Применение противовирусного препарата нового поколения Аллокин-альфа в терапии социально значимых вирусных инфекций

The incidence of influenza and acute respiratory infections (ARI) continues to grow, including due to limited opportunities for immunoprophylaxis of the most common respiratory infections, in particular, acute respiratory viral infections (ARVI). Attempts are being made to reduce the children susceptibility to respiratory pathogens through the rational use of nonspecific immunoprophylactic agents, among which bacterial lysates (BL) occupy a special place. BL key patterns, contributing to the prevention of viral infections, are innate immune response activation, excessive inflammatory response prevention, adaptive immune response stimulation. BL contain fragments of inactivated various pathogenic bacteria strains that are important in the ARI etiology. Obtaining lysates of bacterial strains is possible by mechanical or chemical lysis. The article discusses the results of preclinical and clinical studies on BL, as well as suggests the expediency of further study concerning the BL pharmacodynamic effects within the modern concept of trained immunity. The authors conclude that BL as a trained immunity inducer according to the rationally selected regimen can contribute to the respiratory infections' prevention both during COVID-19 pandemic and post-pandemic period. KEYWORDS: acute respiratory infections, acute respiratory viral infections, influenza, trained immunity, immunoprophylaxis, bacterial lysate. FOR CITATION: Zaplatnikov A.L., Kanner E.V., Kanner I.D., Girina A.A., Farber I.M., Maximov M.L. Promising immunomodulatory effects of bacterial lysates in the prevention and treatment of acute and recurrent respiratory infections in children. Russian Journal of Woman and Child Health. 2023;6(3):290–297 (in Russ.). DOI: 10.32364/2618-8430-2023-6-3-12.

Введение. Острые респираторные вирусные инфекции – это патология, которая чаще всего встречается в амбулаторной терапевтической практике (около 40 млн случаев в год). Термин «острая респираторная вирусная инфекция» является собирательным понятием и обозначает группу заболеваний вирусной этиологии с преимущественным поражением дыхательных путей. Общие эпидемиологические особенности возбудителей острых респираторных вирусных инфекций заключаются в единых путях передачи: воздушно-капельном и посредством контакта с зараженными предметами. Причины острых респираторных вирусных инфекций могут быть разными, однако у них есть общие эпидемиологические и клинические особенности, которые определяют единую стратегию лечения и профилактики. Результаты. Терапия острых респираторных вирусных инфекций направлена на снижение тяжести симптомов, предотвращение прогрессирования заболевания и достижение полного и стойкого выздоровления. Лабораторная этиологическая диагностика на амбулаторном этапе проводится молекулярно-генетическими методами только в отношении гриппа А и В, а также COVID-19; для идентификации других возбудителей острых респираторных вирусных инфекций ее проведение целесообразно только по клинико-эпидемиологическим показаниям, поскольку полученные результаты не влияют на дальнейшую тактику ведения пациента. Обязательным компонентом лечения является немедикаментозная терапия, включающая в себя постельный режим, диету и обильное питье. Медикаментозное лечение острых респираторных вирусных инфекций и гриппа включает этиотропные препараты, средства патогенетической и симптоматической терапии. В качестве этиотропной терапии применяют противовирусные препараты прямого и непрямого действия. Ингибиторы нейраминидазы, как и ингибиторы кэп-зависимой эндонуклеазы, используются в терапии гриппа А и В и, к сожалению, не активны в отношении других возбудителей острых респираторных вирусных инфекций. В связи с отсутствием препаратов прямого противовирусного действия, активных в отношении возбудителей острых респираторных вирусных инфекций, основными этиотропными препаратами выступают препараты непрямого (иммуномодулирующего) действия, обладающие широким противовирусным спектром, к которым, в частности, относятся индукторы интерферона. Заключение. В статье представлен анализ литературы на тему оптимизации терапии острых респираторных вирусных инфекций и гриппа в амбулаторных условиях за счет применения препаратов группы индукторов интерферона. В результате проведенного анализа был сделан вывод о необходимости комплексного подхода, включающего противовирусную терапию, в лечении любых форм острых респираторных вирусных инфекций и гриппа. Background. Acute respiratory viral infections are a pathology that most often occurs in outpatient therapeutic practice (about 40 million cases per year). The term acute respiratory viral infection is a collective concept and denotes a group of diseases of viral etiology with predominant damage to the respiratory tract.The general epidemiological features of acute respiratory viral infections pathogens consist in common transmission: airborne droplets and through contact with contaminated objects. Although the causes of acute respiratory viral infections may be different, they have common epidemiological and clinical features that determine a unified strategy for treatment and prevention. Results. Treatment of acute respiratory viral infections is aimed at reducing the severity of symptoms, preventing progression of the disease, and achieving a complete and lasting recovery. Laboratory etiological diagnosis at the outpatient stage is carried out using molecular genetic methods only for influenza A and B, as well as COVID-19; to identify other pathogens of acute respiratory viral infections, it is advisable only for clinical and epidemiological indications, since the results obtained do not affect further tactics of patient management. A required component of treatment is non-drug therapy, including bed rest, diet and plenty of fluids.Drug treatment of acute respiratory viral infections and influenza includes etiotropic drugs, pathogenetic and symptomatic therapy. Direct and indirect antiviral drugs are used as etiotropic therapy. Neuraminidase inhibitors, like cap-dependent endonuclease inhibitors, are used in the treatment of influenza A and B, and, unfortunately, are not active against other pathogens of acute respiratory viral infections. Due to the lack of drugs with direct antiviral action active against acute respiratory viral infections pathogens, the main etiotropic drugs are drugs of indirect (immunomodulatory) action with a wide antiviral spectrum, which include interferon inducers. Conclusion. The article presents an analysis of the literature on the topic of optimizing the treatment of acute respiratory viral infections and influenza in an outpatient setting using drugs from the group of interferon inducers.As a result of the analysis, it was concluded that an integrated approach is necessary, including antiviral therapy in the treatment of any forms of acute respiratory viral infections and influenza.

