Immunogenicity and protective capacity of a CpG ODN adjuvanted alum adsorbed bivalent meningococcal outer membrane vesicle vaccine.

Invasive meningococcal disease (IMD) is caused by Neisseria meningitidis, with the main serogroups responsible for the disease being A, B, C, W, X, and Y. To date, several vaccines targeting N. meningitidis have been developed albeit with a short-lived protection. Given that MenW and MenB are the most common causes of IMD in Europe, Turkey, and the Middle East, we aimed to develop an outer membrane vesicle (OMV) based bivalent vaccine as the heterologous antigen source. Herein, we compared the immunogenicity, and breadth of serum bactericidal activity (SBA) assay-based protective coverage of OMV vaccine to the X serotype with existing commercial meningococcal conjugate and polysaccharide (PS) vaccines in a murine model. BALB/c mice were immunized with preclinical batches of the W + B OMV vaccine, either adjuvanted with Alum, CpG ODN, or their combinations, and compared with a MenACYW conjugate vaccine (NimenrixTM, Pfizer), and a MenB OMV-based vaccine (Bexsero®, GSK), The immune responses were assessed through enzyme-linked immunosorbent assay (ELISA) and SBA assay. Antibody responses and SBA titers were significantly higher in the W + B OMV vaccine when adjuvanted with Alum or CpG ODN, as compared to the control groups. Moreover, the SBA titers were not only significantly higher than those achieved with available conjugated ACYW vaccines but also on par with the 4CMenB vaccines. In conclusion, the W + B OMV vaccine demonstrated the capacity to elicit robust antibody responses, surpassing or matching the levels induced by licensed meningococcal vaccines. Consequently, the W + B OMV vaccine could potentially serve as a viable alternative or supplement to existing meningococcal vaccines.

Plasma Extracellular Vesicles Derived from Pediatric COVID-19 Patients Modulate Monocyte and T Cell Immune Responses Based on Disease Severity.

BACKGROUND: The COVID-19 pandemic has caused significant morbidity and mortality globally. The role of plasma-derived extracellular vesicles (EVs) in pediatric COVID-19 patients remains unclear. METHODS: We isolated EVs from healthy controls (n = 13) and pediatric COVID-19 patients (n = 104) with varying severity during acute and convalescent phases using serial ultracentrifugation. EV effects on healthy PBMCs, naïve CD4+ T cells, and monocytes were assessed through in vitro assays, flow cytometry, and ELISA. RESULTS: Our findings indicate that COVID-19 severity correlates with diverse immune responses. Severe acute cases exhibited increased cytokine levels, decreased IFNγ levels, and lower CD4+ T cell and monocyte counts, suggesting immunosuppression. EVs from severe acute patients stimulated healthy cells to express higher PDL1, increased Th2 and Treg cells, reduced IFNγ secretion, and altered Th1/Th17 ratios. Patient-derived EVs significantly reduced proinflammatory cytokine production by monocytes (p < .001 for mild, p = .0025 for severe cases) and decreased CD4+ T cell (p = .043) and monocyte (p = .033) populations in stimulated healthy PBMCs. CONCLUSION: This study reveals the complex relationship between immunological responses and EV-mediated effects, emphasizing the impact of COVID-19 severity. We highlight the potential role of plasma-derived EVs in early-stage immunosuppression in severe COVID-19 patients.

Acute kidney injury in children with moderate-severe COVID-19 and multisystem inflammatory syndrome in children: a referral center experience.

