ABSTRACT
The COVID-19 pandemic has presented a global challenge to the health system. More than 200 years of world epidemiological experience since the first mass use of vaccines have convincingly shown that effective vaccines are the key tools in the fight against dangerous infectious diseases, especially epidemic and pandemic ones. In the context of a rapidly spreading pandemic of a new infectious agent, it is crucial not only to develop fundamentally new vaccines, but also to be able to quickly organise their large-scale production. In the Russian Federation, in 2020, a team of the National Research Centre for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya developed an innovative vector vaccine, Gam-COVID-Vac, for the prevention of coronavirus disease caused by the SARS-CoV-2 virus. A number of pharmaceutical companies faced the challenge of producing the vaccine. The aim of the study was to optimise the production technology of Gam-COVID-Vac for scaling and increasing the production capacity. In the course of the work, the authors established critical quality attributes of the product, optimised analytical methods for their control, identified poorly scalable technological stages, streamlined the technological process before its transfer to production, and modified non-scalable and technologically unfeasible stages. The work resulted in the launch of industrial-scale production of active pharmaceutical ingredients for both components of Gam-COVID-Vac, which made it possible not only to meet the critical need for COVID-19 immunoprophylaxis in the Russian Federation, but also to supply this vaccine to a number of foreign countries.Copyright © 2023 Safety and Risk of Pharmacotherapy. All rights reserved.
ABSTRACT
The COVID-19 pandemic has presented a global challenge to the health system. More than 200 years of world epidemiological experience since the first mass use of vaccines have convincingly shown that effective vaccines are the key tools in the fight against dangerous infectious diseases, especially epidemic and pandemic ones. In the context of a rapidly spreading pandemic of a new infectious agent, it is crucial not only to develop fundamentally new vaccines, but also to be able to quickly organise their large-scale production. In the Russian Federation, in 2020, a team of the National Research Centre for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya developed an innovative vector vaccine, Gam-COVID-Vaс, for the prevention of coronavirus disease caused by the SARS-CoV-2 virus. A number of pharmaceutical companies faced the challenge of producing the vaccine. The aim of the study was to optimise the production technology of Gam-COVID-Vac for scaling and increasing the production capacity. In the course of the work, the authors established critical quality attributes of the product, optimised analytical methods for their control, identified poorly scalable technological stages, streamlined the technological process before its transfer to production, and modified non-scalable and technologically unfeasible stages. The work resulted in the launch of industrial-scale production of active pharmaceutical ingredients for both components of Gam-COVID-Vac, which made it possible not only to meet the critical need for COVID-19 immunoprophylaxis in the Russian Federation, but also to supply this vaccine to a number of foreign countries.
ABSTRACT
Introduction. The determination of antibodies against the Spike (S) protein of the novel coronavirus is widely used to confirm current or past infection with SARS-CoV-2, and as an indicator of the effectiveness of vaccination against COVID-19. The most common method for detecting anti-S-antibodies is enzyme-linked immunosorbent assay (ELISA), which uses a recombinant S-protein. Immunofluorescence followed by flow cytometry provides an alternative approach to detect anti-S-antibodies, where a protein in the native transmembrane conformation is used as the S-antigen. The aim of the study was to develop a method for determining anti-S-antibodies using flow cytometry, and to select the most appropriate method for processing experimental data. Material and methods. The study involved 22 volunteers (7 men and 15 women aged 25 to 70 years, median 48). All volunteers were vaccinated with two doses of the <<Sputnik V>> vaccine between January and February 2021. Donor sera samples were collected before vaccination with <<Sputnik V>> and 3 months after vaccination. 5 volunteers had already had a mild form of COVID-19 before the time of vaccination. The remaining 17 volunteers did not encounter the SARS-CoV-2. Antibodies against S-protein were determined by immunofluorescence with registration on a flow cytometer. HEK293 cells were transiently transfected with a plasmid encoding the wild type S-protein which was used as target. Transfection was performed by the calcium phosphate method. Cells were incubated with serially diluted sera and then stained with anti-IgG-PE and anti-IgM-FITC secondary antibodies. The fluorescence level was measured using a flow cytometer. As a measurement result, the mean fluorescence intensity (MFI) obtained at 1:18 serum dilution, or the area under the titration curve (area under curve, AUC) was used. Anti-RBD-antibodies were determined using enzyme immunoassay, and virus-neutralizing activity using pseudotyped or surrogate virus-neutralization analysis (pVNA and sVNA). Results. Using the developed method, the formation of anti-S antibodies of the IgG and IgM isotypes was shown 3 months after immunization with the <<Sputnik V>> vaccine. In a simplified version of the method, the relative concentration of antibodies was determined at a single dilution of the test serum by measuring the mean fluorescence intensity (MFI) of the target cells. More reliable results were obtained by construction the titration curve and calculating the area under the curve (AUC). The results thus obtained correlated well with the detection of anti-RBD antibodies by ELISA, as well as with virus neutralization data in pseudotyped and surrogate assays. Conclusion. Flow cytometry is a convenient method for the simultaneous determination of anti-S antibodies of IgG and IgM isotypes in human serum. The advantages of the method include the fact that the S-protein is presented in a native transmembrane conformation. After minor modification, the established method can be used to determine the level of anti-S-antibodies against mutant variants of SARS-CoV-2. Copyright © 2022 Meditsina Publishers. All rights reserved.
