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Convalescent plasma in Covid-19: Possible mechanisms of action
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible of the coronavirus disease 2019 (COVID-19) pandemic. Therapeutic options including antimalarials, antivirals, and vaccines are under study. Meanwhile the current pandemic has called attention over old therapeutic tools to treat infectious diseases. Convalescent plasma (CP) constitutes the first option in the current situation, since it has been successfully used in other coronaviruses outbreaks. Herein, we discuss the possible mechanisms of action of CP and their repercussion in COVID-19 pathogenesis, including direct neutralization of the virus, control of an overactive immune system (i.e., cytokine storm, Th1/Th17 ratio, complement activation) and immunomodulation of a hypercoagulable state. All these benefits of CP are expected to be better achieved if used in non-critically hospitalized patients, in the hope of reducing morbidity and mortality. © 2020 The Author(s
Microneutralization reaction compared to hemagglutination inhibition assay to evaluate immunogenicity of influenza vaccines and influenza diagnostics
The aim of this study was to compare the results of the hemagglutination inhibition test (HI-test) and micro-neutralization reaction in detection of antibodies to influenza A(H1N1), A(H1N1)pdm09, and A(H3N2) viruses in human sera, as well optimize microneutralization reaction conditions. The proposed variant of microneutralization reaction is based on detecting decreased influenza virus reproduction in infected MDCK cells in the presence of virus-specific serum antibodies. Virus reproduction was evaluated by enzyme-linked immunosorbent assay in 96-well cell culture plates using type-specific anti-influenza A viruse NP-protein monoclonal antibodies. In parallel, in microneutralization reaction and HI-test paired sera collected from 205 volunteers inoculated with inactivated seasonal influenza vaccines were analyzed, as well as from 117 adult patients with laboratory-confirmed influenza. The rationale for treatment of human serum with receptor-destroying enzyme (RDE) was proved not only for HI-test, but also for microneutralization reaction. Compared to HI-assay, the microneutralization reaction displayed higher sensitivity. According to microneutralization data, seroconversion rates and increase in antibody titer against influenza A viruses in both vaccinated and infected persons were superior to HI-test data by 1.4-2.5-fold. Moreover, higher sensitivity of this method was of great importance for the diagnostics of disease caused by new pathogens. The efficacy of influenza A(H1N1)pdm09 serodiagnostics in PCR-positive patients was 1.5 times higher based on microneutralization reaction vs. HI-assay data. According to the data from early studies, it is commonly believed that 1/40 titer of f lu-specific antibodies detected by HI-test is set as protective. However, a consensus on protective level for virus-specific antibodies in neutralization reaction has not been established yet. It was found that serum antibody levels detected by the proposed version of microneutralization reaction were significantly higher than those in HI-assay. In the post vaccination sera collected from vaccinated volunteers, average titers of virus neutralizing antibodies corresponding to 1/40 in HI-test were 1/195, 1/203, and 1/426-1/430 for influenza A(H1N1), A(H1N1)pdm09 and A(H3N2), respectively, whereas in influenza patients they were 1/285, 1/215 and 1/488, respectively. Thus, it was suggested to consider a threshold value for "conditionally protective" level of neutralizing antibodies in adult vaccinated volunteers or infected patients, an average titer 1/160 for A(H1N1) and A(H1N1)pdm09 viruses, as well as 1/320 - for A(H3N2) virus, which agree with data published elsewhere. © 2019 Saint Petersburg Pasteur Institute. All rights reserved
Features of hemorrhagic fever with renal syndrome with diabetes mellitus
Aim. Diabetes mellitus (DM) is known to be a risk factor in adverse outcomes and complications in many infectious diseases. In the combination of hemorrhagic fever with renal syndrome (HFRS) and DM there are mutually exclusive pathogenetic States – hyperosmolarity, characteristic of DM is layered on the reduction of osmotic blood pressure in HFRS. Under these conditions, the effect of one disease (DM) on the clinical manifestations of another (HFRS) is not obvious. The aim of the work is to find out the clinical features during hfps in patients with DM. Materials and methods. The study is based on the results of the retrospective studies "case–control" – studied the information contained in medical records of patient (form 003/u), who suffered HFRS in 2006-2018. The Selection of cards produced randomly. In the end, there were formed two groups: the first – 981 patient who suffered HFRS and had no signs of diabetes; the second, 33 patients who suffered HFRS on the background of previously existing (28 people), or the first identified (5) diabetes. Results. With a combination of HFRS and DM, a mild course of the disease is 2.5 times more common, there are no severe forms. Among this group of patients, complications are almost 10 times less common, less likely to develop infectious-toxic shock, acute kidney damage (class F by RIFLE), pulmonary edema. The combination of DM and HFRS is manifested by less high and prolonged fever, less high levels of urea and creatinine in the blood. Conclusion. HFRS in combination with DM is easier, apparently, high osmolarity of the blood is a stabilizing factor during the disease. © 2019 Consilium Medikum. All rights reserved
Review of current and future directions of antiviral therapy of influenza and acute respiratory viral infections in Russia
