Coronavirus Infection Research Articles

Application of computer-aided drug design in drug discovery and development: Updating knowledge

Coronavirus (CoV) diseases are widespread throughout the world and have caused considerable socio-economic disruptions. For this reason, efforts have been made to develop a direct or indirect antiviral drugs against these diseases. However, no specific antiviral drug has yet been approved by the Food and Drug Administration (FDA) for CoV infections. Thus, the challenge in discovering therapeutic molecules against these infections remains pertinent. Computer-aided drug design (CADD) is one of the modern techniques for drug discovery and development. It accelerates the process, minimizes costs, and reduces research time. In this article, we present the three CADD approaches, namely structure-based drug discovery (SBDD), ligand-based drug discovery (LBDD) and high-throughput virtual screening (HTVS). The different methods used in these three approaches CADD, such as molecular modelling, target structure analysis, molecular docking, molecular dynamics simulation, pharmacophore modelling, quantitative structure-activity relationship (QSAR), ligand-based virtual screening (LBVS) and structure-based virtual screening (SBVS) are detailed. In addition, the bioinformatics tools and databases commonly used in these different CADD techniques are also described.

Stimulator of interferon genes (STING) inhibits coronavirus infection by disrupting viral replication organelles.

Stimulator of interferon genes (STING) is an endoplasmic reticulum (ER) protein that plays a crucial role in cytosolic DNA-mediated innate immunity. Both STING agonists and antagonists have demonstrated their ability to enhance mouse survival against coronavirus, however, the physiological role of endogenous STING in coronavirus infection remains unclear. Our research unveils that STING inhibits coronavirus replication by impeding the formation of the ER-derived double-membrane vesicles (DMVs), the organelles in which coronavirus replicates. We found that STING was still capable of inhibiting coronavirus OC43 infection in cells, regardless of the knockout of cGAS or MAVS, or blocking type I interferon receptor. Moreover, STING disrupted the interaction between two crucial proteins, NSP4 and NSP6, involved in DMV formation, leading to the disruption of DMV formation. Taken together, our study sheds light on a novel antiviral role of STING in coronavirus infection, elucidating how it disrupts the formation of viral replication organelles, thereby impeding the replication process.

Chinese Public Attitudes and Opinions on Health Policies During Public Health Emergencies: Sentiment and Topic Analysis.

By the end of 2021, the new wave of COVID-19 sparked by the Omicron variant spread rapidly due to its highly contagious nature, affecting more than 170 countries worldwide. Nucleic acid testing became the gold standard for diagnosing novel coronavirus infections. As of July 2022, numerous cities and regions in China have implemented regular nucleic acid testing policies, which have had a significant impact on socioeconomics and people's lives. This policy has garnered widespread attention on social media platforms. This study took the newly issued regular nucleic acid testing policy during the COVID-19 pandemic as an example to explore the sentiment responses and fluctuations of netizens toward new policies during public health emergencies. It aimed to propose strategies for managing public opinion on the internet and provide recommendations for policy making and public opinion control. We collected blog posts related to nucleic acid testing on Weibo from April 1, 2022, to July 31, 2022. We used the topic modeling technique latent Dirichlet allocation (LDA) to identify the most common topics posted by users. We used Bidirectional Encoder Representations from Transformers (BERT) to calculate the sentiment score of each post. We used an autoregressive integrated moving average (ARIMA) model to examine the relationship between sentiment scores and changes over time. We compared the differences in sentiment scores across various topics, as well as the changes in sentiment before and after the announcement of the nucleic acid price reduction policy (May 22) and the lifting of the lockdown policy in Shanghai (June 1). We collected a total of 463,566 Weibo posts, with an average of 3799.72 (SD 1296.06) posts published daily. The LDA topic extraction identified 8 topics, with the most numerous being the Shanghai outbreak, nucleic acid testing price, and transportation. The average sentiment score of the posts was 0.64 (SD 0.31), indicating a predominance of positive sentiment. For all topics, posts with positive sentiment consistently outnumbered those with negative sentiment (χ27=24,844.4, P<.001). The sentiment scores of posts related to "nucleic acid testing price" decreased after May 22 compared with before (t120=3.882, P<.001). Similarly, the sentiment scores of posts related to the "Shanghai outbreak" decreased after June 1 compared with before (t120=11.943, P<.001). During public health emergencies, the topics of public concern were diverse. Public sentiment toward the regular nucleic acid testing policy was generally positive, but fluctuations occurred following the announcement of key policies. To understand the primary concerns of the public, the government needs to monitor social media posts by citizens. By promptly sharing information on media platforms and engaging in effective communication, the government can bridge the information gap between the public and government agencies, fostering a positive public opinion environment.