CD8+ T cell dysfunction contributes to severe respiratory viral infection outcomes in older adults. CD8+ T cells are the primary cell type responsible for viral clearance. With increasing age, CD8+ T cell function declines in conjunction with an accumulation of cytotoxic tissue-resident memory (TRM) CD8+ T cells. We sought to elucidate the role of PD-1 signaling on aged CD8+ T cell function and accumulation of CD8+ TRM cells during acute viral respiratory tract infection, given the importance of PD-1 regulating CD8+ T cells during acute and chronic infections. PD-1 blockade or genetic ablation in aged mice yielded improved CD8+ T cell granzyme B production comparable to that in young mice during human metapneumovirus and influenza viral infections. Syngeneic transplant and adoptive transfer strategies revealed that improved granzyme B production in aged Pdcd1-/- CD8+ T cells was primarily cell intrinsic because aged wild-type CD8+ T cells did not have increased granzyme B production when transplanted into a young host. PD-1 signaling promoted accumulation of cytotoxic CD8+ TRM cells in aged mice. PD-1 blockade of aged mice during rechallenge infection resulted in improved clinical outcomes that paralleled reduced accumulation of CD8+ TRM cells. These findings suggest that PD-1 signaling impaired CD8+ T cell granzyme B production and contributed to CD8+ TRM cell accumulation in the aged lung. These findings have implications for future research investigating PD-1 checkpoint inhibitors as a potential therapeutic option for elderly patients with severe respiratory viral infections.

