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.

The early safety profile of simultaneous vaccination against influenza and Respiratory Syncytial Virus (RSV) in patients with high-risk heart failure.

The safety of simultaneous vaccination for Respiratory Syncytial Virus (RSV) and influenza in vulnerable high-risk heart failure (HF) patients remains unclear. In an open-label, prospective study, 105 patients received concurrent influenza (Vaxigrip Tetra, season 2023/2024, Sanofi) and RSV (Arexvy, GSK) vaccinations from September 15th to November 17th, 2023. Adverse events were collected on the fourth-day post-vaccination. Overall, the vaccination was well tolerated, with the most common reaction being injection site pain (63 %). General symptoms occurred in 33 % of patients, predominantly fatigue (23 %), myalgia (12 %), and headache (9 %). Grade 3 reactions were observed in 6 % of patients, and a few experienced temperature elevation or flu-like symptoms, managing them with antipyretics. Notably, there were no exacerbations of HF, hospitalizations, or deaths within a week post-vaccination. This study indicates the safety of simultaneous influenza and RSV vaccination in high-risk HF patients, with a low incidence of mild adverse events.

Safety and Immunogenicity of a ChAd155-Vectored Respiratory Syncytial Virus Vaccine in Infants 6-7 Months of age: A Phase 1/2 Randomized Trial.

BACKGROUND: Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infections in infants. This phase 1/2, observer-blind, randomized, controlled study assessed the safety and immunogenicity of an investigational chimpanzee-derived adenoviral vector RSV vaccine (ChAd155-RSV, expressing RSV F, N, and M2-1) in infants. METHODS: Healthy 6- to 7-month-olds were 1:1:1-randomized to receive 1 low ChAd155-RSV dose (1.5 × 1010 viral particles) followed by placebo (RSV_1D); 2 high ChAd155-RSV doses (5 × 1010 viral particles) (RSV_2D); or active comparator vaccines/placebo (comparator) on days 1 and 31. Follow-up lasted approximately 2 years. RESULTS: Two hundred one infants were vaccinated (RSV_1D: 65; RSV_2D: 71; comparator: 65); 159 were RSV-seronaive at baseline. Most solicited and unsolicited adverse events after ChAd155-RSV occurred at similar or lower rates than after active comparators. In infants who developed RSV infection, there was no evidence of vaccine-associated enhanced respiratory disease (VAERD). RSV-A neutralizing titers and RSV F-binding antibody concentrations were higher post-ChAd155-RSV than postcomparator at days 31, 61, and end of RSV season 1 (mean follow-up, 7 months). High-dose ChAd155-RSV induced stronger responses than low-dose, with further increases post-dose 2. CONCLUSIONS: ChAd155-RSV administered to 6- to 7-month-olds had a reactogenicity/safety profile like other childhood vaccines, showed no evidence of VAERD, and induced a humoral immune response. Clinical Trials Registration. NCT03636906.

Key Considerations during the Transition from the Acute Phase of the COVID-19 Pandemic: A Narrative Review.

The COVID-19 pandemic has been met with an unprecedented response from the scientific community, leading to the development, investigation, and authorization of vaccines and antivirals, ultimately reducing the impact of SARS-CoV-2 on global public health. However, SARS-CoV-2 is far from being eradicated, continues to evolve, and causes substantial health and economic burdens. In this narrative review, we posit essential points on SARS-CoV-2 and its responsible management during the transition from the acute phase of the COVID-19 pandemic. As discussed, despite Omicron (sub)variant(s) causing clinically milder infections, SARS-CoV-2 is far from being a negligible pathogen. It requires continued genomic surveillance, particularly if one considers that its future (sub)lineages do not necessarily have to be milder. Antivirals and vaccines remain the essential elements in COVID-19 management. However, the former could benefit from further development and improvements in dosing, while the seasonal administration of the latter requires simplification to increase interest and tackle vaccine hesitancy. It is also essential to ensure the accessibility of COVID-19 pharmaceuticals and vaccines in low-income countries and improve the understanding of their use in the context of the long-term goals of SARS-CoV-2 management. Regardless of location, the primary role of COVID-19 awareness and education must be played by healthcare workers, who directly communicate with patients and serve as role models for healthy behaviors.

Cardiac Involvement in Patients with Multisystem Inflammatory Syndrome in Children (MIS-C) in Poland.

