Pathologic Analysis of Twenty-one Appendices From Children With Multisystem Inflammatory Syndrome Compared to Specimens of Acute Appendicitis: A Cross-sectional Study.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a rare, severe complication of coronavirus disease 2019, commonly involving the gastrointestinal tract. Some children with MIS-C undergo appendectomy before the final diagnosis. There are several hypotheses explaining the pathomechanism of MIS-C, including the central role of the viral antigen persistence in the gut, associated with lymphocyte exhaustion. We aimed to examine appendectomy specimens from MIS-C patients and assess their pathologic features, as well as the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens. METHODS: In this cross-sectional study we included 21 children with MIS-C who underwent appendectomy. The control group included 21 sex- and age-matched children with acute appendicitis (AA) unrelated to SARS-CoV-2 infection. Histologic evaluation of appendiceal specimens included hematoxylin and eosin staining and immunohistochemical identification of lymphocyte subpopulations, programmed cell death protein-1 (PD-1) and SARS-CoV-2 nucleocapsid antigen. RESULTS: Appendices of MIS-C patients lacked neutrophilic infiltrate of muscularis propria typical for AA (14% vs. 95%, P < 0.001). The proportion of CD20+ to CD5+ cells was higher in patients with MIS-C (P = 0.04), as was the proportion of CD4+ to CD8+ (P < 0.001). We found no proof of SARS-CoV-2 antigen presence, nor lymphocyte exhaustion, in the appendices of MIS-C patients. CONCLUSIONS: The appendiceal muscularis of patients with MIS-C lack edema and neutrophilic infiltration typical for AA. SARS-CoV-2 antigens and PD-1 are absent in the appendices of children with MIS-C. These findings argue against the central role of SARS-CoV-2 persistence in the gut and lymphocyte exhaustion as the major triggers of MIS-C.

COVID-19 mRNA BNT162b2 vaccine immunogenicity among children with a history of paediatric multisystem inflammatory syndrome temporally associated with COVID-19 (PIMS-TS).

We conducted a prospective cohort study of 20 patients with a history of paediatric multisystem inflammatory syndrome temporally associated with COVID-19 (PIMS group, median age seven years, 70% male) and 34 healthy controls without such a history (CONTROL group, median age eight years, 38% male) aged 5-12 years, to assess the immunogenicity of Pfizer-BioNTech COVID-19 mRNA BNT162b2 vaccine (Comirnaty®). Patients received two doses of COVID-19 mRNA BNT162b2 vaccine (10 ug/dose) 21 days apart. Pre-vaccine anti-S SARS-CoV-2 IgG antibodies were measured on the day of the first dose and at the median of 23 days after the second dose. The study was conducted during the COVID-19 wave dominated by the Omicron variant of the virus. Anti-NCP SARS-CoV-2 IgG antibodies were measured twice to evaluate incidents of infection during the study period. Pre-vaccine quantification of both types of antibodies allowed us to differentiate patients into COVID-19 naive and previously infected in order to compare hybrid immunity with vaccine-induced immunity. Before vaccination, anti-S IgG serum geometric mean concentration (GMC) was 61.17 BAU/ml in the PIMS group and 24.97 in the CONTROL group, while post-vaccination GMC was 3879.14 BAU/ml and 3704.87 BAU/ml, respectively, and did not significantly differ between the groups. Hybrid immunity (regardless of PIMS history) resulted in a higher concentration of SARS-CoV-2 anti-S antibodies after vaccination. Four (20%) of the children in the PIMS group and 11 (32%) in the CONTROL group got infected with SARS-CoV-2 during the study period, yet all of them asymptomatically, and this event has not significantly altered post-vaccination anti-S titers. In conclusion, COVID-19 vaccination was highly immunogenic in children, including those with a history of PIMS-TS; hybrid immunity overperforms vaccine-induced immunity in terms of serological response in children. However, vaccination effectiveness in preventing SARS-CoV-2 infections in children should be further evaluated.

COVID-19 mRNA BNT162b2 vaccine safety and B-cell and T-cell reactogenicity among children with a history of paediatric multisystem inflammatory syndrome temporally associated with COVID-19 (PIMS-TS) - preliminary study.