Impact of a new coronavirus infection on the level of inflammatory, haemostasis markers and microcirculatory parameters of patients with arterial hypertension

Relevance. The COVID-19 pandemic and its consequences have significantly affected the health of the population as a whole. Persons who have undergone coronavirus infection against the background of chronic cardiovascular diseases and obesity deserve special attention. Aim. To study and compare the main indicators of carbohydrate and lipid metabolism the level of inflammatory and haemostasis markers, microvascular changes in obesity AH patients and in AH patients with normal body weight 1 month after a new coronavirus infection in moderate to severe form. Materials and methods. The study included 87 patients of both sexes, aged from 18 to 55 years, from which three groups were formed: the first group included people with AH and normal body weight (BMI&lt;25 kg/m²) who had undergone COVID-19 within a month, the second group included people with AH and obesity (BMI≥30 kg/m²) who had undergone COVID-19 within a month, the control group consisted of 20 people with AH and obesity without COVID-19. The parameters of height, weight, waist circumference, and BMI were assessed in all subjects. The parameters of lipid profile, glucose level were determined, inflammatory markers and haemostasis parameters. All participants underwent laser Doppler flowmetry (LDF) on the forearm with constrictor and dilator functional tests, and single-photon emission computed tomography (SPECT) in combination with x-ray computed tomography (SPECT/CT). Results. Patients of groups 1 and 2 naturally differed from each other in anthropometric indicators. Lipid and carbohydrate metabolism rates were also significantly higher in group 2 patients compared to group 1 patients (p &lt; 0.05). The CRP level in the group of people with hypertension and obesity who underwent COVID-19 was significantly higher than in people with hypertension without obesity (p &lt; 0.001) and than in people with hypertension and obesity without a history of COVID-19. When comparing microcirculation parameters by LDF, there was a decrease in tissue hemoperfusion (M), blood flow reserve (RK) in all three groups (p &lt; 0.001), the most pronounced dysfunction of neurogenic and myogenic blood flow regulation was detected in the group of people with hypertension andobesity who underwent COVID-19. Conclusion. The study of microcirculation indicators by LDF method in persons with hypertension and obesity after suffering a coronavirus infection indicates the predominance of the spastic type of microcirculation, which, together with an increase in the levels of inflammatory markers, indicates a higher risk of thrombosis and cardiovascular complications, requiring more careful monitoring and treatment of this group of patients.

Clinical and immunological characteristics of COVID-19 in patients with disease dynamics

The aim is to study the clinical and immunological indicators of COVID-19 in the dynamics of the disease with the determination of predictors of the development of changes in the lungs. Materials and methods. The object of the study was 35 patients aged 22 to 75 years in the acute period and dynamics of COVID-19 disease, divided into two groups according to the identified clinical and immunological disorders. Markers of cellular (CD-3, CD-4, CD-8, CD-19) and humoral immunity, cytokines (IL-6,8, TGF-β, TNF-α), CEC were determined in all examined patients. Statistical processing of the obtained results was carried out using the computer program Statistica 10.0. Results. It was found that all the subjects retained clinical and immunological changes during the entire follow-up period, which indicates an ongoing disease. At the same time, significant differences in the severity of changes in individuals were revealed, taking into account age and the presence of chronic somatic pathology, expressed primarily in violation of the parameters of the T-system of immunity. In patients with the development of postcovoid changes in the lungs, characteristic immunological features were revealed, taking into account age. Conclusions. A violation of the detected indicators of the immune system may indicate the persistence of the virus, which means a prolongation of a specific inflammatory response with the risk of extensive tissue damage. Within three months after recovery, the tendency towards the formation of humoral immunity persists in both groups, which occurs by the end of 1 month after the disease in both groups and continues throughout the entire follow-up period. In the risk group for the development of pneumofibrosis in the outcome of a new coronavirus infection, the combination of IL-8 and TGF-β is the most optimal, despite their significant decrease in dynamics compared with the acute period.

