Severe Disease In Children Research Articles

Incidence and Risk of Coronavirus Disease 2019 Hospitalization Among Unvaccinated Children.

The aim of this study is to determine the incidence and risk factors associated with COVID-19 hospitalization among unvaccinated children. Children aged 0- < 18 years, members of Kaiser Permanente Northern California (KPNC), were followed from March 1, 2020, until the earliest occurrence of: chart-confirmed COVID-19 hospitalization, disenrollment from KPNC, age 18 years, receipt of COVID-19 vaccine, death, or study end (December 31, 2022). We calculated the incidence rate of hospitalization by SARS-CoV-2 variant period and by age group. We determined risk factors for hospitalization using Poisson regression. We also conducted descriptive analyses of hospitalized cases. Among 1,107,799 children, 423 were hospitalized for COVID-19 during follow-up. The incidence of hospitalization increased with each new SARS-CoV-2 variant and was highest among children aged < 6 months. Among the < 6-month-olds, the incidence rate per 100,000 person-months was 7 during predelta, 13.3 during delta, and 22.4 during omicron. Black (RR = 2.05, 95% CI: 1.33-3.16) and Hispanic children (RR = 1.82, 95% CI: 1.34-2.46) and children with any comorbidities were at high risk of hospitalization (RR = 3.81, 95% CI: 2.94-4.95). Overall, 20.3% of hospitalized children were admitted to an intensive care unit (ICU), but ICU admission was 36.1% among 12- < 18-year-olds. The majority of ICU admits (91.8%) had no comorbidities. Children too young to be vaccinated had the highest incidence of COVID-19 hospitalization, while adolescents had the highest proportion of ICU admissions. To prevent severe disease in children and adolescents, everyone eligible should be vaccinated.

Genetic aspects of vulnerability to COVID-19 and their influence on individual susceptibility to severe disease in children

Despite the lower prevalence of COVID-19 (COronaVIrus Disease 2019) infection in children, such threatening conditions as severe SARS-CoV-2-associated pneumonia and Multisystem Inflammatory Syndrome in Children (MIS-C) pose a challenge in differential diagnosis, early hospitalization and treatment. Therefore, the purpose of the study was to investigate the genetic characteristics of children's susceptibility to the occurrence of severe COVID-19 and MIS-C, with the determination of predictors and risk factors. Genetic factors were evaluated on the basis of a literature search, and phenotypic manifestations were assessed on the basis of the analysis of medical documentation of 119 patients, who were treated in infectious departments with the diagnoses of COVID-19 (n=38), MIS-C (n=8), influenza (n=45), and acute viral respiratory infection (n=28). The results of the study revealed differential diagnostic criteria for severe forms of COVID-19 and MIS-C. Among COVID-19 symptoms, gastrointestinal manifestations prevailed, such as nausea, vomiting, diarrhea and abdominal pain. While rash, bilateral conjunctivitis, lymphadenopathy, gastrointestinal and cardiovascular disorders were chara­cteristic of MIS-C. Based on the analysis of genetic features, risk factors and co-morbidities that aggravate the course of covid infection have been determined in order to create algorithms for ambulatory supervision and dispensation of children from risk groups. Thus, children with asthma, diabetes, obesity, congenital immunodeficiencies and heart defects need dispensary supervision from the point of view of risk of severe COVID-19. Outpatient supervision for a month is required for practically healthy children who have had positive COVID-19 test or have been in contact with patients with COVID-19. The determination of blood laboratory parameters, electrocardiography and ultrasound of the abdominal organs should be performed for early diagnosis of MIS-C. Keywords: multisystem inflammatory syndrome MIS-C, severe form of COVID-19, risk factors, genetic features, dispensation, diagnostic criteria.

Clinical Features and Outcomes of Pediatric and Adult Patients Hospitalized for Coronavirus Disease 2019: A Comparison Across Age Strata.