Multisystem inflammatory syndrome in children (MIS-C) is an immune-mediated complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Cardiovascular system is commonly involved. Acute heart failure (AHF) is the most severe complication of MIS-C, leading to cardiogenic shock. The aim of the study was to characterise the course of MIS-C with a focus on cardiovascular involvement, based on echocardiographic (echo) evaluation, in 498 children (median age 8.3 years, 63% boys) hospitalised in 50 cities in Poland. Among them, 456 (91.5%) had cardiovascular system involvement: 190 (48.2%) of patients had (most commonly atrioventricular) valvular insufficiency, 155 (41.0%) had contractility abnormalities and 132 (35.6%) had decreased left ventricular ejection fraction (LVEF < 55%). Most of these abnormalities improved within a few days. Analysis of the results obtained from two echo descriptions (a median of 5 days apart) revealed a >10% increase in LVEF even in children with primarily normal LVEF. Lower levels of lymphocytes, platelets and sodium and higher levels of inflammatory markers on admission were significantly more common among older children with contractility dysfunction, while younger children developed coronary artery abnormality (CAA) more often. The incidence of ventricular dysfunction might be underestimated. The majority of children with AHF improved significantly within a few days. CAAs were relatively rare. Children with impaired contractility as well as other cardiac abnormalities differed significantly from children without such conditions. Due to the exploratory nature of this study, these findings should be confirmed in further studies.

Clinical Course and Severity of COVID-19 in 940 Infants with and without Comorbidities Hospitalized in 2020 and 2021: The Results of the National Multicenter Database SARSTer-PED.

This study aimed to analyze the differences in severity and clinical characteristics of COVID-19 in infants hospitalized in Poland in 2021, when the dominance of variants of concern (VOCs) alpha and delta was reported, compared to 2020, when original (wild) SARS-CoV-2 was dominant (III-IV vs. I-II waves of the pandemic, respectively). In addition, the influence of the presence of comorbidities on the clinical course of COVID-19 in infants was studied. This multicenter study, based on the pediatric part of the national SARSTer database (SARSTer-PED), included 940 infants with COVID-19 diagnosed between March 1, 2020, and December 31, 2021, from 13 Polish inpatient centers. An electronic questionnaire, which addressed epidemiological and clinical data, was used. The number of hospitalized infants was significantly higher in 2021 than in 2020 (651 vs. 289, respectively). The analysis showed similar lengths of infant hospitalization in 2020 and 2021, but significantly more children were hospitalized for more than 7 days in 2020 (p < 0.009). In both analyzed periods, the most common route of infection for infants was household contact. There was an increase in the percentage of comorbidities, especially prematurity, in children hospitalized in 2021 compared to 2020. Among the clinical manifestations, fever was predominant among children hospitalized in 2021 and 2020. Cough, runny nose, and loss of appetite were significantly more frequently observed in 2021 (p < 0.0001). Severe and critical conditions were significantly more common among children with comorbidities. More infants were hospitalized during the period of VOCs dominance, especially the delta variant, compared to the period of wild strain dominance, even though indications for hospitalization did not include asymptomatic patients during that period. The course of COVID-19 was mostly mild, characterized mainly by fever and respiratory symptoms. Comorbidities, particularly from the cardiovascular system and prematurity, were associated with a more severe course of the disease in infants.

A Phase III, multicenter, randomized, double-blind, active comparator-controlled study to evaluate the safety, tolerability, and immunogenicity of V114 compared with PCV13 in healthy infants (PNEU-PED-EU-1).

