Novel coronavirus infection (COVID-19) is a highly contagious respiratory disease caused by the SARS-CoV-2 coronavirus. COVID-19 is known to affect both the respiratory, digestive, excretory, and nervous systems. The incidence of chronic effects of the novel coronavirus infection is now on the rise. This paper is aimed to review the epidemiology, pathogenesis and components of post-COVID asthenia. Material and methods. Sixty-three references published between 2005 and 2023 and indexed in the PubMed, CyberLeninka, Russian Citation Index, Semantic Scholar, and Google Scholar databases were included in this review. Results. The study revealed the most common symptoms of post-COVID asthenia are fatigue, muscle weakness, shortness of breath, sleep disturbances, anxiety or depression, impaired memory and cognitive functions (“foggy brain”), hyposmia, and reduced work performance. One of the specific symptom complexes for post-COVID is asthenovegetative syndrome, the incidence of which according to the meta-analysis ranged from 13.1 to 72.8 %, with a cumulative percentage of 45 ± 0.05 % (95 % confidence interval 0.31–0.54). Conclusions. Nowadays, post-COVID asthenia is becoming extremely severe. It is necessary to review in detail the available data on the epidemiology and components of post-COVID asthenia in order to develop an adequate strategy for post-COVID management.

Aim: to optimize outcomes of the treatment and prevention of gastrointestinal diseases in adults and children. Key points. The Methodological Guidelines contain sections on the terminology, classification, mechanisms of action, requirements for sale in the Russian Federation, requirements for proving the efficacy and safety of probiotics, prebiotics, synbiotics and metabiotics, as well as functional foods enriched with them. An overview of relevant data allowing to include these drugs and products in the treatment an d prevention of gastrointestinal diseases in adults and children is presented. Conclusion. The clinical efficacy of probiotics, prebiotics, synbiotics and metabiotics depends on the specificity and quantity of their components, the dosage form, the regimen and duration of treatment. Products and functional foods with proven efficacy and safety are recommended for the treatment and prevention of gastrointestinal diseases in adults and children.

Objective. To evaluate the effect of the Saccharomyces boulardii CNCM I-745 probiotic on the development of antibioticassociated syndrome (AAS) in children receiving systemic antibacterial therapy for respiratory tract infections. Patients and methods. We examined 80 children patients with community-acquired pneumonia aged 1 to 14 years, who received antibacterial therapy, including in combination with the Saccharomyces boulardii CNCM I-745 probiotic (38 patients). Gastrointestinal symptoms and stool characteristics according to the Bristol scale, the condition of the skin and open mucous membranes were assessed. Results. During antibacterial therapy, symptoms of AAS developed in 60% of the patients with pneumonia. Manifestations of AAS were recorded 2 times less often in children receiving «Enterol», than other children group without probiotic correction, p < 0.05. The most common manifestations of AAS were symptoms of gastrointestinal tract damage, and along with the classic manifestations – the appearance of loose, frequent stools, patients complained of abdominal pain, bloating, stool retention, up to constipation and the appearance of “sheep” stool. Exintestinal manifestations of AAS included the development of stomatitis in 23.7% of the examined groups, while in children receiving the probiotic, stomatitis developed less frequently – 7.9% versus 38.1% (p = 0.002). Moreover, 46.1% of girls receiving antibiotic therapy developed vulvovaginitis, but its frequency in the cohort of patients receiving probiotics was significantly lower – 16.7% vs 71.4% (p = 0.001). Conclusion. The use of the probiotic drug «Enterol» containing Saccharomyces boulardii CNCM I-745 in children receiving broad-spectrum antibacterial drugs prevented the development and accelerated the regression of clinical manifestations of AAS. Key words: antibiotics, antibiotic-associated diarrhea, community-acquired pneumonia, children, microbiota, probiotics, Saccharomyces boulardii CNCM I-745, enterol

