COVID-19 Vaccine Acceptance Among Parents of Children With Multisystem Inflammatory Syndrome in Children.

Data on COVID-19 vaccine acceptability among parents of children with multisystem inflammatory syndrome (MIS-C) are limited. In this cohort of children with MIS-C, enrolled in the Swissped RECOVERY trial (NCT04826588), comparing intravenous immunoglobulins or methylprednisolone, who, in accordance with Swiss guidelines, were recommended for SARS-CoV-2 vaccination, 65% (73/112) of parents reported being vaccinated against SARS-CoV-2 before the MIS-C, while 70% were vaccinated after the MIS-C episode of their child. None of the children were vaccinated before the occurrence of the MIS-C, and only 9% (5/56) received the COVID-19 vaccine after the MIS-C. The predominant barriers to COVID-19 vaccination were concerns over potential side effects and insufficient support from their doctors. This emphasizes the crucial role of health care providers in promoting COVID-19 vaccination among children.

Vaccine Immunity in Children After Hematologic Cancer Treatment: A Retrospective Single-center Study.

BACKGROUND: Children lose their vaccine-induced protection and are particularly vulnerable to vaccine-preventable diseases after chemotherapy. However, revaccination guidelines are heterogeneous, and there is often a lack of revaccination post-treatment. AIMS: We conducted a retrospective study of children with hematologic cancer to evaluate vaccine immunity before and after the end of treatment and to determine whether the current institutional revaccination program based on vaccine serology results was followed and effective. MATERIALS AND METHODS: Data of all children treated by chemotherapy between April 2015 and July 2021 were extracted from hospital medical records for analysis. Serum antibody levels and time of vaccination were evaluated for diphtheria, tetanus, Streptococcus pneumoniae , Haemophilus influenzae type b (Hib), measles, varicella, and hepatitis B. RESULTS: We included 31 patients (median age, 9 years). At cancer diagnosis, 90% of children were protected against tetanus, diphtheria, and measles; 65% to 67% were protected against pneumococcus and varicella; and 25% against hepatitis B. At the end of chemotherapy, 67% to 71% of patients were protected against tetanus, varicella, and measles; 40% remained protected against hepatitis B; and 27% to 33% against pneumococcus and diphtheria. Patients were revaccinated at various times after the end of treatment but not systematically. During the first-year post-treatment, 20% to 25% of children remained unprotected against pneumococcus, measles, and hepatitis B, one third against diphtheria, but all were protected against tetanus and varicella. CONCLUSIONS: An effective individualized vaccination program post-cancer based on serology results should be accompanied by an appropriate serology tracking method and follow-up to assess if booster doses are necessary. Our study supports vaccinating all children with a dose of the 13-valent pneumococcal conjugate at cancer diagnosis and at 3 months post-treatment with the combined diphtheria-tetanus-acellular pertussis/poliomyelitis vaccine/hepatitis B virus plus or minus Hib and 13-valent pneumococcal conjugate and meningococcal vaccine, including measles/mumps/rubella-varicella zoster virus vaccine if good immune reconstitution is present.

Cardiac assessment and inflammatory markers in children with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV2 (PIMS-TS) treated with methylprednisolone versus intravenous immunoglobulins: 6-month follow-up outcomes of the randomised controlled Swissped RECOVERY trial.

