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1.
Sci Rep ; 11(1): 22913, 2021 11 25.
Article in English | MEDLINE | ID: covidwho-1537333

ABSTRACT

Inflammation is a physiological process whose deregulation causes some diseases including cancer. Nuclear Factor kB (NF-kB) is a family of ubiquitous and inducible transcription factors, in which the p65/p50 heterodimer is the most abundant complex, that play critical roles mainly in inflammation. Glucocorticoid Receptor (GR) is a ligand-activated transcription factor and acts as an anti-inflammatory agent and immunosuppressant. Thus, NF-kB and GR are physiological antagonists in the inflammation process. Here we show that in mice and humans there is a spliced variant of p65, named p65 iso5, which binds the corticosteroid hormone dexamethasone amplifying the effect of the glucocorticoid receptor and is expressed in the liver of patients with hepatic cirrhosis and hepatocellular carcinoma (HCC). Furthermore, we have quantified the gene expression level of p65 and p65 iso5 in the PBMC of patients affected by SARS-CoV-2 disease. The results showed that in these patients the p65 and p65 iso5 mRNA levels are higher than in healthy subjects. The ability of p65 iso5 to bind dexamethasone and the regulation of the glucocorticoid (GC) response in the opposite way of the wild type improves our knowledge and understanding of the anti-inflammatory response and identifies it as a new therapeutic target to control inflammation and related diseases.


Subject(s)
Inflammation/immunology , Receptors, Glucocorticoid/metabolism , Transcription Factor RelA/metabolism , Adrenal Cortex Hormones/metabolism , Adult , Alternative Splicing , Animals , COVID-19/immunology , Carcinoma, Hepatocellular/metabolism , Dexamethasone/metabolism , Female , Gene Expression/genetics , Gene Expression Regulation/genetics , Glucocorticoids/metabolism , Hepatitis/metabolism , Humans , Inflammation/metabolism , Leukocytes, Mononuclear/metabolism , Liver/metabolism , Liver Diseases/immunology , Liver Neoplasms/metabolism , Male , Mice , Mice, Inbred C57BL , Middle Aged , NF-kappa B/metabolism , Protein Isoforms , Receptors, Glucocorticoid/immunology , SARS-CoV-2/pathogenicity , Transcription Factor RelA/immunology , Transcription Factor RelA/physiology
2.
Hepatol Commun ; 6(2): 255-269, 2022 02.
Article in English | MEDLINE | ID: covidwho-1525435

ABSTRACT

Liver injury, characterized predominantly by elevated aspartate aminotransferase and alanine aminotransferase, is a common feature of coronavirus disease 2019 (COVID-19) symptoms caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). Additionally, SARS-CoV-2 infection is associated with acute-on-chronic liver failure in patients with cirrhosis and has a notably elevated mortality in patients with alcohol-related liver disease compared to other etiologies. Direct viral infection of the liver with SARS-CoV-2 remains controversial, and alternative pathophysiologic explanations for its hepatic effects are an area of active investigation. In this review, we discuss the effects of SARS-CoV-2 and the inflammatory environment it creates on endothelial cells and platelets more generally and then with a hepatic focus. In doing this, we present vascular inflammation and thrombosis as a potential mechanism of liver injury and liver-related complications in COVID-19.


Subject(s)
Blood Platelet Disorders/virology , COVID-19/physiopathology , Endothelium, Vascular/virology , Inflammation/virology , Liver Diseases/virology , Thrombosis/virology , Blood Platelet Disorders/immunology , Blood Platelet Disorders/physiopathology , COVID-19/immunology , Endothelium, Vascular/immunology , Endothelium, Vascular/physiopathology , Humans , Inflammation/immunology , Inflammation/physiopathology , Liver Diseases/immunology , Liver Diseases/physiopathology , Thrombosis/immunology , Thrombosis/physiopathology
3.
J Hepatol ; 75(6): 1434-1439, 2021 12.
Article in English | MEDLINE | ID: covidwho-1376032

