Acute Viral Infections Research Articles

The prevalence and correlates of post-infectious fatigue following dengue infection among adults admitted to two selected hospitals in Colombo District, Sri Lanka

Introduction: Dengue illness, an acute viral infection, is endemic in Sri Lanka causing a substantial public health challenge today in all dimensions of health. Post-infectious fatigue (PIF) after dengue infection had been reported in several studies as well as in textbooks of medicine.Objectives: To describe the prevalence and correlates of PIF at one-month follow-up among adults confirmed with dengue infection admitted to selected healthcare institutions in Colombo District, Sri Lanka.Methods: A longitudinal study was conducted among 480 patients from July 2018 to January 2019. Participants were recruited on discharge from the hospital. We adopted systematic sampling method and followed them up one month after day 1 of the fever. Prevalence was assessed by the culturally adapted and validated Sinhala version of the Chalder Fatigue Questionnaire. Correlates were assessed by a pre-tested interviewer-administered questionnaire. A binomial multiple logistic regression analysis was carried out via the SPSS-21 version.Results: The response rate was 84.58 (406/480). The majority were between 18-35 years (69.2%) and male (60.15%). The prevalence of PIF at one month was 35% (95% CI: 30.3, 39.8). After controlling for confounders, age ≥35 years (adjusted OR (AOR)=4.05; 95% CI: 2.04, 8.04), not being married (AOR=2.7; 95% CI: 1.38, 5.28), having experience of stress full life events (AOR=1.98; 95%CI: 1.16, 3.36), not receiving an adequate quantity of sleep (AOR=2.51; 95% CI: 1.00, 6.31), poor quality of sleep (AOR=15.34; 95% CI: 3.25, 72.49), headache post-discharge (AOR=2.69; 95% CI: 1.6, 4.53), presence of myalgia post-discharge (AOR=3.63; 95% CI: 2.16, 6.11), haemoglobin <11 g/dl at acute stage (AOR=2.01; 95% CI: 1.02, 3.98) and having a platelet count ≤30,000/mm3 (AOR=2.38; 95% CI: 1.42, 3.99) showed significant associations with having PIF.Conclusions & Recommendations: Post-infectious fatigue was present among approximately one in three patients after one month following a dengue infection. The modifiable correlates suggest the indications for screening and prevention which is more applicable to clinicians.

ЦИРКУЛЯЦИЯ ОРВИ У ДЕТЕЙ Г. БЕРДСКА НОВОСИБИРСКОЙ ОБЛАСТИ В СЕЗОН 2022-2023 Г.

Вackground. Acute respiratory diseases are the most common among all infectious diseases, both in the world and in the Russian Federation. Prevention of acute respiratory viral infections and timely detection of the viral etiology of these diseases is an urgent public health task. Purpose of the study. The aim of this work was to identify the viral etiology of acute respiratory diseases in children's age group patients who sought medical help with signs of upper respiratory tract infections at the Berdsk Central City Hospital. Patient Characterization and Research Methods. The target group of the study was patients aged 0-17 years in the acute stage of upper respiratory tract disease who presented with signs of infection. Identification of the genetic material of respiratory viruses was carried out by real-time PCR using the AmpliSens “ARVI - FL” diagnostic kits (FBIS Central Research Institute of Epidemiology of Rospotrebnadzor, Russia). Methods of statistical analysis. Microsoft Office Excel program was used. Results and conclusion. The result of the research revealed that 81.33% of samples of biological material received a positive result for at least one infection. Identified: RNA viruses SARS-CoV-2, influenza A (Influenza virus A), influenza B (Influenza virus B), respiratory syncytial virus (hRSv), metapneumovirus (hMPV), parainfluenza types 1, 2, 4 (hPiv), RNA coronaviruses species OC43, E229, NL63, HKUI (HCoV), RNA of rhinoviruses (hr v), DNA of adenoviruses of groups B, C and E (HAdV), DNA of bokavirus (HBoV), and in 12.59% of cases of the number of positive samples, the presence of coinfections is observed. The results of this work are aimed at verifying the etiological factor of ARVI and strengthening the prevention of the spread of upper respiratory tract infections in the population.

