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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.

Competing Interests: The authors have no funding or conflicts of interest to disclose.

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., Competing Interests: Declaration of competing interest The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

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., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Japanese Society for Immunology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

We aimed to determine the epidemiology and resistance patterns of Gram-negative bacteria, the risk factors and outcome of bloodstream infection (BSI). In all, 412 episodes in children who were hospitalized with the diagnosis of bacteremia were analyzed. The most common microorganisms were Klebsiella spp. (43.9%), Escherichia coli (13.5 %) and Acinetobacter spp. (10.6 %). Among isolates, 41.2 % were multidrug-resistant, 13.5 % were extensively drug-resistant and 0.4 % were pan-drug-resistant. Carbapenem resistance was revealed in 27.6 % of isolates. Carbapenem and colistin resistance increased over the years. The most common risk factors were the presence of a central-venous catheter and pediatric intensive care unit admission. Clinical response and infection-related mortality were significantly different in cases infected with carbapenem-resistant gram-negative (CRGN) vs carbapenem-susceptible gram-negative bacteria. The increase in multi-resistant Klebsiella spp. seems to be the biggest obstacles in fight against nosocomial infections. The increasing number of CRGN infections over the years affects both the clinical response and mortality rate of BSI., Competing Interests: Declaration of competing interest The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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 İhsan Doğramacı 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., (© 2023. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Background: Data on infections in children are scarce in the context of earthquakes. Here, we describe our clinical experiences regarding infections in pediatric victims after the earthquakes in Kahramanmaraş/Türkiye., Methods: Trauma patients after the Kahramanmaraş earthquakes, aged under 18 years and admitted to our hospital, were evaluated retrospectively. The patients' demographic data, pathogen distribution, drug resistance, and antibiotic treatments were analyzed., Results: Thirty pediatric patients were admitted to our hospital from disaster areas. The median duration under the rubble of patients was 24 h (range: 0.3-120 h). The median time for these patients to arrive our hospital was 5 days (range: 2-18 h). All of them had wound infections, 3.3% of patients had both wound infection and urinary tract infection, and 13.3% had both a bloodstream infection and a wound infection. Seventy-nine positive cultures were detected in repeated samples of 19 patients, of which polymicrobial infections accounted for 50.6% and monomicrobial infections constituted 49.4%. Of these, 107 were Gram-negative bacilli (79.9%), and 27 were Gram-positive cocci (20.1%). Pan-drug-resistant (PDR) and extensively drug-resistant (XDR) possible PDR bacteria constituted 73.6% of total Gram-negative bacteria. Carbapenem-based treatments (n = 14, 46.7%) were the commonly preferred antimicrobial regimen. Fasciotomy was performed in 53.3% of the patients (n = 16) and amputation in 30% of the patients (n= 9). All of our patients survived., Conclusion: Factors that reduced mortality and morbidity in the earthquake victims were broad-spectrum antibiotic therapy targeting highly resistant bacteria, and complementary surgical management. In other words, the multidisciplinary approaches of pediatricians and surgical departments were life saving after the earthquake., (© 2024 Japan Pediatric Society.)

Background: There is a crucial balance between oxidant and antioxidant defense mechanisms. We aimed to evaluate the role of the balance of these systems in children with bloodstream infection., Methods: We analyzed prospectively oxidant and antioxidant stress parameters from serum samples of children with BSI besides demographic and clinical data of children. Serum levels of the total antioxidant status (TAS), total oxidant status (TOS), albumin, plasma thiol, disulphide, catalase (CAT), myeloperoxidase (MPO), ischemia-modified albumin (IMA) levels, ferroxidase and arylesterase (ARES) activity were evaluated in both patients and healthy controls., Results: A total of 113 children were evaluated, 50 of them had bacteremia and the remaining 63 were healthy subjects. The median TOS values were 18.5 µmol H2O2/L and 13.1 µmol H2O2/L in patient and control groups, respectively with a statistically significant difference between groups. The mean serum IMA levels were 0.8±0.1 absorbance unit (ABSU) in patients and 0.5±0.09 ABSU in control, the difference between groups was statistically significant. The native thiol, total thiol levels and the disulphide levels were significantly lower in the patient group as compared with the control group. The myeloperoxidase level was 136 U/L in patients and 107 in controls with a statistically significant difference between groups., Conclusions: TOS, IMA, MPO, and particularly plasma thiols seem good candidates for accurate diagnosis of bacteremia in children.