Coronavirus disease 2019 (COVID-19) continues to cause hospitalizations and severe disease in children and adults. This study compared the risk factors, symptoms, and outcomes of children and adults hospitalized for COVID-19 from March 2020 to May 2023 across age strata at 5 US sites participating in the Predicting Viral-Associated Inflammatory Disease Severity in Children with Laboratory Diagnostics and Artificial Intelligence consortium. Eligible patients had an upper respiratory swab that tested positive for severe acute respiratory syndrome coronavirus 2 by nucleic acid amplification. Adjusted odds ratios (aOR) of clinical outcomes were determined for children versus adults, for pediatric age strata compared to adolescents (12-17 years), and for adult age strata compared to young adults (22-49 years). Of 9101 patients in the Predicting Viral-Associated Inflammatory Disease Severity in Children with Laboratory Diagnostics and Artificial Intelligence cohort, 1560 were hospitalized for COVID-19 as the primary reason. Compared to adults (22-105 years, n = 675), children (0-21 years, n = 885) were less commonly vaccinated (14.3% vs 34.5%), more commonly infected with the Omicron variant (49.5% vs 26.1%) and had fewer comorbidities (P < .001 for most comparisons), except for lung disease (P = .24). After adjusting for confounding variables, children had significantly lower odds of receiving supplemental oxygen (aOR, 0.57; 95% confidence interval, .35-.92) and death (aOR, 0.011; 95% confidence interval, <.01-.58) compa--red to adults. Among pediatric age strata, adolescents 12-17 years had the highest odds of receiving supplemental oxygen, high-flow oxygen, and ICU admission. Among adults, those 50-64 years had the highest odds of mechanical ventilation and ICU admission. Clinical outcomes of COVID-19 differed across pediatric and adult age strata. Adolescents experienced the most severe disease among children, whereas adults 50-64 years experienced the most severe disease among adults.

Real-world effectiveness of the heterologous SOBERANA-02 and SOBERANA-Plus vaccine scheme in 2–11 years-old children during the SARS-CoV-2 Omicron wave in Cuba: a longitudinal case-population study

Increased pediatric COVID-19 occurrence due to the SARS-CoV-2 Omicron variant has raised concerns about the effectiveness of existing vaccines. The protection provided by the SOBERANA-02-Plus vaccination scheme against this variant has not yet been studied. We aimed to evaluate the scheme's effectiveness against symptomatic Omicron infection and severe disease in children. In September 2021, Cuba implemented a mass pediatric immunization with the heterologous SOBERANA-02-Plus scheme: 2 doses of conjugated SOBERANA-02 followed by a heterologous SOBERANA-Plus dose. By December, before the Omicron outbreak, 95.4% of 2-18 years-old had been fully immunized. During the entire Omicron wave, we conducted a nationwide longitudinal post-vaccination case-population study to evaluate the real-world effectiveness of the SOBERANA-02-Plus scheme against symptomatic infection and severe disease in children without previous SARS-CoV-2 infection. The identification of COVID-19 cases relied on surveillance through first line services, which refer clinical suspects to pediatric hospitals where they are diagnosed based on a positive RT-PCR test. We defined the Incidence Rate ratio (IRR) as IRvaccinated age group/IRunvaccinated 1-year-old and calculated vaccine effectiveness as VE= (1-IRR)∗100%. 24 months of age being the 'eligible for vaccination' cut-off, we used a regression discontinuity approach to estimate effectiveness by contrasting incidence in all unvaccinated 1-year-old versus vaccinated 2-years-old. Estimates in the vaccinated 3-11 years-old are reported from a descriptive perspective. We included 1,098,817 fully vaccinated 2-11 years-old and 98,342 not vaccinated 1-year-old children. During the 24-week Omicron wave, there were 7003/26,241,176 person-weeks symptomatic COVID-19 infections in the vaccinated group (38.2 per 105 person-weeks in 2-years-old and 25.5 per 105 person-weeks in 3-11 years-old) against 3577/2,312,273 (154.7 per 105 person-weeks) in the unvaccinated group. The observed overall vaccine effectiveness against symptomatic infection was 75.3% (95% CI, 73.5-77.0%) in 2-years-old children, and 83.5% (95% CI, 82.8-84.2%) in 3-11 years-old. It was somewhat lower during Omicron BA.1 then during Omicron BA.2 variant circulation, which took place 1-3 and 4-6 months after the end of the vaccination campaign. The effectiveness against severe symptomatic disease was 100.0% (95% CI not estimated) and 94.6% (95% CI, 82.0-98.6%) in the respective age groups. No child death from COVID-19 was observed. Immunization of 2-11 years-old with the SOBERANA-02-Plus scheme provided strong protection against symptomatic and severe disease caused by the Omicron variant, which was sustained during the six months post-vaccination follow-up. Our results contrast with the observations in previous real-world vaccine effectiveness studies in children, which might be explained by the type of immunity a conjugated protein-based vaccine induces and the vaccination strategy used. National Fund for Science and Technology (FONCI-CITMA-Cuba).