Римантадин в сочетании с альгинатом натрия как средство терапии и профилактики ОРВИ разной этиологии у детей раннего и дошкольного возраста

Римантадин в сочетании с альгинатом натрия как средство терапии и профилактики ОРВИ разной этиологии у детей раннего и дошкольного возраста

The Clinical Outcomes of Acute Myocarditis in Pediatric Population: A Prospective Study

Background: Myocarditis, a serious complication of acute viral infections, is a significant concern in pediatric healthcare. Often underdiagnosed due to its subtle symptoms like cough and easy fatigability, myocarditis can lead to severe cardiac complications. Objectives: The primary objective of this study was to examine the outcomes of acute myocarditis in children who received early diagnosis and management. The study focused on identifying factors influencing these outcomes, rather than comparing different treatment methods. Methods: This prospective study involved 118 pediatric patients (age < 16 years) admitted with acute myocarditis to the Pediatric Cardiology Ward at Lady Reading Hospital. Data were collected using a specialized proforma with informed consent. Comprehensive monitoring included echocardiography for assessing left ventricular function, ECG for arrhythmia detection, and cardiac enzyme levels. Patients were treated with a standard management plan, including immunosuppressive therapy, diuretics, and inotropic support. Follow-up was conducted for an average of six months. Results: The age distribution was as follows: 70 patients in Group-A (below 4 years), 35 in Group-B (5-10 years), and 13 in Group-C (10-16 years). The gender ratio was 53 males to 65 females. Ejection fractions were: 15-20% in 40 patients, 20-25% in 44 patients, and 26-35% in 34 patients. Left Ventricular End-Diastolic Diameter (LVEDD) showed 49 patients in Grade 1, 45 in Grade 2, and 24 in Grade 3. Improvements were observed in 37 patients (31.3%) with normal ventricular functions, 32 (27.1%) with mild dysfunction, and 29 (24.5%) with moderate dysfunction. 20 patients (16.9%) showed no improvement, and complications included LV clot (11%), stroke (2.5%), arrhythmias (1.7%), and mortality (5.9%). Conclusion: Timely diagnosis and appropriate management are crucial for improving outcomes in children with acute myocarditis. Delayed management can lead to severe complications including dilated cardiomyopathy, cardiac thrombi, stroke, arrhythmias, and mortality.

Передчасно закрита артеріальна протока: можливі ризики для новонародженого

Premature closure of the fetal ductus arteriosus is a rare phenomenon that results in increased right ventricular pressure, leading to the development of isolated right ventricular hypertrophy, high pulmonary hypertension, and even death. Purpose - to present a rare clinical case of prenatally closed ductus arteriosus in a newborn boy, that clinically manifested by severe respiratory failure immediately after birth. Clinical case. The child was admitted to the neonatal intensive care unit 5 hours after delivery with clinical signs of severe respiratory failure, child was oxygen-dependent. It is known from the anamnesis that the child was delivered by urgent cesarean section on the basis of a prenatally diagnosed prematurely closed arterial duct. A week before the delivery, the mother had an acute respiratory viral infection accompanied by high fever, which was treated with high doses of over-the-counter ibuprofen. The 2D echocardiography showed severe hypertrophy of the right ventricular wall and tricuspid insufficiency, which was caused by premature closure of the ductus arteriosus. The flow through the ductus arteriosus was not determined. Aortic coarctation as a possible cause of right ventricular hypertrophy in the newborn period was excluded. The infant was switched to constant positive pressure artificial ventilation (CPAP) to reduce pulmonary vascular resistance and afterload of the right ventricle. Over the next 3-4 weeks of oxygen therapy, the child's general condition improved significantly. Hypertrophy of the right ventricular wall regressed to normal size, the child grows and develops according to age. Conclusions. Premature prenatal closure of the arterial duct can be idiopathic or caused drugs intake that suppress prostaglandin production late in the pregnancy. Pregnant women should be counseled about the potential side effects on the fetus caused by the use of NSAIDs, especially in the third trimester of pregnancy. Urgent delivery and oxygen therapy contribute to the regression of intracardiac changes and significantly improve general condition of the child. The study was conducted in accordance with the principles of the Declaration of Helsinki. The informed consent of the child’s parents was obtained for the study. No conflict of interests was declared by the authors.

