COVID-19: etiology, clinical picture, treatment

Whereas the XX century marked the history of acute respiratory disease investigation as a period for generating in-depth system of combating influenza viruses (Articulavirales: Orthomyxoviridae, Alpha-/Betainfluenzavirus) (based on environmental and virological monitoring of influenza A virus in its natural reservoir — aquatic and semi-aquatic birds — to supervising epidemic influenza), a similar system is necessary to build up in the XXI century with regard to especially dangerous betacoronaviruses (Nidovirales: Coronaviridae, Betacoronavirus): Severe acute respiratory syndrome-related coronavirus (SARS-CoV) (subgenus Sarbecovirus), Severe acute respiratory syndrome-related coronavirus 2 (SARSCoV-2) (Sarbecovirus), Middle East respiratory syndrome-related coronavirus (MERS-CoV) (Merbecovirus). This became particularly evident after pandemic potential has been revealed in 2020 by the SARS-CoV-2. This review provides an insight into the historic timeline of discovering this virus, its current taxonomy, ecology, virion morphology, life cycle, molecular biology, pathogenesis and clinical picture of the etiologically related COVID-19 (Coronavirus disease 2019) as well as data available in the scientific literature on the anti-SARS-CoV-2-effectiveness of passive immunotherapy and most debated drugs used to treat COVID-19: Chloroquine, Hydroxychloroquine, Nitazoxanide, Ivermectin, Lopinavir and Ritonavir, Camostat mesilate, Remdesivir, Ribavirin, Tocilizumab, Anakinra, corticosteroids, and type I interferons. The pathogenesis of SARS-CoV-2 infection implicates decreased efficacy of artificial respiration, which, in this case might be replaced by more efficient extracorporeal membrane blood oxygenation supplemented with nitrogen oxide and/or Heliox inhalations

Peculiarities of the influenza viruses circulation and their properties during 2018-2019 epidemic season in Russia and countries of the Northern Hemisphere

Objective. To identify the drift variability of influenza viruses during the period of epidemic rise in the incidence of acute respiratory viral infections in the period 2018-2019. The biological and molecular-genetic properties of epidemic strains isolated in certain territories of the Russian Federation were studied and compared with data from the countries of the Northern Hemisphere. Materials and methods. A range of laboratory diagnostic methods has been applied, including immune fluorescence, RT-PCR, sequencing, methods for determining sensitivity to influenza drugs and receptor specificity. Results and discussion. The proportion of influenza viruses was as follows: A (H1N1) pdm09 - 53 %, A (H3N2) - 46 %, B - about 1 %. Cases of severe acute respiratory infections have most often been associated with influenza A(H1N1) pdm09 virus. According to antigenic properties, isolated strains corresponded to the properties of vaccine viruses (A/Michigan/45/2015 - by 99.6 % and A/Singapore INFIMH-16-0019/2016 - by 86 %). The heterogeneity of influenza A virus strains population was revealed as regards individual mutations in hemaglutinin. The influenza B virus population was equally represented by both evolutionary lines (B/Victoria and B/Yamagata-like). Receptor specificity was favorable for the course and outcome of the disease. Among 70 studied epidemic strains, no strains resistant to anti-neuraminidase drugs, oseltamivir and zanamivir, were detected. The article presents WHO recommendations on the composition of influenza vaccines for the countries of the Northern Hemisphere for 2019-2020, provides data on cases of human infection with avian influenza viruses A(H5N1), A(H5N6), A(H7N9) and A(H9N2)

Особенности функционирования системы врожденного и адаптивного иммунитета у пациентов с COVID-19 старшей возрастной группы

