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Gastrointestinal tract damage is a part of the course of multisystem inflammatory syndrome in children (MVS-D) associated with the new COVID-19 coronavirus infection. According to the results of a retrospective study, gastrointestinal tract damage was detected in 77% of patients with MVS-D and is represented by signs such as abdominal pain, vomiting, diarrhea and peritoneal symptoms. In children with gastrointestinal tract lesions, significant differences were noted in the frequency of occurrence of the following signs: hepatomegaly, splenomegaly, hypotension/shock, as well as conjunctivitis and facial swelling. Among laboratory abnormalities, hypoalbuminemia is more characteristic, but the level of CRP and troponin is higher. The article shows that gastrointestinal tract damage is an important early predictor of the severity of MVS-D.
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Multisystem inflammatory syndrome is the most severe manifestation of a new coronavirus infection in children. The article presents the clinical case of the multisystem inflammatory syndrome features associated with COVID-19 in a teenager. The purpose of the work is to provide information on this topical clinical problem.
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Background/Purpose: Multisystem inflammatory syndrome associated with COVID-19 in children (MIS-C) is a rare but severe disease associated with coronavirus infection, in which various systems and organs are affected, including the heart, lungs, kidneys, brain, skin, eyes and gastrointestinal tract. One of the most severe features of this disease can be hemophagocytosis. The aim of this study is to assess the features of hemophagocytosis in MIS-C. Method(s): The retrospective study included 166 children (99 male, 67 female), aged from 4 months to 17 years (median 8.2 years), who met the WHO criteria for MIS-C. The analysis of the obtained data was performed using the STATISTICA software package, version 10.0 (StatSoft Inc., USA). Result(s): To study the signs of hemophagocytosis in patients with MIS-C they were divided into 2 equal groups: with HScore<=91 (n = 79) and with a HScore value >91 (n = 79). This division was done, since this value was associated with the severe life-threatening course of MIS-C and need in ICU admission (70.9% vs. 32.3%, P = 0.000002). Patients with HScore > 91 were more likely to have symptoms such as cervical lymphadenopathy (80.6% vs 54.1%, P = 0.0007), red dry cracked lips (63% vs 34.3%, P = 0.0007), face swelling (66.7% vs 34.7%, P = 0.001), hepatomegaly (84.2% vs 43.1%, P = 0.000000), splenomegaly (54.7% vs 43.1%, P = 0.0003), hypotension/shock (63.3% vs 25.3%, P = 0.000002), had higher levels of ESR (47 mm/h vs 34 mm/h, P = 0.0001), CRP (175.5 mg/L vs 125.8 mg/L, P = 0.01), D-dimer (2135 ng/mL vs. 1079 ng/mL, P = 0.0003), but lower levels of fibrinogen (3.1 g/L vs 5.6 g/L, P = 0.000002) erythrocytes (3.6 x 1012/L vs 4.0 x 1012/L, P = 0.000005), hemoglobin (98 g/L vs 112 g/L, P = 0.000000), and a tendency to thrombocytopenia (110 x 109/l vs 192 x 109/L, P = 0.0002) in 63.3% of patients. According to EchoCG data, signs of myocardial (45.5% vs 15.6%, P = 0.00006) and pericardial (45.5% vs 14.3%, P = 0.00002) lesions were more common in patients with HScore > 91. Patients with HScore > 91 more often needed treatment with IVIG (66.2% vs 24%, P = 0.000000), acetylsalicylic acid (65.7% vs. 47.1%, P = 0.027) and biological drugs (9.1% vs. 1.6%, P = 0.061). The average duration of hospitalization was also much longer in patients with HScore > 91 (23 days vs 14 days, P = 0.000000). Also, the identification of clinical and laboratory signs that were more common in the group of patients with HScore > 91 was performed using sensitivity and specificity analysis, and calculation of odds ratio. Results are presented in Table 1. Conclusion(s): Hemophagocytic syndrome is one of the most severe manifestations of MIS-C occuring in 35.4% of patients. It was found that HScore > 91 is associated with such a severe signs of MIS-C as myocarditis, pericarditis, hypotension/shock, and ICU admission. HScore is a simple tool that can also be used to assess the severity of MIS-C and dynamic monitoring.