BACKGROUND: V114 (15-valent pneumococcal conjugate vaccine [PCV]) contains all serotypes in 13-valent PCV (PCV13) and additional serotypes 22F and 33F. This study evaluated safety and immunogenicity of V114 compared with PCV13 in healthy infants, and concomitant administration with DTPa-HBV-IPV/Hib and rotavirus RV1 vaccines. METHODS: V114 and PCV13 were administered in a 2+1 schedule at 2, 4, and 11-15 months of age. Adverse events (AEs) were collected on Days 1-14 following each vaccination. Serotype-specific anti-pneumococcal immunoglobulin G (IgG) was measured 30 days post-primary series (PPS), immediately prior to a toddler dose, and 30 days post-toddler dose (PTD). Primary objectives included non-inferiority of V114 to PCV13 for 13 shared serotypes and superiority of V114 to PCV13 for the two additional serotypes. RESULTS: 1184 healthy infants 42-90 days of age were randomized 1:1 to V114 (n = 591) or PCV13 (n = 593). Proportions of participants with solicited AEs and serious AEs were comparable between vaccination groups. V114 met pre-specified non-inferiority criteria for all 13 shared serotypes, based on the difference in proportions of participants with serotype-specific IgG concentrations ≥0.35 µg/mL (response rate; lower bound of two-sided 95% confidence interval [CI] >-10.0) and IgG geometric mean concentration (GMC) ratios (lower bound of two-sided 95% CI >0.5), and pre-specified superiority criteria for serotypes 22F and 33F (lower bound of two-sided 95% CI >10.0 for response rates and >2.0 for GMC ratios). Antibody responses to DTPa-HBV-IPV/Hib and RV1 vaccines met pre-specified non-inferiority criteria, based on antigen-specific response rates to DTPa-HBV-IPV/Hib and anti-rotavirus IgA geometric mean titers. CONCLUSIONS: After a 2+1 schedule, V114 elicited non-inferior immune responses to 13 shared serotypes and superior responses to the two additional serotypes compared with PCV13, with comparable safety profile. These results support the routine use of V114 in infants. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04031846; EudraCT: 2018-003787-31.

The Influence of SARS-CoV-2 Variants B.1.1.7 and B.1.617.2 on a Different Clinical Course and Severity of COVID-19 in Children Hospitalized in 2021 Compared With 2020.

BACKGROUND: This study aimed to analyze the differences in the epidemiologic and clinical characteristics of coronavirus disease 2019 (COVID-19) in children hospitalized in 2021, when the severe acute respiratory syndrome coronavirus 2 variants B.1.1.7 (alpha) and B.1.617.2 (delta) dominated, compared with 2020. METHODS: In this multicenter study based on the pediatric part of the national SARSTer register (SARSTer-PED), we included 2771 children (0-18 years) with COVID-19 diagnosed between March 1, 2020, and December 31, 2021, from 14 Polish inpatient centers. An electronic questionnaire, which addressed epidemiologic and clinical data, was used. RESULTS: Children hospitalized in 2021 were younger compared with those reported in 2020 (mean 4.1 vs. 6.8 years, P = 0 .01). Underlying comorbidities were reported in 22% of the patients. The clinical course was usually mild (70%). A significant difference in the clinical course assessment between 2020 and 2021 was found, with more asymptomatic patients in 2020 and more severely ill children in 2021. In total, 5% of patients were severely or critically ill, including <3% of the participants in 2020 and 7% in 2021. The calculated mortality rate was 0.1% in general and 0.2% in 2021. CONCLUSION: Infections with severe acute respiratory syndrome coronavirus 2 variants alpha and delta lead to a more severe course of COVID-19 with more pronounced clinical presentation and higher fatality rates than infection with an original strain. Most of the children requiring hospitalization due to COVID-19 do not have underlying comorbidities.

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.

COVID-19 mRNA Vaccine Tolerance and Immunogenicity in Hematopoietic Stem Cell Transplantation Recipients Aged 5-11 Years Old-Non-Randomized Clinical Trial.

The SARS-CoV-2 pandemic had a devastating impact on the world's population in the years 2020−2022. The rapid development of vaccines enabled a reduction in the mortality and morbidity of COVID-19, but there are limited data about their effects on immunocompromised children. The aim of this prospective study was to evaluate the safety and efficacy of the mRNA BNT162b2 (Pfizer/Biontech) vaccine in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Material and methods: Two cohorts of 34 children after allo-HSCT and 35 healthy children aged 5−11 years were vaccinated with two doses of the mRNA BNT162b2 (10 µg) vaccine. All children were evaluated for adverse effects with electronic surveys and the immunogenicity of the vaccine was assessed with anti-SARS-CoV-2 IgG titer measurements. Results: All reported adverse events (AEs) were classified as mild. The most common AE was pain at the injection site. All the other AEs (both local and systemic) were rarely reported (<15% patients). Both groups showed a similar response in anti-SARS-CoV-2 IgG production. Patients after allo-HSCT that were undergoing immunosuppressive treatment presented a poorer immunological response than patients off of treatment. Time since HSCT, patient age, lymphocyte count, and total IgG concentration did not correlate with initial/post-vaccination anti-SARS-CoV-2 IgG titers. Most patients who were eligible for a third dose of the vaccine had an excellent humoral response observed after two vaccine doses. Conclusions: The COVID-19 mRNA BNT162b2 vaccine is very well tolerated and highly immunogenic in 5−11-year-old children after HSCT. Children >2 years of age after HSCT who did not receive immunosuppressive treatment presented excellent antibody production after two doses of the vaccine, but children on immunosuppression may require a more intense vaccination schedule.