Goal. Characteristics of innate, cellular and adaptive immunity in patients of the older age group with COVID19.Materials and methods. Blood leukocytes were induced by Newcastle disease virus (α-interferon), phytohemagglutinin (γ-interferon), SARS CoV 2: RBD antigens and S-protein; interferon activity in human fibroblast culture and enzyme immunoassay were evaluated. In serum, IgG antibodies to SARS CoV2 and autoantibodies to interferon and to the endothelium of blood vessels were determined using a mono-layer of human umbilical vein cells. Statistical processing was performed in Excel 2016.Results. A decrease in the production of  α-interferon and γ-interferon was revealed: 1 week -74.2±15.1; 3 week-144.0±35.7 (p=0.01); control – 266.6 ±82 (relative to 3 weeks p=0.004) and IFN γ: 1 week -6.8±2; 3 week – 14.4 ±3.5 (p=0.03); control – 28.87.15 (relative to 3 weeks (p=0.007). Decreased production of γ-interferon by leukocytes of patients with induction by SARS CoV2 RBD and S-trimer anti-gens was revealed. Antibodies to SARS CoV2 were detected starting from the 2nd week of the disease, a large spread of indicators was noted. Autoantibodies to α2-interferon and to vascular surface antigens were detected.Conclusion. The state of innate immunity in patients of the older age group with severe and moderate COVID-19 was characterized by a decrease in the activity of the interferon system. Decreased activity of cellular immunity to SARS CoV2 antigens was noted. Adaptive immunity was characterized by the development of an imbalance in the form of the appearance of autoantibodies to α-interferon and vascular endothelium.Цель: характеристика активности врожденного, клеточного и адаптивного иммунитета у пациентов старшей возрастной группы с COVID19.Материалы и методы: лейкоциты крови пациентов индуцировали вирусом болезни Ньюкастла (α-интерферон), фитогемагглютинином (γ-интерферон), антигенами SARS CoV 2: RBD и S-белком; оценивали активность интерферона в культуре фибробластов человека и методом иммуноферментного анализа. В сыворотке крови определяли: IgG антитела к SARS-CoV-2 и аутоантитела к интерферону и к эндотелию кровеносных сосудов, используя монослой клеток пупочной вены человека. Статистическую обработку выполняли в программе Excel 2016.Результаты: у пациентов старшей возрастной группы с тяжелой и среднетяжелой формами COVID-19 c осложненным течением выявлено снижение продукции α-интерферона и γ-интерферон в течение первых недель заболевания: 1-я неделя – 74,2±15,1; 3-я неделя – 144,0±35,7 (р=0,01); контроль – 266,6 ±82 (относительно 3 недели р=0,004) и ИФН γ: 1-я неделя – 6,8±2; 3-я неделя – 14,4 ±3,5 (р=0,03); контроль – 28,87,15 (относительно 3-й недели (р=0,007)). Выявлена сниженная продукция γ-интерферона лейкоцитами пациентов при индукции антигенами SARS-CoV-2 RBD и S-тримером по сравнению с вакцинированными пациентами. Антитела к SARS-CoV-2 в сыворотке крови обнаруживались, начиная со 2-й недели заболевания, отмечен большой разброс показателей. Обнаружены аутоантитела к α2-интерферону и к поверхностным антигенам эндотелия кровеносных сосудов человека.Заключение: состояние врожденного иммунитета у пациентов старшей возрастной группы с тяжелой и среднетяжелой формой COVID-19 характеризовалось снижением активности системы интерферона. Отмечена сниженная активность клеточного иммунитета к антигенам SARS-CoV-2. Адаптивный иммунитет характеризовался разбросом в показателях продукции IgG антител к SARS-CoV-2 и развитием дисбаланса в виде появления аутоантител к α-интерферону и к эндотелию сосудов

Грипп-2016: клинико-эпидемиологические особенности и современные возможности эффективной терапии (по данным ГБУЗ города Москвы «Инфекционная клиническая больница № 1 Департамента здравоохранения города Москвы»)

