Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children

We found that 19 (10.4%) of 183 unvaccinated children hospitalized for COVID-19 pneumonia had autoantibodies (auto-Abs) neutralizing type I IFNs (IFN-alpha 2 in 10 patients: IFN-alpha 2 only in three, IFN-alpha 2 plus IFN-omega in five, and IFN-alpha 2, IFN-omega plus IFN-beta in two; IFN-omega only in nine patients). Seven children (3.8%) had Abs neutralizing at least 10 ng/ml of one IFN, whereas the other 12 (6.6%) had Abs neutralizing only 100 pg/ml. The auto-Abs neutralized both unglycosylated and glycosylated IFNs. We also detected auto-Abs neutralizing 100 pg/ml IFN-alpha 2 in 4 of 2,267 uninfected children (0.2%) and auto-Abs neutralizing IFN-omega in 45 children (2%). The odds ratios (ORs) for life-threatening COVID-19 pneumonia were, therefore, higher for auto-Abs neutralizing IFN-alpha 2 only (OR [95% CI] = 67.6 [5.7-9,196.6]) than for auto-Abs neutralizing IFN-. only (OR [95% CI] = 2.6 [1.2-5.3]). ORs were also higher for auto-Abs neutralizing high concentrations (OR [95% CI] = 12.9 [4.6-35.9]) than for those neutralizing low concentrations (OR [95% CI] = 5.5 [3.1-9.6]) of IFN-omega and/or IFN-alpha 2

Multisystem inflammatory syndrome in children associated with COVID-19 in 101 cases from Turkey (Turk-MISC study)

Aim Multisystem inflammatory syndrome in children (MIS-C) may cause shock and even death in children. The aim of this study is to describe the clinical features, laboratory characteristics and outcome of children diagnosed with MIS-C in 25 different hospitals in Turkey. Methods The retrospective study was conducted between 8 April and 28 October 2020 in 25 different hospitals from 17 cities. Data were collected from patients' medical records using a standardised form. Clinical and laboratory characteristics and outcomes according to different age groups, gender and body mass index percentiles were compared using multivariate logistic regression analysis. Results The study comprised 101 patients, median age 7 years (interquartile range (IQR) 4.6-9.3); 51 (50.5%) were boys. Reverse-transcriptase polymerase chain reaction (PCR) assay was positive in 21/100 (21%) patients; 62/83 (74.6%) patients had positive serology for SARS-CoV-2. The predominant complaints were fever (100%), fatigue (n = 90, 89.1%), and gastrointestinal symptoms (n = 81, 80.2%). Serum C-reactive protein (in 101 patients, median 165 mg/L; range 112-228), erythrocyte sedimentation rate (73/84, median 53 mm/s; IQR 30-84) and procalcitonin levels (86/89, median 5 mu g/L; IQR 0.58-20.2) were elevated. Thirty-eight patients (37.6%) required admission to intensive care. Kawasaki disease (KD) was diagnosed in 70 (69.3%) patients, 40 of whom had classical KD. Most patients were treated with intravenous immunoglobulin (n = 92, 91%) and glucocorticoids (n = 59, 58.4%). Seven patients (6.9%) died. Conclusion The clinical spectrum of MIS-C is broad, but clinicians should consider MIS-C in the differential diagnosis when persistent fever, fatigue and gastrointestinal symptoms are prominent. Most patients diagnosed with MIS-C were previously healthy. Immunomodulatory treatment and supportive intensive care are important in the management of cases with MIS-C. Glucocorticoids and intravenous immunoglobulins are the most common immunomodulatory treatment options for MIS-C. Prompt diagnosis and prompt treatment are essential for optimal management

Multicenter Hospital-Based Prospective Surveillance Study of Bacterial Agents Causing Meningitis and Seroprevalence of Different Serogroups of Neisseria meningitidis, Haemophilus influenzae Type b, and Streptococcus pneumoniae during 2015 to 2018 in Turkey