Background: Previous findings from the Swissped RECOVERY trial showed that patients with Pediatric Inflammatory Multisystem Syndrome-Temporally Associated with SARS-CoV-2 (PIMS-TS) who were randomly assigned to intravenous immunoglobulins or methylprednisolone have a comparable length of hospital stay. Here, we report the 6-month follow-up outcomes of cardiac pathologies and normalisation of clinical or laboratory signs of inflammation from this study population. Methods: This pre-planned follow-up of patients with PIMS-TS included the Swissped RECOVERY Trial reports on the 6-month outcomes of the cohort after randomisation, with a focus on cardiac, haematological, and biochemical findings. The trial was an investigator-initiated randomised multicentre open-label two-arm trial in children and adolescents hospitalised with PIMS-TS at ten hospitals in Switzerland. Cardiological assessments and laboratory analyses were prospectively collected in the intention-to-treat analysis on pre-defined intervals after hospital discharge. Differences between randomised arms were investigated using Chi-square test for categorical and Wilcoxon test for continuous variables. The trial is registered with the Swiss National Clinical Trials Portal (SNCTP000004720) and ClinicalTrials.gov (NCT04826588). Findings: Between May 21, 2021 and April 15, 2022, 75 patients with a median age of 9.1 years (IQR 6.2-12.2) were included in the intention-to-treat population (37 in the methylprednisolone group and 38 in the intravenous immunoglobulin group). During follow-up, the incidence of abnormal left ventricular systolic function, coronary artery aneurysms (CAA), and other signs of inflammation were comparable in both groups. However, we detected cardiac abnormalities with low incidence and a mild degree grade of pathology. CAAs were observed in 2/38 children (5.3%) in the IVIG group and 1/37 children (2.7%) in the methylprednisolone group at 6-month follow-up (difference proportion 0.75; 95% confidence interval (CI) -0.05 to 1.0; p = 0.39). Interpretation: Methylprednisolone alone may be an acceptable first-line treatment as left ventricular systolic dysfunction and clinical/laboratory evidence for inflammation quickly resolved in all children. However, our findings need further confirmation through larger studies as our sample size is likely to be of insufficient power to address rare clinically relevant adverse outcomes. Funding: NOMIS, Vontobel, and Gaydoul Foundation.

Assessing vaccine-induced immunity against pneumococcus, hepatitis A and B over a 9-year follow-up in pediatric liver transplant recipients: A nationwide retrospective study.

Pediatric liver transplant recipients are particularly at risk of infections. The most cost-effective way to prevent infectious complications is through vaccination, which can potentially prevent infections due to hepatitis B (HBV) virus, hepatitis A virus (HAV), and invasive pneumococcal diseases. Here, we performed a retrospective analysis of HBV, HAV, and pneumococcal immunity in pediatric liver transplant recipients between January 1, 2009, and December 31, 2020, to collect data on immunization and vaccine serology. A total of 94% (58/62) patients had available vaccination records. At transplant, 90% (45/50) were seroprotected against HBV, 63% (19/30) against HAV, and 78% (18/23) had pneumococcal immunity, but immunity against these 3 pathogens remained suboptimal during the 9-year follow-up. A booster vaccine was administered to only 20% to 40% of patients. Children who had received >4 doses of HBV vaccine and > 2 doses of HAV vaccine pretransplant displayed a higher overall seroprotection over time post-solid organ transplant. Our findings suggest that a serology-based approach should be accompanied by a more systematic follow-up of vaccination, with special attention paid to patients with an incomplete vaccination status at time of transplant.

Influence of Timing of Maternal Pertussis Immunization on the Avidity of Transferred Antibodies in Term and Preterm Neonates.

The timing of maternal pertussis vaccination influences the titers of cord-blood anti-pertussis antibodies. Whether it affects their avidity is unknown. We demonstrate in 298 term and 72 preterm neonates that antibody avidity is independent of the timing of maternal vaccination, whether comparing second with third trimester or intervals before birth.

Antibody response in children with multisystem inflammatory syndrome related to COVID-19 (MIS-C) compared to children with uncomplicated COVID-19.

Objectives: To comprehensively analyze the quality of the antibody response between children with Multisystem inflammatory syndrome (MIS-C) and age-matched controls at one month after SARS-CoV-2 exposure, and infected in the same time-period. Methods: Serum from 20 MIS-C children at admission, and 14 control children were analyzed. Antigen specific antibody isotypes and subclasses directed against various antigens of SARS-CoV-2 as well as against human common coronavirus (HCoVs) and commensal or pathogenic microorganisms were assessed by a bead-based multiplexed serological assay and by ELISA. The functionality of these antibodies was also assessed using a plaque reduction neutralization test, a RBD-specific avidity assay, a complement deposition assay and an antibody-dependent neutrophil phagocytosis (ADNP) assay. Results: Children with MIS-C developed a stronger IgA antibody response in comparison to children with uncomplicated COVID-19, while IgG and IgM responses are largely similar in both groups. We found a typical class-switched antibody profile with high level of IgG and IgA titers and a measurable low IgM due to relatively recent SARS-CoV-2 infection (one month). SARS-CoV-2-specific IgG antibodies of MIS-C children had higher functional properties (higher neutralization activity, avidity and complement binding) as compared to children with uncomplicated COVID-19. There was no difference in the response to common endemic coronaviruses between both groups. However, MIS-C children had a moderate increase against mucosal commensal and pathogenic strains, reflecting a potential association between a disruption of the mucosal barrier with the disease. Conclusion: Even if it is still unclear why some children develop a MIS-C, we show here that MIS-C children produce higher titers of IgA antibodies, and IgG antibodies with higher functionality, which could reflect the local gastro-intestinal mucosal inflammation potentially induced by a sustained SARS-CoV-2 gut infection leading to continuous release of SARS-CoV-2 antigens.

