Probiotics and prebiotics have been suggested as natural agents against viral infections and dysbiosis and may encourage clinical applications. This review aims to analyze the main and recent advances related to viral infections such as Covid-19 and its gastrointestinal complications, antiviral immunity generated and possible preventive role that probiotics and/or prebiotics can play in controlling and promoting antiviral immunity. The literature search was performed through a critical analysis of relevant publications reported in PubMed and Scopus databases on clinical trials and assays conducted in vitro on colon cells and in vivo on mice. Some studies using probiotics and prebiotics for the prevention of viral infection in different age groups are discussed. Covid-19 patients have been shown to suffer from gastrointestinal complications in addition to respiratory symptoms due to interactions between the respiratory system and the gastrointestinal tract infected with SARS-CoV-2. Unfortunately, therapies used to prevent (or treat) symptoms of Covid-19 have proven to be of limited effectiveness. In addition, the lack of access to coronavirus vaccines around the world and vaccine hesitancy continue to hamper control of Covid-19. It is therefore crucial to find alternative methods that can prevent disease symptoms. Evidence-based efficacy of certain probiotics (Lactobacillus and Bifidobacterium) that may be useful in viral infections was shown with immunomodulatory properties (pro-inflammatory mediators reduction), promoting antiviral immunity (antibodies production, virus titers) and controlling inflammation (anti-inflammatory effect), as well as viral clearance and antimicrobial potential against opportunistic bacteria (anti-dysbiosis effect). But, available data about clinical application of probiotics in Covid-19 context remain limited and relevant scientific investigation is still in its early stages. Also, evidence for prebiotics potential in this field is limited, since the exact mechanism involved in systemic immune modulation by these compounds is till now unknown. Thus, further research is necessary to explore in the viral infection context the mechanism by which gut and lung interact in the presence of probiotics and prebiotics through more animal and clinical experiments.

Coronavirus disease (COVID-19), caused by severe acquired respiratory syndrome-Coronavirus-2 (SARS-CoV-2), triggered a global pandemic with severe medical and socioeconomic consequences. Although fatality rates are higher among the elderly and those with underlying comorbidities, host factors that promote susceptibility to SARS-CoV-2 infection and severe disease are poorly understood. Although individuals with certain autoimmune/inflammatory disorders show increased susceptibility to viral infections, there is incomplete knowledge of SARS-CoV-2 susceptibility in these diseases. The aim of our study was to investigate whether the autoimmunity risk gene, PTPN2, which also confers elevated risk to develop inflammatory bowel disease, affects susceptibility to SARS-CoV-2 viral uptake.

Using samples from PTPN2 genotyped patients with inflammatory bowel disease, PTPN2-deficient mice, and human intestinal and lung epithelial cell lines, we investigated how PTPN2 affects expression of the SARS-CoV-2 receptor angiotensin converting enzyme 2 (ACE2), and uptake of virus-like particles expressing the SARS-CoV2 spike protein and live SARS-CoV-2 virus.

We report that the autoimmune PTPN2 loss-of-function risk variant rs1893217 promotes expression of the SARS-CoV-2 receptor, ACE2, and increases cellular entry of SARS-CoV-2 spike protein and live virus. Elevated ACE2 expression and viral entry were mediated by increased Janus kinase-signal transducers and activators of transcription signaling and were reversed by the Janus kinase inhibitor, tofacitinib.

Collectively, our findings uncover a novel risk biomarker for increased expression of the SARS-CoV-2 receptor and viral entry, and identify a clinically approved therapeutic agent to mitigate this risk.

The COVID-19 pandemic posed significant challenges in the treatment of chronic diseases, particularly inflammatory bowel diseases (IBDs) such as Crohn's disease and ulcerative colitis. These challenges are multifaceted, encompassing difficulties in maintaining routine care, concerns about the safety of immunosuppressive therapies, disruptions in healthcare delivery, and the complexities of managing IBD in patients who contract COVID-19. This article explores the various obstacles faced in the treatment of IBD during the pandemic and discusses potential strategies to overcome these challenges.

Little is known about immunophenotyping characteristics and clinical outcomes of COVID-19 patients treated with azvudine during the Omicron variant surge.

This study enrolled patients diagnosed with COVID-19 from December 2022 to February 2023. The primary outcome was defined as all-cause mortality, along with a composite outcome reflecting disease progression. The enrolled patients were followed for a period of 60 days from their admission.

A total of 268 COVID-19 patients treated with azvudine were enrolled in this retrospective study. The study found that the counts of lymphocyte subsets were significantly reduced in the composite outcome and all-cause mortality groups compared to the non-composite outcome and discharge groups (all p < 0.001). Correlation analysis revealed a negative association between lymphocyte subsets cell counts and inflammatory markers levels. The receiver operating characteristic (ROC) curve analysis identified low CD4+ T cell count as the most significant predictor of disease progression and all-cause mortality among the various lymphocyte subsets. Additionally, both the Kaplan-Meier curve and multivariate regression analysis demonstrated that low CD4+ T cell count level (< 156.00 cells/μl) was closely associated with all-cause mortality in COVID-19 patients treated with azvudine.

A low CD4+ T cell count may serve as a significant predictive indicator for identifying COVID-19 patients receiving azvudine treatment who are at an elevated risk of experiencing adverse outcomes. These findings may offer valuable insights for physicians in optimizing the administration of azvudine.