The etiology of bacterial meningitis in Turkey changed after the implementation of conjugated vaccines against Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) in the Turkish National Immunization Program (NIP). Administration of Hib vaccine and PCV-7 (7-valent pneumococcal conjugate vaccine) was implemented in NIP in 2006 and 2009, respectively. In 2011, PCV-7 was replaced with PCV-13. Meningococcal vaccines have not yet been included in Turkish NIP. This prospective study comprised 27 hospitals located in seven regions of Turkey and represented 45% of the population. Children aged between 1 month and 18 years who were hospitalized with suspected meningitis were included. Cerebrospinal fluid (CSF) samples were collected, and bacterial identification was made according to the multiplex PCR assay results. During the study period, 994 children were hospitalized for suspected meningitis, and Hib (n = 3, 2.4%), S. pneumoniae (n = 33, 26.4%), and Neisseria meningitidis (n = 89, 71%) were detected in 125 samples. The most common meningococcal serogroup was MenB. Serogroup W comprised 13.9% (n = 5) and 7.5% (n = 4) of the meningococci in 2015 to 2016 and 2017 to 2018, respectively. Serogroup C was not detected. There were four deaths in the study; one was a pneumococcus case, and the others were serogroup B meningococcus cases. The epidemiology of meningococcal diseases has varied over time in Turkey. Differing from the previous surveillance periods, MenB was the most common serogroup in the 2015-to-2018 period. Meningococcal epidemiology is so dynamic that, for vaccination policies, close monitoring is crucial

Multisystem inflammatory syndrome in children associated with COVID-19 in 101 cases from Turkey (Turk-MISC study)

Aim Multisystem inflammatory syndrome in children (MIS-C) may cause shock and even death in children. The aim of this study is to describe the clinical features, laboratory characteristics and outcome of children diagnosed with MIS-C in 25 different hospitals in Turkey. Methods The retrospective study was conducted between 8 April and 28 October 2020 in 25 different hospitals from 17 cities. Data were collected from patients' medical records using a standardised form. Clinical and laboratory characteristics and outcomes according to different age groups, gender and body mass index percentiles were compared using multivariate logistic regression analysis. Results The study comprised 101 patients, median age 7 years (interquartile range (IQR) 4.6-9.3); 51 (50.5%) were boys. Reverse-transcriptase polymerase chain reaction (PCR) assay was positive in 21/100 (21%) patients; 62/83 (74.6%) patients had positive serology for SARS-CoV-2. The predominant complaints were fever (100%), fatigue (n = 90, 89.1%), and gastrointestinal symptoms (n = 81, 80.2%). Serum C-reactive protein (in 101 patients, median 165 mg/L; range 112-228), erythrocyte sedimentation rate (73/84, median 53 mm/s; IQR 30-84) and procalcitonin levels (86/89, median 5 mu g/L; IQR 0.58-20.2) were elevated. Thirty-eight patients (37.6%) required admission to intensive care. Kawasaki disease (KD) was diagnosed in 70 (69.3%) patients, 40 of whom had classical KD. Most patients were treated with intravenous immunoglobulin (n = 92, 91%) and glucocorticoids (n = 59, 58.4%). Seven patients (6.9%) died. Conclusion The clinical spectrum of MIS-C is broad, but clinicians should consider MIS-C in the differential diagnosis when persistent fever, fatigue and gastrointestinal symptoms are prominent. Most patients diagnosed with MIS-C were previously healthy. Immunomodulatory treatment and supportive intensive care are important in the management of cases with MIS-C. Glucocorticoids and intravenous immunoglobulins are the most common immunomodulatory treatment options for MIS-C. Prompt diagnosis and prompt treatment are essential for optimal management

Antifungal consumption, indications and selection of antifungal drugs in paediatric tertiary hospitals in Turkey: Results from the first national point prevalence survey