По данным ВОЗ, каждый третий житель планеты ежегодно обращается за медицинской помощью по поводу острой респираторной инфекции. Результаты многих исследований показывают, что коррекция иммунных процессов в очаге воспаления дает больший эффект, чем влияние на иммунокомпетентные клетки кровеносного русла (при системном использовании препаратов). Поэтому логичным подходом к терапии респираторных вирусных инфекций, поражающих респираторный эпителий, является интраназальное применение препаратов интерферонов, которые обеспечивают противовирусное, иммуномодулирующее и противобактериальное действие в месте развития инфекционного процесса. В доступной литературе имеется достаточное количество клинических исследований, посвященных изучению эффективности назальных и аэрозольных форм интерферона альфа при острых респираторных вирусных инфекциях (ОРВИ). В них показано, что рекомбинантный интерферон альфа является эффективным препаратом для лечения и профилактики ОРВИ. Его применение сокращает сроки клинического выздоровления больных, уменьшает степень выраженности клинических симптомов заболевания, позволяет избежать манифестации заболевания. Также препараты интерферонов могут применяться как средство предотвращения ОРВИ и гриппа.

Aim: to evaluate the therapeutic efficacy and tolerability of alpha-glutamyl-tryptophan in intranasal spray form as part of combination therapy for acute respiratory viral infections (ARVI) of the upper respiratory tract in elderly patients with comorbidities. Patients and Methods: a total of 69 elderly outpatient individuals from the high-risk group, presenting with comorbid conditions and diagnosed with ARVI during the 2023–2024 epidemic season, were monitored for 14 days. Patients were divided into two groups: the main group consisted of 39 patients who received alpha-glutamyl-tryptophan in intranasal spray form in addition to standard therapy, while the comparison group included 30 patients treated with standard therapy alone. The efficacy of the therapy was assessed based on the severity and duration of core ARVI symptoms (fever, catarrhal symptoms). Secondary endpoints included the incidence of ARVI-related complications and adverse events. Results: after 14 days of follow-up, 87.2% of patients in the main group were asymptomatic for ARVI and demonstrated no exacerbation of underlying chronic conditions. Patients in the main group exhibited good tolerability to the treatment, with the duration of ARVI symptoms including fever and/or subfebrility reduced by 2.8 days compared to the comparison group. Furthermore, the quality of life improved by over 40% in the main group by day 5 of the study, whereas no significant change was observed in the comparison group. A significant reduction in fatigue severity was noted in the main group by day 14 (p<0.05). The incidence of ARVI-related complications was lower in the main group compared to the control group (12.8% vs. 33.3%, respectively). Conclusion: the inclusion of alpha-glutamyl-tryptophan in intranasal spray form as part of standard therapy for ARVI in elderly patients with comorbid conditions enhances its efficacy in reducing the intensity and duration of key symptoms, improves tolerance to viral infections, and contributes to a notable enhancement in quality of life. Keywords: alpha-glutamyl-tryptophan, acute respiratory viral infections, elderly, fever, fatigue, quality of life. For citation: Malinnikova E.Yu., Maximov M.L., Startseva M.A., Erofeeva M.K., Kakanov A.M., Shakhlanskaya E.V. Open comparative follow- up study on the efficacy and safety of alpha-glutamyl-tryptophan spray as part of combination therapy for acute viral upper respiratory tract infections in elderly patients. RMJ. 2025;1:27–32. DOI: 10.32364/2225-2282-2025-1-6

