Multisystem inflammatory syndrome in children (MIS-C): A nationwide collaborative study in the Greek population.

Multisystem inflammatory syndrome in children (MIS-C) is a rare but severe hyperinflammatory condition that may occur following SARS-CoV-2 infection. This retrospective, descriptive study of children hospitalized with multisystem inflammatory syndrome in children (MIS-C) in 12 tertiary care centers from 3/11/2020 to 12/31/2021. Demographics, clinical and laboratory characteristics, treatment and outcomes are described. Among 145 patients (95 males, median age 8.2 years) included, 123 met the WHO criteria for MIS-C, while 112 (77%) had serological evidence of SARS-CoV-2 infection. Fever was present in 99%, gastrointestinal symptoms in 77%, mucocutaneous involvement in 68% and respiratory symptoms in 28%. Fifty-five patients (38%) developed myocarditis, 29 (20%) pericarditis and 19 (13%) coronary aneurysms. Among the above cases 11/55 (20%), 1/29 (3.4%) and 5/19 (26.3%), respectively, cardiac complications had not fully resolved at discharge. Underlying comorbidities were reported in 18%. Median CRP value was 155 mg/l, ferritin 535 ng/ml, PCT 1.6 ng/ml and WBC 14.2 × 109/mm3. Most patients had elevated troponin (41.3%) and/or NT-pro-BNP (49.6%). Intravenous immunoglobulin plus corticosteroids were used in 117/145 (80.6%), monotherapy with IVIG alone in 13/145 (8.9%) and with corticosteroids alone in 2/145 (1.3%). Anti-IL1 treatment was added in 15 patients (10.3%). Thirty-three patients (23%) were admitted to the PICU, 14% developed shock and 1 required ECMO. Mortality rate was 0.68%. The incidence of MIS-C was estimated at 0.69/1000 SARS-CoV-2 infections. Patients who presented with shock had higher levels of NT-pro-BNP compared to those who did not (p < 0.001). Acute kidney injury and/or myocarditis were associated with higher risk of developing shock. CONCLUSION: MIS-C is a novel, infrequent but serious disease entity. Cardiac manifestations included myocarditis and pericarditis, which resolved in most patients before discharge. Timely initiation of immunomodulatory therapy was shown to be effective. NT-pro-BNP levels may provide a better prediction and monitoring of the disease course. Further research is required to elucidate the pathogenesis, risk factors and optimal management, and long-term outcomes of this clinical entity. WHAT IS KNOWN: • MIS-C is an infrequent but serious disease entity. • Patients with MIS-C present with multi-organ dysfunction, primarily involving the gastrointestinal and cardiovascular systems. WHAT IS NEW: • NT-pro-BNP levels may provide a better prediction and monitoring of the disease course. • Acute kidney injury and/or myocarditis were associated with higher risk of developing shock.

SARS-CoV-2 seroprevalence among children in Greece during Omicron variant period.

The Omicron variant is associated with increased transmissibility, but evidence about the impact of Omicron in seropositivity of children is limited. This study aims to evaluate SARS-CoV-2 seroprevalence in children during the different variants' subperiods. A prospective multicenter seroprevalence study was conducted in 7 University public hospitals in Greece from November 2021 to August 2022 (3 subperiods: November 2021-February 2022, March 2022-May 2022, June 2022-August 2022). Children from different age groups, admitted to the hospital or examined in outpatient clinics for reasons other than COVID-19 were enrolled. Neutralizing antibodies (Nabs), anti-Spike (anti-S) and anti-nucleocapsid (anti-N) SARS-CoV-2 IgG in serum were evaluated. A total of 2127 children (males:57,2%; median age:4,8years) were enrolled. Anti-N IgG seropositivity increased from 17,8% in the first sub-period to 40,7% in the second sub-period and then decreased in the third sub-period (36,7%). Anti-S IgG seropositivity appeared to have an increasing trend over the study period, starting from 34,8% and reaching 80,7%. Children aged 1-4 years old have significantly higher anti-N IgG titers compared to children aged 0-1 years old (p < 0,001). Infants have significantly lower anti-S IgG titers compared to all other age groups (p < 0,001). Immunocompromised children and infants have the lowest seropositivity for NAbs.Conclusions During the Omicron period, seropositivity significantly increased, as a result of higher transmissibility. Neonates and infants have lower antibody titers compared to other age groups, while young children aged 1-4 years old present higher antibody titers, suggesting that this age group may mount a higher antibody response. Continuous surveillance seroprevalence studies are needed in children, in order to identify the true extent of SARS-CoV-2 and guide the planning of adequate public health measures.

