Marian Špajdel

Background Exposure to repetitive head impacts (RHI) has been shown to be associated with cognitive impairment and markers of neurodegeneration in professional male soccer players. However, data on the effects of RHI in female players are very limited. In this exploratory study, we investigated changes in blood biomarkers along with the cognitive status of elite female soccer players and compared the effect of RHI with outcomes in male players. Methods In a cohort study, elite female soccer players (age 16–41 years) performed training without heading the ball (n = 36) and training including heading (n = 30). Athletes were evaluated for the parameters of physical activity (heart rate) and neuropsychological testing (focused attention and cognitive flexibility) before and 1 h after each training. The levels of plasma tau, pTau₁₈₁, pTau₂₁₇ and microRNAs were determined at four timepoints: before training, 1 h, 24 h, and 48 h after each training session. Parameters in females were compared with control male players (n = 32). Results The levels of tau, pTau₁₈₁ and pTau₂₁₇ are significantly increased in the plasma of female soccer players 1 hour after physical exercise (tau, 1.4-fold; pTau₁₈₁, 1.3-fold; pTau₂₁₇, 1.2-fold) and repetitive head impacts (tau, 1.2-fold; pTau₁₈₁, 1.3-fold; pTau₂₁₇, 1.3-fold) compared to pre-training levels. The ratio of pTau₁₈₁ to tau fold change is significantly higher 1 hour after heading and remains elevated specifically in the heading group even after 48 h. The analysis of deregulated microRNAs in plasma reveals enrichment of neuroprotective pathways after heading training. Female soccer players show worse cognitive functions after heading compared to exercise and also compared to male soccer players. Conclusions RHIs may lead to acute disbalance of tau and phosphorylated tau in plasma, and are associated with short-term decline in cognitive performance and neuroprotective pathways in elite female soccer players. The sexual dimorphism in response to RHI may reflect biological risk factors potentially relevant to the different degree of susceptibility to neurological disorders in females and males in later life.

Slovenská akadémia vied vykonáva špičkový základný výskum, dlhodobý strategický a aplikovaný výskum a vývoj a poskytuje prístup k vedeckej infraštruktúre.

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.

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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.

Inosine pranobex (Isoprinosine®) is an immunomodulatory drug approved in several countries for the treatment of viral infections. This study compared the efficacy and safety of inosine pranobex versus placebo in subjects with clinically diagnosed influenza-like illness, including subjects with laboratory-confirmed acute respiratory viral infections. Subgroup analyses evaluated the efficacy of inosine pranobex compared to placebo in otherwise healthy (without related ongoing disease) subjects that were less than 50 years of age and healthy subjects that were at least 50 years of age. The effect of body mass index (BMI) was evaluated in subjects less than 50 years of age. A total of 463 subjects were randomly assigned to receive inosine pranobex (n = 231) or placebo (n = 232) in this Phase 4, randomised, double-blind, multicentre study. The primary efficacy endpoint was time to resolution of all influenza-like symptoms present at baseline to none. Safety was evaluated through analysis of adverse events, vital signs, and physical examinations. The difference in time to resolution of all influenza-like symptoms between treatment groups was not statistically significant but showed a faster improvement in subjects in the inosine pranobex group versus those in the placebo group - Hazard Ratio = 1.175; (95 % CI: 0.806–1.714). P-value = 0.324. In the subgroup analysis for subjects less than 50 years of age, statistically significant differences in time to resolution of influenza-like symptoms that favoured the inosine pranobex group over the placebo group were observed in those without related ongoing disease and those who were non-obese (BMI <30 kg/m2). The differences between the inosine pranobex and placebo groups in subjects at least 50 years of age without related ongoing disease and in subjects less than 50 years of age who were obese (BMI ≥30 kg/m2) were not statistically significant. Inosine pranobex was generally well tolerated, and no deaths were reported. The study results indicate the safety of inosine pranobex for the treatment of subjects with confirmed acute respiratory viral infections and confirm the efficacy of inosine pranobex versus placebo in healthy non-obese subjects less than 50 years of age with clinically diagnosed influenza-like illnesses. EWO-ISO-2014/1, EudraCT 2014-001863-11 ; Date of registration: 29 APR 2014; Detail information web link: https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-001863-11/results