The results of numerous randomized clinical trials indicate the relationship of a new coronavirus infection (NCI) with the development of acute myocardial injury (AMI). Of great importance in the defeat of the heart belongs to the change in the cytokine and chemokine status, which determines the inflammatory potential. The aim of this work was a comprehensive assessment of clinical and laboratory indicators of the state of the heart in a new coronavirus infection and the determination of immunopathogenetic mechanisms of myocardial damage. 180 patients hospitalized with a diagnosis of «coronavirus infection COVID-19, virus identified (U07.1), moderate form» were examined. Risk factors, levels of cytokines and chemokines (IFN-α, IL-6, IL-17, MIP-1b), markers of cardiac damage/dysfunction (troponin I and FAFA, NTproBNP), and antimyocardial IgG antibodies were assessed. Statistical processing was carried out using the Microsoft Office package (Microsoft Excel), as well as the statistical package STATISTICA 9.0. The Shapiro-Wilk W test was used to check the normality of the distribution. Differences were considered significant at p ≤ 0.05, unreliable at p ≥ 0.05. It has been established that in the acute period, 45% of patients have an increase in troponin I values. They also have significantly higher levels of IL-6, IL-17 and MIP-1b against the background of inhibition of IFN-α production. In the acute period, a third of patients have antimyocardial antibodies, which are detected significantly more often and in higher titers in patients with AMI. The presence of a direct correlation between the level of antimyocardial antibodies and an increase in the amount of CRP, MIP-1b and IL-17 was established. The most significant risk factors for the development of myocardial damage in NCI are the presence of a burdened history of cardiovascular diseases, an increased body mass index, and diabetes mellitus. Thus, high levels of CRP, MIP-1b IL-17, antimyocardial antibodies, with a continuing deficiency without a tendency to restore the level of IFN-α, in the presence of the above risk factors, are diagnostically significant markers of AMI in patients with moderate NCI.

Issues of nephrological complications of the acute period of acute intestinal infections (AII) are currently concentrated mainly on the problem of critical conditions associated with the development of hemolytic-uremic syndrome (HUS). Taking into account the introduction into clinical practice of new highly specific biological markers of acute kidney injury (AKI), which make it possible to diagnose this condition before the development of uremia, new prospects for the early diagnosis of AKI are opening up, which will allow timely modification of treatment tactics that prevent its progression to chronic kidney disease and reduce disability in patients, which is important at the present stage of development of pediatrics and infectious diseases. Objective. To assess the prevalence of AKI in children with moderate AII without the formation of HUS, as well as to asses the diagnostic significance of modern biological markers of kidney damage. Patients and methods. 270 patients aged 1 to 7 years with moderate AII without the development of HUS (study group), as well as 55 somatic healthy children (comparison group) were examined. Over time, standard laboratory and instrumental studies were carried out, assessment of the levels of biomarkers of structural kidney damage (lipocalin-2, cystatin C, acute kidney injury molecules-1 (KIM-1)), as well as calculation of glomerular filtration rate using various formulas. Results. It was found that upon admission, 38% of children in the main group had reduced diuresis, 13% had an increase in serum creatinine levels, while the urea level was increased in only 3% of children. When assessing the level of AKI markers in patients with AII upon admission, an increase in the level of KIM-1 in the urine was detected in 90% of patients, cystatin C and lipocalin-2 in the blood serum in 18.9% of patients. A comprehensive assessment of identified renal dysfunction (based on decreased diuresis, increased serum creatinine, decreased glomerular filtration rate) in AEI without the development of HUS made it possible to diagnose the development of AKI in 13.7%, predominantly (in 97.3% of cases) – 1th stage according to KDIGO. Among the factors of unfavorable premorbid background in children of the main group who developed AKI, anemia (in 62.2% of patients) suffered during the last 6 months was significantly more common. AII (51.4%) and SARS (51.4%) (p < 0.001). Conclusion. With moderate AII in children, the development of AKI is registered in 13.7% of cases. Clinical factors associated with the development of AKI are: febrile fever lasting 4–6 days, degree II exacerbation, repeated vomiting lasting more than 3 days, diarrhea lasting 5–8 days, and the predominance of viral etiology of the disease. In order to optimize the diagnosis of AKI in children with AII, it is advisable to include in the examination plan the determination of the level of cystatin C and lipocalin-2 in the blood serum, which have a significantly higher sensitivity (94.6 and 97.3%) and specificity (84.5 and 85.8% respectively) compared to creatinine levels. Key words: children, acute intestinal infection, acute kidney injury, cystatin C, lipocalin-2, NGAL, KIM-1

