[A Case Report of Monkeypox Disease in an Adolescent]. / Adölesan Bir Olguda Maymun Çiçegi Hastaligi.

Monkeypox virus (MPXV) infection is a zoonotic disease characterized by smallpox-like rashes. It is endemic in Central and West Africa. The World Health Organization (WHO) declared the disease as an epidemic due to a significant increase in the number of reported cases, starting from Europe and spreading to other regions, particularly in certain areas, in May 2022. On July 23, 2022, it was recognized as a public health problem of international importance. Our country has also been affected by this epidemic, and the official number of reported cases is twelve. In this case report, an adolescent case diagnosed with MPXV infection was presented. A 17-year-old male patient admitted with the complaints of sores around the mouth and genital area, fever and headache. The patient had a history of sexual contact with three different males in the last six months. Honey-colored crusted papules and plaques were observed in the perioral area, as well as crusted papules on the penile and gluteal areas. Ulcerative sores were present in the oral cavity. Laboratory tests for sexually transmitted diseases confirmed the patient's HIV-positive status and MPXV infection through PCR (polymerase chain reaction) testing. Antiviral treatment for human immunodeficiency virus (HIV) was initiated after the HIV RNA level resulted in 263000 copies/mL. Additionally, a glycopeptide was added to the treatment regimen when methicillin-resistant Staphylococcus aureus growth was detected in the swab culture taken from the wounds on the patient's face. No specific treatment was administered for MPXV due to the patient's uncomplicated clinical course and overall well-being. This case report aims to raise awareness about monkeypox disease in children by highlighting the clinical findings and potential risk factors.

A snapshot of pediatric inpatients and outpatients with COVID-19: a point prevalence study from Turkey.

This multi-center point prevalence study evaluated children who were diagnosed as having coronavirus disease 2019 (COVID-19). On February 2nd, 2022, inpatients and outpatients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were included in the study from 12 cities and 24 centers in Turkey. Of 8605 patients on February 2nd, 2022, in participating centers, 706 (8.2%) had COVID-19. The median age of the 706 patients was 92.50 months, 53.4% were female, and 76.7% were inpatients. The three most common symptoms of the patients with COVID-19 were fever (56.6%), cough (41.3%), and fatigue (27.5%). The three most common underlying chronic diseases (UCDs) were asthma (3.4%), neurologic disorders (3.3%), and obesity (2.6%). The SARS-CoV-2-related pneumoniae rate was 10.7%. The COVID-19 vaccination rate was 12.5% in all patients. Among patients aged over 12 years with access to the vaccine given by the Republic of Turkey Ministry of Health, the vaccination rate was 38.7%. Patients with UCDs presented with dyspnea and pneumoniae more frequently than those without UCDs (p < 0.001 for both). The rates of fever, diarrhea, and pneumoniae were higher in patients without COVID-19 vaccinations (p = 0.001, p = 0.012, and p = 0.027).  Conclusion: To lessen the effects of the disease, all eligible children should receive the COVID-19 vaccine. The illness may specifically endanger children with UCDs. What is Known: • Children with COVID-19 mainly present with fever and cough, as in adults. • COVID-19 may specifically threaten children with underlying chronic diseases. What is New: • Children with obesity have a higher vaccination rate against COVID-19 than children without obesity. • Among unvaccinated children, fever and pneumoniae might be seen at a higher ratio than among vaccinated children.

Intestinal microbiota composition of children with infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and multisystem inflammatory syndrome (MIS-C).