Multisystem inflammatory syndrome in children (MIS-C) is a serious condition characterized by excessive inflammation that can arise as a complication of SARS-CoV-2 infection in children. While our understanding of COVID-19 and MIS-C has been advancing, there is still uncertainty regarding the optimal treatment for MIS-C. In this study, we aimed to compare the clinical and laboratory outcomes of MIS-C patients treated with IVIG plus corticosteroids (CS) to those treated with IVIG plus CS and an additional biologic drug. We used the propensity score (PS)-matching method to assess the relationships between initial treatment and outcomes. The primary outcome was a left ventricular ejection fraction of less than 55% on day 2 or beyond and/or the requirement of inotrope support on day 2 or beyond. We included 79 MIS-C patients (median age 8.51 years, 33 boys) followed in our center. Among them, 50 children (25 in each group) were allocated to the PS-matched cohort sample. The primary outcome was observed in none of the patients in the IVIG and CS group, while it occurred in eight patients in the IVIG plus CS and biologic group ( p = 0.04). MIS-C is a disorder that may progress rapidly and calls for extensive care. For definitive recommendations, further studies, including randomized control trials, are required.

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., (© 2023 Japan Pediatric Society.)

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., (© 2023 Japan Pediatric Society.)

Backgrounds: Abdominal pain is one of the most common symptoms of multisystem inflammatory syndrome in children (MIS-C). Abdominal pain can vary from mild to severe and may present as acute abdomen. Severe abdominal pain in patients with MIS-C should be differentiated from surgical causes of acute abdomen to prevent unnecessary surgery., Methods: The diagnosis of MIS-C was based on WHO and CDC recommended criteria. Records of children treated for MIS-C between September 2020 and January 2021 were reviewed retrospectively., Results: In a short time, we encountered seven patients who were diagnosed with MIS-C and showed acute abdomen findings. There were four male and three female patients. The median age was 9 years. Fever, abdominal pain and distension were present in all. The median duration of symptoms was 4 days. Five patients had general abdominal tenderness mimicking acute abdomen. Three patients had right lower quadrant tenderness mimicking acute appendicitis. After the initiation of immunomodulatory therapy and antibiotics, the physical examination findings were improved step by step in all. The median time to initiate oral feeding was 2 days. The median length of hospitalization time was 8 days., Conclusion: Serial abdominal examinations performed by the same surgeon enabled us to follow these patients conservatively and thus avoid unnecessary surgical intervention., (© 2022 Royal Australasian College of Surgeons.)

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., (© 2022. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