BACKGROUND: Data on the characteristics of acute kidney injury (AKI) in pediatric COVID-19 and MIS-C are limited. We aimed to define the frequency, associated factors and early outcome of AKI in moderate, severe or critical COVID-19 and MIS-C; and to present a tertiary referral center experience from Türkiye. METHODS: Hospitalized patients ≤ 18 years of age with confirmed COVID-19 or MIS-C at Ihsan Dogramaci Children's Hospital, Hacettepe University, between March 2020-December 2021 were enrolled. The characteristics of AKI in the COVID-19 group were investigated in moderate, severe and critically ill patients; patients with mild COVID-19 were excluded. RESULTS: The median (Q1-Q3) age in the COVID-19 (n = 66) and MIS-C (n = 111) groups was 10.7 years (3.9-15.2) and 8.7 years (4.5-12.7), respectively. The frequency of AKI was 22.7% (15/66) in COVID-19 and 15.3% (17/111) in MIS-C; all MIS-C patients with AKI and 73.3% (11/15) of COVID-19 patients with AKI had AKI at the time of admission. Multivariate analyses revealed need for vasoactive/inotropic agents [Odds ratio (OR) 19.233, p = 0.002] and presence of vomiting and/or diarrhea (OR 4.465, p = 0.036) as independent risk factors of AKI in COVID-19 patients; and need for vasoactive/inotropic agents (OR 22.542, p = 0.020), procalcitonin and ferritin levels as independent risk factors of AKI in the MIS-C group. Age was correlated with lymphocyte count (r = -0.513, p < 0.001) and troponin level (r = 0.518, p < 0.001) in MIS-C patients. Length of hospital stay was significantly longer in both groups with AKI, compared to those without AKI. Mortality was 9.1% in the COVID-19 group; and was associated with AKI (p = 0.021). There was no mortality in MIS-C patients. AKI recovery at discharge was 63.6% in COVID-19 survivors and 100% in MIS-C patients. CONCLUSIONS: Independent risk factors for AKI were need for vasoactive/inotropic agents and vomiting/diarrhea in moderate, severe or critical COVID-19 patients; and need for vasoactive/inotropic agents and severe inflammation in MIS-C patients. Our findings suggest that inflammation and cardiac dysfunction are associated with AKI in MIS-C patients; and the association with age in this group merits further studies in larger groups. Early outcome is favorable; long-term follow-up for kidney functions is needed.

Is the high dose extended infusion of meropenem useful in the treatment of highly resistant gram-negative bacteria in children?

OBJECTIVES: Multidrug resistant infections present a treatment challenge for clinicians. These infections have been associated with increased morbidity and mortality. Recently, there has been increasing discussion in the literature that high dose extended infusion of meropenem may be helpful. We aimed to evaluate the clinical efficacy of high dose extended infusion of meropenem in the treatment of highly resistant Gram-negative infections. METHODS: This retrospective observational study was conducted between December 2014 and December 2020 at Hacettepe University Ihsan Dogramaci Children's Hospital. Clinical and microbiological data of children diagnosed with invasive multidrug and extremely drug resistant Gram-negative infections were studied. The findings of patients given high dose extended infusion of meropenem were compared with patients who received colistin or tigecycline. RESULTS: Overall, 158 pediatric patients infected with multidrug and extremely drug resistant gram-negatives were enrolled; 76 treated with high-dose prolonged infusion of meropenem; 60 treated with colistin and 22 with tigecycline. The overall clinical response at the end of the treatment was 81.6 % in meropenem group, 83.3 % in colistin group and 77.3 % in tigecycline group (P = 0.821). Microbiological response at the end of the treatment was 81.1 % in meropenem group, 76.4 % in colistin group and 72.2 % in tigecycline group (P = 0.694). CONCLUSION: Meropenem, with an adjusted dose (high-dose and extended), seems a crucial and robust fighting agent in the treatment of pediatric patients infected with highly-resistant Gram-negative bacteria. It may also be useful in preventing the use of the latest fighting tools such as colistin and tigecycline during the antibacterial stewardship process.

Changing Disease Course of Crimean-Congo Hemorrhagic Fever in Children, Turkey.

