SARS-CoV-2 microbiome dysbiosis linked disorders and possible probiotics role.
ABSTRACT: In December 2019, a pneumonia outbreak of unknown etiology was reported which caused panic in Wuhan city of central China, which was later identified as Coronavirus disease (COVID-19) caused by a novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) by the Chinese Centre for Disease Control and Prevention (CDC) and WHO. To date, the SARS-CoV-2 spread has already become a global pandemic with a considerable death toll. The associated symptoms of the COVID-19 infection varied with increased inflammation as an everyday pathological basis. Among various other symptoms such as fever, cough, lethargy, gastrointestinal (GI) symptoms included diarrhea and IBD with colitis, have been reported. Currently, there is no sole cure for COVID-19, and researchers are actively engaged to search out appropriate treatment and develop a vaccine for its prevention. Antiviral for controlling viral load and corticosteroid therapy for reducing inflammation seems to be inadequate to control the fatality rate. Based on the available related literature, which documented GI symptoms with diarrhea, inflammatory bowel diseases (IBD) with colitis, and increased deaths in the intensive care unit (ICU), conclude that dysbiosis occurs during SARS-COV-2 infection as the gut-lung axis cannot be ignored. As probiotics play a therapeutic role for GI, IBD, colitis, and even in viral infection. So, we assume that the inclusion of studies to investigate gut microbiome and subsequent therapies such as probiotics might help decrease the inflammatory response of viral pathogenesis and respiratory symptoms by strengthening the host immune system, amelioration of gut microbiome, and improvement of gut barrier function.
Project description: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.
Project description:<h4>Background</h4>Patients with COVID-19 caused by SARS-CoV-2 exhibit diverse clinical manifestations and severity including enteric involvement. Commensal gut bacteria can contribute to defense against potential pathogens by promoting beneficial immune interactions. Interventions targeting the gut microbiome may have systemic anti-viral effects in SARS-CoV-2 infection.<h4>Scope and approach</h4>To summarise alterations of gut microbiota in patients with COVID-19 including impact of specific bacteria on disease severity, discuss current knowledge on the role of probiotics, prebiotics and dietary approaches including vitamin D in preventing and reducing disease susceptibility and review clinical studies using probiotics to target coronavirus. A literature review on SARS-CoV-2, COVID-19, gut microbiome and immunity was undertaken and relevant literature was summarised and critically examined.<h4>Key findings and conclusions</h4>Integrity of gut microbiome was perturbed in SARS-CoV-2 infections and associated with disease severity. Poor prognosis in SARS-CoV-2 infection was observed in subjects with underlying co-morbidities who had increased gut permeability and reduced gut microbiome diversity. Dietary microbes, including probiotics or selected prebiotics of Chinese origin, had anti-viral effects against other forms of coronavirus, and could positively impact host immune functions during SARS-CoV-2 infection. Numerous studies are investigating the role of probiotics in preventing and reducing susceptibility to SARS-CoV-2 infection in healthcare workers, household contacts and affected patients. An approach to strengthen intestinal barrier and lower pro-inflammatory states by adopting a more diversified diet during COVID-19 pandemic.SARS-CoV-2 infection is associated with immune dysfunction and gut microbiota alterations. Delineating mechanisms of probiotics, prebiotics and diet with anti-SARS-CoV-2 immunity present opportunities for discovery of microbial therapeutics to prevent and treat COVID-19.
Project description:Interspecies transmissions of viruses between animals and humans may result in unpredictable pathogenic potential and new transmissible diseases. This mechanism has recently been exemplified by the discovery of new pathogenic viruses, such as the novel severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) pandemic, Middle-East respiratory syndrome-coronavirus epidemic in Saudi Arabia, and the deadly outbreak of Ebola in West Africa. The. SARS-CoV-2 causes coronavirus disease-19 (COVID-19), which is having a massive global impact in terms of economic disruption, and, above all, human health. The disease is characterized by dry cough, fever, fatigue, myalgia, and dyspnea. Other symptoms include headache, sore throat, rhinorrhea, and gastrointestinal disorders. Pneumonia appears to be the most common and severe manifestation of the infection. Currently, there is no vaccine or specific drug for COVID-19. Further, the development of new antiviral requires a considerable length of time and effort for drug design and validation. Therefore, repurposing the use of natural compounds can provide alternatives and can support therapy against COVID-19. In this review, we comprehensively discuss the prophylactic and supportive therapeutic role of probiotics for the management of COVID-19. In addition, the unique role of probiotics to modulate the gut microbe and assert gut homeostasis and production of interferon as an antiviral mechanism is described. Further, the regulatory role of probiotics on gut-lung axis and mucosal immune system for the potential antiviral mechanisms is reviewed and discussed.Key points• Gut microbiota role in antiviral diseases• Factors influencing the antiviral mechanism• Probiotics and Covid-19.
