Objective. To analyze the results of treatment of patients with chronic hepatitis D (CHD) in Krasnodar Krai in the conditions of real practice using bulevirtide, an HBV/HDV entry inhibitor. Patients and methods. Interim treatment outcomes were studied in 11 patients with CHD, predominantly at the cirrhotic stage (82%), with the presence of portal hypertension (55%), liver failure (n = 3), and hepatocellular carcinoma (n = 2, detected during treatment). Patients received bulevirtide as monotherapy (n = 7) or in combination with peginterferon (n = 4); evaluation periods ranged from 24–96 weeks of treatment. Results. All patients with known baseline HDV RNA level (n = 5) achieved virologic response, HDV RNA level reduction was -1.8 and -5.5 log10 after 24 and 96 weeks of monotherapy, -2.0–4.9 log10 after 24–72 weeks of combined therapy, with aviremia in 1 patient. In patients with unknown baseline HDV RNA level (n = 6) its dynamics during treatment corresponded to virologic response in 4 patients (decrease from -1.5 to -4.0 log10 in the period from 12/24/48 to 72 weeks of monotherapy, with aviremia in 1 patient). Efficacy improved as treatment continued to 72–96 weeks in 5 of 7 patients (4 received monotherapy, 1 received combination therapy). The overall virologic response rate was 82%, aviremia 18%, and biochemical response (ALT level reduction/normalization) 55%/45%, respectively. All patients with liver dysfunction (n = 3) showed virological and biochemical response, including aviremia and ALT normalization (1 and 2 patients, respectively). Treatment was characterized by good tolerability, absence of severe and serious adverse reactions, cases of treatment withdrawal, stability of liver function indices, including cirrhosis with dysfunction. In 1 patient after hepatectomy for HCC there was a temporary deterioration of liver function with the transition of class A to class B according to Child-Pugh, unrelated to treatment. Conclusion. Interim results of HDV treatment in real practice have demonstrated efficacy, safety and good tolerability of bulevirtide in monotherapy or combination therapy, including in patients with liver dysfunction. Further development of an optimal treatment algorithm is necessary, taking into account the results of ongoing studies, in order to improve patient prognosis and achieve cure of HDV infection. Key words: bulevirtide, hepatocellular carcinoma, decompensated cirrhosis, monotherapy, combination therapy, chronic hepatitis D, liver cirrhosis

The olfactory dysfunction is one of the clinical manifestations of coronavirus infection. Unlike a decrease in the sense of smell, which can be observed with mucosal edema in influenza and other acute respiratory infections, with coronavirus infection, there is often a complete shutdown of the sense of smell – anosmia. This condition can be observed in patients not only in the acute period of infection, but also persist for a long time during the period of convalescence, which significantly reduces the quality of life of such patients. The presented clinical analysis shows, using examples from clinical practice, various variants of the influence of olfactory dysfunction disorders on the quality of life of patients and emphasizes the importance of the problem for the healthcare provider. Key words: coronavirus infection, anosmia, parosmia