WHAT IS KNOWN: • Seroprevalence surveys among children may be extremely useful, in order to properly monitor the immunity, either natural or acquired, through the quantification of IgG antibodies and to plan further immunization policies. • There are variations in the seroprevalence of COVID-19 between the different periods, according to the vaccination rates, the type of circulating variant and the transmissibility of the virus. • The Omicron variant is associated with increased transmissibility, but evidence about the impact of Omicron in seropositivity of children is limited. WHAT IS NEW: • In this large multicenter seroepidemiological study, SARS-CoV-2 seroprevalence rate in children is higher during the Omicron period in comparison to the previous pandemic waves, due to the high transmissibility of the virus and the increased rates of reinfection. • Neonates and infants have lower antibody titers compared to other age groups, while young children aged 1­4 years old present higher antibody titers, indicating that the children of this age group mount a higher antibody response. • This study provides essential information about immunity and the level of protection in the pediatric population, as neutralizing antibodies were evaluated, in addition to the anti-N and anti-S IgG antibodies.

Seroprevalence of anti-SARS-CoV-2 antibodies among children and their parents in Greece.

School closures were enforced as measures to restrain the COVID-19 pandemic, based on the assumption that young children may play a key role in SARS-CoV-2 spread. This study aims to determine the prevalence of SARS-CoV-2 IgG antibodies in children and corresponding parents, in order to improve surveillance and estimate the prevalence of asymptomatic or subclinical COVID-19 cases. A prospective multicenter study was conducted between March and June 2021 in Greece. Children admitted to the hospital or examined in outpatient clinics for reasons other than COVID-19 and their parents were tested for anti-Spike SARS-CoV-2 IgG in serum. A questionnaire about clinical and demographic data was completed. The study included 823 participants: 427 children and 396 corresponding parents. The overall seroprevalence was 16.4% in parents and 13.8% in children. Among families with ≥ 1 seropositive child or parent, the combination of a seropositive parent and a corresponding seronegative child was 29.6%, a seronegative parent and a corresponding seropositive child was 24.7%, and a seropositive child with a corresponding seropositive parent was 45.7%. Age, level of education, and school or work attendance were not significantly associated with increased seropositivity. On the contrary, ethnic minority of Roma, close contact with known COVID-19 case, previous symptoms consistent with COVID-19, and mass gatherings were risk factors for seropositivity. CONCLUSION: The spread of SARS-CoV-2 during a period of lockdown in Greece was low in children and comparable to adults most likely due to intrafamilial transmission. Accordingly, it is unlikely that children have boosted virus transmission. WHAT IS KNOWN: • In the earliest months of the pandemic, it was demonstrated that children had significantly lower seroprevalence rates than the older age groups, due to the fact that children had decreased exposure to the virus, because of early public health interventions, such as school and day care closure. • Later, further studies reported that children have similar incidence rate of SARS-CoV-2 infection compared to adults in households and community settings. WHAT IS NEW: • In this seroprevalence study, the spread of SARS-CoV-2 infection during a period of lockdown in Greece with the predominance of the Alpha-variant was particularly low in children and comparable to adults, most likely due to intrafamilial transmission. • These study findings will be useful for decisions regarding non-pharmaceutical interventions during the pandemic, and especially, to guide in designing and implementing appropriate containment measures for schools and social gatherings.

The impact of COVID-19 on paediatric emergency department visits. A one-year retrospective study.