Project description:Importance:Coronavirus disease 2019 (COVID-19) is a global pandemic and can involve the gastrointestinal (GI) tract, including symptoms like diarrhea and shedding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in feces. Objective:To provide a pooled estimate of GI symptoms, liver enzyme levels outside reference ranges, and fecal tests positive for SARS-CoV-2 among patients with COVID-19. Data Sources:An electronic literature search was performed for published (using MEDLINE/PubMed and Embase) and preprint (using bioRxiv and medRxiv) studies of interest conducted from November 1, 2019, to March 30, 2020. Search terms included "COVID-19," "SARS-Cov-2," and/or "novel coronavirus." Study Selection:Eligible studies were those including patients with SARS-CoV-2 infection who reported GI symptoms. Data Extraction and Synthesis:Data on patients with GI symptoms (ie, diarrhea, nausea, or vomiting), liver enzyme level changes, and fecal shedding of virus were extracted. Quality of studies was examined using methodological index for nonrandomized studies. Pooled estimates (%) were reported with 95% CIs with level of heterogeneity (I2). Main Outcomes and Measures:Study and patient characteristics with pooled detection rates for diarrhea, nausea or vomiting, liver enzyme levels outside reference ranges, and SARS-CoV-2 positivity in feces tests were analyzed. Results:Of 1484 records reviewed, 23 published and 6 preprint studies were included in the analysis, with a total of 4805 patients (mean [SD] age, 52.2 [14.8] years; 1598 [33.2%] women) with COVID-19. The pooled rates were 7.4% (95% CI, 4.3%-12.2%) of patients reporting diarrhea and 4.6% (95% CI, 2.6%-8.0%) of patients reporting nausea or vomiting. The pooled rate for aspartate aminotransferase levels outside reference ranges was 20% (95% CI, 15.3%-25.6%) of patients, and the pooled rate for alanine aminotransferase levels outside reference ranges was 14.6% (95% CI, 12.8%-16.6%) of patients. Fecal tests that were positive for SARS-CoV-2 were reported in 8 studies, and viral RNA shedding was detected in feces in 40.5% (95% CI, 27.4%-55.1%) of patients. There was high level of heterogeneity (I2?=?94%), but no statistically significant publication bias noted. Conclusions and Relevance:These findings suggest that that 12% of patients with COVID-19 will manifest GI symptoms; however, SAR-CoV-2 shedding was observed in 40.5% of patients with confirmed SARS-CoV-2 infection. This highlights the need to better understand what measures are needed to prevent further spread of this highly contagious pathogen.
Project description:COVID-19 is an infectious disease caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), and according to the World Health Organization (WHO), to date, SARS-CoV-2 has already infected more than 91.8 million people worldwide with 1,986,871 deaths. This virus affects mainly the respiratory system, but the gastrointestinal tract (GIT) is also a target, meanwhile SARS-CoV-2 was already detected in oesophagus, stomach, duodenum, rectum, and in fecal samples from COVID-19 patients. Prolonged GIT manifestations in COVID-19, mainly the diarrhea, were correlated with decreased richness and diversity of the gut microbiota, immune deregulation and delayed SARS-CoV-2 clearance. So, the bidirectional interactions between the respiratory mucosa and the gut microbiota, known as gut-lung axis, are supposed to be involved in the healthy or pathologic immune responses to SARS-CoV-2. In accordance, the intestinal dysbiosis is associated with increased mortality in other respiratory infections, due to an exacerbated inflammation and decreased regulatory or anti-inflammatory mechanisms in the lungs and in the gut, pointing to this important relationship between both mucosal compartments. Therefore, since the mucous membranes from the respiratory and gastrointestinal tracts are affected, in addition to dysbiosis and inflammation, it is plausible to assume that adjunctive therapies based on the modulation of the gut microbiota and re-establishment of eubiosis conditions could be an important therapeutic approach for constraining the harmful consequences of COVID-19. Then, in this review, we summarized studies showing the persistence of SARS-CoV-2 in the gastrointestinal system and the related digestive COVID-19 manifestations, in addition to the literature demonstrating nasopharyngeal, pulmonary and intestinal dysbiosis in COVID-19 patients. Lastly, we showed the potential beneficial role of probiotic administration in other respiratory infections, and discuss the possible role of probiotics as an adjunctive therapy in SARS-CoV-2 infection.
