[Fermented milk and probiotic foods are an important part of population diet during SARS-CoV-2 pandemic].

The problem of increasing the population antiviral immunity is of particular importance during the third year of the SARS-CoV-2 pandemic. Concomitant intestinal dysbiosis is known to play an significant role in immune cell dysfunction. Therefore, it is very important to take measures to maintain the gut microbiota using the most affordable nutritional remedies, which include fermented milk and probiotic products designed for mass population consumption and capable of enhancing their immune defence when added to the daily diet. The aim of the study was to analyze scientific evidence highlighting the role of intestinal microbiota in maintaining the macro-organism immunological balance, and to evaluate modern fermented milk and probiotic products in terms of their effect on normalising the gut microbiota and their importance in the prevention and treatment of SARS-CoV-2. Material and methods. The presented scientific and analytical review analyzed the data of electronic resources of the Global Health platform, scientific libraries eLIBRARY.RU, Cochrane Library and CyberLeninka, the search system Google Academy¼, specialized sites for scientific publications ScienceDirect and Elsevier, bibliographic databases of articles on medical sciences MEDLINE, CDC infection diseases, Embase and PubMed- NCBI. The structural-logical, analytical and axiomatic methods were used. Results. It has been shown that normal intestinal microbiota takes part in maintaining metabolism in the digestive tract, increases the body's immune reactivity and regulates the functioning of all organs and systems. The severity of dysbiotic disorders can determine susceptibility to SARS-CoV-2, the severity of this infection course, as well as the level of post-infection and post-vaccination anti-COVID-19 immunity. The high prevalence of gut dysbacteriosis indicates the need to strengthen measures of correcting dysbiotic disorders, including the inclusion of fermented and probiotic products in the daily population diet. Conclusion. Fermented milk and probiotic products, as sources of easily digestible macronutrients, essential micronutrients, biologically active substances and beneficial live microorganisms, should be included in the daily diet during the SARS-CoV-2 pandemic to increase the adaptive capacity and immunity of the population.

Malnutrition and Dietary Habits Alter the Immune System Which May Consequently Influence SARS-CoV-2 Virulence: A Review.

COVID-19, resulting from the SARS-CoV-2 virus, is a major pandemic that the world is fighting. SARS-CoV-2 primarily causes lung infection by attaching to the ACE2 receptor on the alveolar epithelial cells. However, the ACE2 receptor is also present in intestinal epithelial cells, suggesting a link between nutrition, virulence and clinical outcomes of COVID-19. Respiratory viral infections perturb the gut microbiota. The gut microbiota is shaped by our diet; therefore, a healthy gut is important for optimal metabolism, immunology and protection of the host. Malnutrition causes diverse changes in the immune system by repressing immune responses and enhancing viral vulnerability. Thus, improving gut health with a high-quality, nutrient-filled diet will improve immunity against infections and diseases. This review emphasizes the significance of dietary choices and its subsequent effects on the immune system, which may potentially impact SARS-CoV-2 vulnerability.

Secondary Immunodeficiency Related to Kidney Disease (SIDKD)-Definition, Unmet Need, and Mechanisms.

Kidney disease is a known risk factor for poor outcomes of COVID-19 and many other serious infections. Conversely, infection is the second most common cause of death in patients with kidney disease. However, little is known about the underlying secondary immunodeficiency related to kidney disease (SIDKD). In contrast to cardiovascular disease related to kidney disease, which has triggered countless epidemiologic, clinical, and experimental research activities or interventional trials, investments in tracing, understanding, and therapeutically targeting SIDKD have been sparse. As a call for more awareness of SIDKD as an imminent unmet medical need that requires rigorous research activities at all levels, we review the epidemiology of SIDKD and the numerous aspects of the abnormal immunophenotype of patients with kidney disease. We propose a definition of SIDKD and discuss the pathogenic mechanisms of SIDKD known thus far, including more recent insights into the unexpected immunoregulatory roles of elevated levels of FGF23 and hyperuricemia and shifts in the secretome of the intestinal microbiota in kidney disease. As an ultimate goal, we should aim to develop therapeutics that can reduce mortality due to infections in patients with kidney disease by normalizing host defense to pathogens and immune responses to vaccines.

The Exposome and Immune Health in Times of the COVID-19 Pandemic.

