ABSTRACT
BACKGROUND: A single-dose varicella vaccine at 12 months of age was introduced to the National Immunization Program in February 2013 in Turkey. This study aimed to evaluate varicella-related hospitalization in children and the impact of a single-dose live attenuated varicella vaccine over the first 5.5 years of introducing a universal varicella vaccination. METHODS: We analyzed data collected from the medical records of children <18 years old who required hospitalization due to varicella in 17 cities representing 50% of the childhood population in Turkey between 2008 and 2018. We calculated the rate of hospitalization for varicella per 100,000 children during the study period. The main objective of this study was to determine the yearly rate of hospitalization due to varicella and to compare these rates in the pre-vaccine and post-vaccine periods. The secondary objective was to compare demographic features, varicella-related complications, and outcomes between the pre-vaccine and post-vaccine periods. RESULTS: A total of 4373 children (2458 boys and 1915 girls; 72.3% previously healthy) were hospitalized for varicella over a 10-year period, including 2139 children during the pre-vaccine period and 2234 children during the post-vaccine period. Overall, varicella hospitalization rates decreased significantly after the introduction of varicella vaccination [pre-vaccine vs. post-vaccine period; 3.79 vs. 2.87 per 100,000 per year; P < 0.001; odds ratio 0.75; 95% confidence interval 0.64-0.88]. The incidence of varicella-related hospitalization among children between 1 and 5 years of age was significantly lower in the post-vaccine era than in the pre-vaccine era, with a 60.2% decrease in hospitalizations (2.43 vs. 6.12 per 100,000 children; P < 0.001, odds ratio 0.39; 95% confidence interval 0.34-0.46). In both the <1-year and 6- to 10-year age groups, the incidence of varicella-related hospitalizations was similar in the pre-vaccine and post-vaccine periods. The incidence of varicella-related hospitalization was higher in the post-vaccine era among 11-15 years and >15-year-old groups (P < 0.01 and P < 0.05). The mean age was higher during the post-vaccine period than during the pre-vaccine period (P < 0.001). The absolute number of secondary bacterial infections (P < 0.01), respiratory complications (P < 0.01), and neurological complications (P < 0.001) was significantly lower during the post-vaccine period. The incidence of severe varicella was lower during the post-vaccine period than during the pre-vaccine period (P < 0.001). CONCLUSIONS: After 5.5 years of routine single-dose varicella vaccine use, we observed the impact of varicella vaccination on the incidence of varicella-related hospitalizations, especially in the target age group. However, we did not observe herd protection in the other age groups. The implementation of a second dose of the varicella vaccine in the National Immunization Program would help control disease activity.
ABSTRACT
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.
Subject(s)
COVID-19 , Adult , Humans , Child , Female , Aged , Male , COVID-19/epidemiology , SARS-CoV-2 , COVID-19 Vaccines , Outpatients , Cough , Inpatients , Turkey/epidemiology , Prevalence , Obesity , Chronic DiseaseABSTRACT
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.
Subject(s)
COVID-19 , Interferon Type I , Humans , Young Adult , Adult , Middle Aged , SARS-CoV-2 , Toll-Like Receptor 3/genetics , Toll-Like Receptor 7 , AutoantibodiesABSTRACT
Mendelian susceptibility to mycobacterial diseases (MSMD) is a rare primary immune deficiency (PID). IL-12Rß1 deficiency is the most frequently observed of more than 16 genetic defects that have been identified for MSMD. Genetic and immunological tests are remarkable in the diagnosis of PID. In this study, it was aimed to determine the expression of IFN-γR1 and IL-12Rß1 in patients with MSMD, their relatives, and healthy individuals and to evaluate the importance of flow cytometry as a fast and reliable method in the diagnosis of MSMD. IFN-γR1 and IL-12Rß1 expression levels were analyzed in 32 volunteers including six patients, six relatives, and 20 healthy individuals. The normal range of IFN-γR1 and IL-12Rß1 levels among healthy individuals were determined. IL-12Rß1 expression level in lymphocytes was found to be low in one patient's relative, and less than 1% in three patients and in one patient's relative. It was observed that the IL-12Rß1 expression levels of the patient with STAT1 deficiency were increased compared to the healthy individuals. No difference was found in the expression levels of IFN-γR1 and IL-12Rß1 in one patient, but IFN-γR1 expression was decreased in one patient compared to healthy individuals. Our results show that the determination of IL-12Rß1 and IFN-γR1 deficiencies by flow cytometry can be used as a rapid and reliable method for the diagnosis of MSMD. The use of this method as a screening test will enable early diagnosis especially in patients whose genetic diagnosis has not been confirmed and clinically compatible with MSMD. In addition, it is thought that IL-12Rß1 and IFN-γR1 range data obtained from healthy individuals will be considered as a reference source in routine and research studies to be conducted with MSMD.