BACKGROUND: The number of paediatric emergency department (ED) visits and hospital admissions was recorded in a tertiary referral centre during the first year of the COVID-19, March 2020-February 2021, and compared with those of the preceding year. METHODS: The number of visits and admissions and the reason of visit and admission were prospectively recorded from 15,087 patients' files. RESULTS: A substantial decline in the total number of visits and increase in the admission rate were documented during the COVID-19 year compared to the preceding year (10691 vs 4396 patients, 22.59% vs 18.15% (OR: 1.316, CI 95%: 1.208-2.242, p < 0.0001), respectively). Fever and/or respiratory symptoms were the commonest reported symptoms in both periods. Possible explanations include: (i) restricted overall infection transmission due to confinement and self-protective measures, (ii) avoidance of unnecessary hospital visits in the absence of severe symptoms and (iii) reduced or delayed access to medical care due to parental fear of children's exposure to COVID-19. CONCLUSION: This study is the first worldwide to investigate the impact of COVID-19 on ED visits and admissions throughout the whole year of the pandemic, and to highlight the need for re-evaluation of future protective strategies to infections, adjustment of health-care systems and parental education so that medical care in a health-care setting is sought in a more appropriate manner. IMPACT: A significant decline in paediatric ED visits and increase in the admission rate was observed during the first year of COVID-19 in a tertiary referral centre, possibly due to reduced overall infection transmission, limited ED overuse, but also ED underuse due to parental fear of children's exposure to SARS-CoV-2. COVID-19 may serve as an opportunity for societies to re-evaluate future strategies to infections, adjust health-care systems accordingly, and reinforce parents to seek medical care more appropriately. Although the incidence of critical illness in children due to COVID-19 and in general is low, special attention should be devoted to identifying children at risk early.

Potential benefit from the implementation of the Kaiser Permanente neonatal early-onset sepsis calculator on clinical management of neonates with presumed sepsis.

To assess the potential benefit from the implementation of the Kaiser Permanente early-onset sepsis calculator (EOS-C), in terms of antibiotic use and requested laboratory tests, in a network of neonatal intensive care units (NICUs) in Greece, and to determine the incidence of early-onset sepsis (EOS) in Greek NICUs, a prospective surveillance study was conducted in 7 NICUs between April 2018 and June 2019. Data were collected for all newborns ≥ 34 weeks' gestation receiving empiric antibiotic therapy within the first 3 days of life. The number of live births and positive blood or cerebrospinal fluid cultures within the first 3 days of life were used for calculation of EOS incidence. Evaluation of possible impact of implementing the calculator was done by comparing the clinicians' recorded management to the calculator's suggested course of action. The unit-specific incidence of culture-proven EOS ranged between 0 and 2.99/1000 live births. The weighted incidence rate for all 7 units was 1.8/1000 live births. Management of EOS guided by the calculator could lead to a reduction of empiric antibiotic initiation up to 100% for the group of "well-appearing" neonates and 86% for "equivocal," lowering exposure to antibiotics by 4.2 and 3.8 days per neonate, respectively. Laboratory tests for blood cultures drawn could be reduced by up to 100% and 68%, respectively. Sensitivity of the EOS-C in identifying neonates with positive blood cultures was high.Conclusion: Management strategies based on the Kaiser Permanente neonatal sepsis calculator may significantly reduce antibiotic exposure, invasive diagnostic procedures, and hospitalizations in late preterm and term neonates. What is Known: • Neonates are frequently exposed to antibiotics for presumed EOS. • The Kaiser Permanente sepsis calculator can reduce antibiotic exposure in neonates.. What is New: • EOS calculator can be an effective antibiotic stewardship tool in a high prescribing country and can reduce invasive diagnostic procedures and mother-baby separation. • Incidence of EOS in Greece is higher compared to other European countries.

Influenza vaccination among caregivers and household contacts of children with congenital heart disease before and during COVID-19 pandemic.

AIM: We aimed to investigate the influenza immunisation status of caregivers and household contacts of children with congenital heart disease (CHD) and potential barriers to vaccine uptake. METHODS: Prospective questionnaire-based survey over two influenza seasons (2019-2020 and 2020-2021) on 161 children with CHD attending a tertiary paediatric cardiology clinic and their families. Logistic regression and factor analysis were performed to identify factors associated with influenza vaccine uptake. RESULTS: Influenza vaccination coverage of children was 65%, whereas that of their fathers and mothers was 34% and 26%, respectively. Children with unvaccinated siblings represented 43% and those with unvaccinated adults in the household 79% of our study population. No statistically significant differences were found before and during COVID-19 pandemic on vaccine uptake. Logistic regression analysis showed that higher education level, understanding the risk of contracting the disease and vaccination status of the child determined the vaccination status of parents, regardless of their age, age of their child, severity of CHD, beliefs about vaccine safety and efficacy and risk of transmission if not vaccinated. Factor analysis revealed distinct groups among unvaccinated parents (76.3% of the variation in the responses). CONCLUSIONS: Vaccination coverage of caregivers and household contacts of children with CHD is suboptimal. Influenza vaccination campaigns should take into consideration the specific characteristics of parental groups and target interventions accordingly to increase their vaccine uptake and indirectly protect children with CHD.

