World's First Experience of the Low-Dose Radionuclide Inhalation Therapy in the Treatment of COVID-19-Associated Viral Pneumonia: Phase 1/2 Clinical Trial.

OBJECTIVE: Previously, low-dose radiation therapy was used for pneumonia treatment. We aimed to investigate the safety and effectiveness of carbon nanoparticles labeled with Technetium isotope (99mTc) in a form of ultradispersed aerosol in combination with standard COVID-19 therapy. The study was a randomized phase 1 and phase 2 clinical trial of low-dose radionuclide inhalation therapy for patients with COVID-19 related pneumonia. METHODS: We enrolled 47 patients with confirmed COVID-19 infection and early laboratory signs of cytokine storm and randomized them into the Treatment and Control groups. We analyzed blood parameters reflecting the COVID-19 severity and inflammatory response. RESULTS: Low-dose 99mTc-labeled inhalation showed a minimal accumulation of radionuclide in lungs in healthy volunteers. We observed no significant differences between the groups before treatment in WBC-count, D-dimer, CRP, Ferritin or LDH levels. We found that Ferritin and LDH levels significantly raised after the 7th day follow-up only in the Control group (p < 0.0001 and p = 0.0005, respectively), while mean values of the same indicators did not change in patients in the Treatment group after the radionuclide treatment. D-dimer values also lowered in the radionuclide treated group, however, this effect was not statistically significant. Furthermore, we observed a significant decrease in CD19+ cell counts in patients of the radionuclide-treated group. CONCLUSION: Inhalation low-dose radionuclide therapy of 99mTc aerosol affects the major prognostic indicators of COVID-19- related pneumonia restraining inflammatory response. Overall, we identified no evidence of major adverse events in the group receiving radionuclide.

Implementation of Horizontal Connections in the Course of Mathematics by Combining Pedagogical and Digital Technologies

The study examines three experiments of implementing the “learning through teaching” approach combined with the development of digital technologies and explores the influence of these methods on the quality of education for undergraduate engineering students at an urban technical university in Russia. In the first experiment, small independent groups of students within the same cohort developed individual Java modules with the goal of creating an intelligent system to support solving problems using graphs. In the second experiment, each student peer-taught the topic of their choice to three other students and then administered an oral exam to these students to assess their understanding. In the third experiment, each participant selected a problem to develop a solution and recorded a video that explained this solution to other students. All recorded videos were made available to all students, and the combined collection consisted of 100 videos. During the final exam, students were randomly assigned one of these problems and had to present their solutions to the instructor. Analysis of the experiments demonstrated that integrating “learning through teaching” led to an increase in student interest in the discipline and an improvement in conceptual understanding, more so for students in the role of teacher than in the role of learner. Overall, combining pedagogical and digital technologies improved the quality of education for engineering students.

Data and Text Mining Help Identify Key Proteins Involved in the Molecular Mechanisms Shared by SARS-CoV-2 and HIV-1.

Viruses can be spread from one person to another; therefore, they may cause disorders in many people, sometimes leading to epidemics and even pandemics. New, previously unstudied viruses and some specific mutant or recombinant variants of known viruses constantly appear. An example is a variant of coronaviruses (CoV) causing severe acute respiratory syndrome (SARS), named SARS-CoV-2. Some antiviral drugs, such as remdesivir as well as antiretroviral drugs including darunavir, lopinavir, and ritonavir are suggested to be effective in treating disorders caused by SARS-CoV-2. There are data on the utilization of antiretroviral drugs against SARS-CoV-2. Since there are many studies aimed at the identification of the molecular mechanisms of human immunodeficiency virus type 1 (HIV-1) infection and the development of novel therapeutic approaches against HIV-1, we used HIV-1 for our case study to identify possible molecular pathways shared by SARS-CoV-2 and HIV-1. We applied a text and data mining workflow and identified a list of 46 targets, which can be essential for the development of infections caused by SARS-CoV-2 and HIV-1. We show that SARS-CoV-2 and HIV-1 share some molecular pathways involved in inflammation, immune response, cell cycle regulation.

