A digital health platform for assisting the diagnosis and monitoring of COVID-19 progression: An adjuvant approach for augmenting the antiviral response and mitigating the immune-mediated target organ damage.

Coronavirus disease 2019 (COVID-19), which is a respiratory illness associated with high mortality, has been classified as a pandemic. The major obstacles for the clinicians to contain the disease are limited information availability, difficulty in disease diagnosis, predicting disease prognosis, and lack of disease monitoring tools. Additionally, the lack of valid therapies has further contributed to the difficulties in containing the pandemic. Recent studies have reported that the dysregulation of the immune system leads to an ineffective antiviral response and promotes pathological immune response, which manifests as ARDS, myocarditis, and hepatitis. In this study, a novel platform has been described for disseminating information to physicians for the diagnosis and monitoring of patients with COVID-19. An adjuvant approach using compounds that can potentiate antiviral immune response and mitigate COVID-19-induced immune-mediated target organ damage has been presented. A prolonged beneficial effect is achieved by implementing algorithm-based individualized variability measures in the treatment regimen.

Pathogenesis of the inflammatory bowel disease in context of SARS-COV-2 infection.

To date, the latest research results suggest that the novel severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) can enter host cells directly via the gastrointestinal tract by binding to the enterocyte-expressed ACE2 receptor, or indirectly as a result of infection of type II alveolar epithelial cells. At the same time, entry of SARS-CoV-2 through the gastrointestinal tract initiates the activation of innate and adaptive immune responses, the formation of an excessive inflammatory reaction and critical increase in the expression of proinflammatory cytokines, which, subsequently, can presumably increase inflammation and induce intestinal damage in patients suffering from inflammatory bowel disease (IBD). The aims of the present review were to reveal and analyze possible molecular pathways and consequences of the induction of an innate and adaptive immune response during infection with SARS-CoV-2 in patients with IBD. A thorough literature search was carried out by using the keywords: IBD, SARS-CoV-2, COVID-19. Based on the screening, a number of intracellular and extracellular pathways were considered and discussed, which can impact the immune response during SARS-CoV-2 infection in IBD patients. Additionally, the possible consequences of the infection for such patients were estimated. We further hypothesize that any virus, including the new SARS-CoV-2, infecting intestinal tissues and/or entering the host's body through receptors located on intestinal enterocytes may be a trigger for the onset of IBD in individuals with a genetic predisposition and/or the risk of developing IBD associated with other factors.

Cytomegalovirus as an Uninvited Guest in the Response to Vaccines in People Living with HIV.

In stark contrast to the rapid development of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an effective human immunodeficiency virus (HIV) vaccine is still lacking. Furthermore, despite virologic suppression and CD4 T-cell count normalization with antiretroviral therapy (ART), people living with HIV (PLWH) still exhibit increased morbidity and mortality compared to the general population. Such differences in health outcomes are related to higher risk behaviors, but also to HIV-related immune activation and viral coinfections. Among these coinfections, cytomegalovirus (CMV) latent infection is a well-known inducer of long-term immune dysregulation. Cytomegalovirus contributes to the persistent immune activation in PLWH receiving ART by directly skewing immune response toward itself, and by increasing immune activation through modification of the gut microbiota and microbial translocation. In addition, through induction of immunosenescence, CMV has been associated with a decreased response to infections and vaccines. This review provides a comprehensive overview of the influence of CMV on the immune system, the mechanisms underlying a reduced response to vaccines, and discuss new therapeutic advances targeting CMV that could be used to improve vaccine response in PLWH.

SARS-CoV-2-Indigenous Microbiota Nexus: Does Gut Microbiota Contribute to Inflammation and Disease Severity in COVID-19?

Gut microbiome alterations may play a paramount role in determining the clinical outcome of clinical COVID-19 with underlying comorbid conditions like T2D, cardiovascular disorders, obesity, etc. Research is warranted to manipulate the profile of gut microbiota in COVID-19 by employing combinatorial approaches such as the use of prebiotics, probiotics and symbiotics. Prediction of gut microbiome alterations in SARS-CoV-2 infection may likely permit the development of effective therapeutic strategies. Novel and targeted interventions by manipulating gut microbiota indeed represent a promising therapeutic approach against COVID-19 immunopathogenesis and associated co-morbidities. The impact of SARS-CoV-2 on host innate immune responses associated with gut microbiome profiling is likely to contribute to the development of key strategies for application and has seldom been attempted, especially in the context of symptomatic as well as asymptomatic COVID-19 disease.