Anxiety levels in parents of asymptomatic neonates and young infants referred for echocardiography.

INTRODUCTION: Previous studies in children with innocent murmurs have shown that parental concern is common. METHODS: We assessed the anxiety levels among parents of asymptomatic neonates or infants up-to 6 weeks referred for cardiologic consultation because of a heart murmur. A six-item short-form of the state scale of the Spielberger State-Trait Anxiety Inventory (STAI) was completed by the parents before and after consultation. RESULTS: The average STAI score decreased from 14.42 ± 4.54 on arrival to 9.69 ± 4.26 after the consultation (p < 0.001). Overall, the parents felt more calm, less tense, less upset, more relaxed, more content and less worried after the consultation (p < 0.001). Multivariable linear regression analysis showed that the STAI score prior to consultation was related to infants age (coefficient ß = - 0.172; P = 0.046) and STAI score post consultation was related to the final diagnosis (ß = 0.312; P < 0.001). CONCLUSION: In conclusion, parents of asymptomatic neonates and young infants with a murmur exhibit moderate levels of anxiety which can be ameliorated after consultation. Parental education in the field is of paramount importance and the role of both paediatric cardiologists as well as primary care physicians is crucial and decisive.

SARS-CoV-2 testing and infection control strategies in European paediatric emergency departments during the first wave of the pandemic.

Between February and May 2020, during the first wave of the COVID-19 pandemic, paediatric emergency departments in 12 European countries were prospectively surveyed on their implementation of SARS-CoV-2 disease (COVID-19) testing and infection control strategies. All participating departments (23) implemented standardised case definitions, testing guidelines, early triage and infection control strategies early in the outbreak. Patient testing criteria initially focused on suspect cases and later began to include screening, mainly for hospital admissions. Long turnaround times for test results likely put additional strain on healthcare resources.Conclusion: Shortening turnaround times for SARS-CoV-2 tests should be a priority. Specific paediatric testing criteria are needed. What is Known: • WHO and public health authorities issued case definitions, testing and infection control recommendations for COVID-19 in January. • SARS-CoV-2 testing was made available across Europe in February. What is New: • Paediatric emergency departments implemented COVID-19-specific procedures rapidly, including case definitions, testing guidelines and early triage. • A third of surveyed departments waited more than 24 h for SARS-CoV-2 test to be reported, resulting in additional strain on resources.

Association of lifestyle factors with a high prevalence of overweight and obesity in Greek children aged 10-16 years.

AIM: To investigate the prevalence of overweight, obesity and central obesity in students of primary and secondary education, and the association with lifestyle parameters. METHODS: A total of 3504 students, aged 10-16 years old, from Western Greece participated in this cross-sectional epidemiological study (participation rate: 90%). Demographic, socioeconomic, dietary, physical activity and screen time data were obtained using a questionnaire. Anthropometric measurements were also obtained. Overweight and obesity were estimated using the Centers for Disease Control and Prevention (CDC) and International Obesity Task Force (IOTF) criteria and central obesity using the WHtR ≥0.5 and IDF criteria. RESULTS: The prevalence of overweight and obesity was 19.2% and 12.1% with CDC criteria, respectively, and 20.9% and 7.2%, with IOTF criteria respectively. Central obesity was 31.1 and 32.8% using the Waist-to-Height ratio (WHtR) ≥0.5 and International Diabetes Federation (IDF) criteria respectively. Male gender, small number of meals, breakfast skipping, frequent consumption of school food and sweets and the presence of a computer in children's rooms, were identified as the strongest lifestyle factors affecting weight. CONCLUSION: Overweight, obesity and central obesity rates remain high among children and adolescents in Greece. The identification of risk factors associated with the manifestation of obesity and central obesity, may contribute to the implementation of targeted prevention and treatment interventions.

Parental anxiety and misperceptions in children with innocent murmurs.