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Background: COVID-19 is still changing problem for pediatric rheumatologist, not only related with multisystem inflammatory syndrome. SARS-CoV- 2 can damage blood vessel endothelium through direct invasion, immune system dysregulation (hyperproduction of pro-inflammatory cytokines, interferonopathy) and hypercoagulation, and in this way triggers vasculitis. There are some data in the literature about skin vasculitis, central nervous system vasculopathy, associated with COVID-19 in children, but data are scarce. The aim of our study was to describe the cases, associated with COVID-19 in children. Method(s): in the retrospective-prospective case series study we included information about five children with COVID-19 associated vasculitis. In every case we have morphological description and the etiology was confirmed by RT-PCR in tissue biopsy. Result(s): The patients' demography, type of SARS-CoV- 2 identification, disease characteristics are in the tables 1-2. All patients required systemic corticosteroids and immunosuppression to control inflammation and recovering tissue damage.
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Background/Purpose: Multisystem inflammatory syndrome in children (MIS-C), associated with COVID-19 infection is a life-threatening condition, required intensive care. The aim of this study was to determine risk factors for severe/life-threatening course of MIS-C. Method(s): The retrospective study included 166 children (99 male, 67 female), aged from 4 months to 17 years (median 8.2 years), who met the WHO criteria for MIS-C. The criterion of severity was the fact of the ICU admission. The analysis of the obtained data was performed using the STATISTICA software package, version 10.0 (StatSoft Inc., USA). Result(s): To assess the factors associated with the severe course of MIS-C, patients were divided into two groups: those who were hospitalized in the ICU (n = 84;50.6%), and those who did not (n = 82;49.4%). Patients with a more severe course of MIS-C were significantly older. They had a high frequency of signs such as rash, edema, hepatomegaly, splenomegaly, neurological and respiratory symptoms. Hypotension/shock and myocardial damage were much more common in patients hospitalized in the ICU. Among the laboratory changes there were significant differences in the levels of hemoglobin, leukocytes and platelets, CRP, creatinine, troponin and D-dimer. The presence of macrophage activation syndrome was higher in patients, admitted in the ICU. Children, required intensive care required high dose corticosteroids and IVIG more often (table 1). FIGURE: 1) The first symptoms of progeria in infancy: scleroderma-like changes in the skin of the lower extremities and stiffness of knee joints at the age of 2 months. 2) Girl at the age of 3 years 5 months. Almost total alopecia with the absence of eyebrows and eyelashes. Pronounced venous pattern in the forehead, nasal bridge and nasolabial triangle. Conclusion(s): MIS-C is potentially a severe life-threatening condition, in which more than half (50.6%) of patients needed the ICU admission. The main factors determining the severity of MIS-C were: cardiovascular, resiratory and central nervous system disorders. It has been found that factors such as hepatomegaly, splenomegaly, D-dimer >2568 ng/ml, troponin >10 pg/ml, make it possible to identify a group of patients with high risk of severe MIS-C who may potentially need hospitalization in the ICU.