Human germline heterozygous gain-of-function STAT6 variants cause severe allergic disease.

STAT6 (signal transducer and activator of transcription 6) is a transcription factor that plays a central role in the pathophysiology of allergic inflammation. We have identified 16 patients from 10 families spanning three continents with a profound phenotype of early-life onset allergic immune dysregulation, widespread treatment-resistant atopic dermatitis, hypereosinophilia with esosinophilic gastrointestinal disease, asthma, elevated serum IgE, IgE-mediated food allergies, and anaphylaxis. The cases were either sporadic (seven kindreds) or followed an autosomal dominant inheritance pattern (three kindreds). All patients carried monoallelic rare variants in STAT6 and functional studies established their gain-of-function (GOF) phenotype with sustained STAT6 phosphorylation, increased STAT6 target gene expression, and TH2 skewing. Precision treatment with the anti-IL-4Rα antibody, dupilumab, was highly effective improving both clinical manifestations and immunological biomarkers. This study identifies heterozygous GOF variants in STAT6 as a novel autosomal dominant allergic disorder. We anticipate that our discovery of multiple kindreds with germline STAT6 GOF variants will facilitate the recognition of more affected individuals and the full definition of this new primary atopic disorder.

Methylprednisolone versus intravenous immunoglobulins in children with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS): an open-label, multicentre, randomised trial.

BACKGROUND: The emergence of paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) led to the widespread use of anti-inflammatory treatments in the absence of evidence from randomised controlled trials (RCTs). We aimed to assess the effectiveness of intravenous methylprednisolone compared with intravenous immunoglobulins. METHODS: This is an open-label, multicentre, two-arm RCT done at ten hospitals in Switzerland in children younger than 18 years hospitalised with PIMS-TS (defined as age <18 years; fever and biochemical evidence of inflammation, and single or multiorgan dysfunction; microbiologically proven or putative contact with SARS-CoV-2; and exclusion of any other probable disease). Patients were randomly assigned 1:1 to intravenous methylprednisolone (10 mg/kg per day for 3 days) or intravenous immunoglobulins (2 g/kg as a single dose). The primary outcome was length of hospital stay censored at day 28, death, or discharge. Secondary outcomes included proportion and duration of organ support. Analyses were done by intention-to-treat. The study was registered with Swiss National Clinical Trials Portal (SNCTP000004720) and ClinicalTrials.gov (NCT04826588). FINDINGS: Between May 21, 2021, and April 15, 2022, 75 patients with a median age of 9·1 years (IQR 6·2-12·2) were included in the intention-to-treat population (37 in the methylprednisolone group and 38 in the intravenous immunoglobulins group). The median length of hospital stay was 6·0 days (IQR 4·0-8·0) in the methylprednisolone group and 6·0 days (IQR 5·0-8·8) in the intravenous immunoglobulins group (estimated effect size -0·037 of the log10 transformed times, 95% CI -0·13 to 0·065, p=0·42). Fewer patients in the methylprednisolone group (ten [27%] of 37) required respiratory support compared with the intravenous immunoglobulin group (21 [55%] of 38, p=0·025). Need and duration of inotropes, admission to intensive care units, cardiac events after baseline, and major bleeding and thrombotic events were not significantly different between the study groups. INTERPRETATION: In this RCT, treatment with methylprednisolone in children with PIMS-TS did not significantly affect the length of hospital stay compared with intravenous immunoglobulins. Intravenous methylprednisolone could be an acceptable first-line treatment in children with PIMS-TS. FUNDING: NOMIS Foundation, Vontobel Foundation, and Gaydoul Foundation.

[Which immunological pathologies are targeted by precision medicine?] / Quelles pathologies immunologiques sont ciblées par la médecine de précision ?