Congenital thrombotic thrombocytopenic purpura in children

Introduction. Congenital thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening genetic disorder characterized by recurrent episodes of microangiopathic hemolytic anemia, thrombocytopenia, and organ dysfunction due to the defi ciency or dysfunction of the ADAMTS13 enzyme. Despite the availability of clinical and laboratory diagnostic criteria the diagnosis remains challenging due to a wide range of diseases with similar appearance.Aim: to analyze the clinical manifestations and treatment results of identifi ed cases of congenital TTP at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology.Methods. This article reviews 11 clinical cases with congenital TTP genetically confi rmed or with typical clinical and laboratory signs.Results. Clinical and laboratory signs of TTP are highly variable and nonspecifi c, which was observed in the described cohort of patients. One of the trigger factors is often an acute respiratory viral infection, and stabilization of the disease can occur after transfusions of blood components. A delay of diagnosis can often lead not only to a delay of correct therapy, but also to the prescription of wrong therapy. The main diagnosis confi rmatory method was a molecular genetic test, which was carried out in 8 cases. All patients diagnosed with congenital TTP were successfully treated with FFP therapy.Conclusion. Early diagnosis of TTP is diffi cult due to the lack of specifi c clinical manifestations and easily accessible laboratory tests

Targeting the tissue factor coagulation initiation complex prevents antiphospholipid antibody development

AbstractAntiphospholipid antibodies (aPL) in primary or secondary antiphospholipid syndrome (APS) are a major cause for acquired thrombophilia, but specific interventions preventing autoimmune aPL development are an unmet clinical need. Although autoimmune aPL cross react with various coagulation regulatory proteins, lipid-reactive aPL, including those derived from patients with COVID-19, recognize the endolysosomal phospholipid lysobisphosphatidic acid presented by the cell surface–expressed endothelial protein C receptor. This specific recognition leads to complement-mediated activation of tissue factor (TF)–dependent proinflammatory signaling and thrombosis. Here, we show that specific inhibition of the TF coagulation initiation complex with nematode anticoagulant protein c2 (NAPc2) prevents the prothrombotic effects of aPL derived from patients with COVID-19 in mice and the aPL–induced proinflammatory and prothrombotic activation of monocytes. The induction of experimental APS is dependent on the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex, and NAPc2 suppresses monocyte endosomal reactive oxygen species production requiring the TF cytoplasmic domain and interferon-α secretion from dendritic cells. Latent infection with murine cytomegalovirus causes TF cytoplasmic domain–dependent development of persistent aPL and circulating phospholipid-reactive B1 cells, which is prevented by short-term intervention with NAPc2 during acute viral infection. In addition, treatment of lupus prone MRL-lpr mice with NAPc2, but not with heparin, suppresses dendritic-cell activation in the spleen, aPL production and circulating phospholipid-reactive B1 cells, and attenuates lupus pathology. These data demonstrate a convergent TF-dependent mechanism of aPL development in latent viral infection and autoimmune disease and provide initial evidence that specific targeting of the TF initiation complex has therapeutic benefits beyond currently used clinical anticoagulant strategies.

STUDY OF THE RISK OF PARENTS’ DISSATISFACTION WITH THE QUALITY OF PROVIDING MEDICAL AID TO CHILDREN WITH RESPIRATORY DISEASES

Introduction. Reforming the health care system requires defining criteria for assessing patients’ dissatisfaction with the quality of medical care. It is known that the previous experience of communication with a doctor affects the quality of further interaction and compliance with medical recommendations.
 The aim was to predict the risk of parents’ dissatisfaction with the quality of medical care for children with respiratory diseases, depending on the number and reasons for visits to pediatricians and family general practitioners (GP), by the results of the questionnaire.
 Materials and methods. Overall, 171 parents were questioned (87.72 %). The analysis was by logistic regression models using the statistical analysis package MedCalc v.19.4.1 (MedCalc Software Inc, Broekstraat, Belgium, 1993-2020).
 Results. The results of the study show that 125 (83.3 %) parents rated satisfaction with the quality of medical care for children with respiratory diseases (RD) in health care facilities as 5 points by a five-point scale.
 The univariate analysis showed a significant relationship between the risk of parents’ dissatisfaction with the quality of medical care for RD children and the number of ARI visits to the GPs per year (p<0.05), namely: the increase in the number of visits is associated with significant decrease in parental dissatisfaction with quality of medical care, for every next visit (p = 0.040), OR = 0.31 (95 % CI 0.10-0.95). The area under the curve of operational characteristics AUC = 0.66 (95 % CI 0.58-0.74) indicates a weak relationship between the risk of parental dissatisfaction and the number of ARI visits to the GPs per year. When using the stepwise regression, 4 factor features were selected for multivariate analysis, namely: the number of cases of acute respiratory viral infections in a child per year, the number of pneumonias in a child during life, the number of visits to the PHC (primary health care) physician, and to the PHC pediatrician per year. According to this model, an increase in the number of visits to the GP is associated with decrease in parents’ dissatisfaction with the quality of medical care, for each repeated visit (when standardizing by the number of ARI cases in a child per year, the number of pneumonia cases in a child, and the number of visits to the PHC pediatrician) (p = 0.026), OR = 0.25 (95 % CI 0.08-0.85).
 Conclusions. The multifactorial factor logistic regression of the parental dissatisfaction with the quality of medical care for ARI children included 4 factors, including the number of cases of acute respiratory viral infections in a child per year, the number of pneumonias in a child during life, the number of visits to the GP, and to the PCH pediatrician per year. For every next RD-associated visit to the physician, the risk of dissatisfaction with the medical care quality significantly reduces. Positive previous experience of communication between parents and the GP leads to further satisfaction with the quality of medical care for RD children.