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The pathogenetic basis for Pediatric Multisystem Inflammatory Syndrome (PMIS) associated with SARS-CoV-2 is systemic vasculitis resulting from hyperproduction of pro-inflammatory cytokines associated with dysregulation of the immune response. Clinical manifestations of PMIS include fever with features of Kawasaki Syndrome (KS) and multi-organ dysfunction coupled with frequent unusual heart involvement, ranging from mild with minimal ECG changes or elevated troponin to fulminant myocarditis or Takotsubo syndrome (TTS). The purpose of the research was to study the characteristics of cardiovascular disorders in Kawasaki-like multisystem inflammatory syndrome associated with COVID-19 in children observed in the East Siberian area of Russia. A single-center retrospective cohort study was carried out on the basis of the Irkutsk Oblast Regional Children's Clinical Hospital (Irkutsk, Russia): 36 patients with PMIS associated with COVID-19 in Nov. 18, 2020 - Dec. 31, 2021, including 21 boys (M/F ratio 1.4:1) at the average age of 7.5 years old (1.5 months to 17 years old). The diagnostic signs of KS were observed in 34 (94%) children, including the complete set of diagnostic signs in 21 (58%). Refractory fever and a sharp increase in inflammatory biomarkers were detected in all 36 (100%) children;multiorgan dysfunction in 31 (86%);thrombocytopenia in 24 (67%);gastrointestinal syndrome in 25 (69%);cerebral dysfunction in 24 (66)%;various cardiovascular disorders in 30 (83%), including: dilatation of the left ventricle (LV) and a decrease in myocardial contractility in 3 (8%);moderate coronary dilatation in 5 (14%);thickening of the posterior LV walls in diastole in 5 (13%);thickening of the interventricular septum in diastole in 6 (16%). According to the MRI results performed in 15 children the signs of myocardial damage were found in 6 (40%). LV dilatation and decreased myocardial contractility were noted in 3 (8%) children, clinically apparent thrombotic complications in 3 (8%) children as well, and severe neurological deficit in one patient (3%). An increase in the level of D-dimer was observed in 26 (72%) patients, thrombocytopenia in 24 (67%), a statistically significant correlation between thrombocytopenia and myocardial damage was found (R=-0.506, p=0.001). The treatment measures were given as follows: inotropic support (dobutrex/dobutamine) was received by 8 (22%), artificial lung ventilation - by 8 (22%), intravenous human immunoglobulin 1.5-2.0 g/kg/course - by 28 (77%), dexamethasone - by 24 (67%), tocilizumab - by 2 (5%) patients. All 36 (100%) patients have survived. Conclusion(s): the Kawasaki-like multisystem inflammatory syndrome associated with COVID-19 was accompanied by the cardiovascular disorders (pericarditis, arrhythmias, abnormal ECG changes, elevated troponin and/or natriuretic peptide, LV thickening on echocardiography, coronary dilatation) in most patients, although LV dilatation and decreased myocardial contractility were observed in a few cases only. A negative correlation between thrombocytopenia and myocardial damage was found, which may indicate the involvement of thrombotic microvascular inflammation in the genesis of myocardial disorders. Copyright © 2022, Pediatria Ltd. All rights reserved.
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Introduction: JIA patients are targeted for vaccination as a population at risk of severe influenza disease. Recent COVID-19 pandemic is an additional challenge;nonetheless, their influenza vaccine coverage remains uncertain. Objectives: To assess the flu vaccination rate in JIA patients & investigate family's attitudes towards it;to identify how COVID-19 pandemic has affected caregiver's decision on flu vaccine administration. Methods: A multi-center cross-sectional study was conducted across 9 countries. Participants completed a questionnaire about the flu vaccination uptake history including the year of 2020-21, sociodemographics and data regarding the disease. Analysis was conducted using SPSSv.20. Results: 655 JIA caregivers were surveyed across 9 countries (Table). The majority was employed (61.2%), married (78.5%) & held a tertiary education (43.1%). Patient's median age was 11y (IQR: 7-15). Principal diagnosis was oligoJIA (34%) & most patients were treated systemically (81%). 21.7% had received influenza vaccine in the past & 18.6% in 2019-20 season;85% were fully vaccinated. 152 children (23.2%) were vaccinated against flu the current season. The majority was informed by their ped rheumatologist (33.5%). Highest uptake was recorded in Greece (79.3%) while lowest in Turkey (1.1%) (p<0.01) (Table). Employed & self-employed and those with tertiary education were more likely to vaccinate their children compared to unemployed & those with elementary education (28.2% & 29.9% vs 13.6%, 28% vs 9.7% respectively, p<0.01). Children with psoriatic & polyJIA had the highest uptake (both 30%) while patients with undifferentiated reported the lowest (7.4%, p<0.01). Among vaccinators, 92.4% were fully vaccinated, 64.6% had been vaccinated in the past & 57.6% in 2019-20 season (p<0.05). An increase was reported in uptake between 2019-20 & 2020-21 seasons (18.6% vs 23.2%, p<0.01). Among non-vaccinators, 52% did not have the chance to discuss their concerns. Major reason for non-vaccination was unawareness of the need (36%);13% reported it was a doctor's advice. Caregivers suggested that informing in advance (67%) may improve uptake. Most of caregivers expressed their concerns regarding their children's vulnerability to SARS-COV-2 due to JIA (51.3%) & their risk of COVID-19 (85.3%);51.3% of them were pro COVID-19 vaccine administration to their children (Table). Those who vaccinated their children against flu in the 2019-20 & 2020-21 seasons were more likely to vaccinate them against SARS-COV-2 (79.5% & 73.4% respectively, p<0.01). Conclusion: Despite variations among countries, flu vaccine uptake remains low in JIA patients. Higher education, thorough informative discussion and notifying families in advance may lead to universal vaccine coverage in children with RDs.