Subject(s)
Genetic Predisposition to Disease , Mycobacterium Infections , Receptors, Interferon , Receptors, Interleukin-12 , Humans , Flow Cytometry , Mutation , Mycobacterium Infections/diagnosis , Mycobacterium Infections/genetics , Receptors, Interleukin-12/genetics , Receptors, Interferon/genetics , Interferon gamma ReceptorABSTRACT
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.
ABSTRACT
Dipeptidyl peptidase 9 (DPP9) is a direct inhibitor of NLRP1, but how it affects inflammasome regulation in vivo is not yet established. Here, we report three families with immune-associated defects, poor growth, pancytopenia, and skin pigmentation abnormalities that segregate with biallelic DPP9 rare variants. Using patient-derived primary cells and biochemical assays, these variants were shown to behave as hypomorphic or knockout alleles that failed to repress NLRP1. The removal of a single copy of Nlrp1a/b/c, Asc, Gsdmd, or Il-1r, but not Il-18, was sufficient to rescue the lethality of Dpp9 mutant neonates in mice. Similarly, dpp9 deficiency was partially rescued by the inactivation of asc, an obligate downstream adapter of the NLRP1 inflammasome, in zebrafish. These experiments suggest that the deleterious consequences of DPP9 deficiency were mostly driven by the aberrant activation of the canonical NLRP1 inflammasome and IL-1ß signaling. Collectively, our results delineate a Mendelian disorder of DPP9 deficiency driven by increased NLRP1 activity as demonstrated in patient cells and in two animal models of the disease.
Subject(s)
Apoptosis Regulatory Proteins , Dipeptidyl-Peptidases and Tripeptidyl-Peptidases , Inflammasomes , Animals , Mice , Adaptor Proteins, Signal Transducing/metabolism , Apoptosis Regulatory Proteins/metabolism , Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/genetics , Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/metabolism , Inflammasomes/metabolism , Interleukin-1/metabolism , NLR Proteins/genetics , ZebrafishABSTRACT
Life-threatening 'breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS-CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals (age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto-Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-α2 and IFN-ω, while two neutralized IFN-ω only. No patient neutralized IFN-ß. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population.
ABSTRACT
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.
Subject(s)
COVID-19 , Chickenpox , Influenza Vaccines , Influenza, Human , Measles , Adult , COVID-19/prevention & control , COVID-19 Vaccines , Child , Health Personnel , Humans , Influenza, Human/prevention & control , Measles/prevention & control , SARS-CoV-2 , VaccinationABSTRACT
Recessive or dominant inborn errors of type I interferon (IFN) immunity can underlie critical COVID-19 pneumonia in unvaccinated adults. The risk of COVID-19 pneumonia in unvaccinated children, which is much lower than in unvaccinated adults, remains unexplained. In an international cohort of 112 children (<16 yr old) hospitalized for COVID-19 pneumonia, we report 12 children (10.7%) aged 1.5-13 yr with critical (7 children), severe (3), and moderate (2) pneumonia and 4 of the 15 known clinically recessive and biochemically complete inborn errors of type I IFN immunity: X-linked recessive TLR7 deficiency (7 children) and autosomal recessive IFNAR1 (1), STAT2 (1), or TYK2 (3) deficiencies. Fibroblasts deficient for IFNAR1, STAT2, or TYK2 are highly vulnerable to SARS-CoV-2. These 15 deficiencies were not found in 1,224 children and adults with benign SARS-CoV-2 infection without pneumonia (P = 1.2 × 10-11) and with overlapping age, sex, consanguinity, and ethnicity characteristics. Recessive complete deficiencies of type I IFN immunity may underlie â¼10% of hospitalizations for COVID-19 pneumonia in children.