Reducing the risk of acute respiratory infections (ARIs) through vitamin D administration is a common preventive strategy used in routine clinical practice. However, the results of clinical trials are often controversial, which makes it necessary to summarize data available so far in order to develop more clear and well-founded clinical guidelines. Materials and methods. This meta-analysis was conducted to summarize the evidence on the preventive efficacy of vitamin D3 (cholecalciferol) against ARIs among adults using the results of randomized clinical trials (RCTs). The primary endpoint in all included studies was the absolute proportion of participants diagnosed with at least one ARI episode (upper/lower respiratory tract infections or infections of mixed locations) during the follow-up period. Results. We found that vitamin D3 intake (n = 11,276) was effective for preventing ARIs vs placebo (n = 10,955): in a random effects model, the odds ratio (OR) was 0.82 (95% confidence interval (CI): 0.69–0.98; p = 0.0355), whereas the number needed to treat (NNT) was 20.43 (between 10.70 and 255.67). There were no differences in efficacy between daily, weekly, or monthly intake of vitamin D3 (p = 0.7884). Given that 7 out of 13 studies included in this meta-analysis analyzed daily vitamin D3 intake and only 1 study assessed weekly intake, we can conclude that daily dosing, in general, has a broader evidence base. Conclusion. Thus, daily intake of D3 at a dose of ≥ 2000 IU/day (NNT = 20.43) was the most effective and studied strategy for preventing ARIs among adults. Key words: acute respiratory viral infections, influenza, COVID-19, nonspecific prevention, vitamin D3, colecalciferol

The new coronavirus infection has been the leading public health problem in all countries for the past two years, causing enormous social and economic damage. The pathogenesis of COVID-19 infection continues to be studied, where the role of microflora of the respiratory and gastrointestinal tract (GIT) is considered to be important. The “intestine - lungs” functional axis, which ensures the interaction of the microbial communities of the respiratory tract and GIT, plays an important role in the immunopathogenesis of the COVID-19 infection, the development of inflammatory reaction in lung tissue and its subsequent restoration, as well as the formation of secondary bacterial complications. The intestinal infection with SARS-CoV-2 virus causes significant changes in the diversity and functional activity of intestine microbiota affecting negatively on the immune response patterns and maintenance of the colonization resistance of the mucous membranes. Summarizing the presented data of scientific publications on the problem of microbiome changes with the new coronavirus infection and the role of the “intestine - lungs” functional axis, the search for the modulation of the intestinal/respiratory microbiome seems promising with the purpose of not only preventing the progression of the disease, but also reducing of the duration of the disease and the severity of the symptoms of lung and GIT injury, as well as post-COVID symptoms prevention.

With the ongoing pandemic of the SARS-CoV-2 virus and the emergence of its new genovariants, along with the relevance of addressing the issue of vaccination of the population, the importance of non-specific prophylaxis, which is designed to reduce the viral load on the body and slow down the rate of virus spread, is increasing. The currently available research and experience in the use of antiseptic drugs or their combinations with the antimicrobial peptide lysozyme can be used for this purpose.Currently available research and experience in the use of antiseptic drugs or their combinations with the antimicrobial peptide lysozyme can be used for this purpose. Under conditions of lysozyme deficiency unhindered accumulation of non-hydrolyzed substrate, which is a constant source of autoantigens, is accompanied by immunity, metabolic and tissue homeostasis disorders. Analysis of a comparative study of different groups of antiseptics showed high virulicidal efficacy of cetylpyridinium chlorideCetylpyridinium chloride has an electrostatic effect on viral membrane lipids, causing their aggregation and dissolution, which leads to disruption of the integrity of the virus membrane, its interaction with mucosal epithelial cells and penetration into target cells, having a direct virulicide effect on SARS-CoV-2. An important factor of innate mucosal immunity is lysozyme, it has antiviral, antibacterial, antifungal and anti-inflammatory effects, normalizes microbiocenosis, restores immune system activity, increases mucosal barrier function. The combination of cetylpyridinium chloride and lysozyme hydrochloride has a dual antiviral effect, reducing the viral load on the body and enhancing the ability to control the spread of SARS-CoV-2 both from patients in the prodromal period of the disease or with its clinical manifestations, and from asymptomatic carriers with confirmed COVID-19 infection status.