Objective. To analyze the results of usage of pangenotype combination glecaprevir/pibrentasvir (GLE/PIB) in real clinical practice in Stavropol Krai within the framework of the regional program on chronic hepatitis C (CHC) treatment. Materials and methods. In the framework of this study, a retrospective analysis of the use of GLE/PIB combination in the period from 2018 to 2022 within the framework of the regional program for the treatment of CHC in the Stavropol region was carried out. The drug was prescribed in accordance with the current label approved in Russia. Patients were observed during the entire period of GLE/PIB therapy and for 12 weeks after treatment completion. Data for analysis were collected from outpatient records and protocols of the “Regional Medical Commission on Diagnosis, Treatment and Drug Supply of Patients with Chronic Viral Hepatitis B and C in Stavropol Krai”. Results. The analysis included 405 patients treated within the framework of the regional program on drug supply of patients with chronic viral hepatitis B and C in the territory of the Stavropol region. The scope of the examination allowed to assess the sustained virologic response 12 weeks after the end of GLE/PIB therapy (SVR12). 92.6% (375/405) of patients had not previously received antiviral therapy. Absence or minimal manifestations of hepatic fibrosis (F0-1) were noted in 50.9% of patients, advanced stage of fibrosis (F3-4 by METAVIR scale) in 34.6%. The distribution by fibrosis stage was as follows: F0 – 21.98% (89/405), F1 – 28.9% (117/405), F2 – 14.6% (59/405), F3 – 13.1% (53/405), F4 (CP-A) – 21.5% (87/405). All patients with liver cirrhosis had compensated stage of the disease – class A according to Child-Pugh. In the study population, genotype (Gt) 3 prevailed, detected in 55.1% (223/405) of patients. Hepatitis C virus (HCV) Gt1 was diagnosed in 29.4% (119/405) of patients. Among them, 16.5% (67/405) of patients had Gt1b, 0.5% (2/405) had Gt1a, and 12.3% (50/405) of patients with Gt1 had no subtype identified. Gt2 was detected in 11.4% of patients (46/405), 3 (0.7%) patients had a genotype other than 1–3, and 14 (3.5%) patients had no HCV genotype determined. 14 (3.6%, 14/405) patients were co-infected with HCV and HIV. 23.5% (95/405) of patients belonged to the age group older than 60 years. The distribution of patients according to the duration of antiviral therapy was as follows: 8 weeks – 89.4% (362/405), 12 weeks – 6.4% (26/405) and 16 weeks – 4,2% (17/405). 405 (100,0%) out of 405 patients achieved SVR12. There were no cases of serious adverse events and treatment withdrawal during antiviral therapy. Conclusion. GLE/PIB has demonstrated high efficacy in patients with different HCV genotypes (including Gt3) and different stages of liver fibrosis (including compensated cirrhosis) in the real-world setting. The SVR12 rate obtained in this analysis is fully consistent with the data of clinical trials and real clinical practice published earlier. Key words: chronic hepatitis C, glecaprevir/pibrentasvir, pangenotypic, real clinical practice

The review presents the features of immunopathogenesis in a new coronavirus infection (COVID-19) and the possibility of correcting the state of the immune system of the patients with the help of a modern domestic synthetic immunomodulator azoximer bromide (Polyoxidonium®). The results of large-scale studies with the inclusion of the drug in the schemes of complex pathogenetic treatment of COVID-19 and immunorehabilitation in post-COVID-19 syndrome (PCS), as well as the possibility of its use for the prevention of acute respiratory infections and COVID-19 in persons with a high risk of infection are considered. High efficacy and safety of azoximer bromide in normalization of the condition in patients, even with severe complicated forms requiring hospitalization in intensive care units (ICU), in reducing the incidence of complications, acute symptoms in post-COVID-19 syndrome, as well as preventing the spread of SARS-CoV-2 virus in the population and the development of symptoms of a new coronavirus infection during prophylactic administration of the drug have been shown. Key words: COVID-19 immunopathogenesis, COVID-19 immunocorrection, azoximer bromide (Polyoxidonium®)

The article presents the experience of using riamilovir in the treatment of a case of severe dengue fever. It describes a case of severe form of dengue fever in a tourist who returned from Thailand and was hospitalized in the State Budgetary Institution Infectious Clinical Hospital No 2 in Moscow and the successful use of off-label nucleoside analogue riamilovir to treat the patient. A patient with dengue fever confirmed by detection of IgM to dengue virus (DV) and DV RNA in serum had widespread petechial rash and profuse uterine bleeding on the 5th day of the disease, and developed thrombocytopenia up to 70·109 cells/liter. A second DV infection was suspected. On the same day, serum examination revealed high titer IgG to DV, and DV genotyping was performed (virus genotype I was detected). The patient's condition was considered as repeated DV infection, development of severe form of infection. Based on the data on the successful use of the nucleoside analog riamilovir for the treatment of classical dengue fever by Russian specialists in the Republic of Guinea, a council of specialists at the medical board decided to use the “off-label” drug to treat the patient. Within a day after the start of therapy, the symptoms of the disease began to regress and on the 10th day of the disease the patient was discharged from the hospital in satisfactory condition. The obtained positive experience of using the nucleoside analog Riamilovir in real clinical practice in the treatment of a patient with severe form of dengue fever opens new opportunities for the treatment of this infection. Full-scale clinical trials of this drug are needed to evaluate the possibility of including a new indication for use. Key words: Dengue fever, severe form, Riamilovir, antiviral therapy, vector-borne viral infections

