Effectiveness of COVID-19 vaccination against school absenteeism in children and adolescents hospitalized with COVID-19.

BACKGROUND: COVID-19 vaccination has been recommended for children to protect them and to enable in-person educational and social activities. METHODS: We estimated COVID-19 vaccination effectiveness (VE) against school absenteeism in children 5-17 years old hospitalized from September 1, 2021 through May 31, 2023. Full vaccination was defined as two vaccine doses. RESULTS: We studied 231 children admitted to hospital with COVID-19, including 206 (89.2 %) unvaccinated/partially vaccinated and 25 (10.8 %) fully vaccinated. Unvaccinated/partially vaccinated children were absent from school for longer periods compared to fully vaccinated children (median absence: 14 versus 10 days; p-value = 0.05). Multivariable regression showed that full COVID-19 vaccination was associated with fewer days of absence compared to no/partial vaccination on average (adjusted relative risk: 0.77; 95 % CI: 0.61 to 0.98). COVID-19 VE was 50.7 % (95 % CI: -11.3 % to 78.2 %) for school absenteeism above the median duration of absenteeism. CONCLUSIONS: Full COVID-19 vaccination conferred protection against school absenteeism in hospitalized school-aged children with COVID-19.

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.

Decreasing Incidence of the Multisystem Inflammatory Syndrome in Children Over 3 Pandemic Waves.

In this nationwide retrospective study, a substantial decline in the incidence of multisystem inflammatory syndrome in children over 3 successive pandemic waves characterized by different severe acute respiratory syndrome coronavirus 2 variants was documented-from 3.4 of 1000 to 1.1 of 1000 and finally to 0.25 of 1000 confirmed severe acute respiratory syndrome coronavirus 2 positive cases (P < 0.0001), respectively, whereas clinical findings and severity did not significantly vary.

Adherence to Recommendations for Βacillus Calmette-Guérin Vaccination of High-risk Neonates in Greece.

In 2016 a Βacillus Calmette-Guérin vaccination policy targeting high-risk neonates for tuberculosis before discharge from maternity hospital was adopted in Greece. Vaccination rates were 38.2% in 2019 and 24.7% in 2020. Vaccination coverage varied by risk group (higher for neonates in close contact with an active noncompliant or multidrug-resistant tuberculosis case and lower for Roma and immigrant neonates).

Molecular surveillance of pneumococcal carriage following completion of immunization with the 13-valent pneumococcal conjugate vaccine administered in a 3 + 1 schedule.

In a cross-sectional study, with the use of molecular methods, we aimed to gain insight into oropharyngeal pneumococcal colonization over time in 1212 Greek children recruited in general pediatric settings throughout the country; they were fully vaccinated with PCV13 (3 + 1 schedule). A single sample was obtained from each child at a time interval of 26 days to 70 months after administration of the 4th (booster) PCV13 dose; sampling time was divided into six time intervals. Carriage of Streptococcus pneumoniae was detected by real-time PCR targeting the lytA gene and isolates were serotyped by singleplex real-time PCR assays. Multiple control procedures to avoid false-positive results were applied. We showed an overall S. pneumoniae carriage rate of 48.6%. Serotyping identified typeable isolates in 82% of the total lytA-positive samples. Non-PCV13 serotypes represented 83.8% of total isolates when excluding serogroups with mixed PCV13 and non-PCV13 serotypes. In multivariate analysis daycare/school attendance emerged as the main contributing factor. Notably, serotypes 19A and 3 were the only two PCV13 serotypes the colonization rate of which increased over time (χ2 for trend P < 0.001 and P = 0.012, respectively). The application of the SP2020 gene on lytA-positive serotyped samples showed pneumococcal colonization in 97% of cases, and the overall colonization profile over time closely resembled that of the lytA gene. With the provisions of the methodological approach and age group of our study, the use of the oropharynx emerges as a reliable alternative to the nasopharynx in estimating pneumococcal carriage in epidemiological studies.

Val66Met polymorphism is associated with decreased likelihood for pediatric headache and migraine.