An Investigation of Pediatric Case-patients With Invasive Haemophilus influenzae in Alaska, 2005-2011.

Haemophilus influenzae (Hi) can cause severe disease in children. This study aimed to identify risk factors related to invasive Hi disease in Alaska children and evaluate carriage in people around them. From 2005 to 2011, we investigated episodes of invasive, typeable Hi disease in Alaska children <10 years old. Three age-matched control children were enrolled for each case-patient. We evaluated oropharyngeal Hi carriage in people in close contact with Hi case-patients (contacts) as well as control children and their household members. Individual and household risk factors for illness and carriage were evaluated using questionnaires and chart reviews. Thirty-eight of 44 (86%) children with invasive, typeable Hi disease were recruited: 20 Hi serotype a (53%), 13 serotype b (Hib) (34%) and 5 serotype f (13%). Children with the invasive Hi disease were more likely than controls to have underlying health problems (67% vs. 24%, P = 0.001), other carriers of any Hi in their household (61% vs. 15%, P < 0.001), and inadequate Hib vaccination (26% vs. 9%, P = 0.005). People who carried Hi were younger than noncarriers (mean 12.7 vs. 18.0 years, P = 0.008). The carriage was clustered within case-patient households, with carriage in 19% of household contacts, while only 6.3% of nonhousehold contacts and 5.5% of noncontacts carried the Hi serotype of interest ( P < 0.001). Factors associated with invasive Hi disease in children included underlying health problems, household carriage and inadequate Hib vaccination. The high level of carriage in case-patient households is important to consider when evaluating treatment and prophylaxis strategies.

Clinical spectrum of disease and outcomes in children with Omicron SARS-COV-2 infection in Cape Town, South Africa.

Children with underlying comorbidities and infants are most severely affected by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, including in low- and middle-income countries with a high prevalence of HIV and TB. We describe the clinical presentation of SARS-CoV-2 infection in children during the Omicron wave, in Cape Town, South Africa. We analysed routine care data from a prospective cohort of children aged 0-13 years, with a positive SARS-CoV-2 real-time reverse-transcription polymerase chain reaction (rRT-PCR) or SARS-CoV-2 antigen test, admitted to Tygerberg Hospital between 1 November 2021 until 1 March 2022. Risk factors for severity of disease were assessed. Ninety-five children tested positive for SARS-CoV-2, of whom 87 (91.6%) were symptomatic. Clinical data were available for 86 children. The median age was 11 months (IQR 3.0-60.0), 37 (43.0%) were females, 21 (24.7%) were HIV-exposed and 7 (8.1%) were living with HIV (CLHIV). In total, 44 (51.2%) children had at least one underlying comorbidity. TB co-infection was seen in 11 children, 6 children were newly diagnosed and 5 children were already on TB treatment at the time of admission. There was no evidence of more severe disease in children living with HIV or TB.

Genetic Characterization of Intimin Gene (eae) in Clinical Shiga Toxin-Producing Escherichia coli Strains from Pediatric Patients in Finland.