Chemokine CCL2 and its receptor CCR2 in different age groups of patients with COVID-19

BackgroundDespite the development of various antiviral drugs, most of them are not effective in the treatment of coronavirus disease 2019 (COVID-19) as a hyperinflammatory disorder. Chemokine (C-C motif) ligand 2 (CCL2) is one of the critical CC chemokines involved in the pathogenesis and severity of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. This study aimed to investigate the expression of CCL2 and CC chemokine receptor 2 (CCR2) in COVID-19 patients.MethodsPeripheral blood samples were collected from 60 confirmed COVID-19 patients and 60 age-matched healthy subjects. The ages of the subjects were categorized as follows: up to 20 years, 20 to 40 years, 40 to 60 years, and more than 60 years. CCL2 serum levels were measured using the enzyme-linked immunosorbent assay (ELISA). CCR2 gene expression in peripheral blood mononuclear cells (PBMCs) was measured employing real-time polymerase chain reaction (PCR).ResultsIn all age groups, CCL2 serum levels were significantly elevated in patients compared to healthy controls (P < 0.0001). CCL2 levels were higher in severe patients than in moderate patients. Moreover, CCR2 expression by PBMCs was higher in patients compared to control subjects. However, a significant difference between patients and controls over 60 years of age was identified (P = 0.0353). There was no significant difference in CCR2 expression between moderate and severe COVID-19 patients.ConclusionsTaken together, the findings demonstrate that CCL2 and CCR2 are upregulated in COVID-19 patients at protein and mRNA levels, respectively. Therefore, the CCL2/CCR2 axis may be a potential therapeutic target in order to improve patient outcomes.

The results of vaccination against novel coronavirus infection in adolescents with allergic diseases

Novel coronavirus infection requires analyzing its course in patients with allergic diseases. Patients with atopic allergic diseases remain insufficiently studied with regard to the peculiarities of the course of both the underlying allergic disease and infectious processes caused by viruses and bacteria. Epithelial cells in bronchial asthma do not respond sufficiently to interferons, suggesting that SARS-CoV-2 infection may suppress spontaneous upregulation of angiotensin-converting enzyme expression, which ultimately reduces disease severity, but at the same time makes patients with allergic atopic diseases susceptible to other viral infections. The results obtained indicate statistically significant differences in the formation of anti-RBD IgG antibodies to SARS-CoV-2 between the group of adolescents with bronchial asthma vaccinated against a new coronavirus infection and those not vaccinated against it. During the follow-up period after 6 months, a statistically significant increase in anti-RBD IgG titer to SARS-CoV-2 due to novel coronavirus infection was observed among the unimmunized children. Clinical parameters indicated a favorable course of atopic process and control of bronchial asthma exacerbations in adolescents who received vaccination against both new coronavirus infection and influenza, while those who did not receive vaccination against these viral infections had bronchial asthma exacerbations due to respiratory infection. Also among patients with bronchial asthma who received influenza vaccination, there were no cases of influenza A and bronchial asthma exacerbations due to respiratory infections. In this regard, influenza vaccination is an important intervention to maintain control of asthma exacerbations. It is noteworthy that no new coronavirus infection was reported among vaccinated adolescents within a year after immunization. At the same time, 6 months after vaccination against a new coronavirus infection, we observed a statistically significant increase in antibody levels in unvaccinated adolescents, indicating the presence of high viral neutralizing activity. Vaccination against novel coronavirus infection in patients with bronchial asthma may be considered a possibility.