Discovered in late 2019, the SARS-CoV-2 coronavirus has caused the largest pandemic of the 21st century, claiming more than seven million lives. In most cases, the COVID-19 disease caused by the SARS-CoV-2 virus is relatively mild and affects only the upper respiratory tract; it most often manifests itself with fever, chills, cough, and sore throat, but also has less-common mild symptoms. In most cases, patients do not require hospitalization, and fully recover. However, in some cases, infection with the SARS-CoV-2 virus leads to the development of a severe form of COVID-19, which is characterized by the development of life-threatening complications affecting not only the lungs, but also other organs and systems. In particular, various forms of thrombotic complications are common among patients with a severe form of COVID-19. The mechanisms for the development of thrombotic complications in COVID-19 remain unclear. Accumulated data indicate that the pathogenesis of severe COVID-19 is based on disruptions in the functioning of various innate immune systems. The key role in the primary response to a viral infection is assigned to two systems. These are the pattern recognition receptors, primarily members of the toll-like receptor (TLR) family, and the complement system. Both systems are the first to engage in the fight against the virus and launch a whole range of mechanisms aimed at its rapid elimination. Normally, their joint activity leads to the destruction of the pathogen and recovery. However, disruptions in the functioning of these innate immune systems in COVID-19 can cause the development of an excessive inflammatory response that is dangerous for the body. In turn, excessive inflammation entails activation of and damage to the vascular endothelium, as well as the development of the hypercoagulable state observed in patients seriously ill with COVID-19. Activation of the endothelium and hypercoagulation lead to the development of thrombosis and, as a result, damage to organs and tissues. Immune-mediated thrombotic complications are termed "immunothrombosis". In this review, we discuss in detail the features of immunothrombosis associated with SARS-CoV-2 infection and its potential underlying mechanisms.

Background and Objectives: Elevated levels of pro-inflammatory cytokines have been linked to increased mortality in COVID-19 patients. Infliximab, a tumor necrosis factor inhibitor, has been reported to improve outcomes in COVID-19 patients by targeting the hyperinflammatory response. Our objective was to evaluate the effectiveness of incorporating Infliximab into standard care guidelines for the management of COVID-19. Materials and Methods: A retrospective analysis was conducted on 111 participants who were moderate to severe COVID-19 patients admitted to the hospital. Among them, 74 individuals received solely standard treatment, while 37 received standard therapy plus Infliximab. The primary outcomes of the study centered around the changes in laboratory test parameters. The secondary clinical findings included clinical recovery defined as improvement in patient oxygenation, time till recovery, and assessing necessity for ICU admission, and mortality rates. Results: There was no statistical difference observed in the inflammatory markers including, LDH, Ferritin, CRP, neutrophil to lymphocyte ratio (NLR), and P/F ratio between both groups and in the clinical outcomes including clinical recovery (p = 1.0), time to improvement (p = 0.436), and mortality rate (p = 0.601). However, there was a significant increase in secondary infection (45.9%, 20.3%; p = 0.005), and in liver enzymes, ALT (79.5, 50.0 IU/L; p = 0.02) and AST (57.5, 38.0 IU/L; p = 0.019) in the Infliximab group and the standard care group, respectively. Conclusions: Infliximab therapy did not demonstrate significant benefits compared to standard of care in moderate to severe hospitalized COVID-19 patients.

Infection with severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) triggers coronavirus disease 2019 (COVID-19), which predominantly targets the respiratory tract. SARS-CoV-2 infection, especially severe COVID-19, is associated with dysregulated immune responses against the virus, including exaggerated inflammatory responses known as the cytokine storm, together with lymphocyte and NK cell dysfunction known as immune cell exhaustion. Overexpression of negative immune checkpoints such as PD-1 and CTLA-4 plays a considerable role in the dysfunction of immune cells upon SARS-CoV-2 infection. Blockade of these checkpoints has been suggested to improve the clinical outcome of COVID-19 patients by promoting potent immune responses against the virus. In the current review, we provide an overview of the potential of checkpoint inhibitors to induce potent immune responses against SARS-CoV-2 and improving the clinical outcome of severe COVID-19 patients.

Limited studies have addressed the exacerbation of symptoms and long COVID in inflammatory bowel disease (IBD) patients following non-severe COVID-19 infection, particularly with post-COVID-19 vaccination. We aim to investigate factors associated with exacerbated gastrointestinal symptoms (EGS) and long COVID in IBD patients with non-severe COVID-19, which is most common situation in daily practice.

This is an observational study by multiple centers in Taiwan from May 2020 to March 2023. We collected clinical manifestation, data, and medication information from IBD patients with non-severe COVID-19. EGS was defined as increased frequency of diarrhea, bloody stool, and abdomen pain within 14 days after SARS-COV-2 infection. Long COVID was defined following the guidelines of the World Health Organization.

Out of 90 patients, most of them (88.9%) received at least standard two doses of COVID-19 vaccination and the majority (87.8%) were mild diseases of COVID-19.30% of patients experienced EGS during COVID-19 with higher ESR levels serving as a predictive factor (Odds ratio: 3.6, 95% confidence interval: 1.2-10.5, P = 0.02). 38.1% of those patients developed long COVID. The patients who experienced EGS during COVID-19 and with a history of longer IBD duration showed a significant association with long COVID (p = 0.03 and p = 0.02).

Our study revealed that EGS and long COVID occurred in one third of IBD patients with non-severe COVID-19, even though most of them had received the standard plus booster vaccination. We identified associated factors for EGS and long COVID, emphasizing the importance of post-COVID-19 follow-up in IBD patients.

Pathogenic infections cause thymic atrophy, perturb thymic T-cell development, and alter immunological response. Previous studies reported dysregulated T-cell function and lymphopenia in coronavirus disease-19 (COVID-19). However, immunopathological changes in the thymus associated with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection have not been elucidated. Here, we report that SARS-CoV-2 infects thymocytes, and induces CD4+CD8+ (double positive; DP) T-cell apoptosis leading to thymic atrophy and loss of peripheral TCR repertoire in K18-hACE2 transgenic mice. Infected thymus led to increased CD44+CD25- T-cells, indicating an early arrest in the T-cell maturation pathway. Thymic atrophy was notably higher in male hACE2-Tg mice than in females and involved an upregulated de-novo synthesis pathway of thymic glucocorticoid. Further, IFN-γ was crucial for thymic atrophy, as anti-IFN-γ -antibody neutralization blunted thymic involution. Therapeutic use of Remdesivir also rescued thymic atrophy. While the Omicron variant and its sub-lineage BA.5 variant caused marginal thymic atrophy, the delta variant of SARS-CoV-2 exhibited severe thymic atrophy characterized by severely depleted DP T-cells. Recently characterized broadly SARS-CoV-2 neutralizing monoclonal antibody P4A2 was able to rescue thymic atrophy and restore the thymic maturation pathway of T-cells. Together, we report SARS-CoV-2-associated thymic atrophy resulting from impaired T-cell maturation pathway which may contribute to dyregulated T cell response during COVID-19.