Background: Migraine is a complex multifactorial disorder and its pathogenesis still remains unclear. Evidence suggests the involvement of the activated trigeminovascular pathway, in which BDNF seems to play an important role. Therefore, BDNF polymorphisms are promising candidate susceptibility factors.Aim: BDNF rs6265 functional polymorphism was analyzed in order to determine its possible association with pediatric headache and migraine risk.Methods: The research included 120 consecutive pediatric patients who were diagnosed with headache and 120 healthy controls. The diagnosis was in compliance with the International Classification of Headache Disorders. Blood samples were collected from all participants and genotyped for rs6265.Results: BDNF rs6265 was significantly associated with decreased headache risk, particularly in the dominant model [Odds Ratio, OR (95% confidence interval, C.I.): 0.47 (0.26-0.85), p = 0.011] and the log-additive model [OR (95% C.I.): 0.48 (0.28-0.82), p = 0.0053]. During the sensitivity analysis, the associations were also maintained among patients with migraine.Conclusions: This is the first study to reveal a significant association of this BDNF variant with headache risk. Additionally, Val66Met was also for the first time related to decreased childhood migraine risk.

Reducing Duration of Antibiotic Use for Presumed Neonatal Early-Onset Sepsis in Greek NICUs. A "Low-Hanging Fruit" Approach.

Antibiotics are commonly prescribed in Neonatal Intensive Care Units (NICU), where stewardship interventions are challenging. Lowering antibiotic consumption is desperately needed in Greece, a country with high antibiotic resistance rates. We sought to assess the effectiveness of a low-cost and -resource intervention to reduce antibiotic use in Greek NICUs implementing a "low-hanging fruit" approach. A prospective quasi-experimental study was conducted in 15/17 public NICUs in Greece (9/2016-06/2019). The intervention selected was discontinuation of antibiotics within 5 days for neonates with gestational age ≥ 37 weeks, no documented signs or symptoms of sepsis, CRP ≤ 10 mg/L and negative cultures within 3 days of antibiotic initiation. Impact was evaluated by the percentage of discontinued regimens by day 5, length of therapy (LOT) and stay. Trends of antibiotic consumption were assessed with days of therapy (DOT) per 1000 patient-days. Overall, there was a 9% increase (p = 0.003) of antibiotic discontinuation in ≤5 days. In total, 7/13 (53.8%) units showed a ≥10% increase. Overall, 615 days on antibiotics per 1000 patients were saved. Interrupted time-series analysis established a declining trend in DOT/1000 patient-days relative to the pre-intervention trend (p = 0.002); a monthly decrease rate of 28.96 DOT/1000 patient-days (p = 0.001, 95%CI [-45.33, -12.60]). The intervention had no impact on antibiotic choice. Antibiotic use was successfully reduced in Greek NICUs using a "low-hanging fruit" approach. In resource-limited settings, similar targeted stewardship interventions can be applied.

Children and Adolescents With SARS-CoV-2 Infection: Epidemiology, Clinical Course and Viral Loads.

BACKGROUND: There is limited information on severe acute respiratory syndrome virus 2 (SARS-CoV-2) infection in children. METHODS: We retrieved data from the national database on SARS-CoV-2 infections. We studied in-family transmission. The level of viral load was categorized as high, moderate, or low based on the cycle threshold values. RESULTS: We studied 203 SARS-CoV-2-infected children (median age: 11 years; range: 6 days to 18.4 years); 111 (54.7%) had an asymptomatic infection. Among the 92 children (45.3%) with coronavirus disease 2019 (COVID-19), 24 (26.1%) were hospitalized. Infants <1 year were more likely to develop COVID-19 (19.5% of all COVID-19 cases) (P-value = 0.001). There was no significant difference between viral load and age, sex, underlying condition, fever and hospitalization, as well as between type of SARS-CoV-2 infection and age, sex, underlying condition and viral load. Transmission from a household member accounted for 132 of 178 (74.2%) children for whom the source of infection was identified. An adult member with COVID-19 was the first case in 125 (66.8%) family clusters. Child-to-adult transmission was found in one occasion only. CONCLUSIONS: SARS-CoV-2 infection is mainly asymptomatic or mild during childhood. Adults appear to play a key role in spread of the virus in families. Most children have moderate or high viral loads regardless of age, symptoms or severity of infection. Further studies are needed to elucidate the role of children in the ongoing pandemic and particularly in light of schools reopening and the need to prioritize groups for vaccination, when COVID-19 vaccines will be available.

emm Types and clusters and macrolide resistance of pediatric group A streptococcal isolates in Central Greece during 2011-2017.