WOS: 000452555000048PubMed ID: 30121343Objectives: The aim of this point prevalence survey was to evaluate the consumption, indications and strategies of antifungal therapy in the paediatric population in Turkey. Methods: A point prevalence study was performed at 25 hospitals. In addition to general data on paediatric units of the institutes, the generic name and indication of antifungal drugs, the presence of fungal isolation and susceptibility patterns, and the presence of galactomannan test and high-resolution computed tomography (HRCT) results were reviewed. Results: A total of 3338 hospitalised patients were evaluated. The number of antifungal drugs prescribed was 314 in 301 patients (9.0%). Antifungal drugs were mostly prescribed in paediatric haematology and oncology (PHO) units (35.2%), followed by neonatal ICUs (NICUs) (19.6%), paediatric services (18.3%), paediatric ICUs (PICUs) (14.6%) and haematopoietic stem cell transplantation (HSCT) units (7.3%). Antifungals were used for prophylaxis in 147 patients (48.8%) and for treatment in 154 patients (50.0%). The antifungal treatment strategy in 154 patients was empirical in 77 (50.0%), diagnostic-driven in 29 (18.8%) and targeted in 48 (31.2%). At the point of decision-making for diagnostic-driven antifungal therapy in 29 patients, HRCT had not been performed in 1 patient (3.4%) and galactomannan test results were not available in 12 patients (41.4%). Thirteen patients (8.4%) were receiving eight different antifungal combination therapies. Conclusion: The majority of antifungal drugs for treatment and prophylaxis were prescribed in PHO and HSCT units (42.5%), followed by ICUs. Thus, antifungal stewardship programmes should mainly focus on these patients within the availability of diagnostic tests of each hospital. (C) 2018 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved

Antifungal consumption, indications and selection of antifungal drugs in paediatric tertiary hospitals in Turkey: Results from the first national point prevalence survey

Objectives: The aim of this point prevalence survey was to evaluate the consumption, indications and strategies of antifungal therapy in the paediatric population in Turkey

X-linked recessive TLR7 deficiency in ~1% of men under 60 years old with life-threatening COVID-19

Publisher Copyright: Copyright © 2021Autosomal inborn errors of type I IFN immunity and autoantibodies against these cytokines underlie at least 10% of critical COVID-19 pneumonia cases. We report very rare, biochemically deleterious X-linked TLR7 variants in 16 unrelated male individuals aged 7 to 71 years (mean, 36.7 years) from a cohort of 1202 male patients aged 0.5 to 99 years (mean, 52.9 years) with unexplained critical COVID-19 pneumonia. None of the 331 asymptomatically or mildly infected male individuals aged 1.3 to 102 years (mean, 38.7 years) tested carry such TLR7 variants (P = 3.5 × 10−5). The phenotypes of five hemizygous relatives of index cases infected with SARS-CoV-2 include asymptomatic or mild infection (n = 2) or moderate (n = 1), severe (n = 1), or critical (n = 1) pneumonia. Two patients from a cohort of 262 male patients with severe COVID-19 pneumonia (mean, 51.0 years) are hemizygous for a deleterious TLR7 variant. The cumulative allele frequency for deleterious TLR7 variants in the male general population is <6.5 × 10−4. We show that blood B cell lines and myeloid cell subsets from the patients do not respond to TLR7 stimulation, a phenotype rescued by wild-type TLR7. The patients’ blood plasmacytoid dendritic cells (pDCs) produce low levels of type I IFNs in response to SARS-CoV-2. Overall, X-linked recessive TLR7 deficiency is a highly penetrant genetic etiology of critical COVID-19 pneumonia, in about 1.8% of male patients below the age of 60 years. Human TLR7 and pDCs are essential for protective type I IFN immunity against SARS-CoV-2 in the respiratory tract.Peer reviewe

Multicenter Hospital-Based Prospective Surveillance Study of Bacterial Agents Causing Meningitis and Seroprevalence of Different Serogroups of Neisseria meningitidis, Haemophilus influenzae Type b, and Streptococcus pneumoniae during 2015 to 2018 in Turkey