The aim of this study was to monitor in-hospital influenza virus infection during 2015 – 2016 epidemic flu season. Methods. Influenza virus was searched in patients hospitalized to a clinical infectious diseases hospital with acute respiratory viral infection during 2015 – 2016 influenza seasonal growth period using real-time RT-PCR method. Influenza virus was isolated from nasal swabs and autopsy material using canine kidney cell line. Other laboratory methods used included complete blood count, blood chemistry, blood gas analysis, urinalysis, and chest X-ray examination. Results. We examined 1,491 patients (375 adults, 546 children, 570 pregnant women with early gestational age). The proportion of hospitalized patients with confirmed A / H1N1pdm09 influenza in January – February, 2016, was 91.3%. A / H3N2 influenza virus was diagnosed in 5.7%, influenza B virus was isolated in 1.2% of patients. Totally, influenza virus was detected in 35.2% of samples, of which 30.1% of samples were obtained from adults, 33.7% of samples were obtained from children, and 39.8% of samples were obtained from pregnant women. The prevalent patient’s age was 15 to 60 years (76.1%) in adults and 3 to 6 years in children. Moderate course of influenza with a high rate of hospital admission was seen more often and was similar to that of 2009 – 2010 epidemic season. Proportion of patients with flu complicated by pneumonia was higher than that in 2014 – 2015 epidemic season. Bilateral lung injury was diagnosed in 48.4% of patients. High mortality in ICU (46.4%) was due to delayed start of antiviral treatment and late admission to a hospital. Conclusion. In 2015 – 2016 epidemic flu season, higher morbidity, complications and poor outcomes were related to predominant infection of A – H1N1pdm09 influenza virus. Risk factors of complications and death were delayed care seeking, lack of modern antiviral medications and comorbidity.Актуальность. В период подъема заболеваемости в сезоне 2015–2016 гг. в рамках эпидемиологического надзора за циркуляцией вирусов гриппа в Российской Федерации Центром экологии и эпидемиологии гриппа (ЦЭЭГ) Института вирусологии им. Д.И.Ивановского ФГБУ «Федеральный научно-исследовательский центр эпидемиологии и микробиологии имени почетного академика Н.Ф.Гамалеи» Минздрава России (Москва) на базе ГБУЗ города Москвы «Инфекционная клиническая больница № 1 Департамента здравоохранения города Москвы» (ГБУЗ г. Москвы «ИКБ № 1 ДЗМ») осуществлялся госпитальный мониторинг в условиях специализированного стационара, целью которого являлось определение количественного и качественного распределения штаммов вирусов гриппа А и В среди госпитализированных пациентов, в т. ч. с тяжелой формой заболевания, а также анализ частоты осложнений и эффективности противовирусной терапии. Материалы и методы. В период подъема заболеваемости гриппом в ГБУЗ г. Москвы «ИКБ № 1 ДЗМ» госпитализированы пациенты с клиническим диагнозом острая респираторная вирусная инфекция. Детекция вирусов гриппа проводилась методом полимеразной цепной реакции с обратной транскрипцией в режиме реального времени. Вирусы гриппа были изолированы из назальных смывов и секционного материала на перевиваемой клеточной линии почки собаки (MDCK). Лабораторная диагностика включала клинический и биохимический анализ крови, анализ газового состава крови, анализ мочи, рентгенологическое исследование органов грудной клетки. Результаты. В январе-феврале 2016 г. доля больных, госпитализированных в ГБУЗ г. Москвы «ИКБ № 1 ДЗМ» с лабораторно подтвержденным гриппом A / H1N1pdm09, составила 91,3 %, A / H3N2 – 5,7 %, В – 1,2 %. Обследованы пациенты (n = 1 491) – взрослые (n = 375), дети (n = 546) и беременные (n = 570) на разных сроках. Доля положительных на грипп проб в целом составила 35,2 %. Среди взрослых положительными на грипп были 30,1 % проб, среди детей – 33,7 %, среди беременных – 39,8 %. В возрастной структуре преобладали (76,1 %) пациенты в возрасте от 15 до 50 лет. В детской популяции наиболее вовлеченными в эпидемию оказались дети в возрасте 3–6 лет. Преобладали среднетяжелые формы гриппа с высокой частотой госпитализаций, сравнимой с сезоном 2009–2010 гг. Доля пациентов с гриппом, осложненным пневмонией, увеличилась в сравнении с эпидемическим сезоном 2014–2015 гг. Двустороннее поражение легких зарегистрировано у 48,4 % больных. Высокий уровень летальности (46,4 %) в отделении реанимации и интенсивной терапии связан с запоздалым началом противовирусной терапии и поздней госпитализацией. Заключение. Высокая заболеваемость, увеличение числа осложнений и неблагоприятных исходов определена доминированием вируса гриппа A / H1N1pdm09. Факторами, увеличивающими риск развития осложнений и летальных исходов, являются позднее обращение за медицинской помощью, отсутствие своевременной противовирусной терапии, сопутствующие заболевания