ABSTRACT
Purpose : COVID-19 pandemic has become a major global public health challenge. The ophthalmology office setting involves close encounters between the patient and the health care workers increasing risk of viral transmission. Use of PPE decreases risk of person-to-person viral transmission. The purpose of the study was to evaluate breath-induced air currents in subjects without a facemask, with a procedure mask, with an improvised face, and in the setting of slit-lamp examination. Methods : Breath-induced air currents were studied in healthy volunteers utilizing a vape pod system and videography during gentle and heavy breathing simulation. Video frames at 2 seconds after the initiation of expiration were captured and analyzed. Results : A total of 210 recordings were made for 7 settings. Without a face mask, the aerosol moved forwards and spread vertically and horizontally reaching a mean distance of 23.1 inches for gentle, and 36.1 inches for heavy breathing at 2 seconds (P< 0.001). Using PPE the airflow patterns included: a) procedure mask- forward 0 cases, upward 19 (63%) cases, side 28 (93%) cases, downward 22 (73%) cases, and backward 22 (73%) cases. Adding a tape at the upper border of the mask eliminated upward flow in all cases. b) Improvised face mask- forward 0 cases, upward 0 cases, side 30 (100%) cases, downward 30 (100%) cases, and backward 17 (57%) cases. In 14 (47%) cases trace of aerosol was detected adjacent to the front surface of the mask. Adding a second layer eliminated the trace of aerosol in all cases. In the setting of simulated slit-lamp examination without the breath shield, the aerosol reached the chin rest in 9 (60%) cases during gentle breathing and in all cases during heavy breathing. The breath shield was effective in blocking forward airflow in all cases. Conclusions : Use of a procedure mask by patients, while effective in blocking forward breath-induced airflow, redirects the flow upwards, potentially increasing the risk of contamination during an office procedure. An improvised facemask alters breath-induced air currents favorably and partially absorbs respiratory droplets.
ABSTRACT
Features of variation of peripheral blood leukocyte formula parameters in 86 patients with coronavirus pneumonia with leukocytosis with a background of glucocorticoid treatment were investigated. All patients were divided into 2 groups. Group 1 was 22 individuals who showed clinical signs of the bacterial infection (purulent sputum cough in combination with neutrophilic leukocytosis at hospital the admission). The 2nd group was made up of 64 patients with the glucocorticoids developed against the background of treatment with glucocorticoids (dexamethasone 20 mg/day or prednisolone 150 mg/day, intravenously for 3 days) leukocytosis >10 x109/l without signs of a bacterial infection. It was found that in patients of the 1st group compared to the 2nd group, levels of the white blood cells and neutrophils were significantly (p < 0.001) exceeded the reference values in the absence of a significant change in the number of monocytes. In patients of the 2nd group after a three-day intravenous application of the glucocorticoids on the 4th day of hospitalization, a statistically significant (p < 0.001) increase in the number of neutrophils and monocytes was established. When comparing the quantitative parameters of the leukocyte formula between the 2nd group on the 4th day of the hospitalization and the 1st group at admission, there were no differences in the level of leukocytes and neutrophils. Number of monocytes in group 2 (1.11 (0.90;1.34) x 109/l), on the contrary, statistically significantly (p < 0.001) exceeded their level in the 1st group (0.59 (0.50;0.77) x 109/l). Thus, an indicator of the number of monocytes in the peripheral blood could be a promising differential diagnostic criterion for the genesis of the leukocytosis in patients with the COVID-19. This parameter may be one of the factors influencing the decision to prescribe the antibacterial therapy.