With the COVID-19 pandemic going to be COVID-19 endemic, the negative impact of COVID-19 on the mental health of IBD patients cannot be ignored. This study aimed to investigate the occurrence of anxiety and depression in IBD patients during the COVID-19 pandemic and analyze the factors associated with mental health.

Patients registered at the IBD center were enrolled. Electronic questionnaires about the IBD patient's demographic information, basic knowledge of COVID-19, public self-prevention measures, daily life changes, and anxiety and depression were distributed.

Two hundred and fifteen IBD patients finished this study and reported to have anxiety (27%) or depression (34%). During the COVID-19 pandemic, 10.2% of IBD patients reported their diet changes, 58.5% of IBD patients changed their daily physical activities from 3.27 ± 3.252 h to 2.30 ± 2.78 h, 33.7% of IBD patients changed their sleeping duration from 7.99 ± 1.322 h to 8.18 ± 1.447 h. IBD patients' waiting time for admission (OR: 3.688, 95%CI: 1.003-13.554), regularly oral medicine administration (OR: 18.407, 95%CI: 1.975-171.530) and diet changes (OR: 6.167, 95%CI: 2.158-17.626) were positively correlated with anxiety or depression. IBD patients' timely periodic infusion of biological agents (OR: 0.586, 95%CI: 0.413-0.830) was negatively correlated with anxiety or depression. IBD patients' knowledge of COVID-19, public self-prevention, physical activities, and sleep duration changes showed no significant correlation with anxiety and depression, all p values > 0.05.

The main factors of IBD patients' mental health were diet changes, waiting time for admission, taking oral medicine regularly, and timely periodic infusions of biological agents. Ensuring the supply of routine treatment and medication for IBD patients and establishing systemic online IBD self-management programs would be the focus of major public health events.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection primarily affects the lung but can also cause gastrointestinal (GI) symptoms. In vitro experiments confirmed that SARS-CoV-2 robustly infects intestinal epithelium. However, data on infection of adult gastric epithelium are sparse and a side-by-side comparison of the infection in the major segments of the GI tract is lacking. We provide this direct comparison in organoid-derived monolayers and demonstrate that SARS-CoV-2 robustly infects intestinal epithelium, while gastric epithelium is resistant to infection. RNA sequencing and proteome analysis pointed to angiotensin-converting enzyme 2 (ACE2) as a critical factor, and, indeed, ectopic expression of ACE2 increased susceptibility of gastric organoid-derived monolayers to SARS-CoV-2. ACE2 expression pattern in GI biopsies of patients mirrors SARS-CoV-2 infection levels in monolayers. Thus, local ACE2 expression limits SARS-CoV-2 expression in the GI tract to the intestine, suggesting that the intestine, but not the stomach, is likely to be important in viral replication and possibly transmission.

In the advancement of Inflammatory Bowel Disease (IBD) treatment, existing therapeutic methods exhibit limitations; they do not offer a complete cure for IBD and can trigger adverse side effects. Consequently, the exploration of novel therapies and multifaceted treatment strategies provides patients with a broader range of options. Within the framework of IBD, gut microbiota plays a pivotal role in disease onset through diverse mechanisms. Bacteriophages, as natural microbial regulators, demonstrate remarkable specificity by accurately identifying and eliminating specific pathogens, thus holding therapeutic promise. Although clinical trials have affirmed the safety of phage therapy, its efficacy is prone to external influences during storage and transport, which may affect its infectivity and regulatory roles within the microbiota. Improving the stability and precise dosage control of bacteriophages-ensuring robustness in storage and transport, consistent dosing, and targeted delivery to infection sites-is crucial. This review thoroughly explores the latest developments in IBD treatment and its inherent challenges, focusing on the interaction between the microbiota and bacteriophages. It highlights bacteriophages' potential as microbiome modulators in IBD treatment, offering detailed insights into research on bacteriophage encapsulation and targeted delivery mechanisms. Particular attention is paid to the functionality of various carrier systems, especially regarding their protective properties and ability for colon-specific delivery. This review aims to provide a theoretical foundation for using bacteriophages as microbiome modulators in IBD treatment, paving the way for enhanced regulation of the intestinal microbiota.

Gastrointestinal manifestations in COVID-19 were attributed to 74-86% of the hospitalised patients due to severe or prolonged pathogenesis. Though it is a respiratory disease, the impact it elicits on the gastrointestinal tract and brain are intense. Inflammatory bowel disease including Crohn's disease and ulcerative colitis are idiopathic inflammatory disorders of the gastrointestinal tract. The intrinsic mechanisms involved in gut inflammations due to a respiratory viral disease can be deciphered when the gene expression profiles of COVID-19 and IBD are compared. The current study utilises an integrated bioinformatics approach to unravel them. The publicly available gene expression profiles of colon transcriptomes infected with COVID-19, Crohn's disease and Ulcerative colitis were retrieved, integrated and analysed for the identification of differentially expressed genes. The inter-relational analysis along with gene annotation and pathway enrichment detailed the functional and metabolic pathways of the genes during normal and diseased conditions. The protein-protein interactions deduced from the STRING database and the identified hub genes predicted potential biomarker candidates for COVID-19, Crohn's disease and ulcerative colitis. The inflammatory response pathways were upregulated and enrichment of chemokine signalling, altered lipid metabolism, coagulation and complement cascades were seen in all three conditions along with impaired transport mechanisms. CXCL11, MMP10, and CFB are predicted to be overexpressed biomarkers, whilst GUCA2A, SLC13A2, CEACAM, and IGSF9 as downregulated novel biomarker candidates for colon inflammations. The three miRNAs hsa-miR-16-5p, hsa-miR-21-5p, and hsa-miR-27b-5p exhibited significant interactions with the upregulated hub genes and four long non-coding RNAs NEAT1, KCNQ1OT1, and LINC00852 capable of regulating miRNA were also predicted. This study offers significant information on the underlying molecular mechanisms of inflammatory bowel disease with identification of potential biomarkers.