Features of the steroid profile of saliva in patients with COVID-19

Material and methods. The study included 16 men aged 28 to 81 years (average age 50.3+13.4 years) with confirmed new coronavirus infection of varying severity, were hospitalized in April 2020 in Moscow COVID hospital. Patients were divided into three groups, depending on the severity of COVID-19: the 1^st group was a mild course (n=7), the 2^nd group was a moderate course (n=7), and the 3^rd group was a severe course of the disease (n=2). All patients were cured. In addition to the steroid profile of saliva, all patients underwent a test for arbitrary breath holding (Stange test), which reflects the reserve capabilities of the lungs, as well as a general blood test. In 6 patients, vitamin D was determined by mass spectrometry. Results and discussion. There was a testosterone deficiency in all patients with COVID-19, while there was a connection between a decrease in testosterone and the severity of the disease: the maximum decrease in testosterone was observed in patients with severe disease. Conclusion. Given the known effect of testosterone on the synthesis of nitric oxide, a deficiency of which leads to the development of not only insulin resistance and oxidative stress, chronic hypoxia, but also bronchospasm and pulmonary edema, it is necessary to include the determination of the steroid profile of saliva in the diagnostic algorithms for managing patients with a new coronavirus infection COVID-19. Материал и методы. В исследование были включены 16 мужчин в возрасте от 28 лет до 81 года (средний возраст 50,3+13,4 года) с подтвержденной новой коронавирусной инфекцией различной тяжести, госпитализированы в апреле 2020 г. в COVID-стационар г. Москвы. Пациенты были разделены на 3 группы, в зависимости от степени тяжести течения COVID-19: 1-я группа - легкая форма течения (n=7), 2-я группа -среднетяжелая форма течения (n=7), 3-я группа - тяжелое течение болезни (n=2). Все пациенты были вылечены. Помимо стероидного профиля слюны, всем пациентам был проведен тест на произвольную задержку дыхания (проба Штанге), отражающий резервные возможности легких, а также общий анализ крови. У б пациентов был определен витамин D методом масс-спектрометрии. Результаты и обсуждение. Выявлен дефицит тестостерона у всех пациентов с COVID-19, при этом отмечена связь между снижением тестостерона и тяжестью течения заболевания: максимальное снижение тестостерона отмечалось у пациентов с тяжелым течением заболевания. Заключение. Учитывая известное влияние тестостерона на синтез оксида азота, дефицит которого ведет к развитию не только инсулинорезистентности и окислительного стресса, хронической гипоксии, но и к бронхоспазму и отеку легких, необходимо включить определение стероидного профиля слюны в диагностические алгоритмы ведения пациентов с новой коронавирусной инфекцией COVID-19.

Mortality from COVID-19 against the backdrop of other twentieth century mortality bursts

Measuring mortality from COVID-19 through direct statistical observation of the causes of death faces a number of intractable obstacles that underestimate the lethality of the pandemic and undermine international comparability of data. An alternative is the indirect demographic method, which consists in comparing the expected mortality (in the absence of a pandemic) with the observed mortality from all causes. Its application leads to the conclusion that COVID-19 is extremely fatal: in the foci of the pandemic, the leaps in mortality that have already taken place are comparable to or exceed most bursts of mortality (except of course for wars) over the previous 100 years. Измерение смертности от COVID-19 посредством прямого статистического наблюдения причин смерти сталкивается с рядом трудноустранимых препятствий, которые приводят к занижению летальности пандемии и подрывают международную сопоставимость данных. Альтернативой является косвенный демографический метод, состоящий в сопоставлении ожидаемой смертности (в отсутствие пандемии) с наблюдаемой смертностью от всех причин. Его применение приводит к выводу о чрезвычайной летальности COVID-19: в очагах пандемии уже состоявшиеся всплески смертности сопоставимы или превышают эффект абсолютного большинства всплесков смертности (разумеется, если не считать войн) за предшествующие 100 лет.