Pediatric immune disorders encompass an array of disorders with either a systemic or tissue-specific expression, whose phenotype and therapeutic approach often depend on age. More recently, genotypic traits and knowledge of the underlying pathophysiological processes have facilitated a more individualized clinical approach. Molecular characterization in primary immune disorders has provided molecular targets for immunotherapies. In immune-mediated disorders of the CNS, better recognition of pediatric characteristics has enabled earlier diagnosis and treatment initiation. For rhumatismal disorders, like all rare immune disorders, the setting up of multi-centre registers and collaborative studies provide the framework for targeted clinical strategies.

Les maladies immunologiques en pédiatrie représentent un vaste répertoire de maladies à expression systémique ou ciblée, dont le phénotype et l'approche thérapeutique varient selon l'âge mais aussi, dernièrement, des données apportées par le génotypage et la pathologie sous-jacente. La caractérisation moléculaire des déficits immunitaires primaires a permis d'y appliquer une thérapie ciblée sur les voies défectueuses impliquées. Dans les atteintes immunologiques du SNC, la reconnaissance des caractéristiques à l'âge pédiatrique permet d'appliquer une intervention thérapeutique précoce et ciblée pour minimiser le cumul d'invalidité. Pour les maladies rhumatismales, comme pour toutes ces maladies immunologiques rares, l'élaboration de registres et des projets multicentriques permettent de définir les stratégies cliniques pratiques.

Autoantibodies to a Nodal Isoform of Neurofascin in Pediatric Chronic Inflammatory Demyelinating Polyneuropathy.

Pediatric chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired immune-mediated disorder of the peripheral nervous system with a number of diagnostic pitfalls. A subset of treatment-resistant CIDP adult patients have been found with antibodies against paranodal proteins. We report the first pediatric case in a 14 year-old adolescent with a severe CIDP phenotype in whom positive anti-neurofascin 155 antibodies were found in his serum. Resistant to conventional therapies, he showed dramatic improvement when treated with Rituximab with mild to moderate functional motor disability at 24 month follow-up. In pediatric CIDP patients that remain refractory to conventional treatments, the presence of antibodies to paranodal proteins warrants investigation as it can have potential therapeutic guidance.

Novel approaches to reactivate pertussis immunity.

INTRODUCTION: Whole cell and acellular pertussis vaccines have been very effective in decreasing the deaths of neonates and infants from Bordetella pertussis. Despite high vaccine coverage worldwide, pertussis remains one of the most common vaccine-preventable diseases, thus suggesting that new pertussis vaccination strategies are needed. Several candidates are currently under development, such as acellular pertussis vaccines that use genetically detoxified pertussis toxin, acellular pertussis vaccines delivered with new adjuvants or new delivery systems, or an intranasally delivered, live attenuated vaccine. AREAS COVERED: This review discusses the different possibilities for improving current pertussis vaccines and the present state of knowledge on the pertussis vaccine candidates under development. EXPERT OPINION: Until there is a safe, effective, and affordable alternative to the two types of existing vaccines, we should maintain sufficient childhood coverage and increase the vaccination of pregnant women, adolescents, and young adults.

Multicenter Randomized Trial of Methylprednisolone vs. Intravenous Immunoglobulins to Treat the Pediatric Inflammatory Multisystem Syndrome-Temporally Associated With SARS-CoV-2 (PIMS-TS): Protocol of the Swissped RECOVERY Trial.

Introduction: In 2020, a new disease entitled Pediatric Inflammatory Multisystem Syndrome temporally associated with COVID-19 (PIMS-TS), or Multisystem Inflammatory Syndrome in Children (MIS-C), emerged, with thousands of children affected globally. There is no available evidence based on randomized controlled trials (RCT) to date on the two most commonly used immunomodulatory treatments, intravenous immunoglobulins (IVIG) and corticosteroids. Therefore, the Swissped RECOVERY trial was conducted to assess whether intravenous (IV) methylprednisolone shortens hospital length of stay compared with IVIG. Methods and Analysis: Swissped RECOVERY is an ongoing investigator-initiated, open-label, multicenter two-arm RCT in children and adolescents <18 years hospitalized with a diagnosis of PIMS-TS. The trial is recruiting at 10 sites across Switzerland. Patients diagnosed with PIMS-TS are randomized 1:1 to methylprednisolone IV (10 mg/kg/day for 3 days) or IVIG (2 g/kg as a single dose). The primary outcome is hospital length of stay censored at day 28, death, or discharge (whichever is first). The target total sample size is ~80 patients 1:1 randomized to each study arm. Ancillary and exploratory studies on inflammation, vaccination acceptance and coverage, long-term outcomes, and healthcare costs are pre-planned. Significance: Currently, robust trial evidence for the treatment of PIMS-TS is lacking, with a controversy surrounding the use of corticosteroids vs. IVIG. This trial will provide evidence for the effectiveness and safety of these two treatments. Ethics and Dissemination: The study protocol, which was designed based on the U.K. RECOVERY trial, the patient information and consent forms, and other study-specific study documents were approved by the local ethics committees (Project ID: 2021-00362). Registration Details: The study is registered on the Swiss National Clinical Trials Portal (SNCTP000004720) and Clinicaltrials.gov (NCT04826588).