Clinical efficiency and safety of riamilovir under various dosage regimens for treatment of acute respiratory viral infections in adults

To evaluate the clinical efficacy and safety of antiviral drug riamilovir in patients with acute respiratory viral infections (ARVI) of non-coronavirus (SARS-CoV-2) etiology with different dosing regimens. The study included 150 patients with ARVI aged 18-27 years (50 patients received riamilovir in the regimen of 250 mg 3 times a day for 5 days, 50 patients received riamilovir in the off label regimen of 250 mg 5 times a day for 5 days, 50 patients received only pathogenetic treatment). The use of riamilovir in both treatment regimens led to a reduction in the duration of inpatient treatment. The shortest periods of hospitalization were noted in patients who received the study drug at higher daily dosages. The use of riamilovir reduced the duration and severity of general infectious manifestations of the disease, while the shortest total duration of fever and a number of respiratory tract syndromes was registered among people who received riamilovir in the regimen of 1250 mg per day for 5 days, no adverse events were registered, additionally, 100% elimination of ARVI pathogens was noted in 1250 mg per day group. Riamilovir has shown clinical efficacy and a good safety profile in in both treatment regimens. The dosage regimen of 1250 mg per day led to more significant clinical effects and to 100% elimination of ARVI pathogens in the study group by the 6th day of hospitalization.

Issues of designing new educational disciplines for training and advanced training of transport security forces

Methodological issues of pedagogical design of creative models of new programs are considered on the example of the construction of the educational program “Features of sanitary and epidemiological protection of passengers and personnel of railway transport and metro enterprises in the conditions of military threat and the spread of acute viral infection” and the program “Features of protection of metro transport infrastructure from acts of unlawful interference in the conditions of escalation of military conflicts and the emergence of epidemics”. for training and advanced training of the security forces transport security. The organizational and pedagogical conditions for the implementation of these models in educational institutions of additional professional education are described. It is shown that the creation of a creative model of a new program should be preceded by a longterm work on the selection and classifi cation of information carriers about the industry of relevant knowledge, technology and technology. The sequence of introduction to the specialty, the content component of lectures, seminars and practical classes, the volume of classroom classes and independent training are substantiated. The presented program models suggest the possibility of their subsequent expansion and deepening, as well as integrated use with existing programs. Attention is drawn to the need for early adoption of measures to restructure the educational process with a sharp aggravation of the military-political situation and in conditions of the spread of acute viral infection.

Comparative content analysis of biologically active substances in citrus peel

The analysis of the documents of the Ministry of Health of the Russian Federation shows that in 2021, there were 38.44 million cases of acute upper respiratory infections of multiple and unspecified localization, which accounted for 75.8% of all infectious and parasitic diseases. Researchers are interested in the creation of drugs for the treatment and prevention of acute respiratory viral infections using extracts and essential oils of plants with antiviral activity. Among the significant number of essential oil plants with potential antibacterial and antiviral effects, plants of the citrus family are of particular interest. The citrus fruits are widely used by the food industry, and the peel of the fruits is an industrial waste of food production. It is known that the peel of orange, tangerine, and lemon contains such valuable biologically active groups of substances as flavonoids, polyphenolic compounds, and essential oil, which allows considering this product as a potential source of novel medicines and preventive agents. The authors conducted a qualitative analysis of aqueous and aqueous-alcoholic extracts from citrus peel using a complex of pharmacopoeial qualitative reactions. The quantitative determination of the content of extractive substances extracted with 45% and 70% ethyl alcohol and water was carried out, and the quantitative content of essential oil, flavonoids, tannins, and ascorbic acid was established.