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., (© Japan College of Rheumatology 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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/mm 3 (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., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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., (© 2022. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Background: The pathogenesis of multiple sclerosis (MS) involves immune-mediated mechanisms, and disease-modifying therapies (DMTs) administered in MS have immunomodulatory effects. The concern about MS patients' susceptibility to coronavirus disease 2019 (COVID-19) has prompted several studies based on clinical observations and questionnaires. Information about COVID-19 in pediatric-onset multiple sclerosis (POMS) is scarce. The objective of this study was to collect information on the experience of POMS patients with COVID-19 during the pandemic., Methods: This cross-sectional study was conducted with POMS patients diagnosed at Hacettepe University Pediatric Neurology Department and under 23 years of age between October 1 and December 31, 2021. Those who experienced COVID-19 or had a history of contact and were found seropositive for COVID-19 were evaluated for the severity of COVID-19, disability, treatment status, and comorbidities., Results: Among the 101 POMS patients, 13 reported having had COVID-19 and five were exposed and seropositive but clinically asymptomatic. Of these 18 patients, 14 were ≤18 years of age at the time of the study. All 13 patients (72%) reported mild symptoms without hospitalization or respiratory support. Four of 18 had a neurological disability (Expanded Disability Status Scale [EDSS] scores ranging between 1 and 7.5), while the remaining had a score of 0. The outcome of COVID-19 was not affected by DMTs, neurological disabilities, and comorbidities., Conclusions: In this single-center POMS series, the small subgroup of patients who had contacted the SARS-CoV-2 virus or developed COVID-19 had reported no or mild symptoms. This may be partly related to the infrequent use of rituximab in this group. Our results corroborate those in adult-onset MS where no increased risk is reported for patients whose EDSS scores are <6 and who are not on B cell-depleting DMTs. Although less frequently than in adult MS, immunosuppressive DMTs may be needed in POMS; therefore, the importance of appropriate vaccination is to be underlined., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: It is not clear whether asthma, the most frequent chronic disease in childhood, is a risk for severe SARS-CoV-2 infection in the pediatric population and how SARS-CoV-2 infection affects the lung functions in these patients., Purpose: We aimed to investigate the course and the consequences of SARS-CoV-2 infection among children with asthma and determine the risk factors for the decline in lung function tests (LFTs)., Methods: In this retrospective study, asthmatic children with coronavirus disease 2019 (COVID-19) were compared with a random control group of asthmatic patients without COVID-19. In addition, the clinical course and the effect on LFTs of COVID-19 among children with asthma were also evaluated., Results: One hundred eighty-nine patients who had COVID-19, and 792 who did not were included in the study. Fever, fatigue, and cough were the most frequent symptoms during COVID-19. Regarding the severity of COVID-19, 163 patients (87.6%) had a mild clinical condition, 13 (7%) had moderate disease, 1 (0.5%) had severe disease, and 2 had (1.1%) critically ill disease. Two patients were diagnosed with multisystem inflammatory syndrome in children (MIS-C), one patient suffered from pneumothorax. LFTs of the patients before and after COVID-19 infection were analyzed; no significant differences were found in FEV 1 % (91.7% vs. 90.9%, p = 0.513), FVC% (89.8% vs. 90.8%, p = 0.502) and FEV 1 /FVC (103.1% vs. 100.6%, p = 0.056), while FEF25%-75% values (107.6% vs. 98.4%, p < 0.001) were significantly lower after the COVID-19 infection. Obesity (odds ratio [OR]: 3.785, 95% confidence interval [CI]: 1.152-12.429, p = 0.028] and having a family history of atopy (OR: 3.359, 95% CI: 1.168-9.657, p = 0.025] were found to be the independent risk factors for ≥25% decrease in FEF25-75 after COVID-19 infection., Conclusion: COVID-19 infection leads to dysfunction of the small airways in asthmatic children and obesity is an independent risk factor for a ≥25% decrease in FEF25-75. The long-term effects of COVID-19 infection especially on small airways require close monitoring in children with asthma., (© 2022 Wiley Periodicals LLC.)

Background: Since December 2019, coronavirus disease 2019 (COVID-19) has become a global pandemic caused by highly transmissible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although respiratory disease and multisystem inflammatory syndrome in children (MIS-C) are main clinical presentations in children, numerous neurological manifestations are being described increasingly. We aimed to investigate new onset neurological symptoms associated with SARS-CoV-2 in pediatric patients in order to establish a possible relationship as well as to understand the underlying pathophysiological mechanisms between SARS-CoV-2 infection and neurological findings., Methods: We analyzed retrospectively children who had neurologic manifestations temporally associated with SARS-CoV-2 infection at Hacettepe University İhsan Doğramaci Children's Hospital. We performed a literature search between March 20, 2020 and March 30, 2021. Articles that report children with COVID-19 related neurological manifestations were included., Results: We have observed 15 consecutive cases with new onset neurological manifestations along with confirmed SARS-CoV-2 infection. Age at hospitalization ranged from three months to 17 years. Ten patients had central nervous system involvement, and most common manifestation was encephalopathy (5/10), which is also one of the most common manifestations of the patients mentioned in the relevant 39 articles we reviewed., Conclusion: Children with COVID-19 can present with neurologic findings such as encephalopathy, seizures, cerebrovascular events as well as abnormal eye movements. Clinical suspicion and awareness are required to show the association between neurologic manifestations and COVID-19., (© 2022 Published by Elsevier Ltd on behalf of European Paediatric Neurology Society.)

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., (© Japan College of Rheumatology 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The rising number of infections due to Severe Acute Respiratory Syndrome Coronavirus-2 (popularly known as COVID-19) has brought to the fore new antiviral drugs as possible treatments, including favipiravir. However, there is currently no data regarding the safety of this drug in patients with kidney impairment. The aim of this paper, therefore, is to share our experience of the use of favipiravir in pediatric patients affected by COVID-19 with any degree of kidney impairment., Methods: The study enrolled pediatric patients aged under 18 years and confirmed as suffering from COVID-19 and multisystem inflammatory syndrome in children (MIS-C) with any degree of kidney injury, who were treated with favipiravir at the time of admission., Results: Out of a total of 11 patients, 7 were diagnosed with MIS-C and 4 with severe COVID-19. The median age of the cases was 15.45 (9-17.8) years and the male/female ratio was 7/4. At the time of admission, the median serum creatinine level was 1.1 mg/dl. Nine patients were treated with favipiravir for 5 days, and 2 patients for 5 days followed by remdesivir for 5-10 days despite kidney injury at the time of admission. Seven patients underwent plasma exchange for MIS-C while 2 severely affected cases underwent continuous kidney replacement therapy (CKRT) as well. One severe COVID-19 patient received plasma exchange as well as CKRT. Serum creatinine values returned to normal in mean 3.07 days., Conclusions: Favipiravir seems a suitable therapeutic option in patients affected by COVID-19 with kidney injury without a need for dose adjustment., (© 2021. IPNA.)