Crimean-Congo hemorrhagic fever (CCHF), endemic in certain regions of the world, is listed as a priority disease with pandemic potential. Since CCHF was first identified in Turkey, children have been known to experience milder disease than adults. However, during the COVID-19 pandemic, we observed an unusually severe disease course, including hemophagocytic lymphohistiocytosis (HLH). We examined cytokine/chemokine profiles of 9/12 case-patients compared with healthy controls at 3 time intervals. Interferon pathway-related cytokines/chemokines, including interleukin (IL) 18, macrophage inflammatory protein 3α, and IL-33, were elevated, but tumor necrosis factor-α, IL-6, CXCL8 (formerly IL-8), and cytokines acting through C-C chemokine receptor 2 and CCR5 were lower among case-patients than controls. Interferon pathway activation and cytokines/chemokines acting through CCR2 and CCR5 improved health results among children with severe CCHF. Children can experience severe CCHF, including HLH, and HLH secondary to CCHF can be successfully treated with intravenous immunoglobulin and steroid therapy.

Methylprednisolone use in children with severe pneumonia caused by severe acute respiratory syndrome coronavirus 2.

BACKGROUND: This study aimed to evaluate the effectiveness and optimal use of corticosteroids in children with severe coronavirus disease 2019 (COVID-19) pneumonia, for which effective treatment is still lacking with respect to this population. METHODS: We conducted a retrospective study and included patients (aged < 18 years) with severe COVID-19 pneumonia and/or acute respiratory distress syndrome (ARDS) who received standard doses (2-4 mg/kg/day) and high doses (>250 mg/day) of methylprednisolone (MPZ). We adjusted for patients on steroid treatments with a propensity score and compared the side effects of different MPZ doses and patient survival. RESULTS: Fifty-nine patients were included: 61% were male, the median age was 8, interquartile range (IQR) 2-15) years. The overall survival was 84.4% in patients treated with standard-dose MPZ (n = 45, 76.3%) and 92.2% in patients treated with high-dose MPZ (n = 14, 23.7%; p = 0.67). The demographic, clinical, and laboratory data did not differ significantly after propensity score matching, apart from bradycardia, which was a prominent feature of the high-dose group. The clinical and radiological response rates on day 7 were higher and the need for invasive mechanical ventilation (IMV) was lower in the high-dose group. CONCLUSION: The patients with high-dose MPZ had better clinical and radiological responses than those with standard-dose MPZ, although the mortality rate did not differ between standard and high-dose regimens of MPZ.

The comparison of COVID-19 vs seasonal influenza in children.

BACKGROUND: Influenza in children has been well described, whereas there has been a paucity of pediatric data regarding COVID-19. It is crucial for clinicians to differentiate cases of COVID-19 from cases of influenza because of the upcoming influenza season in the new pandemic era. METHODS: This retrospective study included pediatric patients who were diagnosed with laboratory-confirmed COVID-19 between March and September 2020, or seasonal influenza between October 2019 and March 2020. RESULTS: A total of 315 children were included in this study; 151 were diagnosed with influenza and 164 had confirmed COVID-19. The median age of patients with COVID-19 was 10 years (interquartile range [IQR]: 3-15 years), whereas the median age of patients with influenza was 4 years (IQR: 1-6 years) (p = 0.001). In the COVID-19 group, 6.3% of patients had underlying diseases, the most frequent being neurological conditions (3%). In the influenza group, 20.9% of patients had an underlying disease, the most frequent being asthma (14.5%). Fever (odds ratio [OR]: 20.476; 95% confidence interval [CI]: 2.438-171.995; p = 0.005), dyspnea/tachypnea (OR 13.950; 95% CI: 2.607-74.634; p = 0.002), and increased C-reactive protein (CRP) (OR: 7.650; 95% CI: 2.094-27.955; p = 0.002) were main predictors of influenza diagnosis in comparison to COVID-19. Lymphopenia was detected in 43.2% of patients with influenza and 19.9% of patients with COVID-19 (p = 0.001). CONCLUSIONS: The accurate differentiation between "influenza or COVID-19" seems possible by evaluating a combination of factors including cough, fever, vomiting, leucopenia, lymphopenia, pneumonia, in pediatric patients with high CRP as well as age.