Can virophages be used for management of viral infections?

Virophages parasitizing giant viruses have been reported in the members of Kingdom Protista. Hyperparasites such as bacteriophages and predators have been used to control bacterial infections and insect pests, respectively. Presently, it is proposed to use the virophages for management of viral infections in humans and animals, especially in terminally ill patients with grave prognosis. It is hypothesised that the use of appropriate virophage will reduce the viral load and promote host cell survival. The testing of hypothesis involves in vitro and in vivo experiments after isolation of candidate virophages through a large scale screening of environmental and clinical samples. Critical challenges will be to identify suitable virophages-viruses pairs that could be associated with mammalian cells of medical and veterinary importance and assessment of their combined interactions with host. If suitably developed, virophage therapy opens new avenues for treatment of acute and slow viral infections, especially in cases where therapeutic managemental options are limited. However, there are major concerns regarding limited understanding of virophage biology, functions of several proteins coded in its genome, chances of integration with host genomes and its implications.

Differential kinetics of splenic CD169+ macrophage death is one underlying cause of virus infection fate regulation

Acute infection and chronic infection are the two most common fates of pathogenic virus infections. While several factors that contribute to these fates are described, the critical control points and the mechanisms that underlie infection fate regulation are incompletely understood. Using the acute and chronic lymphocytic choriomeningitis virus (LCMV) infection model of mice, we find that the early dynamic pattern of the IFN-I response is a differentiating trait between both infection fates. Acute-infected mice generate a 2-wave IFN-I response while chronic-infected mice generate only a 1-wave response. The underlying cause is a temporal difference in CD8 T cell-mediated killing of splenic marginal zone CD169+ macrophages. It occurs later in acute infection and thus enables CD169+ marginal zone macrophages to produce the 2nd IFN-I wave. This is required for subsequent immune events including induction of inflammatory macrophages, generation of effector CD8+ T cells and virus clearance. Importantly, these benefits come at a cost for the host in the form of spleen fibrosis. Due to an earlier marginal zone destruction, these ordered immune events are deregulated in chronic infection. Our findings demonstrate the critical importance of kinetically well-coordinated sequential immune events for acute infection control and highlights that it may come at a cost for the host organism.

A case of development of membranous nephropathy against the background of atypical hemolytic-uremic syndrome activated as a result of acute respiratory viral infection

The article considers a clinical case of atypical hemolytic-uremic syndrome, which was the starting mechanism for the development of membranous nephropathy. Patient X. 23 years after acute respiratory viral infection, signs of nephrotic syndrome, arterial hypertension, and impaired kidney function appeared. Puncture nephrobiopsy was performed and the morphological picture corresponds to immunocomplex glomerulonephritis, most likely membranous nephropathy with the presence of segmental glomerulosclerosis, cellular half-moons. In parallel, the patient had verified signs of thrombotic microangiopathy in the form of microangiopathic anemia, thrombocytopenia, increased lactate dehydrogenase levels as a sign of cytolysis (primarily intravascular hemolysis). During the differential diagnosis, we stopped at the diagnosis of atypical hemolytic-uremic syndrome. The uniqueness of the described clinical case is that cases of glomerulonephritis against the background of atypical hemolytic-uremic syndrome are extremely rare, and membranous nephropathy is described for the first time.