On November 10, 2021, an online meeting of the expert council was held on the conference platform of the First Medical Channel. The subject was “Diarrhea differential diagnosis depending on its pathogenesis in pediatric practice, the role of probiotic medications in its treatment”. Leading Russian experts in the field of clinical pharmacology, gastroenterology, pediatrics, infectious diseases, and allergology-immunology took part in this meeting. As a result of the meeting, the main principles of diagnosis, treatment, and prevention of diarrhea in children were formulated, and an algorithm for using probiotics to treat diarrhea in children was developed. Conclusion. It is preferable to prescribe medicinal probiotics (with registration status) than a dietary supplement containing probiotic bacteria. Medicinal products containing a combination of strains of Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp. lactis BB-12, vitamins B1 and B6, which are approved for use in pediatric practice, are recommended for administration in diarrhea and in suspected antibiotic-associated diarrhea in children, regardless of etiology and pathogenesis, both during the acute period and the next 4 weeks as well as during the entire recovery period (the period of repair and convalescence). Key words: antibiotics, children, diarrhea, treatment, prophylaxis, strain-specific probiotics, Lactobacillus rhamnosus GG, Bifidobacterium animalis subsp. lactis BB-12

The appearance of new high-tech microbiological research methods has significantly changed the understanding of the human microbiome. The purpose of the meeting of the Council of Experts "Dysbiosis. The immediate and long-term consequences of microbiome disorders and options for their correction with probiotics" was the definition of modern positions about possible methods of studying the intestinal microbiome, the possibilities of correcting dysbiosis, the use of Saccharomyces Boulardii CNCM I-745 to correct microbiome disorders in various clinical situations. The microbiota of the large intestine is represented by more than 1000 species of 7 different phyla of the Bacteriae domain, up to 160 numerically prevailing species are detected in one individual. The criteria of the microbiological "norm" for the intestinal microbiome have not been definitively established. To study the microbiome, a set of methods is used that combine cultural and molecular genetic methods that complement each other. Currently, none of the methods is widely available in clinical practice. To study the functional state of the intestinal microbiota, the most accessible is breath testing. Currently, there are no clinical markers of dysbiosis, and laboratory markers of dysbiosis require modification. There is an insignificant spectrum of diseases with such markers: acute intestinal infections, antibiotic-associated C. difficile-diarrhea, IBD, IBS. Probiotics can provide restoration of the intestinal microbiota. The effectiveness and safety of the use of S. boulardii CNCM I-745 for this purpose has been proven. In the case of acute intestinal infection, antibiotic-associated diarrhea, and the consequences of HP infection eradication, studies have a high level of evidence, and the use of Sb CNCM I-745 for treating IBS and IBD in children is promising.

Influenza is an acute respiratory infection, mainly affecting the respiratory tract (often the trachea), with a tendency to develop symptoms rapidly and in most cases not requiring hospitalization. All acute respiratory infections are non-specific, with symptoms of intoxication, catarrhal symptoms (nasal congestion, rhinorrhoea, sore throat or pharyngeal discomfort), fever and cough. Improvement and widespread implementation of molecular methods to identify respiratory pathogens has led to the establishment of a higher frequency of co-infections. A literature review of the frequency of influenza co-infections is presented. Clinical cases of monoinfluenza and co-infections of influenza and respiratory syncytial infection are described, demonstrating the antagonistic effect of the two viruses on the course of the disease. In the first case, the patient, 1 year 1 month old, was hospitalised with a fever of 39 ºC in a moderate condition. A nasopharyngeal swab showed RNA of influenza A virus by PCR and was diagnosed with influenza. In the second case, the patient, 2 years old, at the beginning of the disease complained of an increase in body temperature to 38.7 ºC, cough, and difficulty in nasal breathing. On admission, the patient was in moderate condition with a body temperature of 36.6 ºC, clear consciousness and well-being. On auscultation, breathing in the lungs was rigid, single moist rales, scattered on both sides. A nasopharyngeal swab showed RNA of influenza A virus and respiratory syncytial virus by PCR. A viral acute respiratory infection of combined etiology and acute bronchitis was diagnosed. In the third case, a 14-year-old patient presented with complaints of fever up to 39 ºC, headache, weakness, muscle pain, dry cough. The condition was of moderate severity. The diagnosis of influenza A was confirmed by a rapid test for influenza A/B/C. In the treatment and prevention of both monoinfection and co-infections of influenza and other viruses, these clinical examples demonstrate the effectiveness of oseltamivir. These clinical examples highlight some key parameters: respiratory co-infections change the typical clinical picture of the disease, making it difficult to clinically diagnose the infection, highlighting laboratory diagnosis, which in turn facilitates rapid verification of the diagnosis and timely prescription of adequate therapy.