Project description:<b>Objectives:</b> This work aims to study the gastrointestinal (GI) symptoms in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients and the susceptibility factors of the stomach for SARS-CoV-2. <b>Materials and Methods:</b> We investigated the SARS-CoV-2 susceptibility by analyzing the expression distribution of viral entry-associated genes, <i>ACE2</i> and <i>TMPRSS2</i>, in single-cell RNA sequencing data derived from 12 gastric mucosa samples. We also analyzed the epidemiological, demographic, clinical, and laboratory data of 420 cases with SARS-CoV-2-caused coronavirus disease 2019 (COVID-19). <b>Results:</b> <i>ACE2</i> and <i>TMPRSS2</i> are specifically expressed in enterocytes which are mainly from gastric mucosa samples with <i>Helicobacter pylori</i> (<i>H. pylori</i>) infection history and intestinal metaplasia (IM). A total of 420 patients were surveyed, of which 62 were with and 358 were without GI symptoms. There is a significant difference in average hospital stay (<i>p</i> < 0.001) and cost (<i>p</i> < 0.001) between the two groups. Among 23 hospitalized patients including seven with upper GI symptoms and 16 with lower GI symptoms, six (85.7%) and five (31.3%) had <i>H. pylori</i> infection history, respectively (<i>p</i> = 0.03). Of 18 hospitalized patients with initial upper GI symptoms, none of the eight patients with mucosal protective agent therapy (e.g., sucralfate suspension gel, hydrotalcite tablets) had diarrhea subsequently, whereas six out of 10 patients without mucosal protective agent therapy had diarrhea subsequently (<i>p</i> = 0.01). <b>Conclusion:</b> IM and <i>H. pylori</i> infection history may be susceptibility factors of SARS-CoV-2, and the mucosal protective agent may be useful for the blockade of SARS-CoV-2 transmission from the stomach to the intestine.
Project description:Studies on patients with the coronavirus disease-2019 (COVID-19) have implicated that the gastrointestinal (GI) tract is a major site of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We established a human GI tract cell line model highly permissive to SARS-CoV-2. These cells, C2BBe1 intestinal cells with a brush border having high levels of transmembrane serine protease 2 (TMPRSS2), showed robust viral propagation, and could be persistently infected with SARS-CoV-2, supporting the clinical observations of persistent GI infection in COVID-19 patients. Ectopic expression of viral receptors revealed that the levels of angiotensin-converting enzyme 2 (ACE2) expression confer permissiveness to SARS-CoV-2 infection, and TMPRSS2 greatly facilitates ACE2-mediated SARS-CoV-2 dissemination. Interestingly, ACE2 but not TMPRSS2 expression was significantly promoted by enterocytic differentiation, suggesting that the state of enterocytic differentiation may serve as a determining factor for viral propagation. Thus, our study sheds light on the pathogenesis of SARS-CoV-2 in the GI tract.