Application of Mathematical Models of the Dynamics of the Epidemic Acute Respiratory Viral Infections to Increase the Efficiency of Epidemiological Surveillance

Uncertainty in the calculations of forecasts of the spread of epidemic acute respiratory infections obtained using mathematical models, associated with data error and uncertainty in the choice of a model, as well as the lack of verification of modeling results by interdisciplinary teams including epidemiology specialists, prevent the correct prediction of the effectiveness of disease control measures. In this paper, we propose a solution to these problems by using a software package consisting of a family of epidemic models, methods for estimating the error of output data depending on the error of the initial morbidity data, as well as a graphical interface with the possibility of manual correction of the results of automatic calibration and generation of epidemic bulletins. The novelty of the presented study is the methodology for integrating epidemic models into software tools used by supervisory authorities, which allows to supplement weekly bulletins and annual epidemiological reports in semi-automatic mode with a quantitative interval estimation of the error of calculated indicators. The ultimate goal is to provide the supervisory authorities with informative and promptly obtained calculated data for decision-making in the field of infection control.

Lung dendritic-cell metabolism underlies susceptibility to viral infection in diabetes

People with diabetes feature a life-risking susceptibility to respiratory viral infection, including influenza and SARS-CoV-2 (ref. 1), whose mechanism remains unknown. In acquired and genetic mouse models of diabetes, induced with an acute pulmonary viral infection, we demonstrate that hyperglycaemia leads to impaired costimulatory molecule expression, antigen transport and T cell priming in distinct lung dendritic cell (DC) subsets, driving a defective antiviral adaptive immune response, delayed viral clearance and enhanced mortality. Mechanistically, hyperglycaemia induces an altered metabolic DC circuitry characterized by increased glucose-to-acetyl-CoA shunting and downstream histone acetylation, leading to global chromatin alterations. These, in turn, drive impaired expression of key DC effectors including central antigen presentation-related genes. Either glucose-lowering treatment or pharmacological modulation of histone acetylation rescues DC function and antiviral immunity. Collectively, we highlight a hyperglycaemia-driven metabolic-immune axis orchestrating DC dysfunction during pulmonary viral infection and identify metabolic checkpoints that may be therapeutically exploited in mitigating exacerbated disease in infected diabetics.

SHP-1 Regulates CD8+ T Cell Effector Function but Plays a Subtle Role with SHP-2 in T Cell Exhaustion Due to a Stage-Specific Nonredundant Functional Relay.

SHP-1 (Src homology region 2 domain-containing phosphatase 1) is a well-known negative regulator of T cells, whereas its close homolog SHP-2 is the long-recognized main signaling mediator of the PD-1 inhibitory pathway. However, recent studies have challenged the requirement of SHP-2 in PD-1 signaling, and follow-up studies further questioned the alternative idea that SHP-1 may replace SHP-2 in its absence. In this study, we systematically investigate the role of SHP-1 alone or jointly with SHP-2 in CD8+ T cells in a series of gene knockout mice. We show that although SHP-1 negatively regulates CD8+ T cell effector function during acute lymphocytic choriomeningitis virus (LCMV) infection, it is dispensable for CD8+ T cell exhaustion during chronic LCMV infection. Moreover, in contrast to the mortality of PD-1 knockout mice upon chronic LCMV infection, mice double deficient for SHP-1 and SHP-2 in CD8+ T cells survived without immunopathology. Importantly, CD8+ T cells lacking both phosphatases still differentiate into exhausted cells and respond to PD-1 blockade. Finally, we found that SHP-1 and SHP-2 suppressed effector CD8+ T cell expansion at the early and late stages, respectively, during chronic LCMV infection.

Epidemic manifestations of coronavirus infection caused by «omicron» genovariant in the Volgograd region