Microbiota composition may play a role in the development, prognosis, or post-infection of COVID-19. There are studies evaluating the microbiota composition at the time of diagnosis and during the course of COVID-19, especially in adults, while studies in children are limited and no study available in children with multisystem inflammatory syndrome in children (MIS-C). This study was planned to compare intestinal microbiota composition in children diagnosed with MIS-C and acute COVID-19 infection with healthy children. In this prospective multicenter study, 25 children diagnosed with MIS-C, 20 with COVID-19 infection, and 19 healthy children were included. Intestinal microbiota composition was evaluated by 16 s rRNA gene sequencing. We observed changes of diversity, richness, and composition of intestinal microbiota in MIS-C cases compared to COVID-19 cases and in the healthy controls. The Shannon index was higher in the MIS-C group than the healthy controls (p < 0.01). At phylum level, in the MIS-C group, a significantly higher relative abundance of Bacteroidetes and lower abundance of Firmicutes was found compared to the control group. Intestinal microbiota composition changed in MIS-C cases compared to COVID-19 and healthy controls, and Faecalibacterium prausnitzii decreased; Bacteroides uniformis, Bacteroides plebeius, Clostridium ramosum, Eubacterium dolichum, Eggerthella lenta, Bacillus thermoamylovorans, Prevotella tannerae, and Bacteroides coprophilus were dominant in children with MIS-C. At species level, we observed decreased Faecalibacterium prausnitzii, and increased Eubacterium dolichum, Eggerthella lenta, and Bacillus thermoamylovorans in children with MIS-C and increased Bifidobacterium adolescentis and Dorea formicigenerasus in the COVID-19 group. Our study is the first to evaluate the microbiota composition in MIS-C cases. There is a substantial change in the composition of the gut microbiota: (1) reduction of F. prausnitzii in children with MIS-C and COVID-19; (2) an increase of Eggerthella lenta which is related with autoimmunity; and (3) the predominance of E. dolichum is associated with metabolic dysfunctions and obesity in children with MIS-C. CONCLUSIONS:  Alterations of the intestinal microbiota might be part of pathogenesis of predisposing factor for MIS-C. It would be beneficial to conduct more extensive studies on the cause-effect relationship of these changes in microbiota composition and their effects on long-term prognosis. WHAT IS KNOWN: • Microbiota composition may play a role in the development, prognosis, or post-infection of COVID-19.  • However, the number of studies on children is limited, and no study on multisystem inflammatory syndrome in children is currently available (MIS-C). WHAT IS NEW: • In individuals with MIS-C, the composition of the gut microbiota changed dramatically. • Decreased Faecalibacterium prausnitzii have been observed, increased Eggerthella lenta, which was previously linked to autoimmunity, and predominance of Eubacterium dolichum which was linked to metabolic dysfunction and obesity.

COVID-19 associated multisystemic inflammatory syndrome in 614 children with and without overlap with Kawasaki disease-Turk MIS-C study group.

Multisystemic inflammatory syndrome (MIS-C) diagnosis remains difficult because the clinical features overlap with Kawasaki disease (KD). The study aims to highlight the clinical and laboratory features and outcomes of patients with MISC whose clinical manifestations overlap with or without KD. This study is a retrospective analysis of a case series designed for patients aged 1 month to 18 years in 28 hospitals between November 1, 2020, and June 9, 2021. Patient demographics, complaints, laboratory results, echocardiographic results, system involvement, and outcomes were recorded. A total of 614 patients were enrolled; the median age was 7.4 years (interquartile range (IQR) 3.9-12 years). A total of 277 (45.1%) patients with MIS-C had manifestations that overlapped with KD, including 92 (33.3%) patients with complete KD and 185 (66.7%) with incomplete KD. Lymphocyte and platelet counts were significantly lower in patients with MISC, overlapped with KD (lymphocyte count 1080 vs. 1280 cells × µL, p = 0.028; platelet count 166 vs. 216 cells × 103/µL, p < 0.001). The median serum procalcitonin levels were statistically higher in patients overlapped with KD (3.18 vs. 1.68 µg/L, p = 0.001). Coronary artery dilatation was statistically significant in patients with overlap with KD (13.4% vs. 6.8%, p = 0.007), while myocarditis was significantly more common in patients without overlap with KD features (2.6% vs 7.4%, p = 0.009). The association between clinical and laboratory findings and overlap with KD was investigated. Age > 12 years reduced the risk of overlap with KD by 66% (p < 0.001, 95% CI 0.217-0.550), lethargy increased the risk of overlap with KD by 2.6-fold (p = 0.011, 95% CI 1.244-5.439), and each unit more albumin (g/dl) reduced the risk of overlap with KD by 60% (p < 0.001, 95% CI 0.298-0.559). CONCLUSION: Almost half of the patients with MISC had clinical features that overlapped with KD; in particular, incomplete KD was present. The median age was lower in patients with KD-like features. Lymphocyte and platelet counts were lower, and ferritin and procalcitonin levels were significantly higher in patients with overlap with KD. WHAT IS KNOWN: • In some cases of MIS-C, the clinical symptoms overlap with Kawasaki disease. • Compared to Kawasaki disease, lymphopenia was an independent predictor of MIS-C. WHAT IS NEW: • Half of the patients had clinical features that overlapped with Kawasaki disease. • In patients whose clinical features overlapped with KD, procalcitonin levels were almost 15 times higher than normal. • Lethargy increased the risk of overlap with KD by 2.6-fold in MIS-C patients. • Transient bradycardia was noted in approximately 10% of our patients after initiation of treatment.