The Gastrointestinal Tract Is an Alternative Route for SARS-CoV-2 Infection in a Nonhuman Primate Model.

BACKGROUND & AIMS: Gastrointestinal (GI) manifestations have been increasingly reported in patients with coronavirus disease 2019 (COVID-19). However, the roles of the GI tract in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are not fully understood. We investigated how the GI tract is involved in SARS-CoV-2 infection to elucidate the pathogenesis of COVID-19. METHODS: Our previously established nonhuman primate (NHP) model of COVID-19 was modified in this study to test our hypothesis. Rhesus monkeys were infected with an intragastric or intranasal challenge with SARS-CoV-2. Clinical signs were recorded after infection. Viral genomic RNA was quantified by quantitative reverse transcription polymerase chain reaction. Host responses to SARS-CoV-2 infection were evaluated by examining inflammatory cytokines, macrophages, histopathology, and mucin barrier integrity. RESULTS: Intranasal inoculation with SARS-CoV-2 led to infections and pathologic changes not only in respiratory tissues but also in digestive tissues. Expectedly, intragastric inoculation with SARS-CoV-2 resulted in the productive infection of digestive tissues and inflammation in both the lung and digestive tissues. Inflammatory cytokines were induced by both types of inoculation with SARS-CoV-2, consistent with the increased expression of CD68. Immunohistochemistry and Alcian blue/periodic acid-Schiff staining showed decreased Ki67, increased cleaved caspase 3, and decreased numbers of mucin-containing goblet cells, suggesting that the inflammation induced by these 2 types of inoculation with SARS-CoV-2 impaired the GI barrier and caused severe infections. CONCLUSIONS: Both intranasal and intragastric inoculation with SARS-CoV-2 caused pneumonia and GI dysfunction in our rhesus monkey model. Inflammatory cytokines are possible connections for the pathogenesis of SARS-CoV-2 between the respiratory and digestive systems.

High expression of ACE2 in the human lung leads to the release of IL6 by suppressing cellular immunity: IL6 plays a key role in COVID-19.

OBJECTIVE: The pathogenesis of coronavirus disease 2019 (COVID-19) remains clear, and no effective treatment exists. SARS-CoV-2 is the virus that causes COVID-19 and uses ACE2 as a cell receptor to invade human cells. Therefore, ACE2 is a key factor to analyze the SARS-CoV-2 infection mechanism. MATERIALS AND METHODS: We included 9,783 sequencing results of different organs, analyzed the effects of different ACE2 expression patterns in organs and immune regulation. RESULTS: We found that ACE2 expression was significantly increased in the lungs and digestive tract. The cellular immunity of individuals with elevated ACE2 expression is activated, whereas humoral immunity is dampened, leading to the release of many inflammatory factors dominated by IL6. Furthermore, by studying the sequencing results of SARS-CoV-2-infected and uninfected cells, IL6 was found to be an indicator of a significant increase in the number of infected cells. However, although patients with high expression of ACE2 will release many inflammatory factors dominated by IL6, cellular immunity in the colorectum is significantly activated. This effect may explain why individuals with SARS-CoV-2 infection have severe lung symptoms and digestion issues, which are important causes of milder symptoms. CONCLUSIONS: This finding indicates that ACE2 and IL6 inhibitors have important value in COVID-19.

Increased Fecal Neopterin Parallels Gastrointestinal Symptoms in COVID-19.

INTRODUCTION: Coronavirus disease (COVID-19) has spread from Wuhan, China, and become a worldwide pandemic. Most patients display respiratory symptoms but up to 50% report gastrointestinal symptoms. Neopterin is a surrogate marker for viral inflammation, and its production by macrophages is driven by interferon-γ. METHODS: We measured fecal neopterin in 37 hospitalized COVID-19 patients not requiring intensive care measures and 22 healthy controls. RESULTS: Fecal neopterin was elevated in stool samples from COVID-19 patients compared with that in samples from healthy controls. Especially, patients reporting gastrointestinal symptoms exhibited increased fecal neopterin values. DISCUSSION: COVID-19 is associated with an inflammatory immune response in the gastrointestinal tract.

Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19.

OBJECTIVE: Although COVID-19 is primarily a respiratory illness, there is mounting evidence suggesting that the GI tract is involved in this disease. We investigated whether the gut microbiome is linked to disease severity in patients with COVID-19, and whether perturbations in microbiome composition, if any, resolve with clearance of the SARS-CoV-2 virus. METHODS: In this two-hospital cohort study, we obtained blood, stool and patient records from 100 patients with laboratory-confirmed SARS-CoV-2 infection. Serial stool samples were collected from 27 of the 100 patients up to 30 days after clearance of SARS-CoV-2. Gut microbiome compositions were characterised by shotgun sequencing total DNA extracted from stools. Concentrations of inflammatory cytokines and blood markers were measured from plasma. RESULTS: Gut microbiome composition was significantly altered in patients with COVID-19 compared with non-COVID-19 individuals irrespective of whether patients had received medication (p<0.01). Several gut commensals with known immunomodulatory potential such as Faecalibacterium prausnitzii, Eubacterium rectale and bifidobacteria were underrepresented in patients and remained low in samples collected up to 30 days after disease resolution. Moreover, this perturbed composition exhibited stratification with disease severity concordant with elevated concentrations of inflammatory cytokines and blood markers such as C reactive protein, lactate dehydrogenase, aspartate aminotransferase and gamma-glutamyl transferase. CONCLUSION: Associations between gut microbiota composition, levels of cytokines and inflammatory markers in patients with COVID-19 suggest that the gut microbiome is involved in the magnitude of COVID-19 severity possibly via modulating host immune responses. Furthermore, the gut microbiota dysbiosis after disease resolution could contribute to persistent symptoms, highlighting a need to understand how gut microorganisms are involved in inflammation and COVID-19.

Probiotics in Treatment of Viral Respiratory Infections and Neuroinflammatory Disorders.

Inflammation is a biological response to the activation of the immune system by various infectious or non-infectious agents, which may lead to tissue damage and various diseases. Gut commensal bacteria maintain a symbiotic relationship with the host and display a critical function in the homeostasis of the host immune system. Disturbance to the gut microbiota leads to immune dysfunction both locally and at distant sites, which causes inflammatory conditions not only in the intestine but also in the other organs such as lungs and brain, and may induce a disease state. Probiotics are well known to reinforce immunity and counteract inflammation by restoring symbiosis within the gut microbiota. As a result, probiotics protect against various diseases, including respiratory infections and neuroinflammatory disorders. A growing body of research supports the beneficial role of probiotics in lung and mental health through modulating the gut-lung and gut-brain axes. In the current paper, we discuss the potential role of probiotics in the treatment of viral respiratory infections, including the COVID-19 disease, as major public health crisis in 2020, and influenza virus infection, as well as treatment of neurological disorders like multiple sclerosis and other mental illnesses.

Oral SARS-CoV-2 Inoculation Establishes Subclinical Respiratory Infection with Virus Shedding in Golden Syrian Hamsters.

Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is transmitted largely by respiratory droplets or airborne aerosols. Despite being frequently found in the immediate environment and feces of patients, evidence supporting the oral acquisition of SARS-CoV-2 is unavailable. Using the Syrian hamster model, we demonstrate that the severity of pneumonia induced by the intranasal inhalation of SARS-CoV-2 increases with virus inoculum. SARS-CoV-2 retains its infectivity in vitro in simulated human-fed-gastric and fasted-intestinal fluid after 2 h. Oral inoculation with the highest intranasal inoculum (105 PFUs) causes mild pneumonia in 67% (4/6) of the animals, with no weight loss. The lung histopathology score and viral load are significantly lower than those infected by the lowest intranasal inoculum (100 PFUs). However, 83% of the oral infections (10/12 hamsters) have a level of detectable viral shedding from oral swabs and feces similar to that of intranasally infected hamsters. Our findings indicate that the oral acquisition of SARS-CoV-2 can establish subclinical respiratory infection with less efficiency.

