Role of antiviral therapy in respiratory infections in children: Analysis of clinical and laboratory observations.

Objective. To evaluate the efficacy of therapy for acute respiratory viral infections (ARVIs) in children with antiviral medications: inosine pranobex (Groprinosin, Gedeon Richter) and Kagocel (Kagocel, Niarmedic Pharma LLC) in comparison with symptomatic treatment without etiotropic agents based on clinical and laboratory parameters. Patients and methods. The clinical and laboratory observation was conducted in an outpatient setting in the pre-COVID-19 period between 2018 and 2020. Acute respiratory infections were diagnosed using licensed testing systems by multiplex polymerase chain reaction (PCR) with detection of nucleic acid viral genomes: influenza, rhinovirus, respiratory syncytial virus, metapneumovirus, parainfluenza, seasonal coronaviruses, adenoviruses, and bocavirus). A total of 151 children aged 3 to 15 years were examined and monitored in dynamics, with 78.7% of positive and 21.3% of negative results detected by PCR in the nasopharyngeal and oropharyngeal swabs. The patients were randomized into three groups depending on the antiviral medication prescribed: group 1 (53 children) received Groprinosin;group 2 (52 children) received Kagocel;group 3 (control, 46 children) received only symptomatic therapy without antiviral agents. Results. The study demonstrated a significant positive effect in patients in group 1 treated with Groprinosin (n = 53). At the end of therapy for both mono- and mixed infections, there were 95.8% of negative results (according to PCR diagnosis, that is, the absence of viral genome). In children in group 2 (n = 52) treated with Kagocel, the absence of viral nucleic acids (NAs) was observed less frequently (in 77.3% of cases). In children in group 3 (n = 46) who did not receive etiotropic antiviral therapy, there were only 40.3% of negative results after the end of treatment, and viral NAs were detected in 59.7% of patients. In this case, a 5-day course of Groprinosin was prescribed, after which the PCR results became negative in all patients. Therefore, children with recurrent respiratory infections, mixed infections, and herpesvirus infections require longer therapy. Additionally, a high frequency of ARVI complications was noted in group 3 (5 (10.9%) patients, where otitis was observed in 1 case, sinusitis - in 2 cases, bronchitis - in 2 cases), whereas 1 (1.8%) patient taking Groprinosin had otitis, and 1 (1.9%) patient taking Kagocel had pneumonia. Conclusion. This study was the first to investigate antibody titers to respiratory viruses in dynamics at 3, 6 and 12 months after the onset of ARVI. It showed that the development of antibodies to respiratory viruses is very unstable and does not occur in all patients. Antibodies almost disappeared by the third month after ARVI and were no longer detectable by the sixth month. After 12 months, patients suffered a new ARVI and developed the corresponding antibodies. This information will be especially relevant in conditions of the rise in the incidence of ARVIs, as well as the COVID-19 pandemic observed in recent years.Copyright © 2022, Voprosy Prakticheskoi Pediatrii. All rights reserved.

Role of antiviral therapy in respiratory infections in children: Analysis of clinical and laboratory observations.