The enormous impact of SARS-CoV-2 infection and the insufficiency or lack of established and evidence-based therapeutic measures give rise to fundamental and clinical studies to examine the mechanisms of penetration of the virus into the human body and its subsequent effects on the body. The uniqueness of the pathogenesis of the infection caused by SARS-CoV-2 is primarily due the virus tropism to the receptors angiotensin-converting enzyme type 2 (ACE2), which are on the surface of various cells: pneumocytes, epithelials of the esophagus and intestines, cardiomyocytes, endotheal capillaries, urinary and nervous system, as well as in other organs. It is assumed that the suppression of ACE2, induced by penetration of SARS-CoV-2 into cells, may be particularly harmful for subjects with pre-existing ACE2 deficiency. These considerations provide justification for the study of the role of therapeutic approaches conceptually associated with the activity of the ACE2 receptor.

The article presents general information about etiology, epidemiology, pathogenesis and clinical manifestations infections COVID-19. The features and factors affecting the prevalence of COVID-19 in European countries and in the Russian Federation are given. Mechanisms consideredinvasions of SARSCoV-2 and specific clinical manifestations of COVID-19 encountered in dental practice. Provides supporting facts about three different ways of spreading COVID-19 in dental practice, as well as data that allow making a conclusion and the possibility of infection through other routes. The features of the diagnosis of COVID-19 in dental practice, namely the factors that allow diagnostics in the early stages of the disease, are considered. Conclusions are drawn on the preventionand prospects of studying the spread of COVID-19 in dental

Acute respiratory infections are one of the most common infections in children worldwide. The implementation of novel highly accurate diagnostic methods demonstrated that a significant proportion of respiratory tract infections are caused by more than one pathogen (virus plus virus or virus plus bacterium). Most frequently, mixed infections are observed in young children, which, in addition to non-specificity of most clinical manifestations, necessitates pathogen identification in order to prevent inadequate use of antibiotics. Key words: respiratory infections, children, respiratory pathogen

This paper discusses the spread of the most common causative agents for respiratory viral infections, i.e., respiratory syncytial virus (RSV) and influenza virus (IV), during seasonal peaks and under the COVID-19 pandemic. The COVID-19 pandemic and epidemic control measures reduced the transmission of some respiratory viral pathogens. The authors specify the risks of changes in RSV epidemiology associated with restrictions and their lifting. Possible scenarios of virus "behavior" in 2021–2022 are represented. These scenarios include the return of variants registered at the end of 2019 and the risk of the emergence of a novel strain of zoonotic flu that may result in a novel viral pandemic. It was demonstrated that effective monitoring of causative agent circulation, timely specific prophylaxis (particularly in high-risk groups), and early effective antiviral therapy are crucial irrespective of the possible scenario of respiratory viral infection. Modern principles of complex flu and acute respiratory viral infection treatment using an antiviral agent based on rimantadine and sodium alginate are addressed. KEYWORDS: flu, COVID-19, pandemic, respiratory syncytial infection, children, treatment, rimantadine, sodium alginate. FOR CITATION: Usenko D.V., Tkhakushinova N.Kh., Shaturina T.T. et al. Acute respiratory infections and flu during the COVID-19 pandemic. What to expect in 2021–2022? Russian Medical Inquiry. 2021;5(11):721–727 (in Russ.). DOI: 10.32364/2587-6821-2021- 5-11-721-727.