Objective. To identify risk factors for acute respiratory viral infections (ARVI) (influenza and novel coronavirus infection (NCI) COVID-19) in pregnant women and evaluate the effectiveness of pharmacological prevention. Patients and methods. During the first phase, 152 individual medical records of pregnant women were retrospectively studied: 102 women (the first main group) with acute respiratory viral infections and 50 pregnant women who had no acute respiratory viral infections (the control group). The second phase was a prospective comparative study: the second main group (n = 100) – pregnant women who received recombinant interferon α-2b (IFN-α2b) with vitamins E and C as preventive treatment; the comparison group (n = 100) – without preventive treatment. Results. Risk factors for the incidence of ARVI included anemia (χ2 = 0.003), obesity (χ2 = 0.026), cardiovascular diseases (χ2 = 0.060), diabetes mellitus (χ2 = 0.050), frequent ARVI in medical history (χ2 = 0.028), nicotine intoxication (χ2 = 0.008), urinary tract infections (χ2 < 0.001). The second phase: 10% of pregnant women who received preventive treatment had mild forms of influenza and NCI; 2% of women had a moderate form. In the second main group, 33% of pregnant women were sick (OR = 2.852, 95% CI = 1.354–6.005, χ2 = 0.005): 26% of women had a mild form, 6% of women had a moderate form and 1% of women had a severe form. In the second main group, threatened miscarriage (χ2 < 0.001), preterm birth (χ2 < 0.001), gestational pyelonephritis (χ2 = 0.006), placental insufficiency (χ2 < 0.001), pre-eclampsia (χ2 = 0.006), congenital anomalies of the fetus (χ2 = 0.017) and intrauterine infection (χ2 < 0.001) were more frequent. Conclusions. Among risk factors for ARVI during pregnancy were anemia, obesity, diabetes mellitus, and nicotine intoxication. Preventive treatment with recombinant IFNα-2b with vitamins E and C reduced the incidence of acute respiratory viral infections in pregnant women by 2.8 times and improved perinatal outcomes by 4.7 times. Key words: pregnancy, acute respiratory viral infections, prevention

Background: Currently available over-the-counter cough remedies historically have been criticized for lack of scientific evidence supporting their efficacy. Although the first-generation antihistamine diphenhydramine is classified as an antitussive by the United States Food and Drug Administration, to the authors’ knowledge it has never been shown to inhibit cough reflex sensitivity in subjects with pathological cough. Objective: To evaluate the effect of diphenhydramine on cough reflex sensitivity. Setting: Montefiore Medical Center, an academic medical center in New York City. Methods: Twenty two subjects with acute viral upper respiratory tract infection (common cold) underwent cough reflex sensitivity measurement employing capsaicin challenge on 3 separate days, 2 h after ingesting single doses of study drug (to coincide with peak blood concentrations), administered in randomized, double-blind manner: a multicomponent syrup containing diphenhydramine (25 mg), phenylephrine (10 mg), in a natural cocoa formulation; dextromethorphan (30 mg) syrup; and, placebo syrup. The standard endpoint of cough challenge was used: concentration of capsaicin inducing ≥5 coughs (C5). Main outcome measure: Effect on cough reflex sensitivity (C5). Results: A significant difference (p = 0.0024) was established among groups, with pairwise analysis revealing a significant increase in mean log C5 (0.4 ± 0.55 (SD); p < 0.01) for the diphenhydramine-containing medication versus placebo, but not for dextromethorphan versus placebo. Conclusions: Our results provide the initial evidence of the ability of diphenhydramine to inhibit cough reflex sensitivity in subjects with acute pathological cough. Timing of cough reflex sensitivity measurement may not have allowed demonstration of maximal antitussive effect of dextromethorphan.

Every year, acute respiratory viral infections (ARVI) hold leading positions in terms of morbidity and economic damage both in the world and in the Russian Federation. A medical organization requires the use of not individual preventive measures, but an integrated approach. Objective: to optimize a set of measures aimed at ensuring epidemiological safety during the period of increased incidence of influenza and acute respiratory viral infections. To achieve this goal, a set of measures was adapted for use in medical organizations based on current regulatory documents on the prevention of influenza and acute respiratory viral infections. The work was carried out at the inpatient department of a large multidisciplinary medical center for the period 2020–2024. The developed set of measures included three areas: organizational, preventive and anti-epidemic. Organizational measures were carried out both during the period of no increase in the incidence of influenza and acute respiratory viral infections and during the period of increased incidence. Preventive measures carried out in the hospital are aimed at minimizing the possibility of introducing the infectious agent from outside, eliminating infection directly in the hospital and preventing the removal of the pathogen outside the hospital. The use of the developed set of measures led to a decrease in the number of introductions of ARVI and flu pathogens into the hospital of a medical organization, and the absence of group morbidity.