Safety and immunogenicity of a primary series and booster dose of the meningococcal serogroup B-factor H binding protein vaccine (MenB-FHbp) in healthy children aged 1-9 years: two phase 2 randomised, controlled, observer-blinded studies.

BACKGROUND: The meningococcal serogroup B-factor H binding protein vaccine (MenB-FHbp) is licensed for use in children aged 10 years or older for protection against invasive serogroup B meningococcal disease. Because young children are at increased risk of invasive meningococcal disease, MenB-FHbp clinical data in this population are needed. METHODS: We conducted two phase 2 randomised, controlled, observer-blinded studies including healthy toddlers (age 12-23 months) across 26 Australian, Czech, Finnish, and Polish centres, and older children (age 2-9 years) across 14 Finnish and Polish centres. Exclusion criteria included previous vaccinations against serogroup B meningococcus or hepatitis A virus (HAV), and chronic antibiotic use. Toddlers were randomly allocated (2:1) via an interactive response technology system to receive either 60 µg or 120 µg MenB-FHbp or HAV vaccine and saline (control). Older children were randomly allocated (3:1) to receive 120 µg MenB-FHbp or control, with stratification by age group (2-3 years and 4-9 years). All vaccinations were administered as three doses (0, 2, and 6 months, with only saline given at 2 months in the control group). Toddlers who received 120 µg MenB-FHbp could receive a 120 µg booster dose 24 months after the end of the primary series. The percentages of participants with serum bactericidal activity using human complement (hSBA) titres at or above the lower limit of quantification (LLOQ; all greater than the 1:4 correlate of protection) against four test strains of serogroup B meningococcus 1 month after the third dose (primary immunogenicity endpoint) were measured in the evaluable immunogenicity populations (participants who received the vaccine as randomised, had available and determinate hSBA results, and had no major protocol violations). Not all participants were tested against all strains because of serum sample volume constraints. The frequencies of reactogenicity and adverse events after each dose were recorded in the safety population (all participants who received at least one dose and had safety data available). These studies are registered with ClinicalTrials.gov (NCT02534935 and NCT02531698) and are completed. FINDINGS: Between Aug 31, 2015, and Aug 22, 2016, for the toddler study and between Aug 27, 2015, and March 7, 2016, for the older children study, we enrolled and randomly allocated 396 toddlers (60 µg MenB-FHbp group n=44; 120 µg MenB-FHbp group n=220; control group n=132) and 400 older children (120 µg MenB-FHbp group n=294; control group n=106). 1 month after the third dose, the proportions of participants with hSBA titres at or above the LLOQ ranged across test strains from 85·0% (95% CI 62·1-96·8; 17 of 20 participants) to 100·0% (82·4-100·0; 19 of 19) in toddlers receiving 60 µg MenB-FHbp, and from 71·6% (61·4-80·4; 68 of 95) to 100·0% (96·2-100·0; 95 of 95) in toddlers receiving 120 µg MenB-FHbp, and from 79·1% (71·2-85·6; 106 of 134) to 100·0% (97·4-100·0; 139 of 139) in children aged 2-9 years receiving 120 µg MenB-FHbp. hSBA titres peaked at 1 month after the third primary dose of MenB-FHbp and then declined over time. 24 months after the third dose in the toddler study, the proportions with hSBA titres at or above the LLOQ ranged from 0·0% (0·0-17·6; 0 of 19 participants) to 41·2% (18·4-67·1; seven of 17) in those who received 60 µg MenB-FHbp and from 3·7% (0·8-10·4; three of 81) to 22·8% (14·1-33·6; 18 of 79) in those who received 120 µg MenB-FHbp. 1 month after the booster dose in toddlers, the proportions with hSBA titres at or above the LLOQ were higher than at 1 month after the primary series. MenB-FHbp reactogenicity was mostly transient and of mild to moderate severity. Adverse event frequency was similar between the MenB-FHbp and control groups and less frequent following MenB-FHbp booster than following primary doses. Two participants from the toddler study (both from the 120 µg MenB-FHbp group) and four from the older children study (three from the 120 µg MenB-FHbp group and one from the control group) were withdrawn from the study because of adverse events. INTERPRETATION: MenB-FHbp was well tolerated and induced protective immune responses in a high proportion of participants. These findings support a favourable MenB-FHbp immunogenicity and reactogenicity profile in young children, a population at increased risk of adverse invasive meningococcal disease outcomes. FUNDING: Pfizer.