Meningococcal infection is an actual problem for modern healthcare. Currently, there is an increase in cases of meningococcal infection in our country. The true incidence of rare forms remains unknown, since nosology data are extremely rarely diagnosed. The non-specificity of symptoms, the lack of alertness of clinicians and the need for complex diagnostic methods create prerequisites for making an incorrect diagnosis and can contribute to the epidemic spread of infection. This article presents the main features of the pathogenesis, clinical symptoms and diagnosis of one of the rare forms of meningococcal infection, meningococcal pneumonia, and raises questions about the updating of algorithms for the diagnosis and treatment of this nosology. Key words: menningococcal infection, meningococcal pneumonia, rare forms

Objective. To study the role of the main marker of endothelial dysfunction VEGF-A as a possible predictor of severe COVID-19 formation. Patients and methods. On the basis of the clinic of the Republican Specialized Scientific and Practical Medical Center of Epidemiology, Microbiology, Infectious and Parasitic Diseases (RSSPMCEMIPD) and Samarkand Regional Specialized Medical Center, 210 patients with coronavirus infection were examined during 2020–2022. Patients were divided into 2 groups comparable by main characteristics: I consisted of 98 (47%) patients with a moderate form of COVID-19, II – 112 (53%) with a severe form of the disease. All patients were fully examined at admission to the hospital and at discharge from it. The level of medium molecular peptides (MMP) in blood plasma was determined by the method of N.I.Gabrielyan on spectrophotometer SF-46 in ultraviolet spectrum; the levels of vascular endothelial growth factor (VEGF-A) – in 163 patients – and interleukins 1 and 6 (IL-1, IL-6) in blood serum – by enzyme immunoassay (test systems of Cytokin LLC and Vector-Best JSC). The level of C-reactive protein (CRP) was determined using the immunoenzyme analyzer "MINDRAY MR-96A"; procalcitonin and D-dimer values were determined using an automatic ELISA analyzer mini-VIDAS. The obtained results were processed by methods of descriptive and variation statistics. Differences were considered reliable at (p < 0.05). Results. The clinical picture of COVID-19 complicated by pneumonia was characterized by pronounced symptoms of intoxication, respiratory tract damage, respiratory failure. In group II patients, such comorbidities as ischemic heart disease (23.5 vs. 41.1%), arterial hypertension (9.2 vs. 25.4%), and diabetes mellitus (2.0 vs. 12.5%) were recorded significantly more often. In 119 (56.7%) cases (mostly in the group with severe coronavirus infection), there was a combination of several comorbidities. In 36 (17.1%) patients with elevated blood sugar level before hospitalization for COVID-19 neither clinical nor laboratory signs of diabetes ellitus were present; in group II stable elevated blood sugar level against the background of therapy of the main disease was recorded 2 times more often (23.2 vs. 10.2%, respectively). In the same group, the level of CPR was 1.5 times higher. A significant correlation (p < 0.05) of elevated levels of CRP and D-dimer with the severity of COVID-19 course was established. In 163 patients the mean values of VEGF-A on admission were elevated; in patients from group II this index was significantly (p < 0.01) higher: 303.02 ± 21.47 vs. 390.52 ± 29.05 pg/mL. At discharge, this index increased to 466.56 ± 37.59 pg/mL in group II patients and decreased to 237.60 ± 17.03 pg/mL in group I patients (differences were significant; p < 0.01). In group I, this index returned to normal after 1 month, and in group II, it decreased to 205.05 ± 15.90 pg/mL only 2 months after discharge. A reliable correlation (p < 0.05) of elevated levels of D-dimer, CRP, MMP with high VEGF-A levels, as well as with the severity of the disease and increasing respiratory failure was established. Positive results of bacteriologic study of upper respiratory tract secretions were found in 63 (64.3%) patients of group I and in 78 (69.6%) patients of group II; Staphylococcus aureus predominated in patients from group II (11.1 vs. 38.5%) and Candida spp (85.7 vs. 28.2%) from group I. Conclusion. The relationship between blood levels of VEGF-A and standard inflammatory markers allows us to propose this factor of endothelial dysfunction as a predictor of inflammation and disease progression, as well as to use it to assess the efficacy of therapy. Key words: bacterial pneumonia, novel coronavirus infection, procalcitonin, C-reactive protein, vascular endothelial growth factor, endothelial dysfunction