Epigenetic changes have long-lasting impacts, which influence the epigenome and are maintained during cell division. Thus, human genome changes have required a very long timescale to become a major contributor to the current obesity pandemic. Whereas bidirectional effects of coronavirus disease 2019 (COVID-19) and obesity pandemics have given the opportunity to explore, how the viral microribonucleic acids (miRNAs) use the human's transcriptional machinery that regulate gene expression at a posttranscriptional level. Obesity and its related comorbidity, type 2 diabetes (T2D), and new-onset diabetes due to severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) are additional risk factors, which increase the severity of COVID-19 and its related mortality. The higher mortality rate of these patients is dependent on severe cytokine storm, which is the sum of the additional cytokine production by concomitant comorbidities and own cytokine synthesis of COVID-19. Patients with obesity facilitate the SARS-CoV-2 entry to host cell via increasing the host's cell receptor expression and modifying the host cell proteases. After entering the host cells, the SARS-CoV-2 genome directly functions as a messenger ribonucleic acid (mRNA) and encodes a set of nonstructural proteins via processing by the own proteases, main protease (Mpro), and papain-like protease (PLpro) to initiate viral genome replication and transcription. Following viral invasion, SARS-CoV-2 infection reduces insulin secretion via either inducing β-cell apoptosis or reducing intensity of angiotensin-converting enzyme 2 (ACE2) receptors and leads to new-onset diabetes. Since both T2D and severity of COVID-19 are associated with the increased serum levels of pro-inflammatory cytokines, high glucose levels in T2D aggravate SARS-CoV-2 infection. Elevated neopterin (NPT) value due to persistent interferon gamma (IFN-γ)-mediated monocyte-macrophage activation is an indicator of hyperactivated pro-inflammatory phenotype M1 macrophages. Thus, NPT could be a reliable biomarker for the simultaneously occurring COVID-19-, obesity- and T2D-induced cytokine storm. While host miRNAs attack viral RNAs, viral miRNAs target host transcripts. Eventually, the expression rate and type of miRNAs also are different in COVID-19 patients with different viral loads. It is concluded that specific miRNA signatures in macrophage activation phase may provide an opportunity to become aware of the severity of COVID-19 in patients with obesity and obesity-related T2D.

The long-term impact of the COVID-19 pandemic concerns risk to human health, particularly its potential association with protein misfolding and amyloidosis. This review article explores the causality relationship between SARS-CoV-2 infection, and protein misfolding, leading to amyloid-related conditions. It delves into the mechanisms by which viral proteins may accelerate amyloid formation, exacerbating post-infection complications, including neurological sequelae. Drawing from interdisciplinary research and clinical observations, the potential links between COVID-19, vaccination, and amyloidosis, emphasize the importance of understanding the longterm effect of post-COVID symptoms. This review examines the potential role of COVID-19-related proteins in the formation of amyloid in other related proteins of amyloidosis.

Emerging evidence reveals that SARS-CoV-2 possesses the capability to disrupt the gastrointestinal (GI) homeostasis, resulting in the long-term symptoms such as loss of appetite, diarrhea, gastroesophageal reflux, and nausea. In the current review, we summarized recent reports regarding the long-term effects of COVID-19 (long COVID) on the gastrointestine.

To provide a narrative review of abundant clinical evidence regarding the development and management of long-term GI symptoms in COVID-19 patients.

Long-term persistent digestive symptoms are exhibited in a majority of long-COVID patients. SARS-CoV-2 infection of intestinal epithelial cells, cytokine storm, gut dysbiosis, therapeutic drugs, psychological factors and exacerbation of primary underlying diseases lead to long-term GI symptoms in COVID-19 patients. Interventions like probiotics, prebiotics, fecal microbiota transplantation, and antibiotics are proved to be beneficial in preserving intestinal microecological homeostasis and alleviating GI symptoms.

Timely diagnosis and treatment of GI symptoms in long-COVID patients hold great significance as they may contribute to the mitigation of severe conditions and ultimately lead to the improvement of outcomes of the patients.

The data on the relationship between inflammatory bowel diseases (IBD) and the course of COVID-19 from East-Central Europe are scarce.

To assess the frequency of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in IBD patients and the impact of IBD on the COVID-19 course from the perspective of a Polish tertiary centre.

Data on SARS-CoV-2 infection were retrospectively collected among IBD patients hospitalized in a Polish tertiary centre from March 2020 to May 2021. A questionnaire was used assessing the IBD characteristics, other comorbidities, and the course of COVID-19.

Among 350 patients, SARS-CoV-2 infection was diagnosed in 32 (9%). Severe COVID-19, defined as the need for hospitalization, was reported in 6 (19%) and mild in 26 (81%) cases. Compared to the mild COVID-19 course, patients with a severe course more often showed a higher IBD activity (3 points [IQR 2.25-3] vs. 1 point [IQR 0-2] in a semi-quantitative scale, p = 0.002), more often received steroids (67% vs. 11%, p = 0.02), and were not treated with biologics (0% vs. 46%, p = 0.07). There was a correlation between the duration of symptomatic infection and the number of comorbidities (r = 0.4, p = 0.04). No death or short-term COVID-19 complications were reported. In 25% of cases, SARS-CoV-2 infection caused new gastrointestinal symptoms.