Coalition Shaping the Vaccination Landscape.

In 2022, the National Program for Influenza Prevention coalition will have its 10th anniversary; it is one of Poland's oldest educational initiatives. The National Program for Influenza Prevention was initiated to prevent a further decline and promote influenza prevention in the A(H1N1) post-pandemic years. In this review, we summarize the structure and operational model of the coalition and identify core functional elements that make it a key non-governmental organization involved in the prophylactics of communicable diseases. The coalition-based organization can operate in a complex environment, such as vaccinations requiring scientific, economic, social, and psychological involvement, and communications with different groups. Anchored to the history of the National Program for Influenza Prevention, we review Poland's vaccination landscape changes from the last ten years.

Upper respiratory tract infections and influenza-like illnesses among healthcare workers: are serological tests useful in monitoring influenza and influenza-like illness?

BACKGROUND: Healthcare workers (HCWs) are at high risk for exposure to upper respiratory tract infections (URTIs) and influenza-like illnesses (ILIs). The present study aimed to surveil URTIs and ILIs and their impact among the Department of Pediatric Infectious Diseases in Wroclaw employees and evaluate their humoral response to influenza. MATERIAL AND METHODS: Thirty-six HCWs participated in the first season and 32 HCWs in the second season during years of the study. The authors carried out a URTI/ILI surveillance, and all HCWs were asked to complete a weekly report during 2 influenza seasons: 2016/2017 (S1) and 2017/2018 (S2). In S1 both IgG and IgM antibodies against influenza A and B were assessed. The HCWs with symptoms of ILI were encouraged to undergo PCR tests for influenza. RESULTS: No significant differences in reporting URTI were found among vaccinated and non-vaccinated HCWs and HCWs and the control group. Depending on the year 5.5-17.2% of HCWs were treated with antibiotics because of URTI. In the study 58.7% of participants in S1 and 66.7% in S2 decide to work despite the URTI symptoms. There was no statistical relationship between the concentration of anti-influenza IgG and the number of URTIs and ILIs reported. Only vaccinated were willing to undergo voluntary influenza testing. CONCLUSIONS: The URTI and ILI occur commonly in HCWs, and HCWs contract URTIs as often as the control group. Despite their medical education, HCWs work with the symptoms of infection and overuse antibiotics to treat the URTI. Serology testing is not able to follow the infection's dynamics or identify the people immune to the influenza-like illness. The diagnostic value of IgM antibodies in acute influenza infection is negligible. Vaccinated HCWs are more focused on their health and are more willing to undergo influenza tests. Med Pr. 2022;73(6):441-7.

A tendency to worse course of multisystem inflammatory syndrome in children with obesity: MultiOrgan Inflammatory Syndromes COVID-19 related study.

Background: A new disease entity called multisystem inflammatory syndrome in children (MIS-C) is a rare consequence of COVID-19 infection. The pathophysiology and risk factors of MIS-C are still unclear, and the clinical manifestation ranges from milder forms to cases needing intensive care unit treatment. Based on available data, obesity is linked to pro-inflammatory stimulation. Moreover, several studies showed that obesity could play a role in COVID-19 severity and its comorbidities among the adult and children's populations. This study aimed to investigate the influence of overweightedness/obesity in childhood for the course of MIS-C in Poland. Methods: This study presented data from the national MultiOrgan Inflammatory Syndromes COVID-19 Related Study (MOIS-CoR) collected between 4 March 2020 and 20 February 2021. Of the 371 patients that met the Polish MIS-C criteria, 306 were included for further analysis. Results: Children who are obese (OB with body mass index (BMI) ≥95th percentile) and overweight (OV with BMI ≥85th percentile but <95th percentile) (28 and 49 patients, respectively) represented 25.1% (n=77) of all recruited patients. Complete recovery at the time of discharge presented in 93% of normal body weight (NW) participants and 90% of OV children (p>0.05). Among OB children, 76% recovered fully, which differed from the NW group (p=0.01). Calculated odds ratio (OR) of incomplete recovery for OB children was 4.2. Irrespective of body weight, there were no differences (p>0.05) in the length of hospitalization and the duration of symptoms (for OB, 13 and 16.5 days; for OV and NW, 10 and 14 days, respectively), as well as in the frequency of cardiovascular abnormalities, necessity of oxygen therapy (OB, 26.9%; OV, 23.9%; and NW, 20.7%), and intravenous immunoglobulin and glucocorticosteroid (GCS) treatment. Conclusion: The higher risk of incomplete recovery and observed tendency toward a worsening course of MIS-C in patients with obesity suggest the need for further studies to confirm and understand our findings.