Objective. To evaluate the efficacy of therapy for acute respiratory viral infections (ARVIs) in children with antiviral medications: inosine pranobex (Groprinosin, Gedeon Richter) and Kagocel (Kagocel, Niarmedic Pharma LLC) in comparison with symptomatic treatment without etiotropic agents based on clinical and laboratory parameters. Patients and methods. The clinical and laboratory observation was conducted in an outpatient setting in the pre-COVID-19 period between 2018 and 2020. Acute respiratory infections were diagnosed using licensed testing systems by multiplex polymerase chain reaction (PCR) with detection of nucleic acid viral genomes: influenza, rhinovirus, respiratory syncytial virus, metapneumovirus, parainfluenza, seasonal coronaviruses, adenoviruses, and bocavirus). A total of 151 children aged 3 to 15 years were examined and monitored in dynamics, with 78.7% of positive and 21.3% of negative results detected by PCR in the nasopharyngeal and oropharyngeal swabs. The patients were randomized into three groups depending on the antiviral medication prescribed: group 1 (53 children) received Groprinosin;group 2 (52 children) received Kagocel;group 3 (control, 46 children) received only symptomatic therapy without antiviral agents. Results. The study demonstrated a significant positive effect in patients in group 1 treated with Groprinosin (n = 53). At the end of therapy for both mono- and mixed infections, there were 95.8% of negative results (according to PCR diagnosis, that is, the absence of viral genome). In children in group 2 (n = 52) treated with Kagocel, the absence of viral nucleic acids (NAs) was observed less frequently (in 77.3% of cases). In children in group 3 (n = 46) who did not receive etiotropic antiviral therapy, there were only 40.3% of negative results after the end of treatment, and viral NAs were detected in 59.7% of patients. In this case, a 5-day course of Groprinosin was prescribed, after which the PCR results became negative in all patients. Therefore, children with recurrent respiratory infections, mixed infections, and herpesvirus infections require longer therapy. Additionally, a high frequency of ARVI complications was noted in group 3 (5 (10.9%) patients, where otitis was observed in 1 case, sinusitis - in 2 cases, bronchitis - in 2 cases), whereas 1 (1.8%) patient taking Groprinosin had otitis, and 1 (1.9%) patient taking Kagocel had pneumonia. Conclusion. This study was the first to investigate antibody titers to respiratory viruses in dynamics at 3, 6 and 12 months after the onset of ARVI. It showed that the development of antibodies to respiratory viruses is very unstable and does not occur in all patients. Antibodies almost disappeared by the third month after ARVI and were no longer detectable by the sixth month. After 12 months, patients suffered a new ARVI and developed the corresponding antibodies. This information will be especially relevant in conditions of the rise in the incidence of ARVIs, as well as the COVID-19 pandemic observed in recent years.Copyright © 2022, Voprosy Prakticheskoi Pediatrii. All rights reserved.

Isoprinosine along with Favipiravir or Oseltamivir in Patients with Moderate Covid-19 at RSD Dr. Soebandi Jember

Background: Isoprinosine is an immunomodulator that is now being used to treat Covid-19 patients. Objectives: To evaluate Isoprinosine with Favipiravir or Oseltamivir in moderate Covid-19. Methods: In a retrospective observational analysis, in-hospital moderate Covid-19 patients treated between June 2020 and June 2021 were included. Results: Inclusion criteria for 364 patients were met, with 135 receiving Favipiravir-Isoprinosine (Group 1) and 229 receiving Oseltamivir-Isoprinosine (Group 2). In group 1, the majority of patients (58.50%) were female (35.60%), had no comorbidities (71.60%), were discharged with a positive PCR (74.80%), did not require a breathing apparatus (99.26%), had leukocyte levels between 4,5-11,0 (82.22%), lymphocyte levels between 25-33 (34.07%), and were discharged with no ground-glass opacity (34.07%) (54.10%), LOS was 9-13 days (50.37%), while the mortality rate was 0.70%. In group 2, the majority of patients were male (54.10%), with the highest age range being 42-56 years (35.80%), without comorbidities (69.0%), discharged with a positive PCR (72.50 %), and without the need for a breathing apparatus (99.13%), with leukocyte levels ranging from 4.5 - 11.0 (81.22 %), with lymphocyte levels ranging from 25.0 - 33.0 (26.20 %), and were discharged with no ground-glass opacity (49.34 %), LOS was 9 - 13 days (34.06 %), and the mortality rate was 0.87%.Conclusion: In this trial, it was determined that combining isoprinosine with antivirals favipiravir or Oseltamivir could produce significant clinical improvement. [ FROM AUTHOR]

A Comprehensive Investigation of the Current Subacute Sclerosing Panencephalitis (SSPE) Treatment Options to Improve Patient Quality of Life.

Subacute sclerosing panencephalitis (SSPE) is a progressive, disabling, and deadly neurological disorder related to measles (rubeola) infection occurring primarily in children. The slow but persistent viral infection occurs in children or young adults and affects their central nervous system (CNS). There have been plenty of reports on SSPE throughout the world, but it is considered a rare disease in developed countries. This research focuses on comparing the current treatments available to prolong the life of patients for over three years after the onset of SSPE. The goal was to identify possible patterns or trends among the treatments in order to find the best possible method to lengthen a patient's life. The results indicated that interferon alpha, inosine pranobex, and ribavirin display the most effective treatment plan and indicate the most potential in discovering a more effective therapeutic for SSPE.

Efficacy and Safety of Inosine Pranobex in COVID-19 Patients: A Multicenter Phase 3 Randomized Double-Blind, Placebo-Controlled Trial.