IBD is not a risk factor for SARS-CoV-2 infection. Steroids and higher IBD clinical activity may increase the risk of severe COVID-19. The prognosis for COVID-19 in our cohort was good. SARS-CoV-2 infection was a common cause of gastrointestinal symptoms.

This study aimed to evaluate humoral responses after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) of patients with inflammatory bowel disease (IBD). Patients with IBD enrolled in a tertiary outpatient unit were followed up between September 2021 and September 2022 via serial blood collection. Immunoglobulin G antibody titers against SARS-CoV-2 were measured before administration and 1 and 6 months after the administration of two doses of different vaccination regimens. The results were compared with those of a healthy control group obtained during the same period. The mean pre-vaccination antibody titers were 452.0 and 93.3 AU/mL in the IBD (n = 42) and control (n = 89) groups, respectively. After two doses of the vaccine, the titers significantly increased in both groups (IBD, 8568.0 AU/mL; control, 7471.0 AU/mL; p < 0.001). One month after the second dose, no significant differences were observed between the two groups (p = 0.955). Significant differences between vaccination schemes in the IBD group were observed, with higher titers in those who received Pfizer, younger patients (p < 0.005), and those with a previous coronavirus disease 2019 (COVID-19) infection (p < 0.012). The use of immunosuppressants and immunobiologicals did not affect the overall humoral response to COVID-19 vaccine in patients with IBD, but specific vaccine regimens, age, and previous coronavirus infection significantly did. This study reinforces the positive impact of booster doses and the safety of SARS-CoV-2 vaccination.

There is no uniformity in the available literature concerning the effects of coronavirus disease 2019 (COVID-19) viral illness on people with inflammatory bowel disease (IBD).

We conducted an analysis using the 2020 National Inpatient Sample (NIS) database to compare the outcomes of COVID-19 hospitalized patients with and without IBD.

Of 1,050,040 patients admitted with COVID-19, 5,750 (0.5%) also had IBD. The group with COVID-19 and IBD had higher percentages of females and White individuals and a greater prevalence of chronic lung disease, peripheral vascular disease, and liver disease. However, after accounting for confounding variables, there was no significant difference in mortality rates, length of hospital stays, or hospitalization costs between the two groups.

According to our findings, the presence of IBD does not appear to elevate the risk of COVID-19 complications.

The coronavirus disease (COVID-19) pandemic has had a considerable impact on the global healthcare system and potentially the clinical course of patients with inflammatory bowel disease (IBD). Although IBD is a chronic disease, its therapy (except steroid therapy) does not increase the risk of contracting or aggravating COVID-19. However, the clinical course of patients is significantly influenced by environmental factors. Social restrictions due to the pandemic or the fear of contracting the virus have influenced lifestyle and psychosocial behaviors that may worsen the clinical course of patients with IBD. This narrative literature review summarizes the current evidence on the impact of the COVID-19 pandemic on the lifestyle and psychosocial behaviors of patients with IBD. The COVID-19 pandemic negatively affected the lifestyle and psychosocial behaviors of patients with IBD. Furthermore, patients with IBD failed to maintain medication adherence, thus affecting the clinical course of their condition.

A recently emerged sub-lineage of Omicron, BA.5, together with BA.4, caused a fifth wave of coronavirus disease (COVID-19) in South Africa and subsequently emerged as a predominant strain globally due to its high transmissibility. The lethality of BA.5 infection has not been studied in an acute hACE2 transgenic (hACE2.Tg) mouse model. Here, we investigated tissue-tropism and immuno-pathology induced by BA.5 infection in hACE2.Tg mice. Our data show that intranasal infection of BA.5 in hACE2.Tg mice resulted in attenuated pulmonary infection and pathology with diminished COVID-19-induced clinical and pathological manifestations. BA.5, similar to Omicron (B.1.1.529), infection led to attenuated production of inflammatory cytokines, anti-viral response and effector T cell response as compared to the ancestral strain of SARS-CoV-2, Wuhan-Hu-1. We show that mice recovered from B.1.1.529 infection showed robust protection against BA.5 infection associated with reduced lung viral load and pathology. Together, our data provide insights as to why BA.5 infection escapes previous SARS-CoV-2 exposure induced-T cell immunity but may result in milder immuno-pathology and alleviated chances of re-infectivity in Omicron-recovered individuals.

There are concerns about the serological responses to Coronavirus disease 2019 (COVID-19) vaccines in inflammatory bowel disease (IBD) patients, particularly those receiving anti-TNF therapy. This study aimed to systematically evaluate the efficacy of COVID-19 vaccines in IBD patients receiving anti-TNF therapy.

Electronic databases were searched to identify relevant studies. We calculated pooled seroconversion rate after COVID-19 vaccination and subgroup analysis for vaccine types and different treatments were performed. Additionally, we estimated pooled rate of T cell response, neutralization response, and breakthrough infections in this population.

32 studies were included in the meta-analysis. IBD patients receiving anti-TNF therapy had relatively high overall seroconversion rate after complete vaccination, with no statistical difference in antibody responses associated with different drug treatments. The pooled positivity rate of T cell response was 0.85 in IBD patients receiving anti-TNF therapy. Compared with healthy controls, the positivity of neutralization assays was significantly lower in IBD patients receiving anti-TNF therapy. The pooled rate of breakthrough infections in IBD patients receiving anti-TNF therapy was 0.04.

COVID-19 vaccines have shown good efficacy in IBD patients receiving anti-TNF therapy. However, IBD patients receiving anti-TNF have a relatively high rate of breakthrough infections and a low level of neutralization response.