ABSTRACT
Despite the relatively rare comorbidity with bacterial infections, in most cases treatment of COVID-19-associated pneumonia is accompanied by empirical antibiotic therapy. In addition, the occurrence of leukocytosis in response to glucocorticosteroid (GCS) therapy is often perceived as comorbid bacterial flora and is a reason for initiating antibiotic therapy. Therefore, an urgent task is to properly interpret leukocytosis in response to GCS therapy in COVID-19. The aim of the study was to examine dynamic changes in count of venous blood leukocytes, neutrophils and monocytes in patients with moderate COVID-19 after systemic GCS. We analyzed parameters of complete blood count in 154 patients with verified moderate COVID-19, at the Temporary Infectious Diseases Hospital, the “Patriot” Park of the Moscow Region. The comparison group (I) consisted of 128 patients without clinical signs of bacterial infection and leukocytosis observed on admission, who were prescribed GCS therapy. The control group (II) consisted of 26 subjects showing on admission signs of bacterial infection — a cough with purulent sputum combined with neutrophilic leukocytosis. The dynamics in venous blood cell count was assessed in group I of patients before the onset, 3 and 6 days after beginning GCS therapy. We also compared count of leukocytes, neutrophils and monocytes between patients with developed leukocytosis in group I vs. group II. As a result, an increased count of leukocytes, neutrophils and monocytes was revealed according to assessing complete blood count test in patients from group I on days 3 and 6 of ongoing GCS therapy. All patients with developed leukocytosis after GCS admission (103 subjects) had no clinical signs of bacterial infection. Patients with developed leukocytosis from group I had increased count of monocytes (0.90 (0.84;1.02) on day 3 after GCS onset and 0.94 (0.87;1.26) on day 6 of GCS) compared with group II (0.61 [0.50;0.71]), p < 0.001. The inter-group count of leukocytes and neutrophils did not differ. Monocytosis after GCS therapy may serve as a differential diagnostic criterion to distinguish between glucocorticoid-induced leukocytosis and comorbid bacterial infection. This may be one of the factors influencing a decision to prescribe antibiotic therapy.
ABSTRACT
Methylene blue is known for a wide spectrum of biochemical activity: being reversibly oxidized and reduced, it acts as a hydrogen carrier and can be considered as a model of the active group of the enzyme dehydrase. When harmonic vibrations with a frequency of 7–30 Hz are introduced into an aqueous solution containing methylene blue and ascorbic acid, the kinetics of redox transformations changes: the kinetic dependences of the influence of the acoustic vibrations differ from the data obtained in the absence of low-frequency influences. Under certain conditions, effects such as acceleration and inhibition of the sonochemical process are observed. The paper studies the reaction of hydrogen transfer in the field of low-frequency oscillations. The purpose of the study was to elucidate the role of factors accompanying the effect: we determined the influence of oxygen, the emerging radical forms of methylene blue, and ascorbic acid. By absorption spectroscopy and EPR spectrometry, we specified the parameters of the compounds formed at the intermediate stages of the methylene blue reduction process. Relying on experimental data, we introduce a method for countering the COVID-19 virus using methylene blue. © Author(s), 2022
ABSTRACT
Despite the relatively rare comorbidity with bacterial infections, in most cases treatment of COVID-19-associated pneumonia is accompanied by empirical antibiotic therapy. In addition, the occurrence of leukocytosis in response to glucocorticosteroid (GCS) therapy is often perceived as comorbid bacterial flora and is a reason for initiating antibiotic therapy. Therefore, an urgent task is to properly interpret leukocytosis in response to GCS therapy in COVID-19. The aim of the study was to examine dynamic changes in count of venous blood leukocytes, neutrophils and monocytes in patients with moderate COVID-19 after systemic GCS. We analyzed parameters of complete blood count in 154 patients with verified moderate COVID-19, at the Temporary Infectious Diseases Hospital, the "Patriot" Park of the Moscow Region. The comparison group (I) consisted of 128 patients without clinical signs of bacterial infection and leukocytosis observed on admission, who were