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Introduction: COVID-19 in children is often asymptomatic or with only mild symptoms. However, since April 2020 there are many reports that the new coronavirus infection might be associated with pediatric hyperinflammatory condition, that fully or partially meets the criteria for Kawasaki disease (KD). This phenomenon was later called multisystem inflammatory syndrome in children (MIS-C) or pediatric inflammatory multisystem syndrome temporarily associated with SARS-CoV-2 (PIMS-TS). Objectives: Our study aimed to evaluate main clinical and laboratorial features and course of MIS-C and compare it with Kawasaki disease in children. Methods: The retrospective study included 50 children (34 male, 16 female), aged from 7 months to 16 years 9 months (median 8.8 years), who met the WHO criteria for MIS-C and 60 patients (34 male, 26 female, aged from 3 months to 6 years (median 2 years) with Kawasaki disease. Results: Prior COVID-19 infection in MIS-C group was confirmed by positive SARS-CoV2 test using RT-PCR (n=11) or IgM (n=21), IgG (n= 38) and/or close contact with a person with confirmed COVID-19 (n= 21) clinical features of previous COVID-19 infection were noted in 22 patients. Clinical sings of MIS-C included fever (100%), gastrointestinal disorders (81.6%), rash (90%), conjunctivitis (93.6%), sore throat (68.1%) cheilitis (54.6%), cervical lymphadenopathy (68.2%), hands and feet erythema/oedema (69.8%), hepathomegaly (64.6%). In the majority of patients elevated levels of inflammatory biomarkers, D-dimer, troponin, ferritin were found. Most of patients had a tendency to anemia (median hemoglobin 105 g/l). Platelet levels varied greatly (8-919∗109/l), 37.5% of patients had thrombocytopenia. Carditis and coronary artery dilatation were found in 48.9% and 22.7%, respectively. Arterial hypotension/shock was in 52.5%. Heart MRI showed signs of myocarditis (n=5): T1 prolongation (n=2);signs of myocardial edema, pericarditis, severe arrhythmia, and a tendency to diastolic overload (n=1), but no signs of ischemic or non-ischemic myocardial damage, and the global systolic function stayed normal. Patients were treated with high-dose glucocorticoids (93.6%), low-weighted heparin (100%), low dose of aspirin (64.4%), intravenous immunoglobulin (37.8%);Tocilizumab was used in three patients (6%). The median duration of hospitalization was 22 days, and 65.9% of patients required an ICU admission. Some of the most informative indicators for the differential diagnosis of MIS-C and KD are shown in the table. Conclusion: MIS-C is severe life-threatening condition in children, which pathogenesis and relation to COVID-19 requires further research. There are differences in the frequency of some signs that possibly can be used as a basis for differential diagnosis of the studied conditions.
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Multisystem inflammatory syndrome in children and adolescents associated with SARS-CoV-2 (MBS-D) is a new challenge for pediatricians around the world. Scientific data is updated daily and patient treatment regimens are developed. The involvement of the heart in the inflammatory process complicates the course of the disease and further rehabilitation of patients. The article describes 12 patients with heart disease in the structure of MVS-D, who underwent laboratory tests and instrumental studies, including MRI of the heart, and also provides detailed descriptions of three clinical cases and a review of literature data. © 2021, Pediatria Ltd.. All rights reserved.