Clinical characteristics of children with MIS-C fulfilling classification criteria for macrophage activation syndrome.

Background: Macrophage activation syndrome (MAS) is a potentially life-threatening complication of various inflammatory disorders, including multisystem inflammatory syndrome in children (MIS-C). MIS-C refractory to treatment should raise suspicion of MAS, which can be fatal if a definitive diagnosis is delayed. Unfortunately, there is a lack of data on MAS in children with MIS-C. Objective: Our study aims to analyze the risk factors for the development of MAS in MIS-C, its clinical course and response to treatment, and identify predictive factors for pediatric intensive care. Material and methods: We analyzed data from the Polish MIS-C registry of the MultiOrgan Inflammatory Syndromes COVID-19 Related Study. Patients were diagnosed according to the WHO MIS-C definition and treated according to national guidelines (Polish Pediatric Society) based on international consensus. MAS definition was based on 2016 Classification Criteria for Macrophage Activation Syndrome Complicating Systemic Juvenile Idiopathic Arthritis. Results: Two-hundred and seventy four children met the study inclusion criteria. Fifty-nine patients fulfilled MAS classification criteria, nine of which required admission to the pediatric intensive care unit (PICU). MIS-C patients with MAS were significantly older than patients without MAS (median 11.2 vs. 8.1 years). Multivariable analysis showed that age, symptoms characteristic of atypical Kawasaki disease, and skin erosions were significant factors associated with MAS in MIS-C patients. Analysis of laboratory parameters showed that on admission, MIS-C patients with MAS had significantly lower median lymphocyte and platelet counts, albumin and sodium levels, and higher median levels of C-reactive protein, procalcitonin, ferritin, D-dimers, triglycerides, serum creatinine, urea, and γ-glutamyl transpeptidase, and neutrophil count. Multivariate analysis showed that higher procalcitonin, ferritin, and fibrinogen levels at admission were predictive of MAS. Only elevated troponin level was a factor indicating a requirement of PICU hospitalization for children with MAS. MIS-C patients fulfilling MAS criteria were treated more often with intravenous immunoglobulins and steroids than children without MAS. Children with MAS more often required mechanical ventilation. None of the patients required biological agents. Conclusions: The clinical course of MAS in MIS-C seems milder, treatment less aggressive, and the prognosis better than expected based on the current knowledge on MAS complicating other rheumatological diseases.

A phase III, multicenter, randomized, double-blind, active comparator-controlled study to evaluate the safety, tolerability, and immunogenicity of catch-up vaccination regimens of V114, a 15-valent pneumococcal conjugate vaccine, in healthy infants, children, and adolescents (PNEU-PLAN).