In modern conditions, the state faces the strategic task of improving the reproductive health of the female population and increasing the birth rate. The most important component of this strategy is to ensure the well-being of the health of the woman and the expectant mother throughout the entire gestation period. According to the World Health Organization (WHO), acute respiratory viral infections (ARVI) account for 90-95% of the total number of infectious diseases [10]. In Russia, the incidence rate of acute respiratory viral infections has remained consistently high in recent years, with the proportion of pregnant women among all patients diagnosed with acute respiratory viral infections reaching 40% [1]. Acute respiratory viral infections are diagnosed in 2-9% of pregnant women, but the clinical significance of this condition is often underestimated, which leads to serious consequences for both the mother and the developing fetus [5]. Due to hormonal and physiological changes in the body, pregnant women are at increased risk of severe illness and complications for both themselves and the fetus [8]. Viruses penetrating through the placental barrier can provoke serious pathologies in the fetus, especially at the stage of embryogenesis [9]. Based on the analysis of the epidemiological situation in recent decades, WHO experts have included pregnant women in the high-risk group for the development of complicated forms of acute respiratory viral infections [2]. The conducted research examines the role and key stages of the pharmaceutical consulting process. Specific aspects requiring special attention of pharmaceutical specialists in the provision of pharmaceutical care to pregnant women with acute respiratory viral infectious diseases (ARVI) have been identified.

Aim. Study effect of cellulose powder on the functional state of the ciliary epithelium in children with bronchial obstruction. Design. Open prospective non-randomized clinical study. Material and methods. The study involved 60 children from 3 to 11 years, with a history of frequent acute respiratory viral infections (ARVI), occurring with bronchial obstruction or exacerbation of bronchial asthma. Motor activity of the ciliary epithelium was registered with the digital high-speed videomicroscopy method initially and 3 months after the start of the three-month course of its application. Patients were also assessed for the frequency of acute respiratory viral infections; the objective and subjective symptoms of ARVI episodes were evaluated with a point scale during the follow-up period. Results. After completing the three-month course of cellulose powder with wild garlic extract usage, it was revealed that 55 (91.7%) children did not get ARVI during follow-up, 5 (8.3%) children had ARVI once. There was a reduction in the duration of the disease, a decrease in the severity of symptoms compared with those in previous years, on the scale of severity assessment of symptoms in patients with ARVI: in previous years — 17 (16; 18) points, when interviewed after the use of the studied drug — 9 (7; 10) points (p &lt; 0.05). Of the five children who were ill, only one child developed obstructive bronchitis on the background of a viral infection. The relative number of cells with motile cilia: the middle nasal concha (MNC) — 25% (20%; 30%), the inferior nasal concha (INC) — 25% (15%; 30%); 3 months after the start of taking the cellulose powder: MNC — 40% (30%; 45%), INC — 35% (35%; 45%) (p &lt; 0.01). Ciliary beat frequency in patients initially: MNC — 4.7 (4.2; 5.9) Hz, INC — 4.9 (4.2; 5.7) Hz; 3 months after MNC — 5.9 (5.7; 7.9) Hz (p &lt; 0.01), INC — 6.2 (5.5; 7.2) Hz (р &lt; 0.05). Conclusion. The use of cellulose powder for preventive purposes prevents infection with ARVIs, protects against reinfection, and also helps to reduce the duration and the severity of the disease manifestations. There is a positive dynamics in the functional status of the ciliary epithelium of the upper respiratory tract, which may reflect a more complete restoration of the mucosa against the background of the absence of ARVI. Keywords: ciliary epithelium, cilia, prevention of acute respiratory viral infections, children, fine cellulose powder.