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Introduction. The issue of protection against vaccine-preventable diseases has acquired new urgency in connection with the decrease in the vaccination rate established by WHO against the background of the COVID-19 pandemic. This creates the conditions for outbreaks and puts patients with immunopathological diseases at particular risk, who are most often not vaccinated from the moment of diagnosis Purpose of the study – to assess the safety of specific antibodies to measles, mumps, rubella and diphtheria in children with JIA, depending on the duration of vaccination, the duration of the disease and the therapy received. Materials and methods. The vaccination rate of 171 children with juvenile idiopathic arthritis (JIA) aged (11,31±0,31 years) with the duration of the disease at the time of examination was 4,69±0,29 years, who had previously received 1-2 vaccinations against measles, mumps, rubella and 3-6 vaccinations against diphtheria. Antibodies to these infections were determined by ELISA. Results. 42.1% of children had no protective titers of antibodies to measles, 19,9% – to mumps, 9,4% – to rubella and 16,4% – to diphtheria. Among 93 vaccinated and revaccinated patients, there were no protective titers of antibodies to measles – 40,9% (38 children), mumps – 13,9% (13 people), rubella – 5,4% (5 children), and among 78 vaccinated once, respectively: measles – 43.6% (34 children), mumps – 25.6% (20 children), rubella – 14,1% (11). The level of protection against diphtheria was comparable for those who received 3-5 vaccinations. Depending on the therapy, 3 groups were identified: group 1-71 children received metatrexate and glucocorticosteroids, 2-82 children received modifying anti-rheumatic drugs (DMARD) and 18 children without this therapy (Group 3). Children of the 2nd group were on average older (12,48±0,42 years) than in the 1st and 3rd groups (10,04±0,48 and 10,96±0,96 years, respectively), they had significantly more frequent systemic variant and polyarthritis (64,6% compared to 36,6% and 16,7%, px2<0,001). The number of vaccine doses received by children in all groups before the onset of the disease did not significantly differ. The average level of antibodies to measles in children of group 2 (0,32±0,07 IU/ml) was 2,8 times less than in group 3 and significantly less than in group 1 (0,78±0,16, Pt=0.009), the average value of antibodies to rubella was also significantly less in group 2 (84,48±7,34 IU/ml) than in group 1 (109,73±8,09, Pt=0,022) and in group 3 (120,01±15,42, Pt=0,042). The analysis showed that the safety of antibodies to antigens of live vaccines, especially against measles, is negatively affected by the duration of the disease and the nature of therapy. Children who received combined therapy with anti-TNF, anti-IL-6 and anti-CD-80 drugs had a longer duration of the disease (7,5±0,97 years)=0,00082 compared to those who received only anti-IL-6 (2,9±0,7 years) and anti-TNF therapy (6,1±0,5 years) and with a comparable number of vaccine doses received, significantly lower average values of antibodies and a larger number of unprotected ones. Conclusions. The duration of the disease, the lack of timely age-related revaccinations, as well as the presence of combination therapy aimed at suppressing various mechanisms of the immune response in children with JIA are factors that lead to an increase in the number of unprotected from controlled infections. Immunity to measles suffers the most – 40.9% of revaccinated people are unprotected.
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Since March 2020, the first reports have appeared about the increasing, almost everywhere, number of children who have undergone a new coronovirus infection caused by SARS-Cov-2 with a symptom complex resembling the manifestations of Kawasaki disease. A special feature of the clinical manifestations of this syndrome, which is called “Pediatric multisystem inflammatory syndrome associated with COVID-19”, is the high incidence of life-threatening conditions caused by the sharp development of arterial hypotension against the background of cardiogenic or vasogenic shock. In St. Petersburg, since the end of November 2020, there has been a sharp surge in admissions of children to the ICU of various hospitals with the clinic of Pediatric multisystem inflammatory syndrome, who have laboratory confirmation of the transferred COVID-19. The purpose of this article is to attract the attention of doctors of various profiles, to combine efforts to study this pathology, to determine the criteria for verifying the diagnosis, optimal treatment regimens and dispensary monitoring of patients who have been ill. © 2021 Interregional public organization Association of infectious disease specialists of Saint-Petersburg and Leningrad region (IPO AIDSSPbR). All rights reserved.