To assess the safety of Pfizer-BioNTech COVID-19 mRNA BNT162b2 vaccine (Comirnaty®) among patients with the anamnesis of paediatric inflammatory syndrome temporally associated with COVID-19 (PIMS-TS), we conducted a prospective cohort study of 21 patients with history of PIMS (PIMS group, median age 7.4 years, 71% male) and 71 healthy controls without such an anamnesis (CONTROL group, median age 9.0 years, 39% male) aged 5-18 years. Among them, 85 patients (all PIMS patients and 64 CONTROL patients) completed the two dose schedule of vaccination administered 21 days apart and 7 children in the CONTROL group received a single, age appropriate dose of a COVID-19 mRNA BNT162b2 vaccine during the study period. The frequency and character of reported adverse events (AEs) after each dose and results of flow cytometry (FC) 3 weeks after a second dose were compared between those groups. COVID-19 mRNA BNT162b2 vaccine safety profile was very good and comparable in both groups. No severe AEs were observed. 30% of all patients reported some general AE after any vaccine dose and 46% - some local AE. Frequency of reported AEs did not differ between groups except for local hardening at injection site, more common in PIMS group (20% vs 4% after any vaccine dose, p = 0,02). All AEs were benign, general AEs lasted up to 5 days and localised - up to 6 days after a vaccine dose. COVID-19 mRNA BNT162b2 vaccine did not induce any PIMS-like symptoms in any patient. We did not observe any significant T cells or B cells subset abnormalities in the PIMS group compared to the CONTROL group three weeks after a second dose except for terminally differentiated effector memory T cells that were higher in PIMS group (p < 0.0041). To sum up COVID-19 mRNA BNT162b2 vaccine in children with PIMS-TS was safe. Further studies are required to support our findings.

Pneumonia hospitalizations of children aged <2 years in Poland before (2013-2016) and after (2017-2018) universal mass vaccination with 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine.

As infection with Streptococcus pneumoniae is an important cause of pneumonia in children, the World Health Organization recommends childhood pneumococcal conjugate vaccines (PCVs). In January 2017, PCV universal mass vaccination (UMV) was introduced in Poland for children aged <2 years. The objective of this study was to estimate and describe the trends in the incidences of various types of pneumonia hospitalizations in Poland before (2013-2016) and after (2017-2018) introduction of the UMV program. The study was conducted at the regional hospitals of Opole and Bialystok and included all hospitalized children aged <2 years with a primary or secondary diagnosis of pneumonia in their electronic medical records. Pneumonia diagnoses were identified based on International Classification of Diseases 10th revision (ICD-10) codes for bacterial, viral, and other/unknown-cause pneumonias. The effect of the implementation of PCV UMV was modeled via an inferential multivariate model. Among 4,168 children included in the study, 64.3% were admitted before PCV UMV. The number of radiograph-confirmed likely bacterial pneumonia cases varied between 55 and 176 cases per 100,000 person-years, and no trend was observed over time. However, inferential modeling showed statistically significant decreasing trends in the incidence rates of bacterial-coded pneumonia (28.48%), viral-coded pneumonia (35.36%), all-cause pneumonia (24.60%), and radiograph-confirmed likely non-bacterial pneumonia (24.98%) among children eligible for UMV. This might be the first indication of the impact of the PCV UMV program in Poland.

What is the context? Infection with the bacteria Streptococcus pneumoniae is a key cause of pneumonia in children worldwide.Pneumococcal vaccines are available to help prevent this infection.In 2017, a pneumococcal vaccination program was introduced in Poland, free of charge for children aged less than 2 years.The impact of this vaccination program on the incidence of pneumonia hospitalizations is unknown.What is new? This study evaluated the incidence of pneumonia hospitalizations in children following the implementation of the vaccination program (2017-2018) and compared it with the incidence before implementation (2013-2016).The study was carried out in two regional hospitals and included all children aged less than 2 years hospitalized with pneumonia.Pneumonia cases were identified using International Classification of Diseases codes and bacterial cases were confirmed with chest x-rays.During the 2 years after the vaccination program was introduced, we observed:No clear trend in the incidence of bacterial pneumonia confirmed by chest x-ray.A statistically significant decline in the likelihood of developing other types of pneumonia among children eligible for the pneumococcal vaccination program.The incidence of pneumonia was higher in children from the region of Opole and for those who were admitted to hospital in winter and at a younger age.What is the impact? Pneumococcal vaccination might reduce the number of pneumonia hospitalizations. However, more research is needed to confirm these results.