Shiga toxin (Stx)-producing Escherichia coli (STEC) infections cause outbreaks of severe disease in children ranging from bloody diarrhea to hemolytic uremic syndrome (HUS). The adherent factor intimin, encoded by eae, can facilitate the colonization process of strains and is frequently associated with severe disease. The purpose of this study was to examine and analyze the prevalence and polymorphisms of eae in clinical STEC strains from pediatric patients under 17 years old with and without HUS, and to assess the pathogenic risk of different eae subtypes. We studied 240 STEC strains isolated from pediatric patients in Finland with whole genome sequencing. The gene eae was present in 209 (87.1%) strains, among which 49 (23.4%) were from patients with HUS, and 160 (76.6%) were from patients without HUS. O157:H7 (126, 60.3%) was the most predominant serotype among eae-positive STEC strains. Twenty-three different eae genotypes were identified, which were categorized into five eae subtypes, i.e., γ1, β3, ε1, θ and ζ3. The subtype eae-γ1 was significantly overrepresented in strains from patients aged 5-17 years, while β3 and ε1 were more commonly found in strains from patients under 5 years. All O157:H7 strains carried eae-γ1; among non-O157 strains, strains of each serotype harbored one eae subtype. No association was observed between the presence of eae/its subtypes and HUS. However, the combination of eae-γ1+stx2a was significantly associated with HUS. In conclusion, this study demonstrated a high occurrence and genetic variety of eae in clinical STEC from pediatric patients under 17 years old in Finland, and that eae is not essential for STEC-associated HUS. However, the combination of certain eae subtypes with stx subtypes, i.e., eae-γ1+stx2a, may be used as risk predictors for the development of severe disease in children.

HOIL1 Regulates Group 3 Innate Lymphoid Cells in the Colon and Protects against Systemic Dissemination, Colonic Ulceration, and Lethality from Citrobacter rodentium Infection.

Heme-oxidized IRP2 ubiquitin ligase-1 (HOIL1)-deficient patients experience chronic intestinal inflammation and diarrhea as well as increased susceptibility to bacterial infections. HOIL1 is a component of the linear ubiquitin chain assembly complex that regulates immune signaling pathways, including NF-κB-activating pathways. We have shown previously that HOIL1 is essential for survival following Citrobacter rodentium gastrointestinal infection of mice, but the mechanism of protection by HOIL1 was not examined. C. rodentium is an important murine model for human attaching and effacing pathogens, enteropathogenic and enterohemorrhagic Escherichia coli that cause diarrhea and foodborne illnesses and lead to severe disease in children and immunocompromised individuals. In this study, we found that C. rodentium infection resulted in severe colitis and dissemination of C. rodentium to systemic organs in HOIL1-deficient mice. HOIL1 was important in the innate immune response to limit early replication and dissemination of C. rodentium. Using bone marrow chimeras and cell type-specific knockout mice, we found that HOIL1 functioned in radiation-resistant cells and partly in radiation-sensitive cells and in myeloid cells to limit disease, but it was dispensable in intestinal epithelial cells. HOIL1 deficiency significantly impaired the expansion of group 3 innate lymphoid cells and their production of IL-22 during C. rodentium infection. Understanding the role HOIL1 plays in type 3 inflammation and in limiting the pathogenesis of attaching and effacing lesion-forming bacteria will provide further insight into the innate immune response to gastrointestinal pathogens and inflammatory disorders.

Evaluation of the safety profile and therapeutic efficacy of remdesivir in children with SARS-CoV-2 infection – a single-center, retrospective, cohort study