In recent years, significant breakthroughs have been made in the study of etiology, pathogenesis, and the development of accessible diagnostic methods, as well as in the treatment of acute intestinal infections, resulting in a significantly lower frequency of their severe course and adverse outcomes and in reducing the frequency and duration of hospitalization. At the same time, the emergence of modern biochemical markers of injury of different organs and systems makes it possible to investigate new pathological conditions that were previously detected in the stage of clinical manifestations. These include the problem of early diagnosis of acute kidney injury in children, the frequency and timing of which have not yet been studied. Objective. Comparative evaluation of the diagnostic value of glomerular filtration rate and serum cystatin C levels for early diagnosis of kidney failure in children with acute intestinal infections (AII). Patients and methods. This study included 80 children with acute intestinal infection who were hospitalized in G.N.Speransky Children’s Clinical Hospital No 9. In all cases the course of disease was moderate-to-severe without developing hemolyticuremic syndrome. To assess kidney function in the acute period of intestinal infection, we studied glomerular filtration rate (GFR) by the “bedside” Schwartz equation, as well as serum cystatin C levels. Results. In the acute period of AII in children under 3 years of age, GFR was 98.56 ± 2.84 mL/min/1.73 m2 according to the “bedside” Schwartz equation of 2009. In the group of children over 3–7 years of age, these values were 108.85 ± 3.84 mL/min/1.73 m2, differences are statistically significant (p < 0.001). High (>950 ng/mL) serum cystatin C levels were found in 22% of patients. In other patients, cystatin C levels remained within or below the normal range. The analysis showed that 10% of children in the age group of 1–3 years and 2.5% of children in the age group of 3–7 years were at risk of developing acute kidney injury in AII, according to the GFR estimation based on the Schwartz “bedside” equation and cystatin C-based equation. When assessing the risk of developing acute kidney injury according to the GFR estimation using the cystatin C-based equation, the proportion of such patients in the age group of 1–3 years was 20% and in the age group of 3–7 years – 22%, and when assessing GFR according to the Schwartz “bedside” equation only, the proportion of children was 7.5% and 7.5%, respectively. Conclusion. Determination of cystatin C levels in children in the early period of acute intestinal infections of moderate severity is an earlier and more accurate marker of acute kidney injury, regardless of age and sex of patients, in comparison with the evaluation of glomerular filtration rate. Inclusion of cystatin C in laboratory test plan allows timely identification of patients who are in the risk group of developing acute kidney injury. Key words: children, kidney failure, acute intestinal infection, acute kidney injury, cystatin C, glomerular filtration rate

Acute respiratory infections hold the leading position in the structure of infectious pathology in children and are one of the main reasons for visits to the doctor. Most often causative agents of acute respiratory infections are viruses. In recent years, respiratory infections of combined etiology are becoming an increasingly significant problem, the proportion of which is increasing. In co-infections, clinical diagnosis is difficult, which once again emphasizes the importance of the widespread introduction of highly sensitive etiological diagnostic methods, in particular polymerase chain reaction. Data on the tendency to a more severe course of co-infections compared to mono-infections are ambiguous, which seems to depend on the specific causative agent and the level of viral load. Another urgent problem of acute respiratory infections in children is the frequent registration of concomitant respiratory viral and herpes virus infections. The clinical picture of acute respiratory tract infections is not very diverse: fever, intoxication symptoms, cough, nasal congestion, rhinorrhea, sore throat, etc. At the same time, pathognomonic symptoms can be identified in some monoinfections, but in coinfections such clinical diagnosis is difficult, suggesting the importance of etiological diagnosis, especially polymerase chain reaction (PCR). All of the above, as well as age and clinical manifestations largely determine the rational selection of antiviral therapy simultaneously effective against both respiratory viruses and herpes viruses. One such drug is Cycloferon, which has not only a broad antiviral spectrum, but also a high level of safety. Inclusion of an interferon inducer in the treatment of acute respiratory infections will reduce the need to prescribe other drugs, including antibiotics, and reduce the medication load on the body.