Influenza and Other Prophylactic Vaccination Coverage in Polish Adult Patients Undergoing Allergen Immunotherapy-A Survey Study among Patients and Physicians.

Vaccines against infectious diseases may raise safety concerns in patients undergoing allergen immunotherapy (AIT). The objective of our study was to investigate influenza vaccine and other selected prophylactic vaccines coverage in patients treated with AIT and the attitude of physicians towards vaccinations in this group of patients. We conducted a questionnaire-based study among patients undergoing AIT and physicians. The patients' survey evaluated influenza and other prophylactic vaccines coverage. The physicians' survey assessed their experience and opinions on prophylactic vaccinations during AIT. In total, 176 patients (aged 18−79 years) and 120 doctors filled the questionnaires. Patients were assigned to two groups­inhaled allergens group (n = 101) and insect venoms group (n = 68). The number of patients who received any dose (36% and 45%, p = 0.26), as well as two or more doses (17% and 22%, p = 0.43) of influenza vaccine was comparable between two groups. However, in both groups there was a significant (p < 0.0001) decrease in influenza vaccine uptake after the beginning of AIT. Patients from the inhaled allergens group declared a higher tetanus vaccine rate (41% vs. 19%, p = 0.004). The groups did not differ in the pneumococcal and tick-borne encephalitis vaccination coverage. A majority of doctors believe that prophylactic vaccinations in patients undergoing AIT are safe and effective (96% and 94%, respectively); however, as many as 87% of them identify with the need to create clear recommendations regarding vaccinating patients undergoing AIT. Prophylactic vaccine coverage is not satisfactory among Polish adult patients undergoing AIT. Polish doctors are convinced of the validity of prophylactic vaccinations during AIT.

D-dimer concentrations in acute urticaria in children.

INTRODUCTION: Urticaria is a clinical entity presenting as wheals, angioedema, or both simultaneously. Elevated D-dimer levels were reported in the course of chronic spontaneous urticaria. Data regarding D-dimer levels in acute urticaria in children are limited. OBJECTIVES: To assess potential associations between duration of glucocorticosteroid (GCS) therapy and D-dimer concentrations in children with acute urticaria. PATIENTS, MATERIALS, AND METHODS: Hospital records of 106 children (59 females), aged 5.57 ± 4.91 years, hospitalized in 2014-2018 were analyzed retrospectively. The study group consisted of pediatric patients admitted to the hospital due to severe acute urticaria resistant to antihistaminic treatment that was ordered in the ambulatory care (out-patient clinic). Patients were divided into subgroups: no GCS treatment, short-duration treatment (up to 5 days) and long-duration treatment (6 and more days) GCS treatment. Simultaneously, patients received antihistaminic drugs. D-dimer level and other inflammatory factors such as white blood cell (WBC) count, platelet (PLT) count, and C-reactive protein (CRP) in each group were analyzed. RESULTS: The D-dimer level was elevated in 51% of cases. In the subgroup with longer GCS treatment, D-dimer concentration was significantly higher in comparison to patients with a shorter GCS course. There were no differences in the distribution of CRP, PLT, and WBC concentrations between these subgroups. CONCLUSIONS: In the studied group of children, there was a tendency for higher D-dimer levels in patients, who required a longer GCS treatment. This finding is hypothesis-generating and requires further investigation to confirm if D-dimers can be used as a prognostic factor in acute urticaria in children.

[Could Legionella pneumophila infection cause bronchial hyperreactivity]. / Czy przyczyna nadreaktywnosci oskrzeli u dzieci moglo byc zakazenie Legionella pneumophila.

11 children with bronchial hyperreactivity were tested for Legionella pneumophila serotype 1 and 2-14, including 3 girls, who were treated a year before because of atypical pneumonia, probably caused by Legionella pneumophila, 2 brothers of the girls and 6 children from a different village as well as 5 adults--parents of the girls. In all of them a significant level of antibodies against Legionella pneumophila serotype 2-14 was detected with indirect immunofluorescence. One of previously treated girls presented with increased level of IgG antibodies (ELISA), the remaining two had increased levels of IgA against Legionella pneumophila serotype 1. Other patients in the group presented no IgM, IgA or IgG against Legionella pneumophila serotype 1. Patients with bronchial hypersensitivity received clarithromycin and inhalation steroids with good clinical effect.