Безопасность применения двухкомпонентного препарата моноклональных антител к SARS-CoV-2 (тиксагевимаб + цилгавимаб) для доконтактной профилактики новой коронавирусной инфекции у детей с ревматическими заболеваниями

New coronavirus infection (COVID-19) is an acute respiratory disease caused by the SARS-CoV-2 coronavirus. Tixagevimab+cilgavimab has been developed for the prevention and treatment of COVID-19. The purpose of this research was to evaluate the safety of the use of the two-component drug of monoclonal antibodies to SARS-CoV-2 (tixagevimab+cilgavimab) for pre-exposure prophylaxis of the new coronavirus infection in children with rheumatic diseases (RDs). Materials and methods used: a single-center retrospective study with prospective stage had been carried out that included 300 pediatric patients aged 12 to 18 y/o with RDs. The safety of pre-exposure prophylaxis of COVID-19 was assessed based on the dynamics of clinical and laboratory parameters as well as the total indices of RD activity. The effectiveness of pre-exposure prophylaxis was assessed based on recording the incidence of the new coronavirus infection. Safety and effectiveness were assessed after 3, 6, and 9 months after the administration of tixagevimab+cilgavimab drug. Results: no statistically significant increase in RDs activity was registered during 9 months of observation after pre-exposure prophylaxis of COVID-19. On the contrary, in patients with various types of juvenile arthritis, systemic lupus erythematosus and juvenile ankylosing spondylitis during the observation period against the background of antirheumatic therapy, a statistically significant decrease in the activity indices was registered - JADAS71 (p&lt;0.001, p=0.002, p=0.030), SELENA-SLEDAI (p&lt;0.001, p=0.027, p=0.570) and JSpADA (p=0.009, p=0.205, p=1.000), respectively; in patients with juvenile dermapolymyositis, systemic sclerosis and systemic vasculitis - a tendency to decrease in activity indices - DAS (p=0.002, p=0.050, p=0.193), J4S (p=0.840, p=0.720, p=1.000), PVAS (p=0.120, p=0.230, p=1.000 for the new and p=0.360, p=1.000, p=0.860 for the constant attributes), respectively. The new coronavirus infection was suffered by 6/300 (2%) patients within 9 months after pre-exposure prophylaxis. Conclusion: pre-exposure prophylaxis of COVID-19 with the two-component drug of monoclonal antibodies to SARS-CoV-2 (tixagevimab+cilgavimab) may be considered as both effective and safe and can therefore be suggested to pediatric patients with RDs.

Updated insights into adverse events associated with mepolizumab: a disproportionality analysis from the FDA adverse event reporting system database

BackgroundMepolizumab, a monoclonal antibody targeting interleukin-5, is used to treat severe eosinophilic asthma and other eosinophilia-related conditions. Given its growing use, there is a pressing need for the latest data to improve the understanding and management of its adverse events (AEs). This study aimed to investigate the safety of mepolizumab by analyzing the pharmacovigilance database of the US Food and Drug Administration.MethodsThe AE signals associated with mepolizumab from 2015 to 2024 were analyzed and the correlations using reporting ratios (RORs) quantified. Subgroup analyses were conducted to understand AEs in individuals ≤ 18 years of age. We also used time-to-onset (TTO) analysis to examine AE occurrence patterns.ResultsIn total, 82,478 AE reports linked to mepolizumab therapy were included. Our analysis, involving 24,156 patients, revealed a predominance of female patients, with the highest incidence of AEs occurring in those aged 18–65 years. Disproportionality analyses revealed significant signals across various system organ classifications (SOCs), most prominently respiratory, thoracic, and mediastinal disorders (ROR = 5.12, 95% confidence intervals [CI] 5.03–5.21), infections and infestations (ROR = 1.86, 95% CI 1.81–1.90), and immune system disorders (ROR = 1.14, 95% CI 1.08–1.21). The highest ROR was found for asthma crisis (ROR = 104.90, 95% CI 95.31–115.44) at the preferred term (PT) level, and the other notables were coronavirus infection (ROR = 7.33, 95% CI 6.05–8.88) and coronavirus disease 2019 (COVID-19) (ROR = 1.34, 95% CI 1.23–1.47). A subgroup analysis of patients ≤ 18 years old identified four significant SOC signals, with the highest ROR in respiratory, thoracic, and mediastinal disorders (ROR = 5.28, 95% CI 4.17–6.68). PT analysis revealed significant AEs, such as wheezing, bronchospasm, and chest discomfort. TTO analysis revealed that 18.5% of AEs occurred within the first 30 days of treatment. The Weibull shape parameter indicated an “early failure-type” pattern for mepolizumab-associated AEs, underscoring the need for vigilant monitoring during the initial stages of therapy.ConclusionOur study highlights the importance of post-market surveillance for monitoring the safety of mepolizumab, which revealed significant AE signals, particularly for respiratory diseases, infections, and immune system complications. The association with opportunistic infections, including COVID-19, highlights the need for vigilant surveillance and further research.