BACKGROUND: Despite widespread use of pneumococcal conjugate vaccines (PCVs) in children, morbidity and mortality caused by pneumococcal disease (PD) remain high. In addition, many children do not complete their PCV course on schedule. V114 is a 15-valent PCV that contains two epidemiologically important serotypes, 22F and 33F, in addition to the 13 serotypes present in PCV13, the licensed 13-valent PCV. METHODS: This phase III descriptive study evaluated safety and immunogenicity of catch-up vaccination with V114 or PCV13 in healthy children 7 months-17 years of age who were either pneumococcal vaccine-naïve or previously immunized with lower valency PCVs (NCT03885934). Overall, 606 healthy children were randomized to receive V114 (n = 303) or PCV13 (n = 303) via age-appropriate catch-up vaccination schedules in three age cohorts (7-11 months, 12-23 months, or 2-17 years). RESULTS: Similar proportions of children 7-11 months and 2-17 years of age reported adverse events (AEs) in the V114 and PCV13 groups. A numerically greater proportion of children 12-23 months of age reported AEs in the V114 group (79.0%) than the PCV13 group (59.4%). The proportions of children who reported serious AEs varied between different age cohorts but were generally comparable between vaccination groups. No vaccine-related serious AEs were reported, and no deaths occurred. At 30 days after the last PCV dose, serotype-specific immunoglobulin G geometric mean concentrations were comparable between vaccination groups for the 13 shared serotypes and higher in the V114 group for 22F and 33F. CONCLUSIONS: Catch-up vaccination with V114 in healthy individuals 7 months-17 years of age was generally well tolerated and immunogenic for all 15 serotypes, including those not contained in PCV13, regardless of prior pneumococcal vaccination. These results support V114 catch-up vaccination in children with incomplete or no PCV immunization per the recommended schedule.

Recommendations of the Polish Society of Gynaecologists and Obstetricians, Polish Paediatric Society, Polish Society of Family Medicine, Polish Society of Vaccinology, Polish Society of Oncological Gynaecology and Polish Society of Colposcopy and Pathophysiology of the Uterine Cervix on prophylactic vaccinations against infections with human papillomaviruses in Poland.

Several hundred million people are infected with genital genotypes of the human papillomavirus (HPV) annually in the world. The infections transmitted mainly through sexual routes are usually asymptomatic, but can lead to the development of cervical, vulvar, vaginal, anal, penile cancers, some head and neck cancers and genital warts (condylomas). The fraction HPV-related cancers range from nearly 100% in the case of cervical cancer to several/over a dozen percent in the case of other cancers and diseases. There are no effective drugs against HPV, but prophylactic HPV vaccines are available free of charge in immunization programmes in many countries around the world. In Poland, HPV vaccinations have so far been executed out on the pocket or in free-of-charge, local-governmental prevention programs, but the vaccination coverage of the target population does not exceed 10%. From November 2021, one of the vaccines is available with a 50% reimbursement, work is underway to reimburse the next ones, and the National Oncology Strategy assumes the implementation of the HPV immunization programmes and vaccination of 60% of the teen population by 2028. Three prophylactic HPV vaccines are registered. All of them are safe and their effectiveness in the prevention of diseases caused by vaccine genotypes reaches almost 100%, provided that full post-vaccination immunity is obtained before the contact with the virus. Girls aged 11-13 are the priority target cohort for HPV vaccination in Poland. The implementation of routine, free-of-charge HPV immunization in the Preventive Immunization Program (PIP) for all adolescents should be pursued. Persons over the age of 13 may also benefit from HPV vaccination and should be vaccinated according to product specifications. In addition to free access under the PIP, the key element for the success of the implementation of HPV vaccinations in Poland will be the education of medical personnel and parents of adolescents to be vaccinated.

Use of broad-spectrum antibiotics in children diagnosed with multisystem inflammatory syndrome temporarily associated with SARS-CoV-2 infection in Poland: the MOIS-CoR study.

OBJECTIVES: Multisystem inflammatory syndrome in children (MIS-C) is the result of an immune response triggered by a previous exposure to SARS-CoV-2. The clinical presentation of MIS-C overlaps with other life-threatening bacterial infections, in which antimicrobials are the mainstay therapy. The aim of study was to describe the use of antibiotics in children with MIS-C in Poland. METHODS: The analysis of 345 children reported from 42 Polish cities to the national MultiOrgan Inflammatory Syndromes COVID-19 Related Study (MOIS-CoR Study) from June 2020 to April 2021. RESULTS: At least one antibiotic was used in 310 (90%) children, mainly third-generation cephalosporin (251/310). Broad-spectrum antibiotics were used in 258 (75%) children and 224 (87%) received this treatment for more than 3 days. Concentrations of serum procalcitonin >2 µg/l and the presence of lower respiratory symptoms were associated with increased odds of receiving any antibiotic. CONCLUSION: Although bacterial infections in patients with MIS-C are uncommon, we show that MIS-C poses a challenge to clinicians who are faced with the decision to start, continue, or stop antimicrobial therapy. Antibiotic stewardship in patients with MIS-C should be improved to ensure that likely pathogens are treated and that antimicrobials are stopped when bacterial infections are excluded and the diagnosis of MIS-C is made.