Antiviral and Anti-Inflammatory Activities of Fluoxetine in a SARS-CoV-2 Infection Mouse Model.

The coronavirus disease 2019 (COVID-19) pandemic continues to cause significant morbidity and mortality worldwide. Since a large portion of the world's population is currently unvaccinated or incompletely vaccinated and has limited access to approved treatments against COVID-19, there is an urgent need to continue research on treatment options, especially those at low cost and which are immediately available to patients, particularly in low- and middle-income countries. Prior in vitro and observational studies have shown that fluoxetine, possibly through its inhibitory effect on the acid sphingomyelinase/ceramide system, could be a promising antiviral and anti-inflammatory treatment against COVID-19. In this report, we evaluated the potential antiviral and anti-inflammatory activities of fluoxetine in a K18-hACE2 mouse model of SARS-CoV-2 infection, and against variants of concern in vitro, i.e., SARS-CoV-2 ancestral strain, Alpha B.1.1.7, Gamma P1, Delta B1.617 and Omicron BA.5. Fluoxetine, administrated after SARS-CoV-2 infection, significantly reduced lung tissue viral titres and expression of several inflammatory markers (i.e., IL-6, TNFα, CCL2 and CXCL10). It also inhibited the replication of all variants of concern in vitro. A modulation of the ceramide system in the lung tissues, as reflected by the increase in the ratio HexCer 16:0/Cer 16:0 in fluoxetine-treated mice, may contribute to explain these effects. Our findings demonstrate the antiviral and anti-inflammatory properties of fluoxetine in a K18-hACE2 mouse model of SARS-CoV-2 infection, and its in vitro antiviral activity against variants of concern, establishing fluoxetine as a very promising candidate for the prevention and treatment of SARS-CoV-2 infection and disease pathogenesis.

Impact of the COVID-19 pandemic on the mental health of citizens of the Republic of Bulgaria

Introduction: The emergence of the new coronavirus SARS-CoV-2 and the resulting COVID-19 pandemic have challenged all aspects of social and economic life in different countries, their health care systems, as well as the mental health of the population. The introduction of anti-epidemic measures with different duration and severity temporarily deprived of any of democratic freedoms and achievements and marked social communication with new rules. The tension and fear of the unknown, caused by the new disease, limited access to health facilities, impoverishment and job loss, increased mortality, restriction of contacts affected somewhat the mentality of every human being. Various researchers, including in Bulgaria, report significant negative effects on mental health, as this situation shows a clear negative trend. Aim: The article aims to present the second phase of the NCPHA study on the impact of COVID-19 pandemic on the mental health of Bulgarian citizens.

The effects of exercise on cognitive dysfunction in patients with Coronavirus and sports recommendations for their recovery

Background & Aims: Beginning in 2020, a deadly disease called COVID-19 spread throughout the world, plunging all countries into a viral infection. Viral infections are naturally associated with upper respiratory tract infections, which are commonly reported with fever, headache, and cough. COVID-19 virus can infect a person's respiratory system and lungs, eventually leading to death. The virus can first activate and infect macrophages. Macrophages then transfer COVID 19 to T cells and make them weak. In addition, by weakening T cells, T cell subsets are activated to increase cytokines to enhance the immune response. T cells, CD4 + T cells and CD8 + T cells play an important antiviral role in the body. It is noteworthy that CD4 + T cells in the body produce T cell-dependent (B) cells to increase virus-specific antibodies. On the other hand, CD8 + T cells are a toxic cell and can kill virus-infected cells. Most published studies have focused on the effect of aerobic exercise on immune system function. Recent studies have shown that tai chi and yoga exercises can also be beneficial for immune system function. Exercise has long been known as an important modulator of inflammatory processes. Exercise can apparently have both tonic and suppressive effects on the immune system. The effect of exercise on innate and acquired safety parameters depends on the intensity, load and duration of exercise. As the severity increases, immune function and ultimately the risk of infection increase. These risks depend on immune system regulators (genetics, nutritional status, psychological stress, circadian rhythms), environmental stressors (extreme temperatures, airway irritants) that increase inflammation. In response to exercise, immune cells grow, proliferate, and produce molecules such as cytokines and cytotoxic granules. Prolonged exercise, at least in healthy individuals, appears to reduce basal inflammatory status by reducing the circulation of inflammatory cytokines. Regular periods of short-term training (i.e., up to 45 minutes) with moderate intensity boost the immune system (increase T cells) while frequent periods of long-term high-intensity training (> 2 hours) can suppress the immune system. Acute exercise, even in healthy individuals, leads to a strong inflammatory response that is mediated by leukocyte mobilization (even for short periods of 6 minutes) and increases potent inflammatory mediators such as TNF-a, IL-1. The effect of increasing aerobic capacity on improving lung function and preventing lung injury can be summarized in four mechanisms. The first mechanism of aerobic exercise can prevent the suppression of the immune system by affecting the immune system and increase anti-inflammatory factors. The second mechanism contains the role of aerobic capacity in restoring the elasticity of lung tissue to normal and increasing the strength and endurance of the respiratory muscles, which helps increase ventilation, and reduce lung damage. The third mechanism includes the role of aerobic capacity as an antioxidant to limit the production of free radicals and oxidative damage. The fourth mechanism involves the role of aerobic capacity in reducing cough and clearing the airways by improving pulmonary safety and autonomic modulation.