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 µg/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.

Staphylococcus aureus endocarditis and pyomyositis: Rare complications of rotavirus gastroenteritis.

Rotavirus may cause life-threatening complications in untreated patients during the course of gastroenteritis. Electrolyte imbalance, bacteremia and sepsis are the most common complications of rotavirus gastroenteritis (RG). It is believed that translocation of intestinal microorganisms as a result of intestinal epithelium dysfunction is the underlying mechanism of bacteremia in RG. Although Gram-negative bacteremia has been noted as a complication in RG, Staphylococcus aureus bacteremia and endocarditis have not been reported previously. A 22-month-old boy was admitted with complaints of fever, diarrhea and dehydration. He was diagnosed with RG complicated with S. aureus bacteremia, pyomyositis and endocarditis. We call attention to these complications in patients with prolonged or late-onset fever during RG as rare complications of the disease.

Nasopharyngeal carriage of Streptococcus pneumoniae in healthy Turkish children after the addition of PCV7 to the national vaccine schedule.

UNLABELLED: The aim of this study was to determine serotype distribution and investigate antimicrobial resistance patterns of Streptococcus pneumoniae in healthy Turkish children in the era of community-wide pneumococcal conjugate vaccine (PCV7). The study was conducted on 1,101 healthy children less than 18 years of age. Specimens were collected with nasopharyngeal swabs between April 2011 and June 2011. Penicillin and ceftriaxone susceptibilities were determined by E-test according to the 2008 Clinical Laboratory Standards Institute, and serotypes of the isolates were determined by Quellung reaction. The nasopharyngeal pneumococcal carriage rate was 21.9 % (241/1,101). Using the meningitis criteria of minimum inhibitory concentration values, 73 % of the isolates were resistant to penicillin and 47.7 % of them were resistant to ceftriaxone. Half of all pneumococcal isolates were serotyped as 19F (15.2 %), 6A (15.2 %), 23F (10.3 %), and 6B (9.3 %) and surprisingly, no serotype 19A was isolated. Serotype coverage rates of PCV7 and non-PCV7 were 46.2 and 53.8 %, respectively. The most common penicillin- and ceftriaxone-resistant serotypes were 6A, 6B, 14, 19F, and 23F. Penicillin- and ceftriaxone-resistant isolates were more prevalent in serotypes covered by PCV7 than the non-PCV7 serotypes. CONCLUSION: After the community-wide PCV7 vaccination, more non-PCV7 serotypes were isolated from the carriers compared to the time before PCV7 was used especially the serotype 6A, and the antimicrobial resistance of pneumococci was significantly increased.

Comparison of Bordetella pertussis Antibody Levels in Pregnant Women and Umbilical Cord Blood: A Multicenter Study.