COVID-19: Can the symptomatic SARS-CoV-2 infection affect the homeostasis of the gut-brain-microbiota axis?

COVID-19 is associated with acute and lethal pneumonia, causing the severe acute respiratory syndrome (SARS), which is not confined to the respiratory tract, as demonstrated by clinical evidence of the involvement of multiple organs, including the central nervous system (CNS). In this context, we hypothesized that both oligosymptomatic and symptomatic patients present an imbalance in the microbiota-gut (immune system) and nervous system axis, worsening the clinical picture. The brain constantly receives a direct and indirect influence from the intestine, more specifically from the immune system and intestinal microbiota. The presence of SARS-CoV-2 in the intestine and CNS, can contribute to both neurological disorders and gut immune system imbalance, events potentialized by an intestinal microbiota dysbiosis, aggravating the patient's condition and causing more prolonged harmful effects.

Immunological co-ordination between gut and lungs in SARS-CoV-2 infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into a major pandemic called coronavirus disease 2019 (COVID-19) that has created unprecedented global health emergencies, and emerged as a serious threat due to its strong ability for human-to-human transmission. The reports indicate the ability of SARS-CoV-2 to affect almost any organ due to the presence of a receptor known as angiotensin converting enzyme 2 (ACE2) across the body. ACE2 receptor is majorly expressed in the brush border of gut enterocytes along with the ciliated cells and alveolar epithelial type II cells in the lungs. The amino acid transport function of ACE2 has been linked to gut microbial ecology in gastrointestinal (GI) tract, thereby suggesting that COVID-19 may, to some level, be linked to the enteric microbiota. The significant number of COVID-19 patients shows extra-pulmonary symptoms in the GI tract. Many subsequent studies revealed viral RNA of SARS-CoV-2 in fecal samples of COVID-19 patients. This presents a new challenge in the diagnosis and control of COVID-19 infection with a caution for proper sanitation and hygiene. Here, we aim to discuss the immunological co-ordination between gut and lungs that facilitates SARS-CoV-2 to infect and multiply in the inflammatory bowel disease (IBD) and non-IBD patients.

Potential contribution of beneficial microbes to face the COVID-19 pandemic.

The year 2020 will be remembered by a never before seen, at least by our generation, global pandemic of COVID-19. While a desperate search for effective vaccines or drug therapies is on the run, nutritional strategies to promote immunity against SARS-CoV-2, are being discussed. Certain fermented foods and probiotics may deliver viable microbes with the potential to promote gut immunity. Prebiotics, on their side, may enhance gut immunity by selectively stimulating certain resident microbes in the gut. Different levels of evidence support the use of fermented foods, probiotics and prebiotics to promote gut and lungs immunity. Without being a promise of efficacy against COVID-19, incorporating them into the diet may help to low down gut inflammation and to enhance mucosal immunity, to possibly better face the infection by contributing to diminishing the severity or the duration of infection episodes.

A butterfly flaps its wings: Extinction of biological experience and the origins of allergy.

OBJECTIVE: To explore links between biodiversity on all scales and allergic disease as a measure of immune dysregulation. DATA SOURCES: PubMed and Web of Science were searched using the keywords biodiversity, nature relatedness, allergic disease, microbiome, noncommunicable diseases, coronavirus disease 2019, and associated terms. STUDY SELECTIONS: Studies were selected based on relevance to human health and biodiversity. RESULTS: Contact with natural environments enriches the human microbiome, promotes regulated immune responses, and protects against allergy and both acute and chronic inflammatory disorders. These important links to ecopsychological constructs of the extinction of experience, which indicates that loss of direct, personal contact with biodiversity (wildlife and the more visible elements of the natural world), might lead to emotional apathy and irresponsible behaviors toward the environment. CONCLUSION: The immune system is a useful early barometer of environmental effects and, by means of the microbiome, is a measure of the way in which our current experiences differ from our ancestral past. Although we would benefit from further research, efforts to increase direct, personal contact with biodiversity have clear benefits for multiple aspects of physical and mental health, the skin and gut microbiome, immune function, food choices, sleep, and physical activity and promote environmental responsibility.