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During the COVD-19 pandemic, some pediatric patients in many countries around the world experienced a syndrome resembling a severe Kawasaki disease (KD), often accompanied by shock. Due to the incomplete signs of the classic KD in the era before the present pandemic, in many publications from European countries and the United States, this condition was called «multisystem inflammatory syndrome in children - MIS-C» or «hyperinflammatory shock» or «Kawasaki-like syndrome». This syndrome with a new coronavirus infection is characterized by refractory fever, frequent gastrointestinal symptoms, heart damage (including coronary dilation in some patients, and acute left ventricular failure in the majority), increased ESR and CRP levels, neutrophilia, extremely high troponin levels, increased ferritin, AST, ALT, lactate dehydrogenase, creatine phosphate kinase, interleukin-6 and interleukin-10, coagulopathy with an increase in D-dimer and fibrinogen, thrombocytopenia, sometimes procalcitonin increase. The manifestations of a cytokine storm may meet the criteria for secondary hemophagocytic syndrome. The mechanism of myocardial damage remains unclear. Treatment with high-dose intravenous immunoglobulin is effective, and in the presence of signs of hemophagocytic syndrome, dexamethasone or methylprednisolone. Further research is needed to understand the pathogenesis, resemblance and differences of this syndrome with classic KD, understanding of heart injuiry and early recognition for the need of urgent care. В ходе пандемии COVD-19 у части пациентов детского возраста во многих странах мира отмечен синдром, напоминающий тяжелый вариант болезни Кавасаки (БК), часто сопровождаемый шоком. Ввиду неполного его соответствия классической БК в эру до настоящей пандемии во многих публикациях из европейских стран и США это состояние получило название «мультисистемный воспалительный синдром», либо «гипервоспалительный шок», либо «Кавасаки-подобный синдром». Для данного синдрома при новой коронавирусной инфекции характерны рефрактерная лихорадка, частые гастроинтестинальные симптомы, поражение сердца (включая коронарную дилатацию у части больных и острую левожелудочковую недостаточность у большинства), повышение уровня СОЭ и СРБ, нейтрофилез, экстремально высокий уровень тропонина, рост ферритина, АСТ, АЛТ, лактатдегидрогеназы, креатинфосфаткиназы, интерлейкина-6 и интерлейкина-10, коагулопатия с увеличением Д-димера и фибриногена, тромбоцитопения, иногда рост прокальцитонина. Проявления цитокинового шторма могут отвечать критериям вторичного гемофагоцитарного синдрома (ГФС). Механизм поражения миокарда остается неясным. Эффективно лечение высокодозным внутривенным иммуноглобулином, при наличии признаков ГФС - дексаметазоном либо метилпреднизолоном. Дальнейшие исследования необходимы для понимания патогенеза, сходства и различия данного синдрома с классической БК, механизма поражения сердца, раннего распознавания для оказания ургентной помощи.
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The risk of a severe course of new coronavirus infection (COVID-19) due to the development of acute respiratory distress syndrome is extremely high, which is especially true for patients with comorbidities. The aim of the study is to demonstrate the peculiarities of the course and intensive care measures in new coronavirus infection COVID-19 in children with comorbidities. Patients and methods: On the example of clinical cases, the characteristics of the course of a new coronavirus infection of COVID-19 in children with systemic lupus erythematosus and bronchopulmonary dysplasia are considered. Results: The main data from the history and clinical laboratory examination are reflected, which made it possible to identify a cytokine storm in a timely manner, a high risk of adverse course and begin timely specific pathogenetic therapy, including immunoglobulins for intravenous administration, hydroxychloroquine, ritonavir in combination with lopinavir, azithromycin and dexamethasone. Particular attention is paid to the need to limit infusion therapy, maintain a negative water balance and optimal blood oxygen capacity, ambiguity of opinions on the need for routine use of albumin and dexamethasone solutions in patients with COVID-19 has been demonstrated. Conclusion: Children with comorbidities are characterized by a severe course of a new coronavirus infection CO-VID-19, which requires timely pathogenetic therapy taking into account the individual characteristics of the patient.