New-Onset Ocular Myasthenia after Multisystem Inflammatory Syndrome in Children.

Neurologic complications have been associated with multisystem inflammatory syndrome in children, possibly involving autoimmune mechanisms. Here, we report a 6-year-old girl who developed myasthenia 11 weeks after severe acute respiratory syndrome coronavirus 2 infection and 8 weeks after the onset of severe multisystem inflammatory syndrome in children.

The difference of the inflammatory milieu in MIS-C and severe COVID-19.

BACKGROUND: Coronavirus disease 19 (COVID-19) may have a severe course in children. Multisystem inflammatory syndrome in children (MIS-C) is the post-COVID complication characterized by an exaggerated inflammation, observed in children. However, data on the underlying pathophysiology are sparse. We therefore aimed to assess the cytokine and chemokine profiles of children with MIS-C and compare these to life-threatening severe SARS-CoV-2 and healthy controls (HCs) to shed light on disease pathophysiology. METHODS: Samples of 31 children with MIS-C, 10 with severe/critical COVID-19 and 11 HCs were included. Cytokine and chemokine profiles were studied and compared in between groups. RESULTS: Most cytokines and chemokines related to IL-1 family and IFN-γ pathway (including IL-18 and MIG/CXCL9) and IL-17A were significantly higher in the MIS-C group when compared to the severe/critical COVID-19 group and HCs. IP-10/CXCL10 and IL-10 were higher in both MIS-C patients and severe/critical COVID-19 compared to HCs. CONCLUSION: Our results suggest that IL-1 and IFN-γ pathways play an important role in the pathophysiology of MIS-C. IMPACT: This study defines a pattern of distinctive immune responses in children with MIS-C and in patients with severe/critical COVID-19. As the COVID-19 pandemic continues, biomarkers to identify MIS-C risk are needed to guide our management that study results may shed light on it.

Age and C-reactive protein as modifiers of Kocher criteria in pediatric septic knee monoarthritis.

INTRODUCTION: Although Kocher criteria can distinguish a septic hip from an aseptic cause, they may not apply to a septic knee. We aimed to identify predictors to discriminate septic and aseptic causes of acute knee monoarthritis in children who underwent arthrocentesis. METHODS: We conducted a retrospective cohort study among children who underwent arthrocentesis for suspected septic arthritis of the knee. Collected data included demographic, clinical and laboratory characteristics. We performed univariate and multivariable analyses to identify predictors of the septic knee. We further investigated accuracy of different predictive models. RESULTS: A total of 60 patients who underwent arthrocentesis for suspected knee septic arthritis were included in this study. Septic arthritis of the knee was confirmed in 32 (53%) patients. Age ≤ 5 years (OR 4.237, [95% CI 1.270-14.127], p = 0.019), WBC > 12,000 cells/mm3 (OR 5.059, [95% CI 1.424-17.970], p = 0.012), and CRP > 2 mg/dL (OR 3.180, [0.895-11.298], p = 0.074) were the most important predictors of a septic knee. Three-tier model comprising these three factors (AUC 0.766) and 4-tier model with addition of fever >38.5°C (AUC 0.776) performed better than Kocher criteria (AUC 0.677), modified Kocher criteria (AUC 0.699) and Full Model (adding age ≤ 5 years and CRP >2 mg/dL to Kocher criteria) (AUC 0.746). Full Model successfully ruled out septic arthritis if all 6 criteria were negative. CONCLUSION: Based on these findings, we propose an algorithm to identify low, intermediate and high-risk patients for knee septic arthritis. Our proposed two-step algorithm incorporating major (age, WBC, CRP) and minor (fever, ESR, non-weight bearing) criteria can serve as a simple decision-support tool to justify arthrocentesis in children with suspected knee septic arthritis.

Impact of the COVID-19 pandemic on the frequency of the pediatric rheumatic diseases.