Despite 3.5 years of the SARS-CoV-2 pandemic, we still lack effective drugs against COVID-19. The first and most widely used drug, remdesivir, has not yet been shown to be effective in adults. Even less is known about its effectiveness in children. Therefore, the aim of this retrospective study was to evaluate the safety and efficacy of remdesivir in pediatric patients with COVID-19 hospitalized in one medical center. The medical records of 328 children with COVID-19 were analyzed. Analysis was performed on the subgroups of children treated and not treated with remdesivir. Clinical data on general health, course of COVID-19 and treatment received were analyzed. Remdesivir was administered to 64 children, 16 to treat severe or critical illness and 48 because of the presence of risk factors to prevent progression to severe COVID-19. In children with severe COVID-19, remdesivir did not reduce the mortality rate. However, in patients with milder disease and risk factors, the drug significantly reduced the risk of progression to severe disease. Among adverse events, only mild aminotransferase elevations were observed in 4 patients, but none of these required discontinuation of treatment.Conclusions: Remdesivir is a safe treatment option for children with COVID-19. However, the efficacy of this therapy is still uncertain. It appears that in children with asymptomatic to moderate COVID-19 and risk factors for severe disease, remdesivir could be an effective method of prophylaxis. However, its efficacy in controlling severe disease is questionable and requires further study.What is Known:• There are still no effective drugs to combat COVID-19, and the efficacy of the widely used remdesivir in adults is controversial.• All recommendations and guidelines on the use of remdesivir in the pediatric population are based mainly on clinical trials in adults.What is New:• Remdesivir is a safe treatment for COVID-19 in the pediatric population.• In children with asymptomatic to moderate COVID-19 and risk factors for severe disease, remdesivir could be an effective drug to prevent disease progression. However, its efficacy in treating severe disease in children needs further exploration.

A Multifaced Aspect of Clostridium difficile Infection in Pediatric Patients with Inflammatory Bowel Disease: Case Series and Literature Review.

Children with inflammatory bowel disease (IBD) have an increased susceptibility to Clostridium difficile infection (CDI), with a rising incidence over time. Differentiating between CDI and IBD exacerbation is challenging due to overlapping symptoms. In our cohort of 55 pediatric IBD patients, 6 were diagnosed with CDI. Upon conducting a thorough patient evaluation and subsequent data analysis, an exhaustive review of the existing literature was undertaken. CDI is more prevalent in ulcerative colitis (UC) than Crohn's disease (CD) patients, as seen in our patients and in the existing literature. The management of a pediatric patient with IBD is itself a challenge for a clinician because of the chronic, possibly relapsing course, and substantial long-term morbidity. When CDI is added, it becomes even more demanding, since CDI leads to more severe disease in children with IBD. A multidisciplinary approach and intensive treatment for possible sepsis, anemia, hypoalbuminemia, and hydro-electrolytic and acid-base imbalances are frequently mandatory in patients with CDI and IBD, which leads to a significant health care burden in hospitalized children with IBD. After the infection is treated with antibiotic therapy, important considerations regarding the future treatment for the underlying IBD are also necessary; in most cases, a treatment escalation is required, as also seen in our study group.

Pediatric infection with the Omicron variant increases the risks of febrile seizures among COVID-19 infected children.

The Omicron variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is less likely to cause severe disease in children than the other variants but has become an increasing cause of febrile seizures (FS) among children. In this case-control study, we aimed to examine the risk factors associated with FS in children infected with the COVID-19 Omicron variant and related treatment modalities. This retrospective case-control study includes 113 subjects infected with the COVID-19 Omicron variant, grouped into 45 cases (those with FS) and 68 controls (those without FS). Data on clinical features, laboratory parameters, and treatment modalities were collected and analyzed. Approximately 5.74% of COVID-19 infected children developed COVID-19-associated FS. Children with COVID-19 and high body temperatures [RR 1.474; (95% CI: 1.196-1.818), p < 0.001], previous history of FS [RR 1.421; (95% CI: 1.088-1.855), p = 0.010], high procalcitonin levels [RR 1.140; (95% CI: 1.043-1.246), p = 0.048] and high neutrophil counts [RR 1.015; (95% CI: 1.000-1.029), p = 0.048] were more likely to experience FS than the controls. In contrast, children with COVID-19 and low eosinophil counts, low hemoglobin levels, and cough had a lower risk of developing FS [RR 0.494; (95% CI: 0.311-0.783), p = 0.003], [RR 0.979; (95% CI: 0.959-0.999), p = 0.044]; and [RR 0.473 (95% CI 0.252-0.890), p = 0.020]; respectively. Children with FS received more anti-flu medications than those without. A significant increase in FS was observed in children with Omicron SARS-CoV-2 infection. A higher body temperature, a history of FS, a higher procalcitonin level, and a high neutrophil count were all associated with an increased risk of FS in children with COVID-19. The risk of developing FS was lower in children with COVID-19 and low eosinophil counts and hemoglobin levels than in those without.