Subject(s)
COVID-19 , Interferon Type I , Pneumonia , Adult , COVID-19/genetics , Child , Humans , Inheritance Patterns , SARS-CoV-2ABSTRACT
BACKGROUND: We aimed to compare the clinical and laboratory characteristics and imaging methods of patients diagnosed with preseptal cellulitis and orbital cellulitis in the pediatric age group. METHODS: The study was designed retrospectively, and the medical records of all patients who were hospitalized with the diagnosis of preseptal cellulitis and orbital cellulitis were reviewed. The findings of preseptal cellulitis and orbital cellulitis groups were compared. The risk factors for the development of orbital involvement were analyzed. RESULTS: A total of 123 patients were included, 90.2% with preseptal cellulitis and 9.8% with cellulitis. The male gender ratio was 60.2%, and the mean age was 72 ± 43 months. While all patients had eyelid swelling and redness, 20.3% had fever. Ocular involvement was 51.2% in the right eye and 4.9% in both eyes. The most common predisposing factor was rhinosinusitis (56.1%). Radiologic imaging (computed tomography/magnetic resonance imaging) was performed in 83.7% of the patients. Subperiostal abscess was detected in 7 cases (5.6%) in which three of the cases were managed surgically and four were treated with medically. The levels of C-reactive protein were significantly higher in patients with orbital involvement (P = 0.033), but there was no difference between the presence of fever, leukocyte and platelet values. CONCLUSIONS: Rhinosinusitis was the most common predisposing factor in the development of preseptal cellulitis and orbital cellulitis. Orbital involvement was present in 9.8% of the patients. It was determined that high C-reactive protein value could be used to predict orbital involvement.
Subject(s)
Eyelid Diseases , Orbital Cellulitis , Abscess/complications , Abscess/epidemiology , Adolescent , C-Reactive Protein/analysis , Child , Child, Preschool , Eyelid Diseases/complications , Eyelid Diseases/diagnosis , Eyelid Diseases/epidemiology , Female , Humans , Infant , Magnetic Resonance Imaging , Male , Orbital Cellulitis/complications , Orbital Cellulitis/diagnosis , Orbital Cellulitis/epidemiology , Retrospective Studies , Rhinitis/complications , Rhinitis/epidemiology , Sinusitis/complications , Sinusitis/epidemiology , Tomography, X-Ray Computed , TurkeyABSTRACT
BACKGROUND: Understanding SARS-CoV-2 seroprevalence among health care personnel is important to explore risk factors for transmission, develop elimination strategies and form a view on the necessity and frequency of surveillance in the future. METHODS: We enrolled 4927 health care personnel working in pediatric units at 32 hospitals from 7 different regions of Turkey in a study to determine SARS Co-V-2 seroprevalence after the first peak of the COVID-19 pandemic. A point of care serologic lateral flow rapid test kit for immunoglobulin (Ig)M/IgG was used. Seroprevalence and its association with demographic characteristics and possible risk factors were analyzed. RESULTS: SARS-CoV-2 seropositivity prevalence in health care personnel tested was 6.1%. Seropositivity was more common among those who did not universally wear protective masks (10.6% vs 6.1%). Having a COVID-19-positive co-worker increased the likelihood of infection. The least and the most experienced personnel were more likely to be infected. Most of the seropositive health care personnel (68.0%) did not suspect that they had previously had COVID-19. CONCLUSIONS: Health surveillance for health care personnel involving routine point-of-care nucleic acid testing and monitoring personal protective equipment adherence are suggested as important strategies to protect health care personnel from COVID-19 and reduce nosocomial SARS-CoV-2 transmission.
Subject(s)
COVID-19 , Pandemics , Antibodies, Viral , Child , Delivery of Health Care , Health Personnel , Humans , SARS-CoV-2 , Seroepidemiologic Studies , Turkey/epidemiologyABSTRACT
Autosomal 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 1,202 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, 5 and 38 years), or moderate (n=1, 5 years), severe (n=1, 27 years), or critical (n=1, 29 years) pneumonia. Two boys (aged 7 and 12 years) 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 < 6.5x10-4 We also 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.
Subject(s)
COVID-19/complications , Genetic Diseases, X-Linked/complications , Immune System Diseases/complications , Toll-Like Receptor 7/deficiency , Adolescent , Adult , Aged , Aged, 80 and over , Alleles , Child , Child, Preschool , Humans , Infant , Male , Middle Aged , Pedigree , Penetrance , Toll-Like Receptor 7/genetics , Young AdultABSTRACT
RATIONALE AND OBJECTIVES: To retrospectively evaluate imaging findings in multisystem inflammatory disease in children associated with COVID-19 (MIS-C). MATERIALS AND METHODS: The radiological imaging findings of 45 pediatric patients aged between 52 days and 16 years, who were diagnosed with MIS-C according to the World Health Organization (WHO) criteria, were evaluated. All the patients underwent chest X-ray and echocardiography. The findings obtained from 25 abdominal radiographs, 24 abdominal US, 7 abdominal CT, 16 thorax CT, 21 cranial MRI and one spinal MRI, MR cholangiography (MRCP) and cardiac MRI examinations were categorized and evaluated according to the affected systems. RESULTS: While the most common findings in chest X-ray were perihilar opacity and peribronchial thickening, pleural effusion was the most finding in thorax CT. Echocardiography findings of myocarditis were observed in 31% of the cases. The most common findings in abdominal radiological evaluation were hepatomegaly and splenomegaly, edema in the gallbladder wall and periportal area, mesenteric lymph nodes in the right lower quadrant, thickening of the intestinal walls, and free fluid. Reversible splenial lesion syndrome (RESLES) was the most common neurological finding. Acute disseminated encephalomyelitis (ADEM)-like lesions, acute hemorrhagic necrotizing encephalomyelitis, and radiological findings consistent with Guillain-Barré syndrome were found in one case each. CONCLUSION: Radiological findings seen in MIS-C in pediatric cases are correlated with the affected system. According to the system involved, there is no specific finding for this disease. Radiological findings are not the primary diagnostic tool but can assist in the evaluation of the affected systems and to guide treatment.