One of the WHO global influenza strategy objectives is to develop more effective antiviral drugs and immunomodulators. Aim: to determine the perspectives for the use of drugs with combined antiviral, anti-inflammatory and immunomodulatory activity on the basis of medical studies of existing antiviral drugs for the treatment of influenza and acute respiratory viral infections in Russia. Materials and methods. A brief review of the antiviral drugs used in Russia for the treatment of influenza and acute respiratory viral infections was conducted on the basis of 37 articles published in Scopus, Web of Science (WoS), and RSCI databases in the period from 1997 to 2018. Results. Resistance to neuraminidase inhibitors (oseltamivir, zanamivir), is slowly developing due to the mutations of the neuraminidase gene H275Y and Q136K. Most influenza A viruses remain resistant to adamantane antivirals. Repeated use of immunomodulators with indirect antiviral action leads to a hyporeactivity of the immune system and, subsequently, to a decrease in their effectiveness. Positive clinical and laboratory data in clinical trials were obtained using Enisamium iodide, a drug with combined action – direct antiviral, and immunomodulatory. Conclusion. According to the WHO strategy, the results of the review demonstrate the need for continued research of medications with combined antiviral and pathogenetic effects on the infectious process caused by influenza and acute respiratory viral infections. © 2019 Consilium Medikum. All rights reserved
SIR+a mathematical model for evaluating and predicting 2016-2017 arvi-influenza incidence by using on the Moscow territory [ОЦЕНКА И ПРОГНОЗ ЗАБОЛЕВАЕМОСТИ ОРВИ-ГРИППОМ С ПОМОЩЬЮ МАТЕМАТИЧЕСКОЙ МОДЕЛИ SIR+A НА ТЕРРИТОРИИ МОСКВЫ В 2016 ГОДУ]
Influenza is a major challenge to global healthcare due to its high transmissivity and ability to cause major epidemics. Influenza epidemics and pandemics are associated with changes in the society structure that contribute to the spread of new viral strains in certain environmental and social settings. Currently, influenza is one of the most common global diseases that results in annual epidemics or even pandemics, often leading to lethal outcome. Influenza viruses are uniquely prone to variability via point mutations, recombination and gene reassortment accompanied with changes in their biological properties considered as the main cause of uncontrolled infection spread. Hence, examining cohorts of predisposed individuals by using probability models provides not only additional information about viral outbreaks, but also allows monitoring dynamics of viral epidemics in controlled areas. Understanding influenza epidemiology is crucial for restructuring healthcare resources. Public healthcare service mainly relies on influenza vaccination. However, there are vulnerable cohorts such as elderly and immunocompromised individuals, which usually contain no protective anti-influenza virus antibody level. Despite advances in the developing vaccines and chemotherapy, large-scale influenza epidemics still continue to emerge. Upon that, no reliable methods for disease prognosis based on rate of ongoing epidemic situation are currently available. Monitoring and predicting emerging epidemics is complicated due to discrepancy between dynamics of influenza epidemics that might be evaluated by using surveillance data as well as platform for tracking influenza incidence rate. However, it may be profoundly exacerbated by mutations found in the influenza virus genome by altering genuine morbidity dynamics. Use of probabilistic models for assessing parameters of stochastic epidemics would contribute to more accurately predicted changes in morbidity rate. Here, an SIR+A probabilistic model considering a relationship between infected, susceptible and protected individuals as well as the aggressiveness of external risks for predicting changes in influenza morbidity rate that allowed to evaluate and predict the 2016 ARVI influenza incidence rate in Moscow area. Moreover, introducing an intensity of infection parameter allows to conduct a reliable analysis of incidence rate and predict its changes. © Контаров Н.А. и соавт., 2019
Enterovirus infection in the Socialist Republic of Vietnam [ЭНТЕРОВИРУСНАЯ ИНФЕКЦИЯ В СОЦИАЛИСТИЧЕСКОЙ РЕСПУБЛИКЕ ВЬЕТНАМ]
Human enterovirus infections comprise a group of infectious diseases caused by viruses of Enterovirus A-D species (genus Enterovirus, family Picornaviridae). Enterovirus infections can vary in clinical manifestations and severity, from asymptomatic infection to serious multisystem diseases. During evolution, enterovirus strains with increased neurovirulence or atypical pathogenicity may emerge exhibiting an epidemic potential. Recently, outbreaks of enterovirus infection with an increased rate of neurological manifestations, a significant percentage of severe cases and lethal outcomes have been observed worldwide, which were associated with enteroviruses EV-A71, EV-D68 etc. The World Health Organization has included EV-A71 and EV-D68 enterovirus infection together with some other dangerous viral diseases considered for inclusion in the List of Blueprint Priority Diseases. In connection with this, global enterovirus surveillance is important for controlling emergence and spread of epidemic enterovirus variants, prediction of establishing epidemic situation, timely conduction of preventive measures and vaccine development. A growing multi-field cooperation between Russia and Vietnam leads to increased two-way population migration, which actualizes scientific and practical collaboration in surveillance and control of infectious disease spread, including enterovirus infection. Currently, epidemiological surveillance of enterovirus infection in Vietnam is based on