The impact of the COVID-19 pandemic, and implemented restrictions on the frequency of pediatric rheumatic diseases remain unknown, while they have probably prevented common infections in children. We present the effects of the COVID-19 on our pediatric rheumatology practice in a main referral center. We retrospectively reviewed the medical records of patients presenting to pediatric rheumatology department in 4 years before March 2020 and compared it to the pandemic year (March 2020-March 2021). Since there was an overall decrease in patient numbers, we calculated the percentage according to the total number of that year. A total of 32,333 patients were evaluated. The mean annual number of patients decreased by 42% during the COVID-19 pandemic. When follow-up visits (25,156) were excluded, there were 2818 new diagnoses of rheumatic diseases. In the pre-pandemic period, familial Mediterranean fever (FMF) (n = 695, 28.1%) was the most frequent, whereas in the pandemic period multisystem inflammatory syndrome in children (MIS-C) (n = 68, 19.2%) was the most common diagnosis. There were no significant differences in the percentages of juvenile idiopathic arthritis, autoimmune diseases, rare autoinflammatory diseases, and other vasculitides. However, there was a significant decrease in patients diagnosed with FMF, IgA vasculitis (IgAV), acute rheumatic fever (ARF), classic Kawasaki disease (KD), and macrophage activation syndrome (MAS) (all p < 0.05). During the pandemic year, the percentage of most common diseases did not differ. On the other hand, we suggest that the decreases in IgAV, KD (classic), and MAS, which parallels the decrease in ARF, confirm the role of infections in the pathogenesis for these diseases.

Differences and similarities of multisystem inflammatory syndrome in children, Kawasaki disease and macrophage activating syndrome due to systemic juvenile idiopathic arthritis: a comparative study.

To compare the clinical and laboratory findings of multisystem inflammatory syndrome in children (MIS-C), patients with Kawasaki disease (KD) and with macrophage activating syndrome due to systemic juvenile idiopathic arthritis (sJIA-MAS) on real-life data. Patients diagnosed with MIS-C, KD, and sJIA-MAS from 12 different centers in Turkey who were followed for at least 6 months were included in the study. Demographic, clinical, and laboratory findings of all patients were analyzed. A total of 154 MIS-C, 59 KD, and 31 sJIA-MAS patients were included. The median age of patients with MIS-C were higher than those with KD while lower than those with sJIA-MAS (8.2, 3, 12 years, respectively). Myalgia (39.6%), cardiac (50.6%), gastrointestinal (72.7%), and neurological (22.1%) involvements were more common in patients with MIS-C compared to others. MIS-C patients had lower levels of lymphocyte (950 vs 1700 cells/µl) and thrombocyte (173,000 vs 355,000 cells/µl) counts and higher pro-BNP (1108 vs 55 pg/ml) levels than KD. Ferritin levels were higher in patients with MIS-C compared to patients with KD while they were lower than patients with sJIA-MAS (440, 170, 10,442 ng/ml, respectively). Patients with MIS-C had a shorter duration of hospitalization than sJIA-MAS (p = 0.02) while they required intensive care unit admission more frequently (55 vs 8 patients, p < 0.001). The median MAS/sJIA score of MIS-C patients was - 1.64 (- 5.23 to 9.68) and the median MAS/sJIA score of sJIA-MAS patients was -2.81 ([- 3.79] to [- 1.27]). MIS-C patients displayed certain differences in clinical and laboratory features when compared to KD and sJIA-MAS. Definition of the differences and similarities between MIS-C and the other intense inflammatory syndromes of childhood such as KD and MAS will help the clinicians while making timely diagnosis.