The gut vascular barrier (GVB) is the deepest layer of the gut barrier. It mainly comprised gut vascular endothelial cells, enteric glial cells, and pericytes. The GVB facilitates nutrient absorption and blocks bacterial translocation through its size-restricted permeability. Accumulating evidence suggests that dysfunction of this barrier correlates with several clinical pathologies including Crohn's disease (CD). Significant progress has been made to elucidate the mechanism of GVB dysfunction and to confirm the participation of disrupted GVB in the course of CD. However, further analyses are required to pinpoint the specific roles of GVB in CD pathogenesis. Many preclinical models and clinical trials have demonstrated that various agents are effective in protecting the GVB integrity and thus providing a potential CD treatment strategy. Through this review, we established a systemic understanding of the role of GVB in CD pathogenesis and provided novel insights for GVB-targeting strategies in CD treatment.

Inflammatory bowel disease is a heterogeneous intestinal inflammatory disorder, including ulcerative colitis (UC) and Crohn's disease (CD). Existing studies have shown that the pathogenesis of IBD is closely related to the host's genetic susceptibility, intestinal flora disturbance and mucosal immune abnormalities, etc. It is generally believed that there are complicated interactions between host immunity and intestinal microflora/microRNAs during the occurrence and progression of IBD. Intestinal flora is mainly composed of bacteria, fungi, viruses and helminths. These commensals are highly implicated in the maintenance of intestinal microenvironment homeostasis alone or in combination. MiRNA is an endogenous non-coding small RNA with a length of 20 to 22 nucleotides, which can perform a variety of biological functions by silencing or activating target genes through complementary pairing bonds. A large quantity of miRNAs are involved in intestinal inflammation, mucosal barrier integrity, autophagy, vesicle transportation and other small RNA alterations in IBD circumstance. In this review, the immunomodulatory roles of gut flora and microRNAs are updated in the occurrence and progression of IBD. Meanwhile, the gut flora and microRNA targeted therapeutic strategies as well as other immunomodulatory approaches including TNF-α monoclonal antibodies are also emphasized in the treatment of IBD.

To analyze the clinical characteristics and prognosis of patients hospitalized with non-severe, severe pneumonia and death in Omicron COVID-19.

We collected clinical data from 118 patients with COVID-19 in China from 18 December, 2022 and 5 February, 2023. According to the outcome, the patients were divided into non-severe group, severe group and death group. Subsequently, we statistically analyzed the general condition, clinical manifestations, laboratory parameters, NLR, MLR, PLR and HALP of these groups. We also retrospectively analyzed the possible factors affecting the prognostic regression of patients with COVID-19.

A total of 118 COVID-19 patients were enrolled in this study, including 64 non-severe patients, 38 severe patients and 16 death patients. Compared with the non-severe group, T lymphocytes, B lymphocytes, Th1, Th2, Th17, Treg cells, IgA, IgG, IgM in the severe and death groups decreased more significantly (P<0.05). The levels of myocardial markers, ALT, AST, BUN, Cr, D-dimer, fibrinogen, NLR, MLR and PLR in the severe and death groups were significantly higher than those in the non-severe group (P<0.05). The level of HALP was significantly lower than that of non-severe group (P<0.05). MLR is not only an independent risk factor for the transition from non-severe to severe disease, but also an independent risk factor for predicting the possibility of death in COVID-19 patients.

The analysis of COVID-19 patients in China showed that severe patients were older, more likely to have related complications, lower lymphocyte count, liver and kidney function disorder, glucose and lipid metabolism disorders, myocardial injury, and abnormal coagulation function, suggesting the need for early anticoagulant therapy. In addition, NLR, MLR, PLR and HALP can be used as biomarkers to evaluate the severity and prognosis of COVID-19 patients.

COVID-19, a serious respiratory disease that has the potential to affect numerous organs, is a serious threat to the health of people around the world. The objective of this article is to investigate the potential biological targets and mechanisms by which SARS-CoV-2 affects benign prostatic hyperplasia (BPH) and related symptoms.

We downloaded the COVID-19 datasets (GSE157103 and GSE166253) and the BPH datasets (GSE7307 and GSE132714) from the Gene Expression Omnibus (GEO) database. In GSE157103 and GSE7307, differentially expressed genes (DEGs) were found using the "Limma" package, and the intersection was utilized to obtain common DEGs. Further analyses followed, including those using Protein-Protein Interaction (PPI), Gene Ontology (GO) function enrichment analysis, and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Potential hub genes were screened using three machine learning methods, and they were later verified using GSE132714 and GSE166253. The CIBERSORT analysis and the identification of transcription factors, miRNAs, and drugs as candidates were among the subsequent analyses.

We identified 97 common DEGs from GSE157103 and GSE7307. According to the GO and KEGG analyses, the primary gene enrichment pathways were immune-related pathways. Machine learning methods were used to identify five hub genes (BIRC5, DNAJC4, DTL, LILRB2, and NDC80). They had good diagnostic properties in the training sets and were validated in the validation sets. According to CIBERSORT analysis, hub genes were closely related to CD4 memory activated of T cells, T cells regulatory and NK cells activated. The top 10 drug candidates (lucanthone, phytoestrogens, etoposide, dasatinib, piroxicam, pyrvinium, rapamycin, niclosamide, genistein, and testosterone) will also be evaluated by the P value, which is expected to be helpful for the treatment of COVID-19-infected patients with BPH.

Our findings reveal common signaling pathways, possible biological targets, and promising small molecule drugs for BPH and COVID-19. This is crucial to understand the potential common pathogenic and susceptibility pathways between them.