Objective. Analysis of the course and outcomes of listeria meningoencephalitis (LME) in patients in the postcovid period. Patients and methods. A retrospective study of 29 patients with listeria meningoencephalitis (LME), who were observed in hospitals in Moscow in the period 2020-2022, was conducted. 17 men (mean age M ± SD 57.8 ± 6.9 years) and 12 women (mean age 42.3 ± 4.7 years) were observed. During the examination of cerebrospinal fluid by polymerase chain reaction (PCR), the DNA of Listeria monocytogenes was detected in all patients. Of particular interest were the medical histories of 9 patients (31%) who had a history of severe COVID-19 during 1 month before LME with the use biological therapy in combination with GCS, average age 46.1 ± 4.3 years. Results. Risk factors such as viral infections, autoimmune diseases, and cancer contribute to the early development of LME. Due to the polymorphism of clinical manifestations in half (55.5%) of patients, LME was not suspected at the initial medical treatment. Diagnosis of LME in the postcovid period presents certain difficulties due to the lack of specific clinical manifestations, and symptoms can be considered LONG-term as LONG-COVID. Upon admission, 78% of LME patients had elevated blood levels of C-reactive protein 36-116 mg/l and fibrinogen 4.6–20.3 g/l. In the cerebrospinal fluid in admission: pleocytosis 760 ± 128 cl/μl, protein 1.2 ± 0.6 g/l, glucose 1.1 ± 0.2 mmol/L, lactate 8.9 ± 1.0 mmol/L. The fatal outcome was recorded in 10 (34.5%) patients with LME on the 9th–51st (on average, 18.25 ± 5.1) days of treatment. The causes of death were late hospitalization, swelling in the brain, subarachnoid hemorrhage, purulent ventriculitis. Conclusion. The lack of alertness towards listeriosis in young patients with neurological symptoms and who had severe COVID-19 with the treating of immunosuppressive and GCS against the background of a decrease in the immune response due to exposure to SARS-CoV-2 leads to late diagnosis of neurolisteriosis and contributes to the long course of the disease and rehabilitation. Key words: listeriosis, meningoencephalitis, COVID-19, SARS-CoV-2, immunodeficiency, immunosuppressive therapy, post-COVID syndrome

Objective. To study the effect of influenza, pneumococcal and SARS-CoV-2 vaccination on the incidence and severity of COVID-19 course in health care workers. Patients and Methods. We examined 547 health care workers divided into group 1 (no history of influenza and pneumococcal vaccination, n = 281) and groups vaccinated between August and October 2020 (before SARS-CoV-2 epidemic II): Group 2 against influenza (n = 98), Group 3 against pneumococcal infection (n = 60), and Group 4 against influenza and pneumococcus (n = 108). Between March and August 2021 (before the SARS-CoV-2 epidemic III outbreak), 98.6% of all employees were vaccinated against COVID-19. We compared COVID-19 incidence rates during Periods II and III epidemic rises (2020–2022) as a function of influenza and pneumococcal vaccination. Results. It was found that with combined vaccination against influenza and pneumococcal infection in the group of medical workers at high risk of infection, the risk of COVID-19 morbidity within 4–5 months was 2 times lower (1.6% vs. 13.2%, p < 0.05) compared to the unvaccinated. Comparative data on COVID-19 incidence in the II and III periods of epidemic rises showed that COVID-19 in medical workers in the III period was registered 36.1% lower in comparison with the index in the II period – 11.2 and 7.1%, respectively (p < 0.05). We found that when comparing II and III periods of epidemic rises among medical workers, the proportion of persons with COVID-19 with moderate forms of disease who received combined vaccination against influenza and pneumococcal infection decreases more than 2-fold (p < 0.05), including in the category with a high risk of infection. Conclusion. The presented data indicate a positive effect of combined vaccination against pneumococcal infection and influenza on the incidence and severity of COVID-19. The proposed approach can be used in public health practice as a method of nonspecific prevention of COVID-19 and other acute respiratory viral infections. Key words: influenza vaccine, pneumococcal vaccine, combined vaccination, epidemic rise, COVID-19