Subject(s)
COVID-19 , Child , Echocardiography , Humans , Middle Aged , Retrospective Studies , SARS-CoV-2 , Systemic Inflammatory Response SyndromeABSTRACT
Most patients with autosomal dominant hyper-IgE syndrome (AD-HIES) carry rare heterozygous STAT3 variants. Only six of the 135 in-frame variants reported have been experimentally shown to be dominant negative (DN), and it has been recently suggested that eight out-of-frame variants operate by haploinsufficiency. We experimentally tested these 143 variants, 7 novel out-of-frame variants found in HIES patients, and other STAT3 variants from the general population. Strikingly, all 15 out-of-frame variants were DN via their encoded (1) truncated proteins, (2) neoproteins generated from a translation reinitiation codon, and (3) isoforms from alternative transcripts or a combination thereof. Moreover, 128 of the 135 in-frame variants (95%) were also DN. The patients carrying the seven non-DN STAT3 in-frame variants have not been studied for other genetic etiologies. Finally, none of the variants from the general population tested, including an out-of-frame variant, were DN. Overall, our findings show that heterozygous STAT3 variants, whether in or out of frame, underlie AD-HIES through negative dominance rather than haploinsufficiency.
Subject(s)
Genes, Dominant , Job Syndrome/genetics , Mutation/genetics , STAT3 Transcription Factor/genetics , Adolescent , Adult , Alleles , Alternative Splicing/genetics , Child , Child, Preschool , Codon, Nonsense/genetics , Evolution, Molecular , Family , Female , Frameshift Mutation/genetics , Genetics, Population , HEK293 Cells , Humans , Infant , Infant, Newborn , Male , Middle Aged , Pedigree , Protein Biosynthesis , RNA, Messenger/genetics , RNA, Messenger/metabolismABSTRACT
Objectives: The aim of this study is to identify the epidemiological, clinical, and laboratory features of coronavirus disease 2019 (COVID-19) in children. Methods: A retrospective study was conducted by pediatric infectious disease specialists from 32 different hospitals from all over Turkey by case record forms. Pediatric cases who were diagnosed as COVID-19 between March 16, 2020, and June 15, 2020 were included. Case characteristics including age, sex, dates of disease onset and diagnosis, family, and contact information were recorded. Clinical data, including the duration and severity of symptoms, were also collected. Laboratory parameters like biochemical tests and complete blood count, chest X-ray, and chest computed tomography (CT) were determined. Results: There were 1,156 confirmed pediatric COVID-19 cases. In total, male cases constituted 50.3% (n = 582) and females constituted 49.7% (n = 574). The median age of the confirmed cases was 10.75 years (4.5-14.6). Of the total cases, 90 were younger than 1 year of age (7.8%), 108 were 1-3 years of age (9.3%), 148 were 3-6 years of age (12.8%), 298 were 6-12 years of age (25.8%), 233 were 12-15 years of age (20.2%), and 268 cases were older than 15 years of age (23.2%). The most common symptom of the patients at the first visit was fever (50.4%) (n = 583) for a median of 2 days (IQR: 1-3 days). Fever was median at 38.4°C (38.0-38.7°C). The second most common symptom was cough (n = 543, 46.9%). The other common symptoms were sore throat (n = 143, 12.4%), myalgia (n = 141, 12.2%), dyspnea (n = 118, 10.2%), diarrhea (n = 112, 9.7%), stomachache (n = 71, 6.1%), and nasal discharge (n = 63, 5.4%). When patients were classified according to disease severity, 263 (22.7%) patients were asymptomatic, 668 (57.7%) patients had mild disease, 209 (18.1%) had moderate disease, and 16 (1.5%) cases had severe disease. One hundred and forty-nine (12.9%) cases had underlying diseases among the total cases; 56% of the patients who had severe disease had an underlying condition (p < 0.01). The need for hospitalization did not differ between patients who had an underlying condition and those who do not have (p = 0.38), but the need for intensive care was higher in patients who had an underlying condition (p < 0.01). Forty-seven (31.5%) of the cases having underlying conditions had asthma or lung disease (38 of them had asthma). Conclusions: To the best of our knowledge, this is one of the largest pediatric data about confirmed COVID-19 cases. Children from all ages appear to be susceptible to COVID-19, and there is a significant difference in symptomatology and laboratory findings by means of age distribution.