Evaluation of rotavirus vaccine administration among a 22q11.2DS patient population.

BACKGROUND: 22q11.2 Deletion Syndrome (22q11.2DS) can result in array of congenital abnormalities including immune dysfunction. International guidelines recommend immune evaluation of 22q11.2DS patients prior to live vaccine administration. A rotavirus vaccination program for infants aged 2 and 4 months was implemented in British Columbia (BC) in 2012. Adherence to immune workup recommendations prior to 2 months of age in patients with 22q11.2DS and adverse events following immunization is not known. METHODS: A retrospective chart review of children diagnosed with 22q11.2DS in BC from January 1, 2012 to January 1, 2019 was conducted. Demographic, clinical, laboratory, immunization data and adverse reactions to vaccines were obtained. International guidelines were used as a reference for adherence to immunologic workup recommendations. RESULTS: Forty-two children with 22q11.2DS were included. Immunization records were available for 39 children, and 22 (52.3%) received at least one dose of a live rotavirus vaccine. No adverse events following immunization were noted in clinical records. While 25 out of 27 (92.6%) of patients who received an immunological workup had a CD4 + lymphocyte count to qualify for safe administration of a live vaccination, only 12 (44%) received the Rotavirus vaccine. Of 22 infants diagnosed with 22q11.DS prior to 8 weeks of age, only ten (45.5%) received an immune workup before the rotavirus vaccine. CONCLUSIONS: The majority of our infant cohort did not receive medical care consistent with international 22q11.2DS vaccination and immunological surveillance recommendations. More effective dissemination of 22q11.2DS guidelines and improved immunological assessment for infants with 22q11.2DS in BC is necessary.

Fitness of B-Cell Responses to SARS-CoV-2 WT and Variants Up to One Year After Mild COVID-19 - A Comprehensive Analysis.

Objective: To comprehensively evaluate SARS-CoV-2 specific B-cell and antibody responses up to one year after mild COVID-19. Methods: In 31 mildly symptomatic COVID-19 participants SARS-CoV-2-specific plasmablasts and antigen-specific memory B cells were measured by ELISpot. Binding antibodies directed against the proteins spike (S), domain S1, and nucleocapsid (N) were estimated using rIFA, ELISA, and commercially available assays, and avidity measured using thiocyanate washout. Neutralizing antibodies against variants of concern were measured using a surrogate-neutralization test. Results: Plasmablast responses were assessed in all participants who gave sequential samples during the first two weeks after infection; they preceded the rise in antibodies and correlated with antibody titers measured at one month. S1 and N protein-specific IgG memory B-cell responses remained stable during the first year, whereas S1-specific IgA memory B-cell responses declined after 6 months. Antibody titers waned over time, whilst potent affinity maturation was observed for anti-RBD antibodies. Neutralizing antibodies against wild-type (WT) and variants decayed during the first 6 months but titers significantly increased for Alpha, Gamma and Delta between 6 months and one year. Therefore, near-similar titers were observed for WT and Alpha after one year, and only slightly lower antibody levels for the Delta variant compared to WT. Anti-RBD antibody responses correlated with the neutralizing antibody titers at all time points, however the predicted titers were 3-fold lower at one year compared to one month. Conclusion: In mild COVID-19, stable levels of SARS-CoV-2 specific memory B cells and antibodies neutralizing current variants of concern are observed up to one year post infection. Care should be taken when predicting neutralizing titers using commercial assays that measure binding antibodies.

Endothelial glycocalyx degradation in multisystem inflammatory syndrome in children related to COVID-19.