Growing evidence supports the importance of lifestyle and environmental exposures-collectively referred to as the 'exposome'-for ensuring immune health. In this narrative review, we summarize and discuss the effects of the different exposome components (physical activity, body weight management, diet, sun exposure, stress, sleep and circadian rhythms, pollution, smoking, and gut microbiome) on immune function and inflammation, particularly in the context of the current coronavirus disease 2019 (COVID-19) pandemic. We highlight the potential role of 'exposome improvements' in the prevention-or amelioration, once established-of this disease as well as their effect on the response to vaccination. In light of the existing evidence, the promotion of a healthy exposome should be a cornerstone in the prevention and management of the COVID-19 pandemic and other eventual pandemics.

Viral Infections, the Microbiome, and Probiotics.

Viral infections continue to cause considerable morbidity and mortality around the world. Recent rises in these infections are likely due to complex and multifactorial external drivers, including climate change, the increased mobility of people and goods and rapid demographic change to name but a few. In parallel with these external factors, we are gaining a better understanding of the internal factors associated with viral immunity. Increasingly the gastrointestinal (GI) microbiome has been shown to be a significant player in the host immune system, acting as a key regulator of immunity and host defense mechanisms. An increasing body of evidence indicates that disruption of the homeostasis between the GI microbiome and the host immune system can adversely impact viral immunity. This review aims to shed light on our understanding of how host-microbiota interactions shape the immune system, including early life factors, antibiotic exposure, immunosenescence, diet and inflammatory diseases. We also discuss the evidence base for how host commensal organisms and microbiome therapeutics can impact the prevention and/or treatment of viral infections, such as viral gastroenteritis, viral hepatitis, human immunodeficiency virus (HIV), human papilloma virus (HPV), viral upper respiratory tract infections (URTI), influenza and SARS CoV-2. The interplay between the gastrointestinal microbiome, invasive viruses and host physiology is complex and yet to be fully characterized, but increasingly the evidence shows that the microbiome can have an impact on viral disease outcomes. While the current evidence base is informative, further well designed human clinical trials will be needed to fully understand the array of immunological mechanisms underlying this intricate relationship.

Potential Association Between Dietary Fibre and Humoral Response to the Seasonal Influenza Vaccine.

Influenza vaccination is an effective public health measure to reduce the risk of influenza illness, particularly when the vaccine is well matched to circulating strains. Notwithstanding, the efficacy of influenza vaccination varies greatly among vaccinees due to largely unknown immunological determinants, thereby dampening population-wide protection. Here, we report that dietary fibre may play a significant role in humoral vaccine responses. We found dietary fibre intake and the abundance of fibre-fermenting intestinal bacteria to be positively correlated with humoral influenza vaccine-specific immune responses in human vaccinees, albeit without reaching statistical significance. Importantly, this correlation was largely driven by first-time vaccinees; prior influenza vaccination negatively correlated with vaccine immunogenicity. In support of these observations, dietary fibre consumption significantly enhanced humoral influenza vaccine responses in mice, where the effect was mechanistically linked to short-chain fatty acids, the bacterial fermentation product of dietary fibre. Overall, these findings may bear significant importance for emerging infectious agents, such as COVID-19, and associated de novo vaccinations.

Role of Gut Microbiome in COVID-19: An Insight Into Pathogenesis and Therapeutic Potential.

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulted in an unprecedented global crisis. Although primarily a respiratory illness, dysregulated immune responses may lead to multi-organ dysfunction. Prior data showed that the resident microbial communities of gastrointestinal and respiratory tracts act as modulators of local and systemic inflammatory activity (the gut-lung axis). Evolving evidence now signals an alteration in the gut microbiome, brought upon either by cytokines from the infected respiratory tract or from direct infection of the gut, or both. Dysbiosis leads to a "leaky gut". The intestinal permeability then allows access to bacterial products and toxins into the circulatory system and further exacerbates the systemic inflammatory response. In this review, we discuss the available data related to the role of the gut microbiome in the development and progression of COVID-19. We provide mechanistic insights into early data with a focus on immunological crosstalk and the microbiome's potential as a biomarker and therapeutic target.

Cross-talk between immune system and microbiota in COVID-19.

INTRODUCTION: Human gut microbiota plays a crucial role in providing protective responses against pathogens, particularly by regulating immune system homeostasis. There is a reciprocal interaction between the gut and lung microbiota, called the gut-lung axis (GLA). Any alteration in the gut microbiota or their metabolites can cause immune dysregulation, which can impair the antiviral activity of the immune system against respiratory viruses such as severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2. AREAS COVERED: This narrative review mainly outlines emerging data on the mechanisms underlying the interactions between the immune system and intestinal microbial dysbiosis, which is caused by an imbalance in the levels of essential metabolites. The authors will also discuss the role of probiotics in restoring the balance of the gut microbiota and modulation of cytokine storm. EXPERT OPINION: Microbiota-derived signals regulate the immune system and protect different tissues during severe viral respiratory infections. The GLA's equilibration could help manage the mortality and morbidity rates associated with SARS-CoV-2 infection.

