Характеристика COVID-19 у детей: первый опыт работы в стационаре Санкт-Петербурга

Objective: to identify the clinical, laboratory and epidemiological features of the new coronavirus (CV) infection in the provision of specialized medical care to children in the megalopolis of the Russian Federation. Methods: 674 cases of hospitalization of patients from birth to 17 years old inclusive with confirmed COVID-19 in the period from March 26 to June 26, 2020 in a children’s multidisciplinary hospital in St. Petersburg. Diagnostics of SARS-COV-2 in upper respiratory tract (URT) smears was carried out by PCR (a set of reagents for detecting RNA of coronavirus 2019-nCoV by PCR with hybridization-fluorescence detection “Vector-PCRRV-2019-nCoV-RG”). Patients underwent 4 (3; 5) repeated examinations depending on the diagnosis of the referral, as well as the duration of the convalescent virus carriage. The analysis of the severity of the course of the disease, the main clinical manifestations and their relationship with the development of pneumonia, as well as the epidemiological features of COVID-19 in children. The duration of inpatient treatment, outcomes and the need for intensive care are described. Changes in a number of laboratory parameters on analyzers made in the USA were assessed: a clinical blood test on a hematological one - Coulter UniCel (Beckman Coulter), a biochemical blood test on a biochemical one - Uni Cel DxC (Beckman Coulter), a coagulogram on a hemostasis analyzer (Instrumentation Laboratory). Results: Overall, there was a favorable course of COVID-19 in children. Intensive therapy was required only in 3.6% of cases with a total mortality rate of 0.15%, Kawasakilike syndrome was recorded in 0.3% of cases. In 1/3 of patients, prolonged viral shedding from the upper respiratory tract was detected. In children, intrafamilial infection from adults was in the lead; schoolchildren accounted for half of all hospitalizations. A distinctive feature of the new infection was mild clinical symptoms with fever and catarrhal symptoms up to 4/5 of cases, gastrointestinal symptoms - in every third patient. There were no significant differences in the severity of the disease by age. Pneumonia, diagnosed in ¾ cases by computed tomography, complicated the course in 13.1% of cases. The defeat of the lungs was accompanied by fever and dry cough, and in a more severe course: desaturation, chest pains, a feeling of insufficiency of inspiration. The age peaks of the incidence of pneumonia were revealed: at 4, 9, 12 years old and at the age of 17 years, the maximum (in 1/3 of cases). Laboratory changes were insignificant and quickly reversible. Conclusion: the course of COVID-19 in children in the megalopolis of Russia is comparable with foreign information. However, taking into account the experience of “Spanish ‘flu”, it is possible that in pediatric practice the number of severe forms and unfavorable outcomes may change in the near future, especially due to the difficulty of diagnosing Kawasaki-like syndrome and the need for a multidisciplinary approach to the treatment of such patients. Currently, the most vulnerable to the new CV are children with severe oncological, neurological and cardiovascular pathology, who have a rapid decompensation of the underlying disease against the background of COVID-19.Цель: выявить клинико-лабораторные и эпидемиологические особенности новой коронавирусной инфекции при оказании специализированной медицинской помощи детям в мегаполисе Российской Федерации. Материалы и методы: 674 случая госпитализации пациентов от рождения до 17 лет включительно с подтвержденным COVID-19 в период с 26 марта по 26 июня 2020 г. в детский многопрофильный стационар СанктПетербурга. Диагностика SARS-COV-2 в мазках из верхних дыхательных путей проводилась методом ПЦР (набор реагентов для выявления РНК коронавируса 2019- nCoV методом ПЦР с гибридизационно-флуоресцентной детекцией «Вектор-ПЦРРВ-2019-nCoV–RG»). Пациентам выполнено 4 (3; 5) повторных исследования в зависимости от диагноза направления, а также длительности реконвалесцентного вирусоносительства. Проведен анализ тяжести течения заболевания, основных клинических проявлений и их взаимосвязи с развитием пневмонии, а также эпидемиологических особенностей COVID-19 у детей. Описана продолжительность стационарного лечения, исходы и потребность в интенсивной терапии. Оценены изменения ряда лабораторных показателей на анализаторах производства США: клинический анализ крови на гематологическом – Coulter UniCel (Beckman Coulter), биохимический анализ крови на биохимическом – Uni Cel DxC (Beckman Coulter), коагулограмма на анализаторе гемостаза (Instrumentation Laboratory). Результаты: в целом, отмечено благоприятное течение COVID-19 у детей. Интенсивная терапия потребовалась лишь в 3,6% случаев с общей летальностью 0,15%, Кавасаки-подобный синдром зафиксирован в 0,3% случаев. У 1/3 пациентов выявлено затяжное вирусовыделение из верхних дыхательных путей. У детей лидировало внутрисемейное заражение от взрослых, школьники составили половину всех случаев госпитализации. Отличительной чертой новой инфекции была неяркая клиническая симптоматика с лихорадкой и катаральными симптомами до 4/5 случаев, желудочно-кишечными симптомами – у каждого третьего пациента. Значимых различий в тяжести заболевания по возрастам выявлено не было. Пневмония, диагностированная в ¾ случаев с помощью компьютерной томографии, осложняла течение в 13,1% случаев. Поражение легких сопровождалось лихорадкой и сухим кашлем, а при более тяжелом течении – десатурацией, болями в грудной клетке, чувством неполноценности вдоха. Выявлены возрастные пики заболеваемости пневмонией: в 4, 9, 12 лет и в возрасте 17 лет максимальный (в 1/3 случаев). Изменения лабораторных показателей были несущественными и быстро обратимыми. Заключение: течение COVID-19 у детей в мегаполисе России сопоставимо с зарубежными данными. Однако, учитывая опыт испанки, не исключено, что в педиатрической практике число тяжелых форм и неблагоприятных исходов может измениться в ближайшем будущем, особенно по причине сложности диагностики Кавасакиподобного синдрома и необходимости мультидисциплинарного подхода к терапии таких пациентов. В настоящее время наиболее уязвимыми в отношении нового коронавируса являются дети с тяжелой онкологической, неврологической и сердечно-сосудистой патологией, у которых происходит быстрая декомпенсация основного заболевания на фоне COVID-19

