On clinical manifestations of the new coronavirus infection in newborns.

The aim of the research. To study the specifics in manifestations of the new coronavirus infection in newborns. Material and methods. A retrospective analysis of observations of 28 newborns diagnosed with the new coronavirus infection SARS-CoV-2 dated from June to December 2020 was performed. The infants were transferred from the perinatal centre for hospitalisation to the infectious department of a children's hospital. The patients were born to mothers with COVID-19 as well as mothers discharged from hospital and hospitalised later due to COVID-19 acquired through family contact. Clinical and laboratory data of 12 female and 16 male children aged 1 to 28 days were studied. Results. Clinical symptoms of the new coronavirus infection in newborns tend to be different: from asymptomatic course in 46.5 % of the patients to evident pneumonia in 50 % of the children. The newborns admitted with COVID-19 acquired through family contact had more severe disease manifestations. Conclusion. Amidst the pandemic rise of its incidence, the new coronavirus infection COVID-19 is not rare among newborns. COVID-19 newborns did not have a registered severe nosocomial infection, sepsis, multisystem inflammatory syndrome.Copyright © 2022, Krasnoyarsk State Medical University. All rights reserved.

Features of Gastrointestinal Disorders in Children with Multisystem Inflammatory Syndrome Associated with Covid-19

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.

COVID-19 -Associated vasculitis in children: The case series, confirmed by tissue RT-PCR

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.

Multisystem inflammatory syndrome associated with COVID-19 in children: Risk factors of severe life-threatening course of the disease

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.

Using HScore for the evaluation of the signs of hemophagocytosis in multisystem inflammatory syndrome associated with covid-19 in children

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.

MONITORING OF CHILDREN WITH KAWASAKI-LIKE (MULTISYSTEM INFLAMMATORY) SYNDROME IN THE EAST SIBERIAN AREA OF RUSSIA

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.

Preliminary results of follow-up of patients with multisystem inflammatory syndrome associated with COVID-19

Background and Aim: Kawasaki-like (multisystem inflammatory) syndrome associated with SARS-CoV-2 infection is characterized by acute severe systemic vasculitis, often with multi-organ dys-function and cardiac involvement. Although most patients recover, long-term outcomes are poorly studied [Gema de Lama Caro-Paton et al., 2021;Guimaraes D. et et al., 2021;Sharma C. et al., 2021]. Method(s): We analyzed the results of laboratory, clinical, radiologi-cal, ECG and EchoCG data in the dynamic observation of 15 patients (M 9, 1.5-16 yo, m = 7) in 3 months after the suffered MIS-C. Result(s): At the disease onset high refractory fever was observed in all cases, symptoms of Kawasaki disease in 12 (80%) of them, shock with multi-organ dysfunction-in 8 (53.3%), including symptoms of acute heart failure-in 5 (33%), concomitant in two cases with severe left ventricular dilatation with low LV EF. Myocardial damage was seen in 11 patients (73%), pericarditis in 12 (80%), coronary dilatation in two (13%);troponin level increased in 5 (33%), CK-MB-in 5 (33%), BNP-in 3 (25%). After 3 months, there were no signs of myocardial dysfunction and/or cardiomegaly in any patient, troponin and BNP levels normalized in all patients, a moderate increase of CK-MB was seen in 8 (53%), and coronary dilatation persisted in one patient. Arrhythmias were documented at onset in 9 (60%) patients, 3 (20%) after 3 months (p = 0.028). Conclusion(s): preliminary results of follow-up of children after MIS-C demonstrate favorable course in the majority of patients by clinical, laboratory, ECG and echocardiographic data. Further observations are needed to determine the long-term prognosis.

On clinical manifestations of the new coronavirus infection in newborns

The aim of the research. To study the specifics in manifestations of the new coronavirus infection in newborns. Material and methods. A retrospective analysis of observations of 28 newborns diagnosed with the new coronavirus infection SARS-CoV-2 dated from June to December 2020 was performed. The infants were transferred from the perinatal centre for hospitalisation to the infectious department of a children’s hospital. The patients were born to mothers with COVID-19 as well as mothers discharged from hospital and hospitalised later due to COVID-19 acquired through family contact. Clinical and laboratory data of 12 female and 16 male children aged 1 to 28 days were studied. Results. Clinical symptoms of the new coronavirus infection in newborns tend to be different: from asymptomatic course in 46.5 % of the patients to evident pneumonia in 50 % of the children. The newborns admitted with COVID-19 acquired through family contact had more severe disease manifestations. Conclusion. Amidst the pandemic rise of its incidence, the new coronavirus infection COVID-19 is not rare among newborns. COVID-19 newborns did not have a registered severe nosocomial infection, sepsis, multisystem inflammatory syndrome. © 2022, Krasnoyarsk State Medical University. All rights reserved.

Multisystem inflammatory syndrome in children associated with SARS-COV-2 and Kawasaki disease: experience of pediatric clinics in Russia

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.