BACKGROUND: In countries where pertussis vaccination is not administered during pregnancy, the determination of pertussis antibody levels in pregnant women is very important in terms of knowing the current seroepidemiology and potential strategies for immunizations. METHODS: We included 396 pregnant women who were admitted to 4 different obstetrics and gynecology clinics. Anti-Bordetella pertussis toxin (PT) IgG and anti-Bordetella pertussis filamentous hemagglutinin IgG levels in maternal and cord blood pairs were determined by the ELISA method. RESULTS: Venous blood serum anti-PT level was below 5 IU/mL in 58.8%, 5-40 IU/mL in 34.8%, 40-100 IU/mL in 5.1% and >100 IU/mL in 1.3% of pregnant women. Cord blood serum anti-PT level was below 5 IU/mL in 47.7%, 5-40 IU/mL in 44.5%, 40-100 IU/mL in 6.8% and >100 IU/mL in 1% of pregnant women. In our study, the anti-PT level was found below 40 IU/mL in 93.6% of pregnant women and 92.2% of cord blood. Our study found the anti-filamentous hemagglutinin level below 40 IU/mL in 81% of pregnant women and 66.2% of cord blood. CONCLUSIONS: Although it is known that pertussis causes serious morbidity and mortality in young infants all over the world and that the most effective and reliable way to prevent it is vaccination of pregnant women, it is a remarkable contradiction that pertussis vaccination rates and therefore seropositivity rates in pregnant women are very low.

Adolescents With Breakthrough COVID-19 Infections Requiring Hospitalization: A Multicenter Retrospective Study.

Background Vaccines have the most important role in the battle against the COVID-19 pandemic. With the widespread use of vaccines, COVID-19 has remarkably declined. Adolescents were vaccinated after approvals for this age group, which was later than adults, and a nationwide vaccination program was implemented in August 2021 in Turkey for adolescents ≥12 years of age. Therefore, we aimed to determine the effects of the COVID-19 nationwide adolescent vaccination program on adolescent hospitalizations due to COVID-19 and multisystem inflammatory syndrome in children (MIS-C) by comparing two periods, including the vaccination period (VP) and the pre-VP (PVP). The second aim of this study is to compare the clinical features and disease severity of vaccine-breakthrough COVID-19 hospitalizations with unvaccinated individuals in the VP. Methods A retrospective multicenter study was conducted to determine and compare the number of hospitalizations due to COVID-19 and MIS-C between the VP (September 1, 2021, to August 31, 2022) and PVP (September 1, 2020, to August 31, 2021). We also compared the characteristics, risk factors, and outcomes of breakthrough infections of adolescents aged 12-18, which required hospitalization with the same age group of unvaccinated hospitalized individuals during the VP. Results During the study period, 3967 children (0-18 years) were hospitalized in the PVP and 5143 (0-18 years) in the VP. Of them, 35.4% were adolescents (12-18 years) in the PVP, and this rate was 18.6% in the VP; relative risk was 0.6467 (95% confidence interval [CI]: 0.6058-0.6904; p < 0.001). Patients with breakthrough COVID-19 were older (201 vs. 175 months, p < 0.001) and less commonly hospitalized for COVID-19 (81.5% vs. 60.4%, p < 0.001, odds ratio [OR]: 0.347 [95% CI: 0.184-0.654]). The majority of these infections were asymptomatic and mild (32% vs.72.9%: p < 0.001, OR: 5.718 [95% CI: 2.920-11.200]), and PICU admission was less frequently required (p = 0.011, OR: 0.188 [95% CI: 0.045-0.793]). Most breakthrough COVID-19 infections occurred within three months after the last vaccine dose (54.2%). Conclusions This study demonstrated a significant decrease in adolescent hospitalizations due to COVID-19 and MIS-C after implementing COVID-19 vaccines in Turkey. Breakthrough cases were less severe and mostly occurred three months after the last dose. This study emphasizes the importance of COVID-19 vaccines and that parents' decisions may be changed, particularly those who hesitate to or refuse vaccination.