Over the last 2 years the lives of millions have changed because of the emergence of Coronavirus disease 2019 (COVID-19). Patients living with inflammatory bowel disease (IBD) represent a sizable population with their own sets of challenges to providers in the wake of so much uncertainty. The Centers for Disease Control considers immunocompromised individuals at higher risk of infection and complications from COVID-19. Early in the pandemic, the specific risks for IBD patients were unclear as guidance was based on expert opinion regarding the management of IBD during a COVID-19 era. Fortunately, after considerable work in the field, the overwhelming evidence suggests that IBD patients as a whole do not appear to be at increased risk for more severe disease from COVID-19. Certain risk factors such as age, steroids, comorbidities, combination immunomodulatory therapy, and IBD disease activity have been associated with worse outcomes. Most IBD medications are low risk, with the exception of immunomodulator monotherapy and combination therapy with thiopurine and anti-TNF. Vaccination remains safe and effective for all IBD patients, although additional booster doses may be necessary, particularly in patients taking anti-TNF agents.

Inflammatory bowel disease (IBD) is a chronic recurrent inflammation of the gastrointestinal tract (GIT). IBD patients are susceptible to various infections such as viral infections due to the long-term consumption of immunosuppressive drugs and biologics. The antiviral and IBD protective traits of flavonoids have not been entirely investigated. This study objective included an overview of the protective role of flavonoids quercetin and silymarin in viral-associated IBD. Several viral agents such as cytomegalovirus (CMV), Epstein-Barr virus (EBV), varicella zoster virus (VZV) and enteric viruses can be reactivated and thus develop or exacerbate the IBD conditions or eventually facilitate the disease remission. Flavonoids such as quercetin and silymarin are non-toxic and safe bioactive compounds with remarkable anti-oxidant, anti-inflammatory and anti-viral effects. Mechanisms of anti-inflammatory and antiviral effects of silymarin and quercetin mainly include immune modulation and inhibition of caspase enzymes, viral binding and replication, RNA synthesis, viral proteases and viral assembly. In the nutraceutical sector, natural flavonoids low bioavailability and solubility necessitate the application of delivery systems to enhance their efficacy. This review study provided an updated understanding of the protective role of quercetin and silymarin against viral-associated IBD.

The clinical manifestation of COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in the respiratory system of humans is widely recognized. There is increasing evidence suggesting that SARS-CoV-2 possesses the capability to invade the gastrointestinal (GI) system, leading to the manifestation of symptoms such as vomiting, diarrhea, abdominal pain, and GI lesions. These symptoms subsequently contribute to the development of gastroenteritis and inflammatory bowel disease (IBD). Nevertheless, the pathophysiological mechanisms linking these GI symptoms to SARS-CoV-2 infection remain unelucidated. During infection, SARS-CoV-2 binds to angiotensin-converting enzyme 2 and other host proteases in the GI tract during the infection, possibly causing GI symptoms by damaging the intestinal barrier and stimulating inflammatory factor production, respectively. The symptoms of COVID-19-induced GI infection and IBD include intestinal inflammation, mucosal hyperpermeability, bacterial overgrowth, dysbiosis, and changes in blood and fecal metabolomics. Deciphering the pathogenesis of COVID-19 and understanding its exacerbation may provide insights into disease prognosis and pave the way for the discovery of potential novel targets for disease prevention or treatment. Besides the usual transmission routes, SARS-CoV-2 can also be transmitted via the feces of an infected person. Hence, it is crucial to implement preventive and control measures in order to mitigate the fecal-to-oral transmission of SARS-CoV-2. Within this context, the identification and diagnosis of GI tract symptoms during these infections assume significance as they facilitate early detection of the disease and the development of targeted therapeutics. The present review discusses the receptors, pathogenesis, and transmission of SARS-CoV-2, with a particular focus on the induction of gut immune responses, the influence of gut microbes, and potential therapeutic targets against COVID-19-induced GI infection and IBD.

Chronic inflammatory gastrointestinal diseases such as Crohn's disease (CD) and ulcerative colitis (UC) are known as inflammatory bowel disorders (IBD). Patients with inflammatory bowel illnesses are more susceptible to viral infections. In people with IBD, viral infections have emerged as a significant issue. Viral infections are often difficult to identify and have a high morbidity and fatality rate. We reviewed studies on viral infections and IBD, concentrating on Cytomegalovirus (CMV), SARS-CoV-2, Epstein-Barr virus (EBV), enteric viruses, and hepatitis B virus (HBV). Also, the effect of IBD on these viral infections is discussed. These data suggest that patients with IBD are more likely to get viral infections. As a result, practitioners should be aware of the increased risk of viral infections in inflammatory bowel disease patients.

The use of immunomodulatory therapy in the setting of coexistence of uveitis and coronavirus disease (COVID-19) remains controversial. We report a case of COVID-19 during systemic steroid therapy for Vogt-Koyanagi-Harada disease (VKH).

A 43-year-old female was diagnosed with VKH and started on steroid pulse therapy (1,000 mg/day) followed by high-dose oral corticosteroids. Two weeks after discharge from the hospital, she was readmitted to the intensive care unit with severe acute respiratory syndrome due to SARS-CoV-2 infection confirmed by PCR test, and fortunately both VKH and COVID-19-induced respiratory disease improved.

Given the absence of international agreement on how to manage COVID-19 patients with steroid-dependent VKH, existing clinical guidelines should be reviewed thoroughly to formulate useful strategies for managing VKH patients on steroid treatment who contract COVID-19. Furthermore, the outcomes of patients with steroid-dependent autoimmune uveitis including VKH who develop COVID-19 should be analyzed.