Rational Design of Macrocyclic Noncovalent Inhibitors of SARS-CoV-2 Mpro from a DNA-Encoded Chemical Library Screening Hit That Demonstrate Potent Inhibition against Pan-Coronavirus Homologues and Nirmatrelvir-Resistant Variants.

The recent global COVID-19 pandemic has highlighted treatments for coronavirus infection as an unmet medical need. The main protease (Mpro) has been an important target for the development of SARS-CoV-2 direct-acting antivirals. Nirmatrelvir as a covalent Mpro inhibitor was the first such approved therapy. Although Mpro inhibitors of various chemical classes have been reported, they are generally less active against nirmatrelvir-resistant variants and have limited pan-coronavirus potential, presenting a significant human health risk upon future outbreaks. We here present a novel approach and utilized DNA-encoded chemical library screening to identify the noncovalent Mpro inhibitor 5, which demonstrated a distinct binding mode to nirmatrelvir. A macrocyclization strategy designed to lock the active conformation resulted in lactone 12 with significantly improved antiviral activity. Further optimization led to the potent lactam 26, which demonstrated exceptional potency against nirmatrelvir-resistant variants as well as against a panel of viral main proteases from other coronaviruses.

Biochemical analysis of packing and assembling heptad repeat motifs in the coronavirus spike protein trimer.

During a coronavirus infection, the spike protein undergoes sequential structural transitions triggered by its receptor and the host protease at the interface between the virus and cell membranes, thereby mediating membrane fusion. After receptor binding, the heptad repeat motif (HR1/HR2) within the viral spike protein bridges the viral and cellular membranes; however, the intermediate conformation adopted by the spike protein when drawing the viral and cellular membranes into close proximity remains unclear due to its transient and unstable nature. Here, we experimentally induced conformational changes in the spike protein of a murine coronavirus by incubating the virus with its receptor, followed by exposure to trypsin. We then treated the virus/receptor complex with proteinase K to probe the tightly packed core structure of the spike protein. The conformations of the spike protein were predicted from the sizes of the protease digestion products detected by western blot analysis. Upon receptor binding, two bands (each showing different reactivity with a fusion-inhibiting HR2-peptide) were detected; we propose that these bands correspond to the packed and unpacked HR1/HR2 motifs. After trypsin-mediated triggering, measurement of temperature and time dependency revealed that packing of the remaining unpacked HR1/HR2 motifs and assembly of three HR1 motifs in a trimer occur almost simultaneously. Thus, the trimeric spike protein adopts an asymmetric-unassembled conformation after receptor binding, followed by direct assembly into the post-fusion form triggered by the host protease. This biochemical study provides mechanistic insight into the previously unknown intermediate structure of the viral fusion protein.IMPORTANCEDuring infection by an enveloped virus, receptor binding triggers fusion between the cellular membrane and the virus envelope, enabling delivery of the viral genome to the cytoplasm. The viral spike protein mediates membrane fusion; however the molecular mechanism underlying this process is unclear. This is because using structural biology methods to track the transient conformational changes induced in the unstable spike trimer is challenging. Here, we harnessed the ability of protease enzymes to recognize subtle differences on protein surfaces, allowing us to detect structural differences in the spike protein before and after conformational changes. Differences in the size of the degradation products were analyzed by western blot analysis. The proposed model explaining the conformational changes presented herein is a plausible candidate that provides valuable insight into unanswered questions in the field of virology.