Management of suspected acute viral upper respiratory tract infection in children with intranasal sodium cromoglicate: a randomised controlled trial

Aim. Comparative study of clinical efficacy and safety of antiviral drug triazavirin and umifenovir in the treatment of patients with acute respiratory viral infections and influenza.&#x0D; Methods. The study included 100 patients aged 18 to 65 years diagnosed with moderate acute respiratory viral infection. Group 1 included 34 patients receiving umifenovir 200 mg 4 times a day for 5 days, and comparison group included 32 patients who received triazavirin 1 capsule (250 mg) 3 times a day for 5 days. Group 3 (control group) included 34 patients not treated with antiviral therapy. Efficacy and safety of the studied antiviral drugs were evaluated based on clinical symptoms in the disease course and were confirmed by adaptive reactions of the organism.&#x0D; Results. Among patients receiving triazavirin, recovery time and fever, headache and catarrhal syndrome resolution time were less than among patients who received umifenovir. On triazavirin treatment with favorable tolerability, symptomatic medications (antipyretics) were discontinued, and the duration of their use was less, than in patients receiving umifenovir. Evaluation of clinical efficacy of umifenovir and triazavirin for the treatment of acute respiratory viral infections and influenza demonstrated that the drugs effectively reverse the main symptoms of the disease (p &lt;0.05), reduce complications incidence (18.1±2.1% vs. 55.9±3.2%, p &lt;0.05) and contribute to the stabilization of adaptive reactions of the organism in contrast to the results of patients not receiving etiotropic therapy (6.9±2.9% vs. 12.8±2.7, p &lt;0.05). During the use of umifenovir by day 4 and during the use of triazavirin by day 3 intoxication and catarrhal syndromes had been reversed, while in case of the absence of antiviral therapy, 55.8% of patients had continuing intoxication and catarrhal symptoms.&#x0D; Conclusion. The results of the study allow defining umifenovir and triazavirin as the first line of defense against acute respiratory viral infections with good efficacy and tolerability of the drugs.

Acute respiratory viral adverse events during use of antirheumatic disease therapies: A scoping review

The issues of immunopathogenesis of acute respiratory viral infections (ARVI) remain relevant, despite a long history of study. The aim of the study was to investigate the characteristics of the content of some cytokines in the blood serum of children with ARVI caused by DNA and RNA-containing viruses. Material and methods. We examined 92 children with ARVI at the age from 1 to 15 years, hospitalized in the hospital of the Children’s Clinical Hospital No. 6 (Novosibirsk). In order to determine the etiological factor, a study was carried out using the RT-PCR method (test systems AmpliSensORVI-screen-FL, “InterLabService”, Russia) of mucus from the nose and throat for the presence of genetic material of viruses that cause ARVI. Determination of the content of IL-8, IL-17, IFN-γ in the blood serum in children of all groups was carried out by the method of solid-phase ELISA using commercial test systems of LLC “Cytokin” (Russia). Results and discussion. 4 groups were formed: group I ( n = 20) children with ARVI caused by DNA-containing viruses (group B, C, E adenoviruses, bocaviruses); group II ( n = 53) children with ARVI caused by RNA viruses (RS virus, metapneumovirus, parainfluenza viruses 1, 2, 3, 4, rhinovirus and coronoviruses); group III ( n = 12) children with ARVI caused by mixed infection; group IV ( n = 7) – the genetic material of the pathogen has not been isolated. Concentration of IL-8, IL-17, IFN-γ was significantly increased in all groups compared to the normative values. Higher values of IFN-γ and IL-8 were revealed in patients with DNA viruses compared with the group with RNA-containing viruses, although the excess of IFN-γ was not statistically significant. Differences in the content of IFN-γ, IL-8 and IL-17 were noted for various etiological viral agents, but they were not significant. Conclusions. The results obtained can serve as confirmation that the functional characteristics of the response of the immune system in children with ARVI are determined not so much by the etiological factor as by its individual state. With ARVI in children, the presence of genetic material from more than one virus, apparently, is not a significant potentiating factor in the activation of the immune response. At the same time, a negative PCR result with a detailed clinical picture of ARVI does not exclude the viral genesis of the disease.

Exacerbation of asthma and airway infection: is the virus the villain?