Objective. To study the anti-inflammatory properties of Tonsilgon N preparation and its effect on the indices of local immunity of oropharyngeal mucosa in patients with acute or exacerbation of chronic pharyngitis without a pronounced systemic inflammatory syndrome. Patients and methods. 60 people diagnosed with acute catarrhal pharyngitis with intoxication syndrome were examined. Group 1 – 30 people took the drug Tonsilgon N in the form of alcohol solution, group 2 – 30 people – sage in the form of tablets for resorption in the oral cavity according to the scheme of 25 drops or 1 tablet every 2 hours for the first 3 days of treatment, then 3 times a day until day 7 inclusive. Pharyngoscopy was performed by an otorhinolaryngologist at each visit on day 1, day 3–4 and day 7–8 of the disease. Using a 10-point visual analogue scale (VAS) with scores from 0 (no sign) to 10, we evaluated the severity of symptoms (pain when swallowing, a feeling of parching in the oropharynx, a feeling of a foreign body in the oropharynx, dry cough, weakness, headache) and the condition of the oropharyngeal mucosa. Additionally, at 3 visits, scrapings from the oropharyngeal mucosa were made with a cytobrush probe and the content of IL-6 and sIgA proteins was determined by enzyme immunoassay. For the control group, 30 conventionally healthy people were taken, not differing in sex and age from the main group of patients and having no inclusion criteria. Results. All patients by day 7 of observation had no expressed complaints, none of them had progression of inflammatory process or development of any complications, patients did not need further continuation of treatment. Pain at swallowing, feelings of foreign body in the oropharynx, feelings of feathering and intensity of hyperemia of the mucous membrane of the posterior pharyngeal wall when treated with Tonsilgon N on the 3–4 day of observation compared to the group of patients taking Sage. On the 7th day of observation at Tonsilgon N treatment all analyzed clinical manifestations of pharyngitis were absent, and in Sage group in some cases weakly expressed symptoms of pain at swallowing, feeling of foreign body in the oropharynx, feeling of fever, intensity of hyperemia of the mucous membrane of the back wall of the pharynx (Me = 0 [0;1] points) and dry cough (Me = 0 [0;0.5] points) remained. On day 1 of observation, an increase in IL-6 protein content compared with normal was noted in pharyngitis, and sIgA levels were low. Further, both groups showed a decrease in IL-6 level, in group 1 in the group receiving Tonsilgon N, its level on the 2nd and 3rd visit was lower compared to group 2. The amount of sIgA on the first day with pharyngitis was minimal, then in group 1 its values increased on day 3 but remained below control, and in group 2 further decreased, on day 7 of observation in group 1 sIgA slightly increased but was below control. In group 2 the sIgA level was determined in minimal values. Conclusion. Tonsilgon N or sage therapy showed a clear relief of clinical symptoms of tonsillopharyngitis during the treatment period without taking non-steroidal anti-inflammatory drugs, and their reduction was significantly faster with Tonsilgon N. Decrease of proinflammatory cytokine IL-6 on the background of treatment was faster on the background of treatment with Tonsilgon N. Increased synthesis of sIgA against the background of Tonsilgon N treatment allows to explain the rapid onset of clinical recovery in patients and to identify an additional mechanism of action of this drug on the local immune response of the oropharyngeal mucosa. It can be assumed that Tonsilgon N is not only pathogenetic, but also immunoregulatory, creating the most effective response of the body to inflammation. Key words: pharyngitis, oropharyngeal mucosa, interleukin-6 (IL-6), secretory immunoglobulin A (sIgA), enzyme-linked immunosorbent assay (ELISA), treatment, Tonsilgon N, sage