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., (© 2021 Wiley Periodicals LLC.)

Background: There are conflicting data with regard to the impact of respiratory and allergic comorbidities on the course of novel coronavirus disease 2019 (COVID-19) in children. Objective: This study aimed to investigate the relationship between allergic diseases and COVID-19 severity in pediatric patients. Methods: Seventy-five pediatric patients with COVID-19 were classified according to clinical severity and evaluated in the allergy/immunology and pulmonology departments 1 to 3 months after the infection resolved. Blood was collected from the patients for a complete blood cell count and assessment of immunoglobulin and total immunoglobulin E (IgE) levels, and skin-prick tests and spirometry tests were performed. Results: A total of 75 patients ages 5-18 years were evaluated. COVID-19 was asymptomatic/mild in 44 patients and moderate/severe/critical in 31 patients. Based on allergy evaluation, allergic rhinitis was diagnosed in 19 patients (25.3%), asthma in 10 patients (13%), and atopic dermatitis in 3 patients (4%). Aeroallergen sensitivity was detected in 26 patients (34.7%). COVID-19 infection was asymptomatic/mild in 15 patients with allergic rhinitis (78.9%) and in 21 with aeroallergen sensitivity (80.8%) (p = 0.038 and p = 0.005, respectively). There was no difference in severity between the patients with and without asthma (p = 0.550). The median (interquartile range) total IgE level was significantly higher in the asymptomatic/mild group (71.8 [30.7-211.2]) (p = 0.015). There were no differences in terms of spirometry parameters. Conclusion: Aeroallergen sensitization and allergic rhinitis in children may be associated with a milder course of COVID-19. The knowledge that atopy is associated with less-severe COVID-19 outcomes in children may guide clinical risk classification.

Background: A crucial balance exists between oxidant and antioxidant mechanisms in the functional immune system. We aimed to evaluate the contributions of balance between these systems to coronavirus disease 2019 (COVID-19), a devastating pandemic caused by viral infection., Method: We analyzed serum oxidant and antioxidant stress parameters according to the clinical and demographic characteristics of children and adults with COVID-19 and compared them against the values of healthy controls. Serum native thiol (NT), total thiol (TT), disulfide, total antioxidant status, total oxidant status, and ischemia-modified albumin levels were evaluated and compared between groups., Results: A total of 79 children and 74 adults were evaluated in the present study, including 46 children and 40 adults with COVID-19, 33 healthy children, and 34 healthy adults. TT, NT, and disulfide levels were significantly lower in the adult COVID-19 group than in all other groups (p = .001, p = .001, and p = .005, respectively). Additionally, TT and NT levels were significantly lower in both pediatric and adult COVID-19 cases with severe disease course than mild/moderate course. TT and NT levels were identified as predictors for the diagnosis of the adult COVID-19 cases and as independent predictors for disease severity in both children and adults with COVID-19., Conclusion: Parameters that reveal the oxidant and antioxidant capacity, including TT and NT, appear to be good candidates for the accurate prediction of the clinical course among patients with COVID-19., (© 2021 Wiley Periodicals LLC.)