Neuropsychiatric Ramifications of COVID-19: Short-Chain Fatty Acid Deficiency and Disturbance of Microbiota-Gut-Brain Axis Signaling.

COVID-19-associated neuropsychiatric complications are soaring. There is an urgent need to understand the link between COVID-19 and neuropsychiatric disorders. To that end, this article addresses the premise that SARS-CoV-2 infection results in gut dysbiosis and an altered microbiota-gut-brain (MGB) axis that in turn contributes to the neuropsychiatric ramifications of COVID-19. Altered MGB axis activity has been implicated independently as a risk of neuropsychiatric disorders. A review of the changes in gut microbiota composition in individual psychiatric and neurological disorders and gut microbiota in COVID-19 patients revealed a shared "microbial signature" characterized by a lower microbial diversity and richness and a decrease in health-promoting anti-inflammatory commensal bacteria accompanied by an increase in opportunistic proinflammatory pathogens. Notably, there was a decrease in short-chain fatty acid (SCFA) producing bacteria. SCFAs are key bioactive microbial metabolites with anti-inflammatory functions and have been recognized as a critical signaling pathway in the MGB axis. SCFA deficiency is associated with brain inflammation, considered a cardinal feature of neuropsychiatric disorders. The link between SARS-CoV-2 infection, gut dysbiosis, and altered MGB axis is further supported by COVID-19-associated gastrointestinal symptoms, a high number of SARS-CoV-2 receptors, angiotensin-cleaving enzyme-2 (ACE-2) in the gut, and viral presence in the fecal matter. The binding of SARS-CoV-2 to the receptor results in ACE-2 deficiency that leads to decreased transport of vital dietary components, gut dysbiosis, proinflammatory gut status, increased permeability of the gut-blood barrier (GBB), and systemic inflammation. More clinical research is needed to substantiate further the linkages described above and evaluate the potential significance of gut microbiota as a diagnostic tool. Meanwhile, it is prudent to propose changes in dietary recommendations in favor of a high fiber diet or supplementation with SCFAs or probiotics to prevent or alleviate the neuropsychiatric ramifications of COVID-19.

Covid 19: Diet Composition and Health.

The virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the disease coronavirus disease 2019 (COVID-19). The cumulative number of cases reported globally is now nearly 197 million and the number of cumulative deaths is 4.2 million (26 July to 1 August 2021). Currently we are focusing primarily on keeping a safe distance from others, washing our hands, and wearing masks, and the question of the effects of diet and diet-dependent risk factors remains outside the center of attention. Nevertheless, numerous studies indicate that diet can play an important role in the course of COVID-19. In this paper, based on select scientific reports, we discuss the structure and replication cycle of SARS-CoV-2, risk factors, dietary standards for sick patients, and the roles of the microbiome and dietary components supporting the immune system in preventing COVID-19.

Plasma 1,3-ß-d-glucan levels predict adverse clinical outcomes in critical illness.

BACKGROUNDThe fungal cell wall constituent 1,3-ß-d-glucan (BDG) is a pathogen-associated molecular pattern that can stimulate innate immunity. We hypothesized that BDG from colonizing fungi in critically ill patients may translocate into the systemic circulation and be associated with host inflammation and outcomes.METHODSWe enrolled 453 mechanically ventilated patients with acute respiratory failure (ARF) without invasive fungal infection and measured BDG, innate immunity, and epithelial permeability biomarkers in serially collected plasma samples.RESULTSCompared with healthy controls, patients with ARF had significantly higher BDG levels (median [IQR], 26 pg/mL [15-49 pg/mL], P < 0.001), whereas patients with ARF with high BDG levels (≥40 pg/mL, 31%) had higher odds for assignment to the prognostically adverse hyperinflammatory subphenotype (OR [CI], 2.88 [1.83-4.54], P < 0.001). Baseline BDG levels were predictive of fewer ventilator-free days and worse 30-day survival (adjusted P < 0.05). Integrative analyses of fungal colonization and epithelial barrier disruption suggested that BDG may translocate from either the lung or gut compartment. We validated the associations between plasma BDG and host inflammatory responses in 97 hospitalized patients with COVID-19.CONCLUSIONBDG measurements offered prognostic information in critically ill patients without fungal infections. Further research in the mechanisms of translocation and innate immunity recognition and stimulation may offer new therapeutic opportunities in critical illness.FUNDINGUniversity of Pittsburgh Clinical and Translational Science Institute, COVID-19 Pilot Award and NIH grants (K23 HL139987, U01 HL098962, P01 HL114453, R01 HL097376, K24 HL123342, U01 HL137159, R01 LM012087, K08HK144820, F32 HL142172, K23 GM122069).