Features of the course of the new coronavirus infection COVID-19 in chronic kidney disease

Purpose of the study. Study of the characteristics of the course of the new coronavirus infection COVID-19 in chronic kidney disease (CKD). Materials and methods. A total of 182 patients who were in the State Budgetary Institution “Emergency Medical Care Hospital” (Cheboksary) with a confirmed diagnosis of COVID-19 were examined. Results. A high incidence of CKD in hospitalized patients is shown. In CKD, there is a high mortality from COVID-19, statistically significant for CKD stage 3, but not for CKD stages 1-2. A number of clinical and laboratory parameters associated with an increased risk of adverse outcome have been identified. CKD is an independent risk factor that increases the risk of death when combined with these parameters. The positive effect of Janus kinase inhibitors is reflected when they are prescribed in the group under 65 years of age and in the first days of patient admission. Conclusion. The results of the study indicate the necessity of studying kidney function in patients with a new coronavirus infection. Patients with chronic kidney disease stages 3-4 require close dynamic monitoring as a risk group for severe disease, affecting survival.

Use of telemedicine technologies in organizing rehabilitation of patients with bronchopulmonary pathology. Myth or reality?

In 2013, telemedicine began to penetrate widely and actively into the activities of the medical community. Telerehabilitation acts as an alternative within the framework of considering and conducting traditional rehabilitation or as an additional therapeutic tool, which allows you to achieve the set goal of recovery faster and more effectively. During the period 2022-2023, 1,318 people participated in the telerehabilitation program: 712 patients who suffered pneumonia caused by the new coronavirus infection COVID-19, 606 patients with chronic obstructive pulmonary disease. During the course, not a single patient was hospitalized for an exacerbation of the disease or for a clinical deterioration of the condition. At the same time, there was a significant improvement in the calculated indicators, which confirmed the relevance of this area of medicine.

Pathomorphological changes in the lung tissues of Syrian hamsters during experimental infection with SARS‐COV‐2

The new coronavirus infection caused by SARS‐CoV‐2 is a dangerous respiratory disease. The aim of the investigation was to study the pathomorphological changes in lungs of Syrian hamsters infected with SARS‐CoV‐2 as is necessary for adequate therapy and prevention of the disease.Syrian hamsters of the SPF category were infected intranasally with a dose of 5×105TCID50 SARS‐CoV‐2/human/RUS/Nsk‐FRCFTM‐1/2020). Animals were euthanised on days 3, 6, 10, 14 and 21 after infection and the lungs were collected. To determine virus replication real‐time RT‐PCR was used. The lungs was used for histological examination. Statistics was performed using Statistics for Windows 10 software.Specific pathological lesions characterising the inflammatory process were detected in all groups of animals. The severity of pathological changes and the volume of lung tissue lesions varied depending on the stage of the disease. The most severe lesions were observed on days 6–10. By day 21, the process of organ structure restoration was noticed.The study showed that pathological changes in the Syrian hamster’s lungs caused by experimental infection with the SARS‐CoV‐2 were multifaceted and complex. In mild cases, congestion and infiltration are observed, and in severe cases, atelectasis and pulmonary edema were life‐threatening. The most severe lesions in lungs were noted on days 6–10. By day 21, the process of restoration was observed.

Clinical and immunologic abnormalities in COVID-19

Objective: to find approaches to improve diagnostics of the debut of rheumatic manifestations, associated with COVID-19.Material and methods. Data from 1000 patients from the COVID-19 registry were included in the prospective cohort study. In all patients, the diagnosis of COVID-19 was confirmed by polymerase chain reaction. Of these patients, 380 (41.8% men and 58.2% women, mean age 47.0±2.5 years) had rheumatic manifestations. Patients were examined using routine clinical methods. Immunological markers of rheumatic diseases were determined, including antibodies against cyclic citrullinated peptide, rheumatoid factor, antiphospholipid antibodies and antinuclear factor (ANF), and an immunoblot for antinuclear antibodies was performed if ANF titer was &gt;1:160.Results and discussion. Patients had the following rheumatic manifestations: arthralgias (in 342), myalgias (in 23), skin rashes (in 15). ANF titers &gt;1:160 were found in 57.6% of patients. No reliable data indicating the development of an antiphospholipid syndrome were found in the study group. Lupus anticoagulant was detected in 5.7% of cases, antibodies against β2-glycoprotein in 5.7%, antibodies against cardiolipin in 3.8%. High ANF titers were found in 63.9% of patients with arthralgia. Gender-specific differences were found when analyzing the correlation between ANF titers and rheumatic manifestations: in men, high ANF tires were associated with myalgias, and in women with arthralgias. The presence of rheumatic manifestations depended directly on the severity of the disease. A correlation between arthralgia and leucopenia was also found – leucocyte count &lt; 3,9 ‧109 /L was a predictor of arthralgias. The sensitivity and specificity of the model were 99.3 and 91.2%, respectively.Conclusion. The results suggest that COVID-19 can provoke the development of immunological abnormalities that may subsequently lead to the development of an autoimmune diseases (AID). The optimal approach to prevention and early detection of AID in patients with coronavirus infection caused by SARS-CoV-2 is to monitor laboratory parameters – leukocyte count and CRP level. If rheumatic manifestations are present, the use of immunological and imaging examinations is also recommended.