prescribed GCS therapy. The control group (II) consisted of 26 subjects showing on admission signs of bacterial infection - a cough with purulent sputum combined with neutrophilic leukocytosis. The dynamics in venous blood cell count was assessed in group I of patients before the onset, 3 and 6 days after beginning GCS therapy. We also compared count of leukocytes, neutrophils and monocytes between patients with developed leukocytosis in group I vs. group II. As a result, an increased count of leukocytes, neutrophils and monocytes was revealed according to assessing complete blood count test in patients from group I on days 3 and 6 of ongoing GCS therapy. All patients with developed leukocytosis after GCS admission (103 subjects) had no clinical signs of bacterial infection. Patients with developed leukocytosis from group I had increased count of monocytes (0.90 (0.84;1.02) on day 3 after GCS onset and 0.94 (0.87;1.26) on day 6 of GCS) compared with group II (0.61 [0.50;0.71]), p < 0.001. The inter-group count of leukocytes and neutrophils did not differ. Monocytosis after GCS therapy may serve as a differential diagnostic criterion to distinguish between glucocorticoid-induced leukocytosis and comorbid bacterial infection. This may be one of the factors influencing a decision to prescribe antibiotic therapy.
ABSTRACT
Background: This study reports incidence, timing, characteristics, and surveillance imaging of mammographic axillary adenopathy following COVID-19 vaccination. As COVID-19 immunizations continue, with possible booster vaccines upcoming, this study offers timing considerations and potential follow-up recommendations for breast imaging after vaccination. Methods: Retrospective analysis of patients (pts) who received at least one COVID-19 vaccine prior to screening (SM) or diagnostic mammography (DM) at Mayo Clinic Florida between January 15 to May 31, 2021. Vaccine-related information was queried by mammography technologists. Adenopathy was assessed by interpreting radiologists and follow-up studies were collated. Mammogram adenopathy included single enlarged node, multiple enlarged nodes, and adenopathy with soft tissue stranding. Ultrasound adenopathy included mildly prominent nodes with preserved fatty hila to rounded nodes with apparent loss of a fatty hilum. Wilcoxon rank-sum test and Fisher's exact test were used to compare continuous and categorical variables, respectively. Multivariable logistic regression model was used to evaluate the association between days from vaccine and adenopathy. Results: Of 2349 pts, 34 (1.4%) had adenopathy (DM=6;SM=28) and 3 (0.1%) were symptomatic. Presence of axillary symptoms was associated with abnormal imaging (p<0.001) with an odds ratio of 33 in multivariable model. Median time after vaccine for pts with adenopathy was significantly shorter at S 14 days compared to 33 days for pts without adenopathy (p<0.001). Incidence of adenopathy decreased as days from vaccine increased (3.4% for 0-14 days, 2.1% for 15-28 days, and 0.4% for > 28 days, p<0.001). After adjusting for being symptomatic, days from vaccine still had a significant impact on finding mammographic adenopathy (for each day after vaccine, OR=0.96, p<0.001). No significant difference was seen based on age (p=0.66), vaccine brand (p=0.66), vaccine dose (p=0.18). ROC analysis to identify a cutoff value for presence/absence of adenopathy was 0.74 (95% CI 0.67-0.81) at 22.5 days following vaccination. Additional imaging with mammogram and/or ultrasound was requested for 31 pts. These included no follow-up (n=4, 12.9%), repeat ultrasound with or without mammogram in 1-3 months (n=26, 83.9%), and biopsy (n=1, 3.2%, pt with ipsilateral breast cancer with negative results, presumably vaccine induced). To date, all pts who underwent surveillance imaging demonstrated normalization of lymph node appearance. The median time for abnormal imaging related to adenopathy to return to BI-RADS 1 or 2 was 84 (range 13-157) days. Conclusion: The incidence of COVID-19 vaccine-induced adenopathy in this study (1.4%) appeared to be lower than self-reported axillary swelling in COVID-19 vaccine trials (16%) but is still higher than the reported incidence of adenopathy on an otherwise normal SM (0.02-0.04%). The incidence of adenopathy decreased significantly over time and was not present in most pts 28 days after the vaccine. In patients with abnormal adenopathy, followup imaging showed resolution of vaccine-induced adenopathy in most patients by 3 months.