The etiology of bacterial meningitis in Turkey changed after the implementation of conjugated vaccines against Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) in the Turkish National Immunization Program (NIP). Administration of Hib vaccine and PCV-7 (7-valent pneumococcal conjugate vaccine) was implemented in NIP in 2006 and 2009, respectively. In 2011, PCV-7 was replaced with PCV-13. Meningococcal vaccines have not yet been included in Turkish NIP. This prospective study comprised 27 hospitals located in seven regions of Turkey and represented 45\% of the population. Children aged between 1 month and 18 years who were hospitalized with suspected meningitis were included. Cerebrospinal fluid (CSF) samples were collected, and bacterial identification was made according to the multiplex PCR assay results. During the study period, 994 children were hospitalized for suspected meningitis, and Hib (n = 3, 2.4\%), S. pneumoniae (n = 33, 26.4\%), and Neisseria meningitidis (n = 89, 71\%) were detected in 125 samples. The most common meningococcal serogroup was MenB. Serogroup W comprised 13.9\% (n = 5) and 7.5\% (n = 4) of the meningococci in 2015 to 2016 and 2017 to 2018, respectively. Serogroup C was not detected. There were four deaths in the study; one was a pneumococcus case, and the others were serogroup B meningococcus cases. The epidemiology of meningococcal diseases has varied over time in Turkey. Differing from the previous surveillance periods, MenB was the most common serogroup in the 2015-to-2018 period. Meningococcal epidemiology is so dynamic that, for vaccination policies, close monitoring is crucial. IMPORTANCE Acute bacterial meningitis (ABM) is one of the most common life-threatening infections in children. The incidence and prevalence of ABM vary both geographically and temporally; therefore, surveillance systems are necessary to determine the accurate burden of ABM. The Turkish Meningitis Surveillance Group has been performing a hospital-based meningitis surveillance study since 2005 across several regions in Turkey. Meningococcus was the major ABM-causing agent during the 2015-to-2018 period, during which MenB was the dominant serogroup

Pediatric Neutropenic Patients Care In Turkey

Objective: Infection is a common complication in children with malignancies. There is no consistent guidance for environmental infection control and isolation precautions for neutropenic patients (NP). There are differences between centers. The aim of this questionnaire study was to determine these differences in Turkey. Material and Methods: A multicenter-descriptive questionnaire was conducted on 36 centers from different geografical locations of Turkey. Bone marrow transplantation units were excluded. Each center was contacted at least three-times. Questionnaire was answered by two different doctors from each center. Results: Thirty-six centers including 20 (55.5%) University Hospitals, 12 (%33.3) Research Hospitals, three (8.3%) State Hospital and one Private University Hospital participated in this survey. 94.3% of the centers had a bed capacity of 50 beds and over. Twenty-one (58.3%) centers had pediatric infection ward that followed febrile NP. All centers had an infection control committee. 25% (9/36) of the centers always followed pediatric neutropenic fever patients in a single room. 66.6% (24/36) of the centers had toilet in all patients' room. The door features of patients' room included mostly (94.1%, 32/34) manually opened door. Ten (27.7%) centers had hepa filter system, five of them had positive-negative pressure room. Thirteen (38.2%, 13/34) centers prefered hickmann catheter for accessing a patient's central line. Training was given for catheteter care in all centers. Sixteen (44.4%) centers had determined policies about keeping toys in patient rooms. Visitor restrictions were performed in all centers. None of the centers allowed plants or flowers in hospital rooms. There was a neutropenic diet specific for pediatric NP provided in twenty-seven centers (75%). Conclusion: The prevention and control of infection contributes to the improvement of the prognosis of patients with hematological malignancies. Physicians must be aware of the infection risks and take precautions for infectious complications through the neutropenic period and standard protocols should be established and implemented for patients with hematological malignancies.WoSScopu