A new class of glycomimetic drugs to prevent free fatty acid-induced endothelial dysfunction

Background: Carbohydrates play a major role in cell signaling in many biological processes. We have developed a set of glycomimetic drugs that mimic the structure of carbohydrates and represent a novel source of therapeutics for endothelial dysfunction, a key initiating factor in cardiovascular complications. Purpose: Our objective was to determine the protective effects of small molecule glycomimetics against free fatty acid­induced endothelial dysfunction, focusing on nitric oxide (NO) and oxidative stress pathways. Methods: Four glycomimetics were synthesized by the stepwise transformation of 2,5­dihydroxybenzoic acid to a range of 2,5­substituted benzoic acid derivatives, incorporating the key sulfate groups to mimic the interactions of heparan sulfate. Endothelial function was assessed using acetylcholine­induced, endotheliumdependent relaxation in mouse thoracic aortic rings using wire myography. Human umbilical vein endothelial cell (HUVEC) behavior was evaluated in the presence or absence of the free fatty acid, palmitate, with or without glycomimetics (1µM). DAF­2 and H2DCF­DA assays were used to determine nitric oxide (NO) and reactive oxygen species (ROS) production, respectively. Lipid peroxidation colorimetric and antioxidant enzyme activity assays were also carried out. RT­PCR and western blotting were utilized to measure Akt, eNOS, Nrf­2, NQO­1 and HO­1 expression. Results: Ex vivo endothelium­dependent relaxation was significantly improved by the glycomimetics under palmitate­induced oxidative stress. In vitro studies showed that the glycomimetics protected HUVECs against the palmitate­induced oxidative stress and enhanced NO production. We demonstrate that the protective effects of pre­incubation with glycomimetics occurred via upregulation of Akt/eNOS signaling, activation of the Nrf2/ARE pathway, and suppression of ROS­induced lipid peroxidation. Conclusion: We have developed a novel set of small molecule glycomimetics that protect against free fatty acidinduced endothelial dysfunction and thus, represent a new category of therapeutic drugs to target endothelial damage, the first line of defense against cardiovascular disease

Characteristics of CoVID-19 in children: the first experience in the hospital of st. Petersburg

Objective: to identify the clinical, laboratory and epidemiological features of the new coronavirus (CV) infection in the provision of specialized medical care to children in the megalopolis of the Russian Federation. Methods: 674 cases of hospitalization of patients from birth to 17 years old inclusive with confirmed COVID-19 in the period from March 26 to June 26, 2020 in a children’s multidisciplinary hospital in St. Petersburg. Diagnostics of SARS-COV-2 in upper respiratory tract (URT) smears was carried out by PCR (a set of reagents for detecting RNA of coronavirus 2019-nCoV by PCR with hybridization-fluorescence detection “Vector-PCRRV-2019-nCoV-RG”). Patients underwent 4 (3; 5) repeated examinations depending on the diagnosis of the referral, as well as the duration of the convalescent virus carriage. The analysis of the severity of the course of the disease, the main clinical manifestations and their relationship with the development of pneumonia, as well as the epidemiological features of COVID-19 in children. The duration of inpatient treatment, outcomes and the need for intensive care are described. Changes in a number of laboratory parameters on analyzers made in the USA were assessed: a clinical blood test on a hematological one - Coulter UniCel (Beckman Coulter), a biochemical blood test on a biochemical one - Uni Cel DxC (Beckman Coulter), a coagulogram on a hemostasis analyzer (Instrumentation Laboratory). Results: Overall, there was a favorable course of COVID-19 in children. Intensive therapy was required only in 3.6% of cases with a total mortality rate of 0.15%, Kawasakilike syndrome was recorded in 0.3% of cases. In 1/3 of patients, prolonged viral shedding from the upper respiratory tract was detected. In children, intrafamilial infection from adults was in the lead; schoolchildren accounted for half of all hospitalizations. A distinctive feature of the new infection was mild clinical symptoms with fever and catarrhal symptoms up to 4/5 of cases, gastrointestinal symptoms - in every third patient. There were no significant differences in the severity of the disease by age. Pneumonia, diagnosed in ¾ cases by computed tomography, complicated the course in 13.1% of cases. The defeat of the lungs was accompanied by fever and dry cough, and in a more severe course: desaturation, chest pains, a feeling of insufficiency of inspiration. The age peaks of the incidence of pneumonia were revealed: at 4, 9, 12 years old and at the age of 17 years, the maximum (in 1/3 of cases). Laboratory changes were insignificant and quickly reversible. Conclusion: the course of COVID-19 in children in the megalopolis of Russia is comparable with foreign information. However, taking into account the experience of “Spanish ‘flu”, it is possible that in pediatric practice the number of severe forms and unfavorable outcomes may change in the near future, especially due to the difficulty of diagnosing Kawasaki-like syndrome and the need for a multidisciplinary approach to the treatment of such patients. Currently, the most vulnerable to the new CV are children with severe oncological, neurological and cardiovascular pathology, who have a rapid decompensation of the underlying disease against the background of COVID-19