Project description:Respiratory viruses, including coronaviruses, are known to have a high incidence of infection during winter, especially in temperate regions. Dry and cold conditions during winter are the major drivers for increased respiratory tract infections as they increase virus stability and transmission and weaken the host immune system. The novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged in China in December 2020 and swiftly spread across the globe causing substantial health and economic burdens. Several countries are battling with the second wave of the virus after a devastating first wave of spread, while some are still in the midst of their first wave. It remains unclear whether SARS-CoV-2 will eventually become seasonal or will continue to circulate year-round. In an attempt to address this question, we review the current knowledge regarding the seasonality of respiratory viruses including coronaviruses and the viral and host factors that govern their seasonal pattern. Moreover, we discuss the properties of SARS-CoV-2 and the potential impact of meteorological factors on its spread.
Project description:Ebselen is an organoselenium compound exhibiting hydroperoxide- and peroxynitrite-reducing activity, acting as a glutathione peroxidase and peroxiredoxin enzyme mimetic. Ebselen reacts with a multitude of protein thiols, forming a selenosulfide bond, which results in pleiotropic effects of antiviral, antibacterial and anti-inflammatory nature. The main protease (Mpro) of the corona virus SARS-CoV-2 is a potential drug target, and a screen with over 10,000 compounds identified ebselen as a particularly promising inhibitor of Mpro (Jin, Z. et al. (2020) Nature 582, 289-293). We discuss here the reaction of ebselen with cysteine proteases, the role of ebselen in infections with viruses and with other microorganisms. We also discuss effects of ebselen in lung inflammation. In further research on the inhibition of Mpro in SARS-CoV-2, ebselen can serve as a promising lead compound, if the inhibitory effect is confirmed in intact cells in vivo. Independently of this action, potential beneficial effects of ebselen in COVID-19 are ascribed to a number of targets critical to pathogenesis, such as attenuation of inflammatory oxidants and cytokines.
Project description:ObjectiveFew studies have explored the clinical features in children infected with SARS-CoV-2 and other common respiratory viruses, including respiratory syncytial virus (RSV), Influenza virus (IV), and adenovirus (ADV). Herein, we reported the clinical characteristics and cytokine profiling in children with COVID-19 or other acute respiratory tract infections (ARTI).MethodsWe enrolled 20 hospitalized children confirmed as COVID-19 positive, 58 patients with ARTI, and 20 age and sex-matched healthy children. The clinical information and blood test results were collected. A total of 27 cytokines and chemokines were measured and analyzed.ResultsThe median age in the COVID-19 positive group was 14.5 years, which was higher than that of the ARTI groups. Around one-third of patients in the COVID-19 group experienced moderate fever, with a peak temperature of 38.27°C. None of the patients displayed wheezing or dyspnea. In addition, patients in the COVID-19 group had lower white blood cells, platelet counts as well as a neutrophil-lymphocyte ratio. Lower serum concentrations of 14 out of 27 cytokines were observed in the COVID-19 group than in healthy individuals. Seven cytokines (IL-1Ra, IL-1β, IL-9, IL-10, TNF-α, MIP-1α, and VEGF) changed serum concentration in COVID-19 compared with other ARTI groups.ConclusionPatients with COVID-19 were older and showed milder symptoms and a favorable prognosis than ARTI caused by RSV, IV, and ADV. There was a low grade or constrained innate immune reaction in children with mild COVID-19.
Project description:Respiratory virus infections are among the most prevalent diseases in humans and contribute to morbidity and mortality in all age groups. Moreover, since they can evolve fast and cross the species barrier, some of these viruses, such as influenza A and coronaviruses, have sometimes caused epidemics or pandemics and were associated with more serious clinical diseases and even mortality. The recently identified Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a Public Health Emergency of International concern and has been associated with rapidly progressive pneumonia. To ensure protection against emerging respiratory tract infections, the development of new strategies based on modulating the immune responses is essential. The use of probiotic components has substantially increased due to their effects on immune responses, in particular on those that occur in the upper/lower respiratory tract. Superinduction of inflammatory reaction, known as a cytokine storm, has been correlated directly with viral pneumonia and serious complications of respiratory infections. In this review, probiotics, as potential immunomodulatory agents, have been proposed to improve the host's response to respiratory viral infections. In addition, the effects of probiotics on different aspects of immune responses and their antiviral properties in both pre-clinical and clinical contexts have been described in detail.