BACKGROUND: The surveillance of emm types and macrolide susceptibility of group A streptococcus (GAS) in various areas and time periods enhances the understanding of the epidemiology of GAS infections and may guide treatment strategies and the formulation of type-specific vaccines. Greece has emerged as a country with high macrolide use. However, studies suggest a gradual reduction in macrolide consumption after 2007. METHODS: During a 7-year period (2011-2017), 604 GAS isolates were recovered from consecutive children presenting with pharyngeal or nonpharyngeal infections in Central Greece; 517 viable isolates underwent molecular analysis, including emm typing. RESULTS: Isolates belonged to 20 different emm types (in decreasing order of prevalence: 1, 89, 4, 12, 28, 3, 75 and 6, accounting for 88.2% of total isolates). The emm types comprised 10 emm clusters (five most common clusters: E4, A-C3, E1, A-C4 and A-C5). The emm89 isolates were acapsular ('new clade'). Overall macrolide resistance rate was 15.4%, and cMLSB emerged as the predominant resistance phenotype (56.4%). The lowest annual resistance rates occurred in 2014 (13.1%), 2016 (5.5%) and 2017(8.0%) (P for trend = 0.002). Consumption of macrolide/lincosamide/streptogramin B declined by 22.6% during 2011-2017. Macrolide resistance and emm28 and emm77 types were associated (both P<0.001). The most frequently identified genetic lineages of macrolide-resistant GAS included emm28/ST52, emm77/ST63, emm12/ST36, emm89/ST101 and emm4/ST39. We estimated that 98.8% of the isolates belonged to emm types incorporated into a novel 30-valent M protein vaccine. CONCLUSIONS: In Central Greece during 2011-2017, the acapsular emm89 isolates comprised the second most prevalent type. Susceptibility testing and molecular analyses revealed decreasing GAS macrolide resistance rates, which may be attributed to the reduction in the consumption of macrolides and/or the reduced circulation of macrolide-resistant clones in recent years. Such data may provide valuable baseline information in targeting therapeutic intervention and the formulation of type-specific GAS vaccines.

Clinical and laboratory features of children with community-acquired pneumonia are associated with distinct radiographic presentations.

Chest radiographs from children with community-acquired pneumonia (CAP) were categorized into three distinct presentations and each presentation was correlated to clinical and laboratory findings. Children < 59 months with CAP presenting to pediatric emergency rooms during two years were enrolled prospectively in eight centers across Europe. Clinical and laboratory data were documented and radiographs obtained from patients. Of the 1107 enrolled patients, radiographs were characterized as 74.9% alveolar CAP, 8.9% non-alveolar CAP, and 16.3% clinical CAP. Alveolar CAP patients had significantly higher rates of fever (90.7%), vomiting (27.6%), and abdominal pain (18.6%), while non-alveolar CAP patients presented more with cough (96.9%). A model using independent parameters that characterize alveolar, non-alveolar, and clinical CAP demonstrated that alveolar CAP patients were significantly older (OR = 1.02) and had significantly lower oxygen saturation than non-alveolar CAP patients (OR = 0.54). Alveolar CAP patients had significantly higher mean WBC (17,760 ± 8539.68 cells/mm3) and ANC (11.5 ± 7.5 cells/mm3) than patients categorized as non-alveolar CAP (WBC 15,160 ± 5996 cells/mm3, ANC 9.2 ± 5.1 cells/mm3) and clinical CAP (WBC 13,180 ± 5892, ANC 7.3 ± 4.7). CONCLUSION: Alveolar CAP, non-alveolar CAP, and clinical CAP are distinct entities differing not only by chest radiographic appearance but also in clinical and laboratory characteristics. Alveolar CAP has unique characteristics, which suggest association with bacterial etiology. TRIAL REGISTRATION: Trial number 3075 (Soroka Hospital, Israel) What is Known: • Community-acquired pneumonia in children is diagnosed based on clinical and radiological definitions. • Radiological criteria were standardized by WHO-SICR and have been utilized in vaccine studies. What is New: • Correlation between the WHO-SICR radiological definitions and clinical and laboratory parameters has not been studied. • Using the WHO-SICR radiological definitions for alveolar community-acquired pneumonia (CAP) and non-alveolar CAP and the study definition for clinical CAP, it was found that the groups are distinct, differing clinically and in laboratory parameters.

Daptomycin Use in Children: Experience With Various Types of Infection and Age Groups.