Pathogens in Pediatric Septic Arthritis: A Multi-Center Study in Turkiye (PEDSART Study).

OBJECTIVES: Septic arthritis (SA) is a serious bacterial infection that must be treated efficiently and timely. The large number of culture-negative cases makes local epidemiological data important. Accordingly, this study aimed to evaluate the etiology, clinical characteristics, and therapeutic approach of SA in children in Turkiye, emphasizing the role of real-time polymerase chain reaction (PCR) techniques in the diagnosis. METHODS: In this multi-center, prospective study, children hospitalized due to SA between February 2018 and July 2020 in 23 hospitals in 14 cities in Turkiye were included. Clinical, demographic, laboratory, and radiological findings were assessed, and real-time PCR was performed using synovial fluid samples. RESULTS: Seventy-five children aged between 3 and 204 months diagnosed with acute SA were enrolled. Joint pain was the main complaint at admission, and the most commonly involved joints were the knees in 58 patients (77.4%). The combination of synovial fluid culture and real-time PCR detected causative bacteria in 33 patients (44%). In 14 (18.7%) patients, the etiological agent was demonstrated using only PCR. The most commonly isolated etiologic agent was Staphylococcus aureus, which was detected in 22 (29.3%) patients, while Streptococcus pyogenes was found in 4 (5.3%) patients and Kingella kingae in 3 (4%) patients. Streptococcus pyogenes and Kingella kingae were detected using only PCR. Most patients (81.3%) received combination therapy with multiple agents, and the most commonly used combination was glycopeptides plus third-generation cephalosporin. CONCLUSIONS: Staphylococcus aureus is the main pathogen in pediatric SA, and with the use of advanced diagnostic approaches, such as real-time PCR, the chance of diagnosis increases, especially in cases due to Kingella kingae and Streptococcus pyogenes.

An unusual cause of secondary capillary leak syndrome in a child: rotavirus diarrhea.

Secondary capillary leak syndrome is characterized by loss of fluid and proteins to the interstitial space due to different causes, which are related to endothelial damage. Rotavirus is the most common pathogen of diarrhea in childhood, especially during the first years of life. This virus is generally responsible for severe diarrhea and electrolyte imbalance in children. Some complications can also occur during the course of the rotavirus diarrhea. An eight-month-old girl with rotavirus diarrhea admitted to our clinic with severe dehydration. After restoring the intravascular volume, hypoalbuminemia and generalized edema were seen in the recruitment phase of the treatment, which was attributed to secondary capillary leak syndrome. She was successfully treated with prednisolone and discharged from the hospital without any sequelae. Herein, we report an infant with rotavirus diarrhea complicated with secondary capillary leak syndrome, which is an unidentified complication of the disease. To our knowledge, this is the first such case in the literature.

The effects of measures taken during the COVID-19 pandemic on the seasonal dynamics of respiratory viruses in children.

BACKGROUND: We aimed to evaluate the effects of public health measures taken during the COVID-19 pandemic on respiratory viruses. METHODS: The study was conducted between February 1, 2021 and December 1, 2022. Patients aged 1 month to 18 years hospitalized for infectious diseases were tested for SARS-CoV-2 and respiratory viruses by multiplex PCR. RESULTS: Of the total 1173 patients, 56.2% were male and 43.8% were female, and 47.5% of the patients were under 24 months of age. The viruses detected were SARS-CoV-2 31.9%, human rhinovirus/enterovirus 19.4%, respiratory syncytial virus (RSV) 9.3%, parainfluenza virus 7%, adenovirus 6%, seasonal coronavirus 5.2%, bocavirus 3.8%, influenza 3.1%, and metapneumovirus 2.8%. Among the patients, 386 were hospitalized with lower respiratory tract infections, 238 with upper respiratory tract infections, 202 to evaluate fever etiology, 111 with acute gastroenteritis and 236 with other diagnoses. Of these patients, 113 were admitted to the intensive care unit. Intensive care unit admission rates were statistically significantly higher for bocavirus and RSV, in those hospitalized between July 1, 2021 and July 1, 2022 (first period when schools were held full-time face-toface at all grades) and in children aged 1-24 months. CONCLUSIONS: Public health measures taken during the COVID-19 pandemic have affected the seasonal distribution of respiratory viruses and the severity of illness in children.