Early is superior to late plasma exchange for severe multisystem inflammatory syndrome in children.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) can be life threatening in severe cases because of uncontrolled inflammation and multi-organ failure. In this study, we report the effect of plasma exchange in the treatment of MIS-C and to emphasize the effect of its early application on outcome. METHOD: In this retrospective observational study, the medical records of children with severe MIS-C admitted to pediatric intensive care unit (PICU) between April 2020 and January 2021 were reviewed. Severe MIS-C patients were treated according to protocol consisting of plasma exchange (PE), intravenous immune globulin, steroids, and anakinra which we called the "PISA" protocol referring to the initials. The patients were divided into two groups as early plasma exchange (E-PE) and late plasma exchange (L-PE) according to the elapse time between hospital admission and the administration of PE. Groups were compared in terms of outcome variables. Primary study outcome was 28-day mortality. Secondary outcome variables were acute phase response time, length of immunomodulatory treatment, frequency of patients requiring mechanical ventilation (MV) and inotropic support, length of inotropic support and MV, length of hospital and PICU stays. RESULTS: Eighteen pediatric patients with MIS-C were included in the study. Seventeen (95%) of the patients presented with decompensated shock and required inotropic support. One of the 17 patients needed extracorporeal membrane oxygenation support (ECMO) PISA protocol was used in all patients. There was no mortality in the E-PE group while the mortality rate was 20% in the L-PE group. Acute phase reactant response was faster in the E-PE group and immunomodulatory treatments could be reduced earlier; the frequency of patients requiring inotropic and mechanical ventilation (MV) support was lower in the E-PE group; the duration of inotropic support, duration of MV, and length of stay in hospital and PICU were significantly shorter in the E-PE group. CONCLUSION: We suggest that in selected cases, timely administration of PE is a beneficial rescue therapy for MIS-C related hyperinflammation presenting with severe cardiovascular collapse.

Management of acute abdomen during the active disease course of COVID-19 and multisystem inflammatory syndrome in children.

PURPOSE: To evaluate the management of children with severe gastrointestinal symptoms during the disease course of COVID-19 and multisystem inflammatory syndrome (MIS-C). METHODS: After ethical approval, we reviewed the medical records, retrospectively, of children with COVID-19 or MIS-C requiring surgical consultation for severe gastrointestinal symptoms. RESULTS: The subjects comprised 15 children, 13 with MIS-C and 2 with COVID-19. Twelve children (80%) had been in known close contact with a person with SARS-CoV-19 and 13 were positive for Anti-SARS-CoV-2 IgG. All the children had experienced fever for at least 1 day and had signs of involvement of two or more systems. Three patients required surgical intervention: one underwent surgical exploration with a presumptive diagnosis of acute appendicitis in the referring center and was transported to our center following clinical deterioration, where a diagnosis of MIS-C was confirmed; and the remaining two developed appendicitis during hospitalization for COVID-19. All three patients had a longer duration of abdominal pain, a higher number of lymphocytes, and a lower level of inflammatory markers than the non-surgically managed patients. None of the patients presenting with MIS-C underwent surgical exploration. CONCLUSION: Gastrointestinal involvement may mimic acute abdomen in children with COVID-19. Thus, children presenting with acute abdomen in the pandemic era require careful evaluation and prompt diagnosis to avoid unnecessary surgical intervention.

Challenges in diagnosing COVID-19 related disease in pediatric patients with rheumatic disease.

OBJECTIVES: Multisystem inflammatory syndrome in children (MIS-C) is a rare but severe condition associated with coronavirus disease 2019. Here we aimed to raise awareness for the symptoms of MIS-C in patients with rheumatic diseases, emphasizing the challenges of the differential features. METHODS: We retrospectively evaluated the demographic and clinical characteristics, laboratory and imaging findings, treatments, and outcomes of six MIS-C patients with previous rheumatic disease. RESULTS: Three of the patients had familial Mediterranean fever (FMF), one had juvenile dermatomyositis, one had systemic juvenile idiopathic arthritis (JIA), and another patient had oligoarticular JIA. All FMF patients presented with fever and abdominal pain, two also had chest pain. The patient with systemic JIA presented with fever, rash, and myalgia. All patients had elevated inflammatory markers and high d-dimer levels. Chest imaging of two FMF patients showed infiltrations compatible with pneumonia. One FMF patient had mildly decreased systolic functions with a shortening fraction of 48% in his echocardiography. Intravenous immunoglobulin and methylprednisolone were administered to all patients. Anakinra was given to four patients. CONCLUSIONS: Clinical and laboratory signs of MIS-C may overlap with the findings of various rheumatic diseases, and this may cause a delay in diagnosis.

