)pubertal at HSCT (HR 0.11; CI 0.05-0.21). Near adult height was more than 2 SDS below mean parental height in 21% of males and 8% of females. Hypothyroidism occurred in 16% of patients; 4% received thyroxin treatment. In conclusion, endocrine complications, especially gonadal dysfunction, are common after pediatric HSCT for nonmalignant conditions. In females, treosulfan seems less gonadotoxic than busulfan. Careful long-term endocrine follow-up is indicated.

S. typhi Vi capsular polysaccharide vaccine-induced humoral immunity in travellers with immunosuppressive therapy for rheumatoid disease.

INTRODUCTION: Typhoid fever is a global health problem, causing significant morbidity and mortality. Currently, the most widely used vaccine is the typhoid Vi capsular polysaccharide (Vi-PS) vaccine. While epidemiological studies on its efficacy have been performed in children in endemic countries, there are no efficacy studies evaluating its use in travel medicine. Response to vaccination may differ in travellers receiving immunosuppressive therapy. This study investigates the humoral response to Vi-PS vaccination in travellers receiving immunosuppressive therapy for rheumatoid disease. METHODS: We recruited patients from the LUMC rheumatology outpatient clinic and travellers from the travel clinic who had previously received Vi-PS vaccination and also immunosuppressive therapy for rheumatoid disease. We analysed blood samples acquired from 42 patients over a period of 3 years. We estimated the length of persistence of protective titres using the survival analysis using multiple cut-off values for protection and measured titre half-life and the influence of immunosuppressive medication on titre half-life using mixed models. RESULTS: Anti-Vi-PS antibody levels stayed above 10 EU/ml for a mean of 13.3 years, above 15 EU/ml for a mean of 10.1 years and above 20 EU/ml for a mean of 8.6 years after Vi-PS vaccination. Titre half-life was 7.5 years (95% CI 5.0-14.7 years, P < 0.001). No significant influence of medication on titre half-life was found. CONCLUSION: Both persistence of protective antibody titres and titre half-life are longer than expected based on other studies. This warrants further study in adult volunteers, both in healthy individuals and patients suffering from rheumatoid disease.