Experience with the use of janus kinase inhibitors in the treatment of COVID-19 in patients in Volgograd

The new coronavirus infection (COVID-19) is characterized by high morbidity and mortality. The main approach to COVID-19 therapy should be the proactive administration of treatment before the development of a complete symptom complex of life-threatening conditions, including acute respiratory distress syndrome. The use of a selective and reversible inhibitor of janus kinase 1 and 2 prevents viral endocytosis, reduces excessive inflammatory response. The purpose of the study - to evaluate the effectiveness of the use of the Janus kinase inhibitor of the drug Baricitinib (Olumiant, manufacturer Lilly del Caribe Inc., Spain) in the treatment of patients with moderate COVID-19 in a hospital setting. During the clinical use of Baricitinib, significant positive changes were obtained compared with the initial level of vital signs and laboratory data. Significant positive changes in the following indicators were obtained: oxygen saturation increased (from 95.3 ± 4.0 to 97.5 ± 3.2 %, p = 0.011), body temperature decreased (from 37.3 ± 0.7 to 36.7 ± 0.5 °C, p = 0.000), C-reactive protein decreased (from 47.1 ± 46.0 to 32.5 ± 41.7 g/l, p = 0.010), the number of platelets increased (from 178.0 ± 59.5 to 249.5 ± 84.5; p = 0.000), when assessing the condition of patients in points on the NEWS-2 scale positive dynamics (from 1.6 ± 1.2 to 1.1 ± 1.3, p = 0.001). The level of C-reactive protein increased simultaneously with an increase in interleukin-6, an increase to 200.0 ± 6.2 pg/ml was recorded. The positive dynamics is an increase in the number of lymphocytes to 2.0 • 109/l. By the end of inpatient treatment, ferritin levels had normalized to reference values of 27.7±2.1 mmol/l and D-dimer to the upper limit of normal. Positive dynamics of changes on the CT scan of the chest organs in the form of a decrease in infiltration. According to the combination of changes in clinical, laboratory signs and CT scan results, the therapy of patients was effective.

Brody's abscess of the humerus is the cause of sepsis in a patient with coronavirus infection (COVID-19)

Purpose: To conduct a clinical and morphological analysis of the case of death as a result of sepsis, the cause of which was Brody's abscess.Material and methods. An analysis of the fatal outcome of a 54–year-old patient who occurred in a hospital of a medical organization where he received medical care for a disease – a new coronavirus infection. The complex of clinical, laboratory and instrumental diagnostic methods could not explain the progressive deterioration of the severity of the patient's condition and the onset of death.Results. During the autopsy, an abscess of the proximal epiphysis of the left humerus was found with the spread of the inflammatory process to the soft tissues of the breast, the parietal pleura with the development of purulent fibrinous pleurisy, left-sided pneumonia, purulent fibrinous pericarditis, hematogenous purulent meningitis.Conclusion. The authors of the article have established a causal cause of death from Brody's abscess, which makes it possible to expand the diagnostic search in the case of sepsis with an unclear primary focus.