monitoring hand, foot and mouth disease (HFMD) rate, laboratory diagnostics of enterovirus infection and identification of enterovirus strains, mainly detected in severe patients. In 2001-2016, 34 non-polio virus types were identified in patients with enterovirus infection, largely represented by viruses EV-A71, CVA6, CVA10, and CVA16. Moreover, the peak incidence of enterovirus infection and related mortality rate were associated with the increased activity of EV-A71 virus. In Vietnam, EVA71 enterovirus of genotypes C1, C4, C5 and B5 circulated at different times. Over the last years, a new pandemic genotype virus CVA6 has been dominating as a causative agent of enterovirus infection in Vietnam as well as the majority of other countries. The data on phylogenetic relation between Vietnamese epidemic EV-A71 and CVA6 strains allowed to find that they underwent multiple between-country spreads, whereas their subsequent in-country dissemination resulted in 2011-2012 enterovirus outbreak and sustained high-level HFMD morbidity. © 2019 Saint Petersburg Pasteur Institute. All rights reserved
The new views on the state of the gut microbiota in obesity and diabetes mellitus type 2 [Новые взгляды на состояние кишечной микробиоты при ожирении и сахарном диабете 2 типа]
Obesity is a worldwide problem of the last century, the prevalence of which has reached pandemic proportions in developed countries. Over the past few years, a considerable amount of data has been gathered, reporting a direct link between changes in gut microbiota and the development of obesity, as well as related diseases, primarily, diabetes mellitus type 2. The elaboration of optimal methods of prevention and treatment regimens of these diseases needs to structure the existing knowledge about the mechanisms of development of metabolic disorders, the role of intestinal microbiota in the latter and possible therapeutic “targets”. This review examines the role of microorganisms in the human body, with the main focus on the developmental origins of metabolic disorders using animal models and accumulated experience of research on their effects on the human body, and also discusses possible treatment options, including bariatric surgery, fecal microbiota transplantation, the use of pre- and probiotics and certain particular groups of glucose-lowering drugs. © Russian Association of Endocrinologists 2019
Mouse-adapted influenza B virus for in vitro and in vivo assessment of therapeutic and preventive efficacy of antiviral drugs [вариант вируса гриппа в, адаптированный к мышам, для изучения лечебной и профилактической Эффективности противовирусных препаратов in vitro и in vivo]
Objective: to develop a new antigenic relevance influenza B virus suitable for modeling influenza infection in mice to assess of in vivo and in vitro therapeutic and preventive efficacy of antiviral drugs. Materials and methods: was carried out an adaptation of influenza B virus in BALB/c mice. Was performed comparative assessment of in vivo and in vitro pathogenicity of the parental virus and adapted influenza B virus. Was assessed inhibition of neuraminidase with antiviral drugs (oseltamivir ethoxyacrylate and Tamiflu) in relation to the adapted influenza B virus. Results: adapted influenza B virus (B/ Novosibirsk/40/2017-MA strain) models non-lethal influenza infection with pronounced clinical signs of the disease in experimental animals. Were described the destructive changes in lungs and brain that increases during infection. Analysis of internal organs (lungs, brain, liver, heart, kidneys, spleen) were revealed viral load only in the lungs. Were evaluated in vivo and in vitro efficacy of antiviral drugs (oseltamivir ethoxysuccinate and Tamiflu®) on the model of influenza infection. Were proved the high efficiency of the innovative drug – oseltamivir ethoxysuccinate. Conclusion: the antigen-relevant adapted influenza B virus (В/Novosibirsk/40/2017-MA strain) can be used to assess the drug effectiveness against influenza, as well as an additional tool for predicting the effectiveness of the vaccine against drifting strains. © 2019 Interregional public organization Association of infectious disease specialists of Saint-Petersburg and Leningrad region (IPO AIDSSPbR). All rights reserved
Genetic characterization of avian influenza A(H5N6) virus clade 2.3.4.4, Russia, 2018
Timely identification of pandemic influenza threats depends on monitoring for highly pathogenic avian influenza viruses. We isolated highly pathogenic avian influenza A(H5N6) virus clade 2.3.4.4, genotype G1.1, in samples from a bird in southwest Russia. The virus has high homology to human H5N6 influenza strains isolated from southeast China. © 2019 Centers for Disease Control and Prevention (CDC). All rights reserved
Combined immunization with attenuated live influenza vaccine and chimeric pneumococcal recombinant protein improves the outcome of virus-bacterial infection in mice
Influenza and its bacterial complications are a leading cause of morbidity and mortality worldwide. The effect of combined immunization with live influenza vaccine and recombinant chimeric pneumococcal protein in dual infection caused by influenza H1N1 and S. pneumoniae (serotype 3) has been studied. The combined vaccine consisted of the strain A/California/2009/38 (H1N1) pdm and chimeric recombinant protein PSPF composed of immunodominant fragments of the surface virulence factors of S. pneumoniae-PsaA, PspA, and Shr1875-associated with modified salmonella flagellin. Vaccinated mice were infected with the influenza virus 24 hours before or 24 hours after the onset of pneumococcal infection. The protective effect of combined vaccination was shown on both models of viralbacterial infection. © 2019 Kramskaya et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credite