Türkiye’ de Pediatrik Nötropenik Hasta İzlemi

Objective: Infection is a common complication in children with malignancies. There is no consistent guidance for environmental infection control and isolation precautions for neutropenic patients (NP). There are differences between centers. the aim of this questionnaire study was to determine these differences in Turkey. Material and Methods: A multicenter-descriptive questionnaire was conducted on 36 centers from different geografical locations of Turkey. Bone marrow transplantation units were excluded. Each center was contacted at least three-times. Questionnaire was answered by two different doctors from each center. Results: Thirty-six centers including 20 (55.5%) University Hospitals, 12 (%33.3) Research Hospitals, three (8.3%) State Hospital and one Private University Hospital participated in this survey. 94.3% of the centers had a bed capacity of 50 beds and over. Twenty-one (58.3%) centers had pediatric infection ward that followed febrile NP. All centers had an infection control committee. 25% (9/36) of the centers always followed pediatric neutropenic fever patients in a single room. 66.6% (24/36) of the centers had toilet in all patients’ room. the door features of patients’ room included mostly (94.1%, 32/34) manually opened door. Ten (27.7%) centers had hepa filter system, five of them had positive-negative pressure room. Thirteen (38.2%, 13/34) centers prefered hickmann catheter for accessing a patient’s central line. Training was given for catheteter care in all centers. Sixteen (44.4%) centers had determined policies about keeping toys in patient rooms. Visitor restrictions were performed in all centers. None of the centers allowed plants or flowers in hospital rooms. There was a neutropenic diet specific for pediatric NP provided in twenty-seven centers (75%). Conclusion: the prevention and control of infection contributes to the improvement of the prognosis of patients with hematological malignancies. Physicians must be aware of the infection risks and take precautions for infectious complications through the neutropenic period and standard protocols should be established and implemented for patients with hematological malignancies.Giriş: Maligniteli hastaların tedavi sürecindeki en önemli komplikasyonlardan biri enfeksiyonlardır. Nötropenik hastalarda enfeksiyon kontrolü ve izolasyon önlemleri için merkezden merkeze değişen farklı uygulamalar mevcuttur. Anket çalışmasının amacı Türkiye’deki bu farklılıkları ve ihtiyaçları belirlemektir. Gereç ve Yöntemler: Çok merkezli tanımlayıcı çalışmaya Türkiye’nin farklı coğrafik bölgelerinden pediatrik nötropenik hasta takip eden 36 merkez dahil edildi. Kemik iliği transplantasyon üniteleri çalışmaya alınmadı. Her merkezle en az üç kez iletişime geçildi. Anketi her merkezden iki doktor yanıtladı. Anket kişisel, genel hasta bakımı ve nötropenik hasta bakımını içeren 64 sorudan oluşmaktaydı. Bulgular: Çalışmaya katılan merkezlerin 20 (%55.5)’si üniversite hastanesi, 12 (%33.3)’si eğitim araştırma hastanesi, 3 (%8.3)’ ü devlet hastanesi ve bir tanesi de özel üniversite hastanesi idi. Merkezlerin %94.3’ünün yatak kapasitesi 50 yatak ve üzerinde idi. Yirmi bir (%58) merkezin çocuk enfeksiyon hastalıkları servisi mevcuttu. Tüm merkezlerin enfeksiyon kontrol komitesi vardı. Merkezlerin %25 (n= 9)‘inde nötropenik ateş (NPA) tanısı alan çocuk hastalar tek kişilik odalarda izleniyordu. Tüm odalarda tuvalet bulunan merkez sayısı 24 (%66.6) idi. Hasta odalarının büyük çoğunluğunda elle açılıp kapanır kapı (%94.1) ve musluk (%97.1) mevcuttu. on (%27.7) merkezin oda havalandırması için hepa-filtreli sistemi vardı. Beşinde negatif basınçlı oda mevcuttu. on üç merkezde kateter olarak hickman kateter tercih edilmişti. Tüm merkezlerde kateter bakımı için eğitim verilmekte idi. Hiçbir merkezde hasta ziyaretine ve hastane odasında bitki veya çiçek bulundurmaya izin verilmemekteydi. Merkezlerin %45.7’sinde hastanede oyuncak bulundurma ile ilgili hastane politikası vardı. Sonuç: Sonuç olarak, nötropenik hastaları enfeksiyondan korumak için hastanelerde çeşitli yaklaşımlar uygulanmaktadır. Rehberler belirlenip bu rehberler ışığında hastane koşulları düzenlenmeli ve nötropenik hasta izlemi yapılmalıdır