Clinical course of COVID-19 infection in paediatric familial Mediterranean fever patients.

OBJECTIVE: To evaluate the course of coronavirus-19 (COVID-19) infection in paediatric familial Mediterranean fever (FMF) patients and to investigate the risk factors for COVID-19 infection. METHODS: Medical records of 100 consecutive paediatric FMF patients and their COVID-19 infection status were evaluated. Age- and gender-matched control group consisted of 51 patients with positive results for severe acute respiratory syndrome coronavirus 2. RESULTS: Twenty-five of 100 paediatric FMF patients were detected to have COVID-19 infection. A history of contact with a COVID-19 case was present in ∼95% of patients in both the FMF and control groups with COVID-19 infection. Asymptomatic infection was detected in two patients in the paediatric FMF group (8.0%) and 17 patients in the control group (33.3%) (P = .017). Mild disease was observed in 23 paediatric FMF patients (92.0%) and 28 control patients (54.9%) (P = .001), whereas moderate disease was present in only 6 control patients (11.7%) (0 vs 11.7%, P = .074). Severe or critical disease was not observed in any patients. CONCLUSION: Paediatric FMF patients receiving colchicine had no moderate COVID-19 disease compared to the control group. We suggest that colchicine use may tune down the severity of the disease even if it does not prevent COVID-19 infection.

Outcome predictors of influenza for hospitalization and mortality in children.

Severity of disease caused by influenza virus and the influencing factors that may be different. Moreover, the disease course actually may not be determined specifically in children because of lower seroprotection rates of children. Herein, the results clinic and outcome data of children with influenza from Turkey were reported. We present here the results from 2013 to 2017. Nasopharyngeal swab samples of the children with influenza were investigated via multiplex polymerase chain reaction. A total of 348 children were diagnosed with influenza; 143 (41.1%) were influenza A, 85 (24.4%) were influenza B, and 120 (34.5%) were mixt infection with other respiratory viruses. Fifty-four percent of children admitted to intensive care unit (ICU) were under 2 years of age (p = .001). Having an underlying disease was detected as the main predictor for both hospitalization and ICU stay according to multiple logistic regression analysis (odds ratio [OR], 11.784: 95% confidence interval [CI], 5.212-26.643; p = .001 and OR, 4.972: 95% CI, 2.331-10.605; p = .001, respectively). Neurological symptoms most frequently seen in cases who died (44.4%; p = .02). Lymphopenia was relatively higher (55.6%) and thrombocytopenia was most frequently seen in cases who died (77.8%) with a significant ratio (p = .001). Underlying diseases was found a risk factor for influenza being hospitalized and being admitted to ICU. Children under 2 years of age and with underlying diseases should be vaccinated particularly in countries where the influenza vaccination is still not routinely implemented in the immunization schedule. Highlights Underlying diseases is a risk factor for influenza to be hospitalized and admitted to ICU. Influenza vaccination is of great importance to prevent life-threatening complications of influenza, particularly in children require ICU admission. The possibility to reduce the outpatient visit number by vaccination has a great impact on disease burden in addition to the underestimated crucial social benefits, as well.

Predictive value of cytokine/chemokine responses for the disease severity and management in children and adult cases with COVID-19.