Methodological model for teaching residents of foreign language professional communication based on an integrated approach

Importance. The widespread use of foreign language education in non-linguistic universities is due to a number of factors that determine the development of professional activity in various industries. Medicine and healthcare are among the key areas of human activity that require regular updating of knowledge and improvement of professional skills of a specialist in the context of scientific and technological progress. Medical professionals are required to keep abreast of the latest achievements of science and technology, to study new methods of diagnosis, treatment and prevention of diseases in order to provide patients with better medical care. Using the example of the COVID-19 pandemic, the world community realized that the emergence of such threats requires rapid response and cooperation between various countries and organizations. Only through the experience of interaction between scientists and medical professionals from different countries, it was possible to jointly normalize the epidemiological situation around the world. The World Health Organization has played a key role in coordinating international efforts to combat coronavirus infection by providing all the necessary information in foreign languages, mainly English and French. In view of this, there is a social demand in the labor market for medical workers who speak English perfectly, and in higher educational institutions there is a demand for language courses from students of residency. The main purpose of the study is to develop a methodological model for teaching residents of foreign language professional communication based on an integrated approach.Research Methods. To achieve the main goal, theoretical and empirical research methods are applied, which make it possible to study and analyze existing theories and concepts on the topic of developing a methodological model for teaching residents of foreign language professional co mmunication based on an integrated approach. Based on the analysis of the academic literature on the research topic, the regularities of the construction of the methodological model, its functions and component composition are revealed. Modeling of the educational process makes it possible to create an effective methodological model for teaching residents of foreign language professional communication based on an integrated approach.Results and Discussion. The conducted research makes it possible to identify the didactic functions of the methodological model: 1) orienting; 2) regulatory; 3) formative; 4) controlling. Based on the identified didactic functions, a methodological model for teaching residents of foreign la nguage professional communication based on an integrated approach is developed, which is structurally presented in the form of five consecutive blocks: 1) prerequisites; 2) goal setting block; 3) content block; 4) operational and activity block; 5) evaluation and performance block.Conclusion. The developed methodological model for teaching residents of foreign language professional communication based on an integrated approach allows creating a simulation of the educational process in order to identify the strengths and weaknesses of the proposed teaching met hodology. The obtained research results are supposed to be used in the methods of foreign language teaching in medical universities in the training of residents.

A case report of late detection of primary mediastinum herm cell tumor

Germ cell tumors are rare malignant neoplasms. Extragondal localization accounts for about 10% of all germ cell tumors, with up to 3% being mediastinal. The low incidence, along with a nonspecific clinical presentation, complicates initial diagnosis and leads to delays in diagnosis and the initiation of specific treatment. Primary care plays a crucial role in detecting such tumors and in patient routing. At the outpatient stage, the patient should be examined and referred to a specialized facility for specific treatment as quickly as possible. For differential diagnosis at the initial stages between mediastinal germ cell tumors and lymphoproliferative diseases, mediastinal sarcomas, thymomas, and others, monitoring tumor markers is necessary: alpha-fetoprotein (AFP), beta-human chorionic gonadotropin (beta-HCG), and lactate dehydrogenase (LDH). When these markers are elevated and time is critical, it is permissible to start specialized antitumor treatment without histological confirmation.Currently, it is also important to consider the role of the new coronavirus infection, which complicates differential diagnosis at the initial stages. This article presents a clinical case of late detection of a germ cell tumor and attempts to conduct systemic therapy in the context of the disease’s complicated progression.

Coronavirus M protein promotes mitophagy over virophagy by recruiting PDPK1 to phosphorylate SQSTM1 at T138

Autophagy plays a dual role in coronavirus infection, facilitating the elimination of either proviral components (virophagy) or antiviral factors such as mitochondria (mitophagy), leading to complex mechanisms of immune evasion. Understanding the mechanisms that govern the switch between the autophagic degradation of deleterious or beneficial substrates in coronavirus infection is crucial for developing precise drug targets to treat virus-induced diseases. However, this switch remains largely unknown. Using a dual split-fluorescence assay, we identify PDPK1 as a negative regulator of innate immunity, directing the transition from virophagy to mitophagy through the phosphorylation of SQSTM1 at T138. Remarkably, a PDPK1-targeting peptide inhibits the replication of various RNA viruses by restoring innate immunity through enhanced virophagy and suppressed mitophagy, thereby protecting female mice from lethal infections. These findings underscore the detrimental role of PDPK1 in innate immunity by orchestrating the shift from virophagy to mitophagy, positioning PDPK1 as a promising pharmacological target for effectively combating a broad spectrum of virus infections.