Severe Disease in Children with Parechovirus-A Infection

Severe Disease in Children with Parechovirus-A Infection

Monocyte anisocytosis corresponds with increasing severity of COVID-19 in children.

Although SARS-CoV-2 infection can lead to severe COVID-19 in children, the role of biomarkers for assessing the risk of progression to severe disease is not well established in the pediatric population. Given the differences in monocyte signatures associated with worsening COVID-19 in adults, we aimed to determine whether monocyte anisocytosis early in the infectious course would correspond with increasing severity of COVID-19 in children. We performed a multicenter retrospective study of 215 children with SARS-CoV-2 infection, Multisystem Inflammatory Syndrome in Children (MIS-C), convalescent COVID-19, and healthy age-matched controls to determine whether monocyte anisocytosis, quantified by monocyte distribution width (MDW) on complete blood count, was associated with increasing severity of COVID-19. We performed exploratory analyses to identify other hematologic parameters in the inflammatory signature of pediatric SARS-CoV-2 infection and determine the most effective combination of markers for assessing COVID-19 severity in children. Monocyte anisocytosis increases with COVID-19 severity and need for hospitalization. Although other inflammatory markers such as lymphocyte count, neutrophil/lymphocyte ratio, C-reactive protein, and cytokines correlate with disease severity, these parameters were not as sensitive as MDW for identifying severe disease in children. An MDW threshold of 23 offers a sensitive marker for severe pediatric COVID-19, with improved accuracy when assessed in combination with other hematologic parameters. Monocyte anisocytosis corresponds with shifting hematologic profiles and inflammatory markers in children with COVID-19, and MDW serves as a clinically accessible biomarker for severe COVID-19 in children.

Viral Detection Is Associated With Severe Disease in Children With Suspected Community-Acquired Pneumonia.

To evaluate the role of virus detection on disease severity among children presenting to the emergency department (ED) with suspected community-acquired pneumonia (CAP). We performed a single-center prospective study of children presenting to a pediatric ED with signs and symptoms of a lower respiratory tract infection and who had a chest radiograph performed for suspected CAP. We included patients who had virus testing, with results classified as negative for virus, human rhinovirus, respiratory syncytial virus (RSV), influenza, and other viruses. We evaluated the association between virus detection and disease severity using a 4-tiered measure of disease severity based on clinical outcomes, ranging from mild ( discharged from the ED) to severe (receipt of positive-pressure ventilation, vasopressors, thoracostomy tube placement, or extracorporeal membrane oxygenation, intensive care unit admission, diagnosis of severe sepsis or septic shock, or death) in models adjusted for age, procalcitonin, C-reactive protein, radiologist interpretation of the chest radiograph, presence of wheeze, fever, and provision of antibiotics. Five hundred seventy-three patients were enrolled in the parent study, of whom viruses were detected in 344 (60%), including 159 (28%) human rhinovirus, 114 (20%) RSV, and 34 (6%) with influenza. In multivariable models, viral infections were associated with increasing disease severity, with the greatest effect noted with RSV (adjusted odds ratio [aOR], 2.50; 95% confidence interval [CI], 1.30-4.81) followed by rhinovirus (aOR, 2.18; 95% CI, 1.27-3.76). Viral detection was not associated with increased severity among patients with radiographic pneumonia (n = 223; OR, 1.82; 95% CI, 0.87-3.87) but was associated with severity among patients without radiographic pneumonia (n = 141; OR, 2.51; 95% CI, 1.40-4.59). The detection of a virus in the nasopharynx was associated with more severe disease compared with no virus; this finding persisted after adjustment for age, biomarkers, and radiographic findings. Viral testing may assist with risk stratification of patients with lower respiratory tract infections.