ABSTRACT
Rhinosinusitis is a common infection and may rarely cause severe life-threatening orbital and intracranial complications. In this study, two cases with preseptal cellulitis and meningitis as a complication of rhinosinusitis were presented in the light of the literature. A nine years and two months old girl was admitted with complaints as fever, redness and swelling in the left eye. Physical examination revealed erythema and edema in the left lower and upper eyelids, and the eye movements were painless and normal in all directions. Her systemic examination was normal and there was no sign of meningeal irritation. Magnetic resonance imaging revealed ethmoid, frontal and sphenoid sinusitis and left cerebral hemisphere dural meningeal contrast enhancement. The patient was diagnosed with meningitis after lumbar puncture. After 14 days of appropriate antibiotic treatment, the patient recovered and was discharged. An eight years and five months old boy presented with fever, redness and swelling in the left eye was admitted. There were erythema and edema in the left lower and upper eyelid; the eye movements were painless in all directions and were complete. Systemic examination was normal; there was no sign of meningeal irritation. Pansinusitis and preseptal cellulitis findings were detected on computer tomography. The patient's fever persisted under treatment and erythema and edema of the eye became more evident. Orbital MRI was performed considering the complication and contrast enhancement was observed in the left frontal region. The patient was diagnosed with meningitis after lumbar puncture. After 14 days of appropriate antibiotic treatment, the patient recovered and was discharged. Intracranial complication due to preseptal sinusitis is rare but life-threatening. In these cases, we recommend the use of MRI as the radiological imaging method.
ABSTRACT
In this paper, we report three cases of pediatric patients with COVID-19 infection who presented with different symptoms and also anosmia and/or ageusia. The common feature of these 3 patients is that the smell and / or taste disorder developed without nasal symptoms such as nasal congestion, nasal obstruction or rhinorrhea. Although 40% of anosmies contains viral etiologies, COVID- 19 differs from other viral anosmies by the lack of nasal congestion and runny nose. Coronaviruses could invade the brain via the cribriform plate close to the olfactory bulb and the olfactory epithelium. We may expect some structural changes in the olfactory bulb so we evaluated our patient with cranial imaging.
Subject(s)
Ageusia/virology , Anosmia/virology , COVID-19/diagnostic imaging , Magnetic Resonance Imaging , Olfactory Bulb/diagnostic imaging , Adolescent , Ageusia/diagnosis , Anosmia/diagnostic imaging , COVID-19/complications , Female , Humans , MaleABSTRACT
OBJECTIVE: Literature related to the imaging of COVID-19 pneumonia, its findings and contribution to diagnosis and its differences from adults are limited in pediatric patients. The aim of this study was to evaluate chest X-ray and chest CT findings in children with COVID-19 pneumonia. METHODS: Chest X-ray findings of 59 pediatric patients and chest CT findings of 22 patients with a confirmed diagnosis of COVID-19 pneumonia were evaluated retrospectively. RESULTS: COVID-19 pneumonia was most commonly observed unilaterally and in lower zones of lungs in chest X-ray examinations. Bilateral and multifocal involvement (55%) was the most observed involvement in the CT examinations, as well as, single lesion and single lobe (27%) involvement were also detected. Pure ground-glass appearance was observed in 41%, ground-glass appearance and consolidation together was in 36%. While peripheral and central co-distribution of the lesions (55%) were frequently observed, the involvement of the lower lobes (69%) was significant. In four cases,the coexistence of multiple rounded multifocal ground-glass appearance and rounded consolidation were observed. CONCLUSION: COVID-19 pneumonia imaging findings may differ in the pediatric population from adults. In diagnosis, chest X-ray should be preferred, CT should be requested if there is a pathologic finding on radiography that merits further evaluation and if clinically indicated. ADVANCES IN KNOWLEDGE: Radiological findings of COVID-19 observed in children may differ from adults. Chest X-ray should often be sufficient in children avoiding additional irradiation, chest CT needs only be done in cases of clinical necessity.