INFLUENZA INFLAMMATION BIOMARKERS FEATURES

Aim. Analysis of inflammation biomarkers using reverse transcription with real time PCR (RT-PCR-RT) and multiplex immunofluorescent analysis xMAP with magnetic beads for the influenza infection. Materials and methods. Analysis of nasopharyngeal swabs, lymphocytes and blood sera of 10 patients with influenza and 10 donors was performed during the first 2 days of the disease by means of RT-PCR-RT and xMAP using the kit «37-plex» (BioRad). Results.The influenza virus A was revealed in 4 samples, the influenza virus B — in 6 swabs without mixed infections with other respiratory viruses. Analysis of the interferons (IFN) showed IFNα gene expression activation in patients’ lymphocytes but both the detection rate and the concentrations of IFNβ, IFNγ and IFNλ RNA were similar for patients and healthy donors. Among 37 inflammation biomarkers the concentrations of 7 proteins were enhanced including IFNα2, cytokines of TNF family (APRIL and BAFF), their soluble receptors sTNF-R1 and sTNF-R2, protein osteopontin and IL10. The concentrations of the complex of glycoprotein gp130 with the soluble receptor IL6 gp130/sIL-6Rβ and the matrix metalloprotease ММР-1 were reduced in patients’ sera. The polarization coefficient PI=[IL10]/[IFNγ]=0.53 for influenza samples suggested Th1 immune response. Conclusion. At the early stage of the influenza infection IFNα gene expression activation along with the induction of TNF family cytokines (APRIL and BAFF), their receptors (sTNF-R1 and sTNF-R2) and osteopontin as well as the inhibition of the complex gp130/sIL-6Rβ and metalloprotease ММР-1 were shown. Th1 immune response regulated by IL10 resulted in the recovery of the patients without complications

Contamination of Hospital Surfaces with Bacterial Pathogens under the Current COVID-19 Outbreak

The SARS-CoV-2 pandemic remains a global health issue for several reasons, such as the low vaccination rates and a lack of developed herd immunity to the evolution of SARS-CoV-2, as well as its potential inclination to elude neutralizing antibodies. It should be noted that the severity of the COVID-19 disease is significantly affected by the presence of co-infections. Comorbid conditions are caused not only by pathogenic and opportunistic microorganisms but also by some representatives of the environmental microbiome. The presence of patients with moderate and severe forms of the disease in hospitals indicates the need for epidemiological monitoring of (1) bacterial pathogens circulating in hospitals, especially the ESKAPE group pathogens, and (2) the microbiome of various surfaces in hospitals. In our study, we used combined methods based on PCR and NGS sequencing, which are widely used for epidemiological monitoring. Through this approach, we identified the DNA of pathogenic bacteria (Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, CoNS, and Achromobacter spp.) on various surfaces. We also estimated the microbiome diversity of surfaces and identified the potential reservoirs of infections using 16S rRNA profiling. Although we did not assess the viability of identified microorganisms, our results indicate the possible risks of insufficient regular disinfection of surfaces, regardless of department, at the Infectious Diseases Hospital. Controlling the transmission of nosocomial diseases is critical to the successful treatment of COVID-19 patients, the rational use of antimicrobial drugs, and timely decontamination measures

Epidemiology Of Hospital Admissions With Influenza During The 2013/2014 Northern Hemisphere Influenza Season: Results From The Global Influenza Hospital Surveillance Network

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