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Background: PIMS-TS (pediatric inflammatory multisystem syndrome-temporally associated with SARS-CoV-2) is a rare but serious condition in children following SARS-CoV-2 infection, characterized by a range of clinical symptoms with varying severity. Understanding risk factors for severe PIMS-TS is crucial for appropriate and timely intervention., Objective: To identify factors associated with increased PIMS-TS severity in children., Methods: In this nationwide prospective observational study, epidemiological and clinical data was collected from children <18 years of age with suspected or confirmed PIMS-TS from all 29 pediatric hospitals in Switzerland. Children were categorized into 3 groups according to admission to intensive care unit (ICU): non-ICU, ICU-moderate and ICU-severe, defined as requirement of invasive ventilation and/or inotropic support., Results: A total of 204 children were included; 99 (49%) were categorized as non-ICU, 50 (25%) as ICU-moderate and 55 (27%) as ICU-severe. In ICU-severe cases, respiratory and neurological symptoms were more frequent compared with non-ICU cases: 72% versus 47%, P < 0.001 and 66% versus 41%, P = 0.001, respectively. Compared with the non-ICU group, children in the ICU-severe group had lower lymphocyte counts, higher neutrophil-lymphocyte ratios, lower platelet counts, as well as higher C-reactive protein, N-terminal pro-B-type natriuretic peptide, troponin T and creatinine levels at admission. Lymphopenia and elevated troponin T levels at admission were associated with an increased risk of being in the ICU-severe group., Conclusion: The severity of PIMS-TS may be predicted using clinical symptoms and laboratory biomarkers, which help clinicians in decision-making and management of patients., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

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., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: A previous study showed that investigation of children with invasive pneumococcal disease (IPD) revealed an immunodeficiency in up to 10% of cases. Following this report, we implemented a protocol to investigate children with IPD, to assess the proportion with an immunodeficiency in our setting., Methods: We retrospectively identified patients who presented with IPD from January 2015 to November 2020 and collected data from medical records. Immunological investigations included complement C3 and C4 levels, classical and alternative pathway complement function, IgG, IgA and IgM levels, specific IgG levels (H. influenza B, tetanus and pneumococcal serotypes), peripheral blood film, lymphocyte subsets, and CD62L-shedding upon activation with Toll-like receptor-agonists in selected cases., Results: We identified a total of 68 children with IPD, with a mortality of 6%. Immunological investigations were performed in 51 children. Four children (8%) had abnormal findings that were deemed of clinical significance. Two children had complement deficiencies (Factor I and C2 deficiency), one child had specific antibody deficiency, and another child had low IgM, low NK-cells and poor persistence of serotype-specific anti-pneumococcal IgG concentrations. Of the 17 children with IPD who were not tested for immunodeficiencies, 4 died and four had possible explanations for the infection., Conclusions: We identified clinically relevant abnormal immunological findings in 4/51 (8%) of children with IPD. Our results support the recommendation to perform immunological investigations in children with IPD, since this might reveal underlying immunodeficiencies, allowing for necessary preventive measures and close follow-up., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Immunization site pain is a common and unpleasant experience for both children and adults. It is a source of anxiety and distress and may ultimately result in nonadherence to vaccination schedules. There is limited information on how different brands of vaccines affect the intensity of immediate pain at the time of vaccine injection., Methods: Children in the United Kingdom (n = 178) were randomized to receive a booster dose of either the 10- or the 13-valent pneumococcal conjugate vaccine (PCV-10 or PCV-13). Immediate immunization site pain was assessed using validated pain assessment tools and crying time to investigate factors that may interfere with parental compliance to vaccination., Results: Pain measurements were available for n ≥ 74 and n ≥ 78 PCV-10 and PCV-13 recipients, respectively. PCV-13 recipients had significantly higher scores on the observer-rated modified behavioral pain scale than did those receiving PCV-10. No significant differences in the induction of pain between the 2 vaccines were found when a parent-rated pain assessment tool or crying time was used., Conclusions: PCV-10 administration was associated with slightly less acute pain compared with the injection of PCV-13, but the size of the difference was small and is of unknown clinical significance.