BACKGROUND: In Greece, there are high rates of methicillin (40%-60%) and clindamycin (15%-25%) resistance among community-acquired Staphylococcus aureus isolates. Therefore, we sought to identify other antimicrobial treatment options such as daptomycin. METHODS: We studied retrospectively all pediatric infections treated with daptomycin at the University General Hospital of Larissa, Greece, from January 1, 2007, to June 16, 2016. RESULTS: Of a total of 128 patients (median age: 2.8 years; range: 8 days to 14.5 years; 76.6% <7 years) treated with daptomycin, 45 (35.2%) had invasive infection, most frequently musculoskeletal, and 83 (64.8%) had noninvasive infection, that is, complicated skin and soft tissue infection. S. aureus was the most commonly recovered pathogen (n = 61) (63.9% methicillin-resistant isolates, 21.3% clindamycin-resistant). The average daily dose of daptomycin was 10 mg/kg qd, and the median duration of therapy was 10 days. Daptomycin was administered alone (n = 61) or in combination therapy (n = 67), most frequently with rifampin (n = 40) and/or a ß-lactam antibiotic (n = 33). Open or closed drainage was performed in 86 (67.2%) of the total number of patients. Of 128 treated patients, 123 (96.1%) achieved clinical success, 114 (89.1%) had complete remission, and 9 (7%) had improvement of their disease. There were no failures with daptomycin therapy. The adverse events were of no clinical significance. CONCLUSIONS: Daptomycin administered alone or in combination with other antimicrobial agents to children was efficacious and well tolerated in the treatment of complicated infections of suspected or proven staphylococcal etiology.

Pneumonia with empyema among children in the first five years of high coverage with 13-valent pneumococcal conjugate vaccine.

BACKGROUND: Parapneumonic effusions in children are usually associated with pneumococcal infections. In Greece, the 7-valent pneumococcal conjugate vaccine was replaced by higher-valent pneumococcal conjugate vaccines (PCVs); 10-valent was introduced in May 2009 and 13-valent (PCV13) in June 2010. Since July 2010, PCV13 has been the most commonly used PCV. In a study conducted at the University General Hospital of Larissa, Central Greece, from January 2012 to January 2016, 85.7% of children born after the implementation of PCV13 and aged 24-59 months had received the complete series (3 + 1 immunization schedule) of PCV13. METHODS: We studied all paediatric community-acquired pneumonia cases with empyema hospitalized at the University General Hospital of Larissa from January 2008 to January 2016. RESULTS: There were 30 cases of parapneumonic empyema. Among 27 empyema cases of known aetiology, 19 (70.4%) were due to Streptococcus pneumoniae (identifiable serotypes 3, 19A, 7F, and 9N/L). After September 2011, no more cases caused by serotypes 7F and 19A were observed, whereas serotype 3 emerged as the predominant pathogen of pneumococcal empyema (9 of 11 cases). Serotype 3 continued to cause empyema despite vaccination with PCV13 either fully with a 3 + 1 schedule (n = 3) or with one booster dose at the age of 21 months (n = 1). CONCLUSION: In Central Greece during the first five years of high coverage with PCV13, serotype 3 was the only PCV13 serotype that clearly persisted in children with empyema.

Comparison between diagnosis and treatment of community-acquired pneumonia in children in various medical centres across Europe with the United States, United Kingdom and the World Health Organization guidelines.

BACKGROUND: The aim of this study was to review the current status and usage of guidelines in the diagnosis and treatment of community-acquired pneumonia (CAP) in European countries and to compare to established guidelines in the United States (US), United Kingdom (UK), and the World Health Organization (WHO). METHODS: A questionnaire was developed and distributed by the Community-Acquired Pneumonia Paediatric Research Initiative (CAP-PRI) working group and distributed to medical centres across Europe. RESULTS: Out of 19 European centres, 6 (31.6 %) used WHO guidelines (3 in combination with other guidelines), 5 (26.3 %) used national guidelines, and 5 (26.3 %) used local guidelines. Chest radiograph and complete blood count were the most common diagnostic examinations, while evaluation of clinical symptoms and laboratory tests varied significantly. Tachypnoea and chest recession were considered criteria for diagnosis in all three guidelines. In US and UK guidelines blood cultures, atypical bacterial and viral detection tests were recommended. In European centres in outpatient settings, amoxicillin was used in 16 (84 %) centers, clarithromycin in 9 (37 %) centers and azithromycin in 7 (47 %) centers, whereas in hospital settings antibiotic treatment varied widely. Amoxicillin is recommended as the first drug of choice for outpatient treatment in all guidelines. CONCLUSIONS: Although local variations in clinical criteria, laboratory tests, and antibiotic resistance rates may necessitate some differences in standard empirical antibiotic regimens, there is considerable scope for standardisation across European centres for the diagnosis and treatment of CAP.

Rotavirus Gastroenteritis in a Neonatal Unit of a Greek Tertiary Hospital: Clinical Characteristics and Genotypes.