The article is devoted to an urgent problem the study of the epidemic manifestations of the new coronavirus infection COVID-19 during the fourth wave of the rise in the incidence, which began in January 2022 in the Volgograd region.
 Materials and methods: We used the official statistical data of the Office of Rospotrebnadzor for the Volgograd Region on the incidence of COVID-19 and the results of SARS-CoV-2 genomic RNA sequencing. The main research method is epidemiological analysis. We analyzed the period from the beginning of the next increase in the incidence, coinciding with the almost complete replacement of other variants of SARS-CoV-2 by omicron (since January 16, 2022), until the decrease and stabilization of the incidence rates on March 30, 2022. Comparison of the epidemiological process indicators was carried out with the period before the appearance of the omicron genovariant (as of December 30, 2021).
 Results and discussion: Since mid-January 2022, there has been a sharp rise in the incidence of COVID-19 in the region up to 2,222 cases per day by mid-February and a subsequent decrease in incidence rates by the end of March. It has been established that the next wave of coronavirus infection is associated both with an increase in interpersonal contacts on holidays and the subsequent introduction of the infection into work and educational teams, and with the change of the SARS-CoV-2 genovariant to omicron. During 2.5 months of the fourth wave, 76,717 people fell ill with coronavirus, which is 36.6 % of the total number of cases registered over the entire observation period. Moreover, the proportion of cases in the age category up to 18 years has significantly increased (by 13.1 %). During the analyzed period, the proportion of cases with a mild course increased by 18.3 % (up to 88.6 %), and the percentage of cases of moderate severity decreased by 10.1% (up to 10.5 %), a severe course decreased by 4.1% (to 0.7 %), asymptomatic also decreased by 4.06 % and accounted for 0.14 % of the total number of detected cases of COVID-19. The share of pneumonia in the total morbidity for 2.5 months decreased by 16.8 % (to 1.6 %). In most cases, the treatment took place on an outpatient basis. The percentage of patients requiring hospitalization decreased to 18.5 %. There is a downward trend in the mortality rate from 4.3 % before the rise in incidence to 3.2 % as of March 30, 2022.
 Conclusions: In the Volgograd region, from January 14, 2022, another rise in the incidence of COVID-19 was registered with the maximum indicators for the entire observation period in February. The omicron genovariant, which has become dominant, has a higher contagiousness and is actively spreading in childrens groups. The disease is characterized by a milder clinical course in the form of acute respiratory viral infections, bronchitis, and a decrease in the proportion of deaths.

The effectiveness of scientifically based monitoring programs and therapeutic and preventive measures for controlled infectious diseases of animals

The aim of the work was to assess the effectiveness of an improved monitoring program for controlled infectious animal diseases and individual vaccination programs for acute respiratory viral infection in cattle. To fulfill the tasks set, serological studies, PCR diagnostics, bacteriological and coprological methods of examining biological samples from animals were carried out. As a result of the work, the main factors influencing the effectiveness of vaccine prophylaxis of acute respiratory viral infection in cattle populations have been identified. It was found that in three administrative and administrative districts of the Sverdlovsk region, the main factors in 35.1% of cases are violations of the rules of vaccination of acute respiratory viral infection of cattle, in 13.5% of cases - violations of zoo-hygienic and veterinary–sanitary conditions of keeping farm animals. A comprehensive assessment of the effectiveness of individual vaccination programs for cattle against acute respiratory viral infection has been carried out, taking into account the epizootological situation in agricultural organizations. It was shown that vaccination of cattle against acute respiratory viral infection according to individual programs ensured the formation of specific immunity in 92.5-95.0% of animals. The number of immunotolerant individuals and animals with a low level of immunoreactivity in the physiological group of young cattle did not exceed 3.5%, in the physiological group of adult animals – 1.25%. The high efficiency of improved scientifically based programs for monitoring, diagnosis, therapeutic, preventive and health measures to protect animals from epizootically significant infectious diseases of cattle among the populations of farm animals of the Ural Federal District has been confirmed.

Chronic cough and refractory chronic cough: An important distinction

Cough is the most common concern for which patients in the United States seek medical attention. Cough is typically classified according to its duration: acute cough (<3 weeks), subacute cough (3‐8 weeks), and chronic cough (>8 weeks). The vast majority of cases of acute cough in patients are due to an acute viral upper respiratory tract infection (common cold) and are self limited. Subacute cough is often due to a prolonged postviral cough. Once a cough meets the definition of chronic, it becomes likely that the cough is due to one or more treatable underlying etiologies: upper airway cough syndrome (formerly, postnasal drip syndrome), asthma and non-asthmatic eosinophilic bronchitis, and gastroesophageal reflux disease. Refractory chronic cough (RCC) refers to chronic cough that persists despite adequate therapeutic trials aimed at the known causes of chronic cough. The term cough hypersensitivity syndrome has recently been introduced to stress the concept that RCC is a distinct disease entity due to vagal hyperactivity causing hypersensitivity of the cough reflex. No medications have ever been approved for chronic cough or RCC in the United States and most of the world. Thus, physicians are limited to the use of off-label medications for their patients with this chronic and often debilitating condition. However, recent insights into the mechanisms of cough have resulted in multiple molecules currently being evaluated as potential antitussives. Among these, furthest along in the drug development pipeline are the P2X3-antagonists, of which, gefapixant has completed phase III trials, and camlipixant is currently in phase III studies.