Background: Vaccine-induced immunity against pneumococcal infection relies on the generation of high concentrations of antibody and B cell memory. Both the 10- and the 13-valent pneumococcal conjugate vaccines (PCV-10 and PCV-13) effectively reduce disease caused by vaccine serotypes. It is unknown whether the generation of B cell memory requires several doses of the same vaccine or whether different PCVs are interchangeable., Methods: Children in the United Kingdom (n=178) who had previously received PCV-13 at 2 and 4 months were randomized 1:1 to receive a PCV-13 or PCV-10 booster at age 12 months. Peripheral blood memory B cells (BMEM) were quantified before and at 1 and 12 months after vaccination using a cultured enzyme-linked immunospot assay for pneumococcal serotypes 1, 3, 4, 9V, 14, 19A, and diphtheria and tetanus toxoid. Correlations between BMEM frequencies and simultaneously measured antibody (IgG and opsonophagocytic assay) was also assessed., Results: A significant rise in postbooster BMEM frequency was seen for 5 out of 6 serotypes in the PCV-13 group and none in the PCV-10 group. In the PCV-13 group, there was a particularly large increase in serotype 3-specific BMEM associated with only a small increase in antibody. Postbooster BMEM responses correlated positively with antibody, but correlations between prebooster BMEM and subsequent BMEM and antibody responses were inconsistent., Conclusions: After priming with PCV-13 in early infancy, a booster dose of PCV-10 does not induce detectable peripheral blood BMEM responses but a PCV-13 booster does induce robust responses. Booster responses to PCVs may be dependent on homologous carrier protein priming.

Background: Both the 13- and 10-valent pneumococcal conjugate vaccines (PCV-13; PCV-10) are immunogenic and effective against vaccine-type pneumococcal disease when given to young children. However, limited data are available regarding the interchangeability of these 2 vaccines., Methods: UK children (n = 178) who had previously been vaccinated with PCV-13 at 2 and 4 months were randomized to receive either a PCV-13 or a PCV-10 booster at 12 months of age. PCV-13 vaccine-type antipolysaccharide serum immunoglobulin G (IgG) concentrations and opsonophagocytic assay titers were measured before and at 1 and 12 months following vaccination. The primary objective was to assess noninferiority of PCV-10 compared with PCV-13., Results: For 8 of the PCV-10 serotypes at least 97% of participants in both groups had IgG concentrations ≥0.35 µg/mL at 1 month after vaccination; inferior responses were seen for serotypes 5 and 9V following the PCV-10 compared with the PCV-13 booster. Post booster geometric mean IgG concentrations and opsonophagocytic assay titers were significantly superior for most serotypes in PCV-13 compared with PCV-10 recipients, whereas similar or inferior responses were seen for serotypes 4, 18C, and 19F. Although some increase in antibody was seen in PCV-10 recipients against the serotypes 6A and 19A (serotypes that cross-react with 6B and 19F in PCV-10, respectively) at 1-month post booster, these responses were significantly lower than in the PCV-13 group., Conclusions: In PCV-13 primed infants, a PCV-10 booster is generally less immunogenic than a PCV-13 booster. For the 3 serotypes in PCV-10 with higher antigen content and/or conjugation to diphtheria or tetanus toxoid carrier proteins, higher or similar booster responses were seen in PCV-10 recipients. Although these findings suggest that responses are generally better with a PCV-13 booster among PCV-13 primed children, the clinical significance of these differences in immunogenicity is unclear.

Skull base osteomyelitis is a rare condition in childhood and can be described according to whether it is associated with spread of infection from the middle ear (otogenic) or not (nonotogenic). Early recognition of this serious disease and prompt treatment are key to preventing extension to adjacent vascular and nervous system structures. Diagnosis can be challenging due to the variable presentation of the disease and potentially subtle radiological appearances. We present 2 cases of nonotogenic skull base osteomyelitis in childhood both affecting the clivus and review the 6 cases previously described. Both children presented with fever, headache and neck stiffness and responded well to medical management alone; detailed imaging was key to making a diagnosis.