BACKGROUND: Previous studies in children with innocent murmurs have shown that parental concern is common. Our aim was to assess the level of anxiety among parents of children referred for cardiology evaluation because of an innocent heart murmur and investigate their perceptions about innocent murmurs. METHODS: A questionnaire was completed by parents before and after consultation. The questionnaire included a six-item short form of the state scale of the Spielberger State-Trait Anxiety Inventory. After the echocardiogram, a detailed consultation was offered including a thorough explanation that the results were normal, as well as a written report. RESULTS: A total of 417 questionnaires were completed by parents of 340 children. Almost half of the parents believed that a heart murmur signifies heart disease or may interfere with child's ability to exercise; 21% of them stated that the siblings should also be investigated irrespective of the presence of a murmur. The mean Spielberger State-Trait Anxiety Inventory questionnaire score before pediatric cardiology consultation was 17.1 ± 4.3 and increased to 22.6 ± 2.8 after the consultation (Wilcoxon P < 0.001). CONCLUSIONS: Parents of infants and children with innocent murmurs exhibit moderate levels of anxiety and this condition can be ameliorated significantly after pediatric cardiology consultation. Focused parental education is of paramount importance and the role of pediatric cardiologists is crucial and decisive.

Antenatal vaccination for influenza and pertussis: a call to action.

Pregnant women should receive influenza and pertussis vaccines according to the National Immunisation Schedule in Greece. The purpose of this study was to assess the knowledge, attitudes and factors associated with antenatal vaccination of women in Greece. A cross-sectional prospective survey was conducted involving 432 pregnant women and women who had recently given birth in Western Greece. Although the majority of women were aware of both diseases (289, 66.9%), they admitted lack of knowledge about antenatal vaccination (317, 73.4%). Overall, there was poor awareness that the vaccination is safe during pregnancy (95, 22%). Only 26 (6%) of women have been offered the vaccines during current pregnancy. Prior vaccination and obstetrician`s recommendation were the stronger predictors of antenatal vaccine uptake. There is substantial room for improvement among antenatal care providers in both patient education and the provision of the vaccines.Impact StatementWhat is already known about the topic? Maternal vaccination has been recognised as an important public health intervention to protect both pregnant women and their offspring from various infectious diseases. Pregnant women should receive influenza and pertussis vaccines according to the National Immunisation Schedules in many countries worldwide. However, scepticism still exists upon vaccine uptake during pregnancy.What do the results of this study add? The purpose of the study was to assess the knowledge, attitudes and factors associated with antenatal vaccination of women in Greece. We found that the knowledge and uptake of influenza and pertussis vaccine among pregnant women in Greece is poor.What the implications are of these findings for clinical practice and/or further research? There is substantial room for improvement among antenatal care providers in both patient education and the provision of the vaccines.

Daptomycin Use for Persistent Coagulase-Negative Staphylococcal Bacteremia in a Neonatal Intensive Care Unit.

During the last two decades, the incidence of late-onset sepsis (LOS) has increased due to improved survival of premature neonates. Persistent bacteremia (PB) in LOS is defined as more than two positive blood cultures obtained on different calendar days during the same infectious episode. Although rare, PB should be treated aggressively to prevent adverse outcomes. Daptomycin, a lipopeptide antibiotic, has been used in neonates with persistent coagulase-negative staphylococci (CoNS) bacteremia with promising results, but studies reporting on the efficacy and safety of the agent are scarce. The purpose of this study was to evaluate the efficacy and safety of daptomycin use for persistent CoNS bacteremia in a neonatal cohort. This is a retrospective, observational, single-center study of neonates treated with daptomycin during 2011-2022 in the Tertiary Neonatal Intensive Care Unit (NICU) of the University General Hospital of Patras, Greece. For the years 2011-2022, there were 3.413 admissions to the NICU. During the last 3 years (2020-2022)-the active epidemiological surveillance period-123 infants (out of 851 admissions, 14.4%) developed CoNS bacteremia (LOS). During the study period, twelve infants with PB were treated with daptomycin. They had a median gestational age of 32 weeks (IQR 31-34) and mean (SD) birth weight of 1.840 (867) grams. CoNS bacteremia isolates were s. epidermidis (50%), s. haemolyticus (20%), s. hominis (20%) and s. warneri (10%). The decision to start daptomycin (6 mg/kg/dose twice daily) was taken on median day 10 (ΙQR 7-15) of infection. None of the infants had focal complications or meningitis. Daptomycin therapy caused no renal, hepatic, muscular or gastrointestinal adverse events. One neonate developed seizures, and one death occurred due to multiple complications of prematurity. Most infants (11/12) were successfully treated and eventually had negative blood culture. Daptomycin monotherapy showed an adequate cure rate in premature neonates with persistent CoNS bacteremia in a tertiary NICU. In our study, daptomycin was effective and well tolerated; the safety profile, however, needs to be confirmed in larger studies and randomized controlled trials.