Coronavirus Disease 2019 (COVID-19) continues to spread rapidly. Monoclonal antibodies as well as anti-tumor necrosis factor are considered promising treatments for COVID-19. A prospective cohort study in which patients are divided into three groups. Group 1: moderate and severe COVID-19 patients received standard treatment; Group 2: moderate and severe COVID-19 patients received tocilizumab; Group 3: moderate and severe COVID-19 patients received treatment with infliximab and tocilizumab. 153 patients were recruited in the study. 40 received standard treatment alone, 70 received tocilizumab with standard treatment, and 43 received tocilizumab/infliximab with standard treatment. There was a significant difference in length of hospital stay (10.3, 8.9, and 7.6 days respectively P = 0.03), need for a non-invasive mechanical ventilator (4, 5, and one patient; P = 1.2E-8), intensive care admission (32, 45, and 16 patients; P = 2.5E-5), the occurrence of sepsis (18, 12, and 10 patients; P = 0.005) and in death (42.5%, 14.2%, and 7%; P = 0.0008) which were significantly lower in tocilizumab/infliximab group compared to tocilizumab and standard of care groups. Our study showed that tocilizumab/ infliximab in addition to standard of care was considered a promising treatment for moderate and severe COVID-19 patients.Trial registration number: ClinicalTrials.gov NCT04734678; date of registration: 02/02/2021.

Probiotic food provide health benefits by regulating intestinal floras via live bacteria, but the shelf life is short and the preservation condition is demanding due to the bacteria being fragile. Owing to these problems, we have tried to find a fermented food that is helpful for inflammatory bowel disease treatment but independent of live bacteria. In addition, the mechanisms of fermented food were investigated. Dextran sulfate sodium was used to model inflammatory bowel disease in mice, and Lactobacillus paracasei TK1501 fermented soybeans and their metabolites were used to treat inflammatory bowel disease.

In this study, TK1501 fermented soybean alleviated colitis. However, the efficacy was associated with bacterial metabolites but not live or dead bacteria. Compositional analysis of soybean before and after fermentation shows that soy carbohydrates were used for bacteria growth and produced functional substances. Further, we display the main active ingredient was lipoteichoic acid and peptidoglycan, because lipoteichoic acid reduced the colonic macrophage and peptidoglycan may increase the mucin-2 expression. A cell experiment displayed that lipoteichoic acid could enhance the phagocytosis of macrophages.

In general, TK1501 fermented soybean alleviating colitis is dependent on metabolites of TK1501, particularly lipoteichoic acid and peptidoglycan. The fermented food may have a long shelf life and lax storage condition. © 2023 Society of Chemical Industry.

Immune checkpoint inhibitors have revolutionized management of advanced malignancies. However, their use is frequently complicated by immune related adverse events (irAEs), immune checkpoint inhibitor enterocolitis (IMEC) being the most common toxicity. IMEC is a distinct form of bowel inflammation that is highly reminiscent of idiopathic inflammatory bowel disorders (Crohn's disease, ulcerative colitis, and microscopic colitis). In this review, we highlight the similarities and differences in the pathophysiology, clinical presentation, evaluation, and management of these overlapping immune inflammatory bowel disorders. IMEC is an inflammatory bowel disease-like irAE that occurs as an outcome of disruption of intestinal immune surveillance and gut dysbiosis. Clinical and endoscopic presentation of both entities is strikingly similar, which often guides management. Though well established in inflammatory bowel disease, little is known about the long term outcomes of IMEC.

Inflammatory bowel disease potentially elevates the risk of infections, independently from age, while the disease activity and medical treatment(s) can also increase the risks. Nevertheless, it is necessary to clarify these preconceptions as well during the COVID-19 pandemic.

An observational, questionnaire based study was conducted in Hungary between February and August 2021. 2 questionnaires were completed. The first questionnaire surveyed the impact of the pandemic on patients with biologic treatments and assessed the severity and outcome of the infection, whereas the second one assessed vaccination rate and adverse events.

472 patients participated in the study. 16.9 % of them acquired the infection and 6.3 % needed hospitalization. None of them required ICU care. Male sex elevated the risk of infection (p = 0.008), while glove (p = 0.02) and mask wearing (p = 0.005) was the most effective prevention strategy. Nevertheless, abstaining from community visits or workplace did not have an impact on the infection rate. Smoking, age, and disease type did not elevate the risk. UC patients had poorer condition during the infection (p = 0.003); furthermore, the disease activity could potentially worsen the course of infection (p = 0.072). The different biological treatments were equally safe; no difference was observed in the infection rate, course of COVID-19. Azathioprine and corticosteroids did not elevate the infection rate. 28 patients (35.0 %) suspended the ongoing biologic treatment, but it had no impact on the disease course. However, it resulted in changing the current treatment (p = 0.004). 9.8 % of the respondents were sceptic about being vaccinated, and 90 % got vaccinated. In one case, a serious flare-up occurred.

Most patients acquired the infection at workplace. Biologic therapies had no effect on the COVID-19 infection, whereas male sex, an active disease, and UC could be larger threat than treatments. Vaccination was proved to be safe, and patient education is important to achieve mass vaccination of the population.

Vedolizumab (VDZ) can be used to treat refractory ulcerative colitis (UC) and Crohn's disease (CD). We assessed whether there are differences in treating UC vs CD with VDZ.

Mayo score in UC and the Harvey-Bradshaw Index (HBI) in CD scored the clinical activity. Achievement and maintenance of clinical remission during the follow-up, and safety were the primary endpoints.

729 patients (475 with UC and 254 with CD), median follow-up of 18 (IQR 6-36) months, were enrolled. Clinical remission at the 6th month of treatment was achieved in 488 (66.9%) patients (74.4% in CD vs 62.9% in UC, p<0.002) while, during the follow-up, no difference was found (81.5% in the UC group and 81.5% pts in the CD group; p=0.537). The clinical remission at the 6th month of treatment (p=0.001) and being naïve to biologics (p<0.0001) were significantly associated with prolonged clinical remission. The clinical response was significantly higher in UC (90.1%) vs CD (84.3%) (p=0.023), and surgery occurred more frequently in CD (1.9% in UC vs 5.1% in CD, p=0.016).

We found differences when using VDZ in UC vs CD in real life. These parameters can help the physician predict this drug's longterm efficacy.