Prevalence and clinical presentation of EV-D68 infections in Kansas City children during the 2022 season

Seasonal EV-D68 infections can strain medical care resources due to increased pediatric hospitalizations for respiratory illness. In this study, we examine Kansas City's 2022 EV-D68 season. Rhinovirus/enterovirus (RV/EV) positive respiratory specimens from standard of care testing were salvaged and tested by EV-D68 specific PCR. Of the 1412 respiratory specimens tested from July 1 to September 15, 2022, 346 (23%) were positive for RV/EV and EV-D68 was detected in 134/319 (42%) salvaged RV/EV positive specimens. The median age of children with EV-D68 infections was 35.2 months (IQR 16.1, 67.3), which was older than children with non-EV-D68 RV/EV infections (16 months, IQR 5, 47.8), but younger than children infected during the 2014 EV-D68 outbreak. EV-D68 infection was more likely to cause severe disease in children with asthma compared to those without asthma. Real-time EV-D68 monitoring for outbreaks could potentially improve resource utilization by hospitals and help prepare for surges of respiratory disease.

Human genetic and immunological determinants of SARS-CoV-2 and Epstein-Barr virus diseases in childhood: Insightful contrasts.

There is growing evidence to suggest that severe disease in children infected with common viruses that are typically benign in other children can result from inborn errors of immunity or their phenocopies. Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a cytolytic respiratory RNA virus, can lead to acute hypoxemic COVID-19 pneumonia in children with inborn errors of type I interferon (IFN) immunity or autoantibodies against IFNs. These patients do not appear to be prone to severe disease during infection with Epstein-Barr virus (EBV), a leukocyte-tropic DNA virus that can establish latency. By contrast, various forms of severe EBV disease, ranging from acute hemophagocytosis to chronic or long-term illnesses, such as agammaglobulinemia and lymphoma, can manifest in children with inborn errors disrupting specific molecular bridges involved in the control of EBV-infected B cells by cytotoxic T cells. The patients with these disorders do not seem to be prone to severe COVID-19 pneumonia. These experiments of nature reveal surprising levels of redundancy of two different arms of immunity, with type I IFN being essential for host defense against SARS-CoV-2 in respiratory epithelial cells, and certain surface molecules on cytotoxic T cells essential for host defense against EBV in B lymphocytes.

Early electrophysiological predictors of progression of hydrocephalus in children with epilepsy

Hydrocephalus is a severe disease in children of all age groups. Failure to treat hydrocephalus in a timely manner can lead to progressive neurological deficits and death. Instead, early diagnosis and treatment of progressive hydrocephalus can completely recover the child. The term «early diagnosis» of hydrocephalus is the most difficult task for a pediatric neurologist. There are no pathognomonic clinical signs of this disease. Detection of electrophysiological signs of hydrocephalus progression in the early stages of the disease could significantly affect on treatment outcomes. The aim of our work is to establish early electrophysiological predictors of the progression of hydrocephalus in children with epilepsy. Materials and methods. 28 children with epilepsy were examined at the Transcarpathian Regional Children’s Hospital and the Medical Center «Diamed» in Uzhhorod from 2018 to 2022. All children were examined prospectively using video-EEG monitoring with sleep fixation, magnetic resonance imaging (MRI), multispiral computer tomography (MSCT). Results. The electrical status epilepticus during slow-wave sleep (ESES) was registered in 35 % of examined patients (8 children). The average duration from detection of the electrical status of sleep to the establishment of shunt system in the brain is 37 days (from 15 to 60 days). The ESES disappeared in 6 children during the first month after the implantation of the shunt system in the brain, in 2 children during the next 3 and 6 months of observation. We have developed our own algorithm for examining children with hydrocephalus and epilepsy up to 1 year and older than 1 year. Conclusion. An intense increase of epileptiform activity and appearance of electrical status of slow-wave sleep may be one of the predictors of the progression and decompensation of hydrocephalus and requires dynamic control. Further randomized trials are needed to assess the significance of these changes. The developed algorithm will increase the effectiveness of the use of additional examination methods for early detection of the progression of hydrocephalus in children with epilepsy.