ABSTRACT
Introduction & Objectives: COVID-19 infection is hypothesized to have a potentially negative effect on male fertility through direct damage to the testes. The current trial is aimed at investigating the effect of SARS-CoV-2 on fertility and determining if viral bodies directly damage testicularfunction.Materials & Methods: This prospective study included controls comprising healthy participants and cases of patients suffering from pneumoniabased on chest CT and a positive of SARS-CoV-2 throat swab exhibited only moderate symptoms in accordance with the WHO classification.Extensive epidemiological, clinical, laboratory (hormonal levels, etc.) and ultrasound data (color doppler ultrasound of the scrotum) were collected. Asperm examination was performed in cases during their COVID-19 related hospital stay and 3 months after the discharge home. We also assessedthe testicles of COVID-19 patients who died of their disease (n=20) obtained during autopsies.Results: A total of 88 participants were included (44 controls and 44 cases). Blood testosterone levels were below normal (local reference values,5-50 nmol/ml) in 27.3% of the cases (12/44). The mean level (7.3±2.7 nmol/ml) was lower than that in the healthy controls (13.5±5.2 nmol/ml,p<0.001). At 3 months after discharge, the level returned to normal (13.7±4.5 nmol/ml) and was no different from that of the controls. An increase inLH and FSH was also detected compared to the healthy controls (p=0.047 and p=0.002). The spermogram revealed decreased motility in COVID-19patients (p=0.001), and higher number of immobile sperm (during COVID-19 – 58.8% and at 3 months 47.4%, p=0.005). All these parametersreturned to normal at 3 months after discharge. As for pathology findings, in the majority of autopsies (18/20) structural disorders of the testiculartissue, with signs of damage to germ cells were observed.Conclusions: COVID-19 and its treatment significantly affect hormone levels and sperm quality during the disease. Postmortem examinationconfirms inflammation and viral infiltration of the testicles. However, in those who had moderate to severe disease, decline in hormone levels andsperm quality was transient with values returning to baseline at 3 months
ABSTRACT
The spread and danger of coronavirus infection for public health led to the transition of educational organizations to distance learning. The article presents the results of studying the adaptation of the cardiovascular system of students to distance learning during the period of COVID-19. To determine the capabilities of bodies to the conditions of distance learning using ICT, we used the Belgian test. The results of the study showed that the health level of boys is undesirable, while that of girls is average. © 2020 Institute of Physics Publishing. All rights reserved.
ABSTRACT
The article examines the problems of digital competence as a phenomenon of modern life, especially aggravated in connection with the COVID-19 pandemic. Digital competence as the latest concept, skills necessary for the modern, connected with the scientific and technical implementation of new technologies in education, economy, politics and production. The development of digital literacy concepts relies on both traditional and diverse media. However, the main difficulty in its development is associated with the digital divide, overcoming which depends on many factors. In the educational environment, digital competence should take into account the age-related physiological, mental and psychological characteristics of schoolchildren, and in preparation for professional activity-support for professional digital competence. The work also provides the author's version of the definition of the concept of digital competence. © Published under licence by IOP Publishing Ltd.
ABSTRACT
The emergence of the COVID-19 pandemic has led to the transition of educational organizations to self-isolation and distance learning. Once in the new conditions, it was necessary to adapt to the fact that the training format had changed. One of the important tasks for us was to study students' health and the peculiarities of their adaptation to the acquisition of knowledge and skills using information and communication technologies remotely. Based on Ryazan State University, studies carried out aimed at studying the adaptation and mental health of students to the conditions of distance learning during the period of COVID-19 in terms of ultradian rhythms of the cardiovascular system using the Belgian test "Reaction of the cardiovascular system to load in the form of inclinations torso. "The obtained biorhythmological data of health status according to the Belgian test showed that the health status of students in the conditions of distance learning in connection with the COVID-19 pandemic and selfisolation corresponded to the working state. Distance education satisfied introverts, not extroverts. © The Authors, published by EDP Sciences, 2020.