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19.

BACKGROUND: We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. METHODS: We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. RESULTS: No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P = 1.1 × 10-4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3-8.2], P = 2.1 × 10-4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1-2635.4], P = 3.4 × 10-3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3-8.4], P = 7.7 × 10-8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10-5). CONCLUSIONS: Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.

Successful treatment of multidrug-resistant Escherichia coli bacteremia with tigecycline in an acute myeloid leukemia child.

The multidrug-resistant bacterial infections cause high mortality in immunocompromised patients because of the limited antibacterial choices. Tigecycline, first member of the glycylcyclines, has in vitro activity against a wide variety of organisms, including multidrug-resistant pathogens; however, it has not yet been approved for use in children. Herein, we report a nine-year-old girl with acute myeloid leukemia who was treated successfully with tigecycline due to multidrug-resistant Escherichia coli bacteremia.

The effectiveness of topical 1% lidocaine with systemic oral analgesics for ear pain with acute otitis media.

BACKGROUND: Acute otitis media (AOM) is one of the most common childhood infections. Ear pain, the main symptom of AOM, results in parents frequently seeking medical assistance for their children. The aim of this study was to compare the effectiveness of topical 1% lidocaine ear drops administered with oral analgesics with that of oral analgesics alone. METHODS: This multicenter randomized, open-labeled study was conducted at 15 centers with 184 pediatric AOM patients with bilateral ear pain (aged 1-5 years) between May 1, 2016, and June 31, 2018. All patients received oral paracetamol or ibuprofen and topical 1% lidocaine, which was administered to each ear according to the randomization list. The ear pain score was evaluated within 48 h using the Face, Legs, Activity, Cry, and Consolability (FLACC) scale, and the patients were followed up for 10 days. RESULTS: The median age was 31.8 months (min-max, 12-84.2 months). Of those patients enrolled, 22.3% received paracetamol, and 24.5% received paracetamol with lidocaine ear drops; 23.4% received ibuprofen, and 29.9% received ibuprofen with lidocaine ear drops. Lower pain scores were significantly measured at baseline and 10th minutes by a reduction 25% (RR 13.64, 95% CI 4.47-41.63, p = 0.001, RR 0.14, 95% CI 0.06-0.35, p = 0.001) and 50% (RR 4.76, 95% CI 1.63-13.87, p = 0.004, RR 0.14, 95% CI 0.05-0.4, p = 0.001) in the paracetamol and lidocaine versus paracetamol groups and the ibuprofen and lidocaine versus ibuprofen groups, respectively. No serious side effects were evident during follow-up. CONCLUSION: This randomized study suggests that topical 1% lidocaine ear drops with paracetamol or ibuprofen seems to provide effective and rapid relief for children presenting with ear pain attributed to AOM.

Evaluation of vaccination status of health care workers for recommended vaccines and their acceptance of SARS-CoV-2 vaccines.

INTRODUCTION: Health care workers (HCWs) are disproportionately exposed to infectious diseases and play a role in nosocomial transmission, making them a key demographic for vaccination. HCW vaccination rates are not optimal in many countries; hence, compulsory vaccination policies have been implemented in some countries. Although these policies are effective and necessary under certain conditions, resolving HCWs' hesitancies and misconceptions about vaccines is crucial. HCWs have the advantage of direct contact with patients; hence, they can respond to safety concerns, explain the benefits of vaccination, and counter antivaccine campaigns that escalate during pandemics, as has been observed with COVID-19. METHOD: A short survey was carried out in May-June 2020 on the vaccination status of HCWs working with pediatric patients with COVID-19. The survey inquired about their vaccination status (mumps/measles/rubella [MMR], varicella, influenza, and diphtheria/tetanus [dT]) and willingness to receive hypothetical future COVID-19 vaccines. The respondents were grouped according to gender, age, occupation, and region. RESULTS: In total, 4927 HCWs responded to the survey. Most were young, healthy adults. The overall vaccination rates were 57.8% for dT in the past 10 years, 44.5% for MMR, 33.2% for varicella, and 13.5% for influenza. Vaccination rates were the highest among physicians. The majority of HCWs (81%) stated that they would be willing to receive COVID-19 vaccines. CONCLUSION: Although vaccination rates for well-established vaccines were low, a majority of HCWs were willing to receive COVID-19 vaccines when available. Education and administrative trust should be enhanced to increase vaccination rates among HCWs.