Патогенетические механизмы тяжелых клинических форм стрептококковой инфекции у детей

Currently, there is a significant increase in the morbidity of streptococcal infections, including the severe cases with a fatal outcomes. In this article we show the general information on the modern features of diseases caused by Streptococcus pyogenes (Group A Streptococcal (GAS) Infections), pathogenicity factors of the microbe and its strain diversity. Various aspects of immunopathogenesis in various clinical forms of streptococcal infection, such as tonsillitis, acute rheumatic fever, toxic shock syndrome, neurological and myocardial complications are discussed. The issues of association between the severe course of GAS infection against the background of previous chickenpox, influenza, infectious mononucleosis are described. Possible mechanisms of interaction of pathogens in combined virus-streptococcal infection are presented. The ways of avoiding streptococcus from the host's protective reactions, the features of the innate and adaptive immune response in various clinical forms of streptococcal infections, as well as the role of viruses in the pathogenesis of severe disease in children are reflected. The tactics of pathogenetic therapy using the medicine of complex action cytoflavin, which allows optimizing the course of generalized streptococcal infection, is noted. Key words: streptococcal infections, viruses, immunopathogenesis, clinic, cytoflavin, strains

African-specific alleles modify risk for asthma at the 17q12-q21 locus in African Americans

BackgroundAsthma is the most common chronic disease in children, occurring at higher frequencies and with more severe disease in children with African ancestry.MethodsWe tested for association with haplotypes at the most replicated and significant childhood-onset asthma locus at 17q12-q21 and asthma in European American and African American children. Following this, we used whole-genome sequencing data from 1060 African American and 100 European American individuals to identify novel variants on a high-risk African American–specific haplotype. We characterized these variants in silico using gene expression and ATAC-seq data from airway epithelial cells, functional annotations from ENCODE, and promoter capture (pc)Hi-C maps in airway epithelial cells. Candidate causal variants were then assessed for correlation with asthma-associated phenotypes in African American children and adults.ResultsOur studies revealed nine novel African-specific common variants, enriched on a high-risk asthma haplotype, which regulated the expression of GSDMA in airway epithelial cells and were associated with features of severe asthma. Using ENCODE annotations, ATAC-seq, and pcHi-C, we narrowed the associations to two candidate causal variants that are associated with features of T2 low severe asthma.ConclusionsPreviously unknown genetic variation at the 17q12-21 childhood-onset asthma locus contributes to asthma severity in individuals with African ancestries. We suggest that many other population-specific variants that have not been discovered in GWAS contribute to the genetic risk for asthma and other common diseases.

Risk factors associated with severe disease in respiratory syncytial virus infected children under 5 years of age.

ObjectiveTo evaluate risk factors for severe disease in children under 59 months of age hospitalized with respiratory syncytial virus (RSV) infection.Study designWe prospectively enrolled 1,096 cases of laboratory confirmed RSV infection during three consecutive RSV seasons in 2015–2018. Potential risk factors for severe disease were retrieved through patient questionnaires and linkage to national health registries. Need for respiratory support (invasive ventilation, bi-level positive airway pressure, or continuous positive airway pressure), and length of stay exceeding 72 h were used as measures of disease severity. Associations were investigated using multivariable logistic regression analyses. Multiple imputation was used to avoid bias and inference induced by missing data.ResultsRisk factors associated with a need for respiratory support included age younger than 3 months of age [aOR: 6.73 (95% CI 2.71–16.7)], having siblings [aOR: 1.65 (95% CI 1.05–2.59)] and comorbidity [aOR: 2.40 (95% CI 1.35–4.24)]. The length of hospital stay >72 h was significantly associated with being younger than 3 months of age [aOR: 3.52 (95% CI 1.65–7.54)], having siblings [aOR: 1.45 (95% CI 1.01–2.08)], and comorbidity [aOR: 2.18 (95% CI 1.31–3.61)]. Sub-group analysis of children younger than 6 months of age confirmed the association between both young age and having siblings and the need for respiratory support.ConclusionIn a large cohort of children <59 months hospitalized with RSV infection, young age, comorbidity, and having siblings were associated with more severe disease.