Project description:ObjectivesRespiratory co-infections have the potential to affect the diagnosis and treatment of COVID-19 patients. This meta-analysis was performed to analyze the prevalence of respiratory pathogens (viruses and atypical bacteria) in COVID-19 patients.MethodsThis review was consistent with Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). Searched databases included: PubMed, EMBASE, Web of Science, Google Scholar, and grey literature. Studies with a series of SARS-CoV-2-positive patients with additional respiratory pathogen testing were included. Independently, 2 authors extracted data and assessed quality of evidence across all studies using Cochrane's Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology and within each study using the Newcastle Ottawa scale. Data extraction and quality assessment disagreements were settled by a third author. Pooled prevalence of co-infections was calculated using a random-effects model with univariate meta-regression performed to assess the effect of study subsets on heterogeneity. Publication bias was evaluated using funnel plot inspection, Begg's correlation, and Egger's test.ResultsEighteen retrospective cohorts and 1 prospective study were included. Pooling of data (1880 subjects) showed an 11.6% (95% confidence interval [CI] = 6.9-17.4, I 2 = 0.92) pooled prevalence of respiratory co-pathogens. Studies with 100% co-pathogen testing (1210 subjects) found a pooled prevalence of 16.8% (95% CI = 8.1-27.9, I 2 = 0.95) and studies using serum antibody tests (488 subjects) found a pooled prevalence of 26.8% (95%, CI = 7.9-51.9, I 2 = 0.97). Meta-regression found no moderators affecting heterogeneity.ConclusionCo-infection with respiratory pathogens is a common and potentially important occurrence in patients with COVID-19. Knowledge of the prevalence and type of co-infections may have diagnostic and management implications.
Project description:Acute viral respiratory tract infections (AVRIs) are a major burden on human health and global economy and amongst the top five causes of death worldwide resulting in an estimated 3.9 million lives lost every year. In addition, new emerging respiratory viruses regularly cause outbreaks such as SARS-CoV-1 in 2003, the "Swine flu" in 2009, or most importantly the ongoing SARS-CoV-2 pandemic, which intensely impact global health, social life, and economy. Despite the prevalence of AVRIs and an urgent need, no vaccines-except for influenza-or effective treatments were available at the beginning of the COVID-19 pandemic. However, the innate RNAi pathway offers the ability to develop nucleic acid-based antiviral drugs. siRNA sequences against conserved, essential regions of the viral genome can prevent viral replication. In addition, viral infection can be averted prophylactically by silencing host genes essential for host-viral interactions. Unfortunately, delivering siRNAs to their target cells and intracellular site of action remains the principle hurdle toward their therapeutic use. Currently, siRNA formulations and chemical modifications are evaluated for their delivery. This progress report discusses the selection of antiviral siRNA sequences, delivery techniques to the infection sites, and provides an overview of antiviral siRNAs against respiratory viruses.
Project description:Molecular analysis of respiratory viruses and the host response to both infection and vaccination have transformed our understanding of these ubiquitous pathogens. Polymerase chain reaction for the rapid and accurate diagnosis of viral infections has led to a better understanding of the epidemiology and impact of many common respiratory viruses and resulted in better patient care. Over the past decade a number of new respiratory viruses including human metapneumovirus and new coronaviruses have been discovered using molecular techniques such as random primer amplification, pan-viral array and next generation sequencing. Analysis of the host transcriptional response during respiratory viral infection using in-vitro, animal models and natural and experimental human challenge have furthered the understanding of the mechanisms and predictors of severe disease and may identify potential therapeutic targets to prevent and ameliorate illness.
Project description:Rapid infectivity of SARS-CoV2 with recent viral variants is posing a challenge in the development of robust therapeutic strategies. On the other hand, microbiota is debated for its involvement in SARS-CoV2 infection with varied opinions. Although ample data about the role of microbiota and probiotics in respiratory viral infections are available, their role in COVID-19 is limited albeit emerging rapidly. The utilization of probiotics for the management of COVID-19 is still under investigation in many clinical trials. Existing information coupled with recent COVID-19 related studies can suggest various ways to use microbiota modulation and probiotics for managing this pandemic. Present article indicates the role of microbiota modulation and probiotics in respiratory infections. In addition, scattered evidence was gathered to understand the potential of microbiota and probiotics in the management of SARS-CoV2. Gut-airway microbiota connection is already apparent in respiratory tract viral infections, including SARS-CoV2. Though few clinical trials are evaluating microbiota and probiotics for COVID-19 management, the safety evaluation must be given more serious consideration because of the possibility of opportunistic infections among COVID-19 patients. Nevertheless, the information about microbiota modulation using probiotics and prebiotics can be helpful to manage this outbreak and this review presents different aspects of this idea.
Project description:Stringent nonpharmaceutical interventions (NPIs) such as lockdowns and border closures are not currently recommended for pandemic influenza control. New Zealand used these NPIs to eliminate coronavirus disease 2019 during its first wave. Using multiple surveillance systems, we observed a parallel and unprecedented reduction of influenza and other respiratory viral infections in 2020. This finding supports the use of these NPIs for controlling pandemic influenza and other severe respiratory viral threats.
Project description:Stringent nonpharmaceutical interventions (NPIs) such as lockdowns and border closures are not currently recommended for pandemic influenza control. New Zealand used these NPIs to eliminate coronavirus disease 2019 during its first wave. Using multiple surveillance systems, we observed a parallel and unprecedented reduction of influenza and other respiratory viral infections in 2020. This finding supports the use of these NPIs for controlling pandemic influenza and other severe respiratory viral threats.