COVID-19 pandemic: insights into molecular mechanisms leading to sex-based differences in patient outcomes.

Recent epidemiological studies analysing sex-disaggregated patient data of coronavirus disease 2019 (COVID-19) across the world revealed a distinct sex bias in the disease morbidity as well as the mortality - both being higher for the men. Similar antecedents have been known for the previous viral infections, including from coronaviruses, such as severe acute respiratory syndrome (SARS) and middle-east respiratory syndrome (MERS). A sound understanding of molecular mechanisms leading to the biological sex bias in the survival outcomes of the patients in relation to COVID-19 will act as an essential requisite for developing a sex-differentiated approach for therapeutic management of this disease. Recent studies which have explored molecular mechanism(s) behind sex-based differences in COVID-19 pathogenesis are scarce; however, existing evidence, for other respiratory viral infections, viz. SARS, MERS and influenza, provides important clues in this regard. In attempt to consolidate the available knowledge on this issue, we conducted a systematic review of the existing empirical knowledge and recent experimental studies following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The qualitative analysis of the collected data unravelled multiple molecular mechanisms, such as evolutionary and genetic/epigenetic factors, sex-linkage of viral host cell entry receptor and immune response genes, sex hormone and gut microbiome-mediated immune-modulation, as the possible key reasons for the sex-based differences in patient outcomes in COVID-19.

Unraveling the Mystery Surrounding Post-Acute Sequelae of COVID-19.

More than one year since its emergence, corona virus disease 2019 (COVID-19) is still looming large with a paucity of treatment options. To add to this burden, a sizeable subset of patients who have recovered from acute COVID-19 infection have reported lingering symptoms, leading to significant disability and impairment of their daily life activities. These patients are considered to suffer from what has been termed as "chronic" or "long" COVID-19 or a form of post-acute sequelae of COVID-19, and patients experiencing this syndrome have been termed COVID-19 long-haulers. Despite recovery from infection, the persistence of atypical chronic symptoms, including extreme fatigue, shortness of breath, joint pains, brain fogs, anxiety and depression, that could last for months implies an underlying disease pathology that persist beyond the acute presentation of the disease. As opposed to the direct effects of the virus itself, the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is believed to be largely responsible for the appearance of these lasting symptoms, possibly through facilitating an ongoing inflammatory process. In this review, we hypothesize potential immunological mechanisms underlying these persistent and prolonged effects, and describe the multi-organ long-term manifestations of COVID-19.

Plasma Markers of Disrupted Gut Permeability in Severe COVID-19 Patients.

A disruption of the crosstalk between the gut and the lung has been implicated as a driver of severity during respiratory-related diseases. Lung injury causes systemic inflammation, which disrupts gut barrier integrity, increasing the permeability to gut microbes and their products. This exacerbates inflammation, resulting in positive feedback. We aimed to test whether severe Coronavirus disease 2019 (COVID-19) is associated with markers of disrupted gut permeability. We applied a multi-omic systems biology approach to analyze plasma samples from COVID-19 patients with varying disease severity and SARS-CoV-2 negative controls. We investigated the potential links between plasma markers of gut barrier integrity, microbial translocation, systemic inflammation, metabolome, lipidome, and glycome, and COVID-19 severity. We found that severe COVID-19 is associated with high levels of markers of tight junction permeability and translocation of bacterial and fungal products into the blood. These markers of disrupted intestinal barrier integrity and microbial translocation correlate strongly with higher levels of markers of systemic inflammation and immune activation, lower levels of markers of intestinal function, disrupted plasma metabolome and glycome, and higher mortality rate. Our study highlights an underappreciated factor with significant clinical implications, disruption in gut functions, as a potential force that may contribute to COVID-19 severity.

The Role of the Gut-Liver Axis in Metabolic Dysfunction-Associated Fatty Liver Disease.