The disease course of children with coronavirus disease 2019 (COVID-19) seems milder as compared with adults, however, actual reason of the pathogenesis still remains unclear. There is a growing interest on possible relationship between pathogenicity or disease severity and biomarkers including cytokines or chemokines. We wondered whether these biomarkers could be used for the prediction of the prognosis of COVID-19 and improving our understanding on the variations between pediatric and adult cases with COVID-19. The acute phase serum levels of 25 cytokines and chemokines in the serum samples from 60 COVID-19 pediatric (n = 30) and adult cases (n = 30) including 20 severe or critically ill, 25 moderate and 15 mild patients and 30 healthy pediatric (n = 15) and adult (n = 15) volunteers were measured using commercially available fluorescent bead immunoassay and analyzed in combination with clinical data. Interferon gamma-induced protein 10 (IP-10) and macrophage inflammatory protein (MIP)-3ß levels were significantly higher in patient cohort including pediatric and adult cases with COVID-19 when compared with all healthy volunteers (p ≤ .001 in each) and whereas IP-10 levels were significantly higher in both pediatric and adult cases with severe disease course, MIP-3ß were significantly lower in healthy controls. Additionally, IP-10 is an independent predictor for disease severity, particularly in children and interleukin-6 seems a relatively good predictor for disease severity in adults. IP-10 and MIP-3ß seem good research candidates to understand severity of COVID-19 in both pediatric and adult population and to investigate possible pathophysiological mechanism of COVID-19.

The association of viral load and disease severity in children with COVID-19.

It is still not fully understood how to predict the future prognosis of patients at the diagnosis coronavirus disease 2019 (COVID-19) due to the wide clinical range of the disease. We aimed to evaluate whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load could predict the clinical course of pediatric patients. This study was conducted retrospectively with medical records of pediatric patients who were tested for SARS-CoV2 between April 12 and October 25, 2020 in the University of Health Sciences, Ankara Educating and Training Hospital and Hacettepe University Faculty of Medicine. We evaluated 518 pediatric patients diagnosed with COVID-19 and classified according to severity as asymptomatic (16.2%), mild (59.6%), moderate (20.2%), and critical/severe (3.9%) cases. We analyzed patients in four groups in terms of ages: <4, 5-9, 10-14, and 15-17 years. There was no statistically significant difference in terms of ∆Ct value among age groups, different gender and the existence of underlying diseases in each disease course. The ∆Ct values were relatively lower in the first 2 days of symptoms than after days in all groups. Our study has indicated that children with COVID-19 have similar amount of viral load in all disease courses irrespective of the age and underlying disease. It should be taken into account that, regardless of the severity of the disease, pediatric patients may have a role in the transmission chain.

Etiological and Clinical Profile of Acute Nonbacterial Encephalitis in Children: A Single-Center Prospective Study.

Encephalitis is a serious neurological syndrome caused by inflammation of the brain. The diagnosis can be challenging and etiology remains unidentified in about half of the pediatric cases. We aimed to investigate demographic, clinical, laboratory, electroencephalographic and neuroimaging findings, and outcome of acute encephalitis of nonbacterial etiology. This prospective study included children hospitalized with the diagnosis of acute encephalitis between 2017 and 2019. Microbiological investigations of the cerebrospinal fluid (CSF) were recorded. All CSF specimens were tested for anti-N methyl D-aspartate receptor (NMDAR) antibodies. In total, 31 children aged 10 months to 17 years (median = 6 years) were included. Pathogens were confirmed in CSF in three patients (9.7%): varicella zoster virus, herpes simplex virus type 1 (HSV-1), and both HSV-1 and NMDAR antibodies. Presenting features included encephalopathy (100%), fever (80.6%), seizure (45.2%), focal neurological signs (29%), and ataxia (19.4%). On clinical follow-up of median 9 (6-24) months, six patients showed neurological deficits: together with two patients who died in hospital, total eight (25.8%) patients were considered to have unfavorable outcome. Need for intubation, receiving immunomodulatory treatment, prolonged hospitalization, and high erythrocyte sedimentation rate at admission were associated with unfavorable outcome. The etiology of encephalitis remains unexplained in the majority of children. HSV-1 is the most frequently detected virus, consistent with the literature. The fact that anti-NMDAR encephalitis was detected in one child suggests autoimmune encephalitis not being rare in our center. The outcome is favorable in the majority while about one-fifth of cases suffer from sequelae.