Project description:COVID-19 is caused by a new strain of coronavirus called SARS-coronavirus-2 (SARS-CoV-2), which is a positive sense single strand RNA virus. In humans, it binds to angiotensin converting enzyme 2 (ACE2) with the help a structural protein on its surface called the S-spike. Further, cleavage of the viral spike protein (S) by the proteases like transmembrane serine protease 2 (TMPRSS2) or Cathepsin L (CTSL) is essential to effectuate host cell membrane fusion and virus infectivity. COVID-19 poses intriguing issues with imperative relevance to clinicians. The pathogenesis of GI symptoms, diabetes-associated mortality, and disease recurrence in COVID-19 are of particular relevance because they cannot be sufficiently explained from the existing knowledge of the viral diseases. Tissue specific variations of SARS-CoV-2 cell entry related receptors expression in healthy individuals can help in understanding the pathophysiological basis the aforementioned collection of symptoms. ACE2 mediated dysregulation of sodium dependent glucose transporter (SGLT1 or SLC5A1) in the intestinal epithelium also links it to the pathogenesis of diabetes mellitus which can be a possible reason for the associated mortality in COVID-19 patients with diabetes. High expression of ACE2 in mucosal cells of the intestine and GB make these organs potential sites for the virus entry and replication. Continued replication of the virus at these ACE2 enriched sites may be a basis for the disease recurrence reported in some, thought to be cured, patients. Based on the human tissue specific distribution of SARS-CoV-2 cell entry factors ACE2 and TMPRSS2 and other supportive evidence from the literature, we hypothesize that SARS-CoV-2 host cell entry receptor-ACE2 based mechanism in GI tissue may be involved in COVID-19 (i) in the pathogenesis of digestive symptoms, (ii) in increased diabetic complications, (iii) in disease recurrence.
Project description:Background:The novel coronavirus SARS-CoV-2 causing COVID-19 disease is yielding a global outbreak with severe threats to public health. In this paper, we aimed at reviewing the current knowledge about COVID-19 infectious risk status in inflammatory bowel disease (IBD) patients requiring immunosuppressive medication. We also focused on several molecular insights that could explain why IBD patients appear not to have higher risks of infection and worse outcomes in COVID-19 than the general population in an attempt to provide scientific support for safer decisions in IBD patient care. Methods:PubMed electronic database was interrogated for relevant articles involving data about common molecular pathways and shared treatment strategies between SARS-CoV-2, SARS-CoV-1, MERS-CoV, and inflammatory bowel diseases. Besides, Neural Covidex, an artificial intelligence tool, was used to answer queries about pathogenic coronaviruses and possible IBD interactions using the COVID-19 Open Research Dataset (CORD-19). Discussions. Few molecular and therapeutic interactions between IBD and pathogenic coronaviruses were explored. First, we showed how the activity of soluble angiotensin-converting enzyme 2, CD209L other receptors, and phosphorylated ? subunit of eukaryotic translation initiation factor 2 might exert protective impact in IBD in case of coronavirus infection. Second, IBD medication was discussed in the context of possible beneficial effects on COVID-19 pathogeny, including "cytokine storm" prevention and treatment, immunomodulation, interferon signaling blocking, and viral endocytosis inhibition. Conclusions:Using the current understanding of SARS-CoV-2 as well as other pathogenic coronaviruses immunopathology, we showed why IBD patients should not be considered at an increased risk of infection or more severe outcomes. Whether our findings are entirely applicable to the pathogenesis, disease susceptibility, and treatment management of SARS-CoV-2 infection in IBD must be further explored.
Project description:Most of reported symptoms of SARS-CoV-2 infection are related to the respiratory system. Extra pulmonary manifestations of this novel virus infection are being increasingly reported in the literature, with increased attention on the gastrointestinal symptoms which might be the only presenting symptoms in some patients. These GI symptoms are nonspecific and little reported cases in the literature of confirmed gastrointestinal manifestations of SARS-CoV-2 infection by imaging. Colitis related to SARS-CoV-2 is even less reported in the literature. We present a case of SARS-CoV-2 infection of a 40-year-old lady who presented with GI manifestations and features of colitis of the caecum and ascending colon on CT scan. The patient did not have respiratory symptoms but had incidental lung changes in the visualized lung bases. These features were completely resolved as evident clinically and on follow-up CT scan after only 2 weeks, with only supportive care for SARS-CoV-2 infection. GI symptoms, in general, are very common presenting complain for many patients visiting the emergency department; hence, early recognition and high index of clinical suspicion for SARS-CoV-2 infection with the presence of supporting laboratory and imaging findings are to be considered for early protective measures to be undertaken to help in reducing the spread of this virus; in particular, in the middle of global pandemic of this virus and the fact that GI symptoms could be the only presenting symptoms without any respiratory symptoms. More studies and further invasive investigations in patients with features of colitis in imaging are needed to further understand the pathogenesis and its relation to SARS-CoV-2 infection.