Introduction: Antibody response developed within 2-3 weeks after exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been shown to decrease over time; however, there is limited data about antibody levels at 6 months or later postinfection, particularly in children., Materials and Method: A prospective multicenter study was performed using 315 samples of 74 confirmed and 10 probable coronavirus disease 2019 pediatric cases. About 20% of these cases were classified as asymptomatic, 74% as mild/moderate and 6% as severe/critical. Patients were included if at least 2 samples were available. The antibody response was classified as either early-period or late-period (14 days-3 months and after 6 months, respectively) for IgG response whereas IgA response was tested on various time intervals, including as early as 4 days up to 3 months. Euroimmun Anti-SARS-CoV-2 IgG and IgA and Genscript SARS-CoV-2 Surrogate Virus Neutralization Kits were used for antibody detection., Results: There was no difference between the early-period and late-period IgG positivity (P = 0.1). However, the median IgG levels were 11.98 in the early periods and 4.05 in the late periods, with a significance of P < 0.001. Although the decrease in IgG levels was significant in asymptomatic and mild/moderate cases (P < 0.008 and P < 0.001, respectively), the decrease in severe/critical cases was moderate (P = 0.285). The sensitivity of the IgG after 15 days was higher than 94%, and the sensitivity of IgA was 88% on days 8-15., Conclusion: SARS-CoV-2 IgG antibody levels decreased after 6 months. The decrease was moderate in severe/critical cases. Overall, 95.8% of the patients remained positive up to 9 months after infection. Although the IgA response may be useful early on, the IgG response is useful after 14 days., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: We aimed to describe the typical clinical and laboratory features and treatment of children diagnosed with multisystem inflammatory syndrome in children (MIS-C) and to understand the differences as compared to severe/critical pediatric cases with COVID-19 in an eastern Mediterranean country., Methods: Children (aged <18 years) who diagnosed with MIS-C and severe/critical pediatric cases with COVID-19 and were admitted to hospital between March 26 and November 3, 2020 were enrolled in the study., Results: A total of 52 patients, 22 patients diagnosed with COVID-19 with severe/critical disease course and 30 patients diagnosed with MIS-C, were included in the study. Although severe COVID-19 cases and cases with MIS-C share many clinical and laboratory features, MIS-C cases had longer fever duration and higher rate of the existence of rash, conjunctival injection, peripheral edema, abdominal pain, altered mental status, and myalgia than in severe cases (p<0.001 for each). Of all, 53.3% of MIS-C cases had the evidence of myocardial involvement as compared to severe cases (27.2%). Additionally, C-reactive protein (CRP) and white blood cell (WBC) are the independent predictors for the diagnosis of MIS-C, particularly in the existence of conjunctival injection and rash. Corticosteroids, intravenous immunoglobulin (IVIG), and biologic immunomodulatory treatments were mainly used in MIS-C cases rather than cases with severe disease course. There were only three deaths among 52 patients, one of whom had Burkitt lymphoma and the two cases with severe COVID-19 of late referral., Conclusion: Differences between clinical presentations, acute phase responses, organ involvements, and management strategies indicate that MIS-C might be a distinct immunopathogenic disease as compared to pediatric COVID-19. Conjunctival injection and higher CRP and low WBC count are reliable diagnostic parameters for MIS-C cases. Key Points • MIS-C cases had longer fever duration and higher rate of the existence of rash, conjunctival injection, peripheral edema, abdominal pain, altered mental status, and myalgia than in severe/critical pediatric cases with COVID-19. • Higher CRP and low total WBC count are the independent predictors for the diagnosis of MIS-C. • MIS-C might be a distinct immunopathogenic disease as compared to pediatric COVID-19., (© 2021. International League of Associations for Rheumatology (ILAR).)

Francisella tularensis is the causative agent of tularemia, a zoonotic bacterial infection that is often fatal if not diagnosed and treated promptly. Natural infection in humans is relatively rare, yet persistence in animal reservoirs, arthropod vectors, and water sources combined with a low level of clinical recognition make tularemia a serious potential threat to public health in endemic areas. F. tularensis has also garnered attention as a potential bioterror threat, as widespread dissemination could have devastating consequences on a population. A low infectious dose combined with a wide range of symptoms and a short incubation period makes timely diagnosis of tularemia difficult. Current diagnostic techniques include bacterial culture of patient samples, PCR and serological assays; however, these techniques are time consuming and require technical expertise that may not be available at the point of care. In the event of an outbreak or exposure a more efficient diagnostic platform is needed. The lipopolysaccharide (LPS) component of the bacterial outer leaflet has been identified previously by our group as a potential diagnostic target. For this study, a library of ten monoclonal antibodies specific to F. tularensis LPS were produced and confirmed to be reactive with LPS from type A and type B strains. Antibody pairs were tested in an antigen-capture enzyme-linked immunosorbent assay (ELISA) and lateral flow immunoassay format to select the most sensitive pairings. The antigen-capture ELISA was then used to detect and quantify LPS in serum samples from tularemia patients for the first time to determine the viability of this molecule as a diagnostic target. In parallel, prototype lateral flow immunoassays were developed, and reactivity was assessed, demonstrating the potential utility of this assay as a rapid point-of-care test for diagnosis of tularemia.