Multisystem inflammatory syndrome in children (MIS-C) represents a rare but severe complication of severe acute respiratory syndrome coronavirus 2 infection affecting children that can lead to myocardial injury and shock. Vascular endothelial dysfunction has been suggested to be a common complicating factor in patients with coronavirus disease 2019 (COVID-19). This study aims to characterize endothelial glycocalyx degradation in children admitted with MIS-C. We collected blood and urine samples and measured proinflammatory cytokines, myocardial injury markers, and endothelial glycocalyx markers in 17 children admitted with MIS-C, ten of which presented with inflammatory shock requiring intensive care admission and hemodynamic support with vasopressors. All MIS-C patients presented signs of glycocalyx deterioration with elevated levels of syndecan-1 in blood and both heparan sulfate and chondroitin sulfate in the urine. The degree of glycocalyx shedding correlated with tumor necrosis factor-α concentration. Five healthy age-matched children served as controls. Patients with MIS-C presented severe alteration of the endothelial glycocalyx that was associated with disease severity. Future studies should clarify if glycocalyx biomarkers could effectively be predictive indicators for the development of complications in adult patients with severe COVID-19 and children with MIS-C. KEY MESSAGES : Children admitted with MIS-C presented signs of endothelial glycocalyx injury with elevated syndecan-1 and heparan sulfate level. Syndecan-1 levels were associated with MIS-C severity and correlated TNF-α concentration. Syndecan-1 and heparan sulfate may represent potential biomarkers for patients with severe COVID-19 or MIS-C.

Childhood-Onset Movement Disorders Can Mask a Primary Immunodeficiency: 6 Cases of Classical Ataxia-Telangiectasia and Variant Forms.

Ataxia-telangiectasia (A-T) is a neurodegenerative and primary immunodeficiency disorder (PID) characterized by cerebellar ataxia, oculocutaneous telangiectasia, immunodeficiency, progressive respiratory failure, and an increased risk of malignancies. It demands specialized care tailored to the individual patient's needs. Besides the classical ataxia-telangiectasia (classical A-T) phenotype, a variant phenotype (variant A-T) exists with partly overlapping but some distinctive disease characteristics. Here we present a case series of 6 patients with classical A-T and variant A-T, which illustrates the phenotypic variability of A-T that can present in childhood with prominent extrapyramidal features, with or without cerebellar ataxia. We report the clinical data, together with a detailed genotype description, immunological analyses, and related expression of the ATM protein. We show that the presence of some residual ATM kinase activity leads to the clinical phenotype variant A-T that differs from the classical A-T. Our data illustrate that the diagnosis of the variant form of A-T can be delayed and difficult, while early recognition of the variant form as well as the classical A-T is a prerequisite for providing a correct prognosis and appropriate rehabilitation and support, including the avoidance of diagnostic X-ray procedures, given the increased risk of malignancies and the higher risk for side effects of subsequent cancer treatment.

Meningitis Caused by the Live Varicella Vaccine Virus: Metagenomic Next Generation Sequencing, Immunology Exome Sequencing and Cytokine Multiplex Profiling.

Varicella vaccine meningitis is an uncommon delayed adverse event of vaccination. Varicella vaccine meningitis has been diagnosed in 12 children, of whom 3 were immunocompromised. We now report two additional cases of vaccine meningitis in twice-immunized immunocompetent children and we perform further testing on a prior third case. We used three methods to diagnose or investigate cases of varicella vaccine meningitis, none of which have been used previously on this disease. These include metagenomic next-generation sequencing and cytokine multiplex profiling of cerebrospinal fluid and immunology exome analysis of white blood cells. In one new case, the diagnosis was confirmed by metagenomic next-generation sequencing of cerebrospinal fluid. Both varicella vaccine virus and human herpesvirus 7 DNA were detected. We performed cytokine multiplex profiling on the cerebrospinal fluid of two cases and found ten elevated biomarkers: interferon gamma, interleukins IL-1RA, IL-6, IL-8, IL-10, IL-17F, chemokines CXCL-9, CXCL-10, CCL-2, and G-CSF. In a second new case, we performed immunology exome sequencing on a panel of 356 genes, but no errors were found. After a review of all 14 cases, we concluded that (i) there is no common explanation for this adverse event, but (ii) ingestion of an oral corticosteroid burst 3-4 weeks before onset of vaccine meningitis may be a risk factor in some cases.