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19.

Background: We previously reported inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity in 1-5% of unvaccinated patients with life-threatening COVID-19, and auto-antibodies against type I IFN in another 15-20% of cases. Methods: We report here a genome-wide rare variant burden association analysis in 3,269 unvaccinated patients with life-threatening COVID-19 (1,301 previously reported and 1,968 new patients), and 1,373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. A quarter of the patients tested had antibodies against type I IFN (234 of 928) and were excluded from the analysis. Results: No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7 , with an OR of 27.68 (95%CI:1.5-528.7, P= 1.1×10 -4 ), in analyses restricted to biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70 [95%CI:1.3-8.2], P= 2.1×10 -4 ). Adding the recently reported TYK2 COVID-19 locus strengthened this enrichment, particularly under a recessive model (OR=19.65 [95%CI:2.1-2635.4]; P= 3.4×10 -3 ). When these 14 loci and TLR7 were considered, all individuals hemizygous ( n =20) or homozygous ( n =5) for pLOF or bLOF variants were patients (OR=39.19 [95%CI:5.2-5037.0], P =4.7×10 -7 ), who also showed an enrichment in heterozygous variants (OR=2.36 [95%CI:1.0-5.9], P =0.02). Finally, the patients with pLOF or bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P= 1.68×10 -5 ). Conclusions: Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.

Impaired IL-23-dependent induction of IFN-γ underlies mycobacterial disease in patients with inherited TYK2 deficiency.

Human cells homozygous for rare loss-of-expression (LOE) TYK2 alleles have impaired, but not abolished, cellular responses to IFN-α/ß (underlying viral diseases in the patients) and to IL-12 and IL-23 (underlying mycobacterial diseases). Cells homozygous for the common P1104A TYK2 allele have selectively impaired responses to IL-23 (underlying isolated mycobacterial disease). We report three new forms of TYK2 deficiency in six patients from five families homozygous for rare TYK2 alleles (R864C, G996R, G634E, or G1010D) or compound heterozygous for P1104A and a rare allele (A928V). All these missense alleles encode detectable proteins. The R864C and G1010D alleles are hypomorphic and loss-of-function (LOF), respectively, across signaling pathways. By contrast, hypomorphic G996R, G634E, and A928V mutations selectively impair responses to IL-23, like P1104A. Impairment of the IL-23-dependent induction of IFN-γ is the only mechanism of mycobacterial disease common to patients with complete TYK2 deficiency with or without TYK2 expression, partial TYK2 deficiency across signaling pathways, or rare or common partial TYK2 deficiency specific for IL-23 signaling.

Aseptic meningitis in a child due to 2009 pandemic influenza A (H1N1) infection.

Neurologic manifestations of seasonal influenza 2009 pandemic influenza A (H1N1) are now known to include encephalitis, acute disseminated encephalomyelitis, Guillain-Barré syndrome, transverse myelitis, and acute necrotizing encephalopathy. We report a case of 2009 pandemic influenza A (H1N1) meningitis in a previously healthy six-year-old girl who presented with fever, headache, abdominal pain, and vomiting. The infection was confirmed via nasopharyngeal and throat swabs. She was treated with oseltamivir successfully. To our knowledge, she is the first child diagnosed as pandemic influenza A (H1N1) meningitis.