Inosine pranobex (IP), an immunomodulatory agent, is used in the treatment of various viral infections. The results of a phase 3 randomized controlled trial are reported, evaluating the efficacy and safety of IP in the treatment of mild to moderate COVID-19. It includes 416 symptomatic patients with confirmed SARS-CoV-2 infection. In addition to a defined standard of care, patients  randomly (1:1) receive either IP 500 mg tablet (IP group) or a matching placebo (placebo group) at 50 mg kg-1 body weight/day rounded to the nearest 500 mg dose (maximum 4 g day-1) administered in 3-4 divided doses for 10 days. Compared to the placebo group, IP group shows significantly higher rates of clinical response (CR) and clinical cure (CC) on Day-6 for both non-hospitalized patients and the total population. IP group shows significantly earlier CR and CC with fewer adverse events and no mortality. Based on these findings and the fact that IP increases natural killer cell-mediated cytotoxicity of virus-infected cells as an early immune response to viral infection and enhances NKG2D ligand expression, it is concluded that IP should be started early to maximize the benefit in mild to moderate COVID-19 patients. (Trial registration number: CTRI/2021/02/030892).

Therapeutic potential of inosine pranobex in enhancing non-specific antiviral protection in patients with COVID-19

The defense mechanisms of the human body determine non-specific resistance of non-immune cells that comprise the majority of cells in the organism and are exposed to various environmental factors (such as radiation, pollutants, microbial infection), as well as innate and acquired immunity aimed at enhancing the response to external (and internal) stimuli. Inosine is one of the drugs that can strengthen the internal protective reserves of non-immune cells of the human body, primarily against various viruses. Inosine in the form of inosine pranobex is the main component of Groprinosin (Gedeon Richter Pharma LLC). It was shown that protective effect of inosine is attributed to its interaction with the surface adenosine A2A receptor from the family of G-protein-coupled receptors, with activation of the peroxisome proliferator-activated receptor gamma (PPAR-g). This results in inhibition of the mevalonate pathway of cholesterol synthesis and restriction of the viral life cycle of both enveloped (herpes viruses, hepatitis, dengue, mumps, influenza, Ebola, coronaviruses SARS-CoV, MERS-CoV, SARS-CoV-2) and non-enveloped (adenovirus, enterovirus, such as Coxsackie, rotavirus) viruses. Therefore, inosine can be included into the existing clinical protocols or used as an alternative to improve treatment efficacy. © 2021, Dynasty Publishing House. All rights reserved.

Inosine Pranobex Deserves Attention as a Potential Immunomodulator to Achieve Early Alteration of the COVID-19 Disease Course.

Since its licensing in 1971, the synthetic compound inosine pranobex has been effectively combating viral infections, including herpes zoster, varicella, measles, and infections caused by the herpes simplex virus, human papillomavirus, Epstein-Barr virus, cytomegalovirus, and respiratory viruses. With the emergence of SARS-CoV-2, new and existing drugs have been intensively evaluated for their potential as COVID-19 medication. Due to its potent immunomodulatory properties, inosine pranobex, an orally administered drug with pleiotropic effects, can, during early treatment, alter the course of the disease. We describe the action of inosine pranobex in the body and give an overview of existing evidence collected to support further efforts to study this drug in a rigorous clinical trial setup.

Inosine Pranobex Significantly Decreased the Case-Fatality Rate among PCR Positive Elderly with SARS-CoV-2 at Three Nursing Homes in the Czech Republic.

During the COVID-19 pandemic, the elderly population has been disproportionately affected, especially those in nursing homes (NH). Inosine pranobex (IP) has been previously demonstrated to be effective in treating acute viral respiratory infections. In three NH experiencing the SARS-CoV-2 virus epidemic, we started treatment with IP as soon as clients tested PCR+. In Litovel, CZ, the difference in case-fatality rate (CFR) for the PCR+ group using vs. not using IP was statistically significant, and the odds ratio (OR) was 7.2. When comparing all those taking IP in the three NH vs. the non-drug PCR+ group in Litovel, the odds ratio was lower for all three NH, but still significant at 2.9. The CFR in all three tested NHs, age range 75-84, compared to the CFR in all NHs in the Czech Republic, was significantly reduced (7.5% vs. 18%) (OR: 2.8); there was also a significant difference across all age groups (OR: 1.7). In our study with 301 residents, the CFR was significantly reduced (OR: 2.8) to 11.9% (17/142) in comparison to a study in Ireland with 27.6% (211/764). We think the effect of IP was significant in this reduction; nevertheless, these are preliminary results that need larger-scale trials on COVID-19 patients.