INTRODUCTION: Rotavirus (RV) infection in neonatal age can be mild or even asymptomatic. Several studies have reported that RV is responsible for 31%-87% of pediatric nosocomial diarrhea and causes gastroenteritis outbreaks in pediatric and neonatal units. OBJECTIVES: Study clinical characteristics, genotypes and risk factors of RV infection in neonatal age. METHODS: A prospective study was conducted from April 2009 till April 2013 in the neonatal special care unit of the largest tertiary pediatric hospital of Greece. Fecal samples and epidemiological data were collected from each neonate with gastrointestinal symptoms. RV antigen was detected with a rapid immunochromatography test. RV positive samples were further genotyped with RT PCR and sequencing using specific VP7 and VP4 primers. RESULTS: Positive for RV were 126/415 samples (30.4%). Mean age of onset was 18 days. Seventy four cases (58%) were hospital acquired. Seasonality of RV infection did not differ significantly throughout the year with the exception of 4 outbreaks. Genotypes found during the study period were G4P[8] (58.7%), G1P[8] (14.7%), G12P[8] (9.3%), G3P[8] (9.3%), G12P[6] (5.3%), G9P[8] (1.3%) and G2P[4] (1.3%). RV cases presented with: diarrhea (81%), vomiting (26.2%), fever (34.9%), dehydration (28.6%), feeding intolerance (39.7%), weight loss (54%), whilst 19% of cases were asymptomatic. Comparing community with hospital acquired cases differences in clinical manifestations were found. CONCLUSIONS: Significant incidence of nosocomially transmitted RV infection in neonatal age including asymptomatic illness exists. Genotypes causing nosocomial outbreaks are not different from community strains. Circulating vaccines can be effective in prevention of nosocomial RV infection through herd immunity.

Kingella kingae sequence type-complex 14 arthritis in a 16-month-old child in Greece.

We describe the first case of Kingella kingae arthritis in a 16-month-old girl in Greece, which has been diagnosed by novel molecular techniques. A joint aspiration of her knee was performed before the initiation of antibiotics, as well as on the 5th and 14th day of empiric antimicrobial therapy. The synovial fluid white blood cell count decreased from 65,000 to 1500 cells/mm, but the percentage of neutrophils remained 90% in all 3 specimens. Molecular analysis of the synovial fluid specimens by real-time polymerase chain reaction and multilocus sequence typing enabled us to reveal the presence of K. kingae belonging to the international sequence type-complex 14, which persisted up to the fifth day of antibiotic therapy.

Dynamics of pneumococcal carriage among day-care center attendees during the transition from the 7-valent to the higher-valent pneumococcal conjugate vaccines in Greece.

BACKGROUND: In Greece recently, higher-valent pneumococcal conjugate vaccines (PCVs) replaced the 7-valent (PCV7); the 10-valent (PCV10) became available in May 2009 and the 13-valent (PCV13) in June 2010. METHODS: We investigated the nasopharyngeal colonization with Streptococcus pneumoniae in day-care center attendees in Athens and the prefecture of Viotia. Between December 2010 and June 2011, nasopharyngeal cultures were obtained 4 times, at enrollment and then every 6 to 8 weeks. RESULTS: Among the 233 children, 225 (96.6%) had been vaccinated with ≥1 dose of PCV7. One tenth of the PCV7 vaccinated attendees had also received ≥1 dose of PCV13 or PCV10. During the 4 samplings, 358 isolates were recovered from a total of 874 samples. Of the 233 children, 183 (78.5%) were found to carry S. pneumoniae at least once. The overall serotype distribution among carriers was similar regardless of the time lapsed since the last PCV7 dose. A high frequency of 19A (17.1%) coincided with a low frequency of 19F (1.4%). Non-PCV13 serotypes accounted for 73.1% of the isolates; 23B, 15B/C, 16F, 21, 11A, 15A, 6C, 10A, 22F and 23A were the most common. Among attendees aged 24-59 months (median age 42 months), prolonged carriage of a non-PCV13 serotype was relatively common, mainly for 21 and 16F. One out of 4 cases of colonization with the prevalent non-PCV13 serotypes was followed by persistent carriage for 5 to 14 weeks. CONCLUSIONS: During this period of transition to the higher-valent PCVs in the day-care center setting, non-PCV13 serotypes dominated and exhibited prolonged colonization. The frequency and the duration of prolonged carriage tends to be increased, if sampling frequency increases and the carriage time before and after positive cultures is taken into consideration. Further studies regarding the fitness of the colonizing non-PCV13 serotypes will likely to be seen in the future.