The complex interplay between the gut microbiota, the intestinal barrier, the immune system and the liver is strongly influenced by environmental and genetic factors that can disrupt the homeostasis leading to disease. Among the modulable factors, diet has been identified as a key regulator of microbiota composition in patients with metabolic syndrome and related diseases, including the metabolic dysfunction-associated fatty liver disease (MAFLD). The altered microbiota disrupts the intestinal barrier at different levels inducing functional and structural changes at the mucus lining, the intercellular junctions on the epithelial layer, or at the recently characterized vascular barrier. Barrier disruption leads to an increased gut permeability to bacteria and derived products which challenge the immune system and promote inflammation. All these alterations contribute to the pathogenesis of MAFLD, and thus, therapeutic approaches targeting the gut-liver-axis are increasingly being explored. In addition, the specific changes induced in the intestinal flora may allow to characterize distinctive microbial signatures for non-invasive diagnosis, severity stratification and disease monitoring.

Intestinal Microbiota-A Promising Target for Antiviral Therapy?

The intestinal microbiota is thought to be an important biological barrier against enteric pathogens. Its depletion, however, also has curative effects against some viral infections, suggesting that different components of the intestinal microbiota can play both promoting and inhibitory roles depending on the type of viral infection. The two primary mechanisms by which the microbiota facilitates or inhibits viral invasion involve participation in the innate and adaptive immune responses and direct or indirect interaction with the virus, during which the abundance and composition of the intestinal microbiota might be changed by the virus. Oral administration of probiotics, faecal microbiota transplantation (FMT), and antibiotics are major therapeutic strategies for regulating intestinal microbiota balance. However, these three methods have shown limited curative effects in clinical trials. Therefore, the intestinal microbiota might represent a new and promising supplementary antiviral therapeutic target, and more efficient and safer methods for regulating the microbiota require deeper investigation. This review summarizes the latest research on the relationship among the intestinal microbiota, anti-viral immunity and viruses and the most commonly used methods for regulating the intestinal microbiota with the goal of providing new insight into the antiviral effects of the gut microbiota.

Classification, structure and mechanism of antiviral polysaccharides derived from edible and medicinal fungus.

The deficiency of chemical-synthesized antiviral drugs when applied in clinical therapy, such as drug resistance, and the lack of effective antiviral drugs to treat some newly emerging virus infections, such as COVID-19, promote the demand of novelty and safety anti-virus drug candidate from natural functional ingredient. Numerous studies have shown that some polysaccharides sourcing from edible and medicinal fungus (EMFs) exert direct or indirect anti-viral capacities. However, the internal connection of fungus type, polysaccharides structural characteristics, action mechanism was still unclear. Herein, our review focus on the two aspects, on the one hand, we discussed the type of anti-viral EMFs and the structural characteristics of polysaccharides to clarify the structure-activity relationship, on the other hand, the directly or indirectly antiviral mechanism of EMFs polysaccharides, including virus function suppression, immune-modulatory activity, anti-inflammatory activity, regulation of population balance of gut microbiota have been concluded to provide a comprehensive theory basis for better clinical utilization of EMFs polysaccharides as anti-viral agents.

Probiotics, Photobiomodulation, and Disease Management: Controversies and Challenges.

In recent decades, researchers around the world have been studying intensively how micro-organisms that are present inside living organisms could affect the main processes of life, namely health and pathological conditions of mind or body. They discovered a relationship between the whole microbial colonization and the initiation and development of different medical disorders. Besides already known probiotics, novel products such as postbiotics and paraprobiotics have been developed in recent years to create new non-viable micro-organisms or bacterial-free extracts, which can provide benefits to the host with additional bioactivity to probiotics, but without the risk of side effects. The best alternatives in the use of probiotics and postbiotics to maintain the health of the intestinal microbiota and to prevent the attachment of pathogens to children and adults are highlighted and discussed as controversies and challenges. Updated knowledge of the molecular and cellular mechanisms involved in the balance between microbiota and immune system for the introspection on the gut-lung-brain axis could reveal the latest benefits and perspectives of applied photobiomics for health. Multiple interconditioning between photobiomodulation (PBM), probiotics, and the human microbiota, their effects on the human body, and their implications for the management of viral infectious diseases is essential. Coupled complex PBM and probiotic interventions can control the microbiome, improve the activity of the immune system, and save the lives of people with immune imbalances. There is an urgent need to seek and develop innovative treatments to successfully interact with the microbiota and the human immune system in the coronavirus crisis. In the near future, photobiomics and metabolomics should be applied innovatively in the SARS-CoV-2 crisis (to study and design new therapies for COVID-19 immediately), to discover how bacteria can help us through adequate energy biostimulation to combat this pandemic, so that we can find the key to the hidden code of communication between RNA viruses, bacteria, and our body.