ABSTRACT

BACKGROUND & AIMS: Liver transplant (LT) recipients or other immunocompromised patients were not included in the registration trials studying the efficacy of vaccines against SARS-CoV-2. Although the clinical efficacy of COVID-19 vaccines in immunocompromised patients is unknown, many societies have recommended vaccination of this highly vulnerable patient population. METHODS: In this prospective study, we determined antibody responses to spike protein, 4 weeks after the 2nd dose of mRNA vaccines or after the single dose of Johnson & Johnson vaccine, in LT recipients and those with chronic liver disease (CLD) with and without cirrhosis. RESULTS: Of the 233 patients enrolled so far, 62 were LT recipients, 79 had cirrhosis (10 decompensated) and 92 had CLD without cirrhosis. Antibody titers were defined as undetectable (<0.40 U/ml), suboptimal (0.40-250 U/ml) and adequate (>250 U/ml). Of the 62 patients who had LT, antibody levels were undetectable in 11 patients and suboptimal (median titer 17.6, range 0.47-212 U/ml) in 27 patients. Among 79 patients with cirrhosis, 3 had undetectable antibody levels and 15 had suboptimal (median titer 41.3, range 0.49-221 U/L) antibody responses. Of the 92 patients without cirrhosis, 4 had undetectable antibody levels and 19 had suboptimal (median titer 95.5, range 4.9-234 U/L) antibody responses. Liver transplantation, use of 2 or more immunosuppression medications and vaccination with a single dose of the Johnson & Johnson vaccine were associated with poor immune response on multivariable analysis. No patient had any serious adverse events. CONCLUSIONS: Poor antibody responses after SARS-CoV-2 vaccination were seen in 61% of LT recipients and 24% of those with CLD. LAY SUMMARY: The clinical efficacy of COVID-19 vaccines in immunocompromised patients is unknown. We performed a prospective study to evaluate immune responses to COVID-19 vaccines (Moderna, Pfizer or Johnson & Johnson) in 62 liver transplant recipients, 79 patients with cirrhosis and 92 with chronic liver diseases without cirrhosis. We found that 17.8% of liver transplant recipients, 3.8% of those with cirrhosis and 4.3% of those with chronic liver diseases without cirrhosis had undetectable antibody levels. In total, 61.3% of liver transplant recipients and 24% of those with chronic liver diseases (with or without cirrhosis) had poor antibody responses (undetectable or suboptimal). Liver transplantation, use of immunosuppressive medications and vaccination with a single dose of Johnson & Johnson vaccine were associated with poor antibody responses when adjusted for other factors.


Subject(s)
Antibodies, Viral/blood , Antibody Formation , COVID-19 Vaccines , COVID-19 , Immunosuppressive Agents/therapeutic use , Liver Diseases , SARS-CoV-2/physiology , Spike Glycoprotein, Coronavirus/immunology , Antibody Formation/drug effects , Antibody Formation/immunology , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/classification , COVID-19 Vaccines/immunology , Chronic Disease , Female , Humans , Immunocompromised Host/drug effects , Liver Diseases/epidemiology , Liver Diseases/immunology , Liver Diseases/therapy , Liver Transplantation/methods , Liver Transplantation/statistics & numerical data , Male , Middle Aged , Outcome Assessment, Health Care , Prospective Studies , United States/epidemiology
4.
Dig Liver Dis ; 53(6): 677-681, 2021 06.
Article in English | MEDLINE | ID: covidwho-1213138

ABSTRACT

The vaccination campaign against Sars-CoV-2 commenced in Italy at the end of December 2020. The first ones to receive the immunization against the virus were the health workers and the residents of nursing homes, following which the vaccine would be available for the entire population, beginning with the most vulnerable individuals. SARS-CoV2 vaccines have been demonstrated to be safe for the general population, although no data for patients with liver diseases or those having undergone liver transplantation are available so far. The present position statement AISF is an attempt to suggest, based on the published data on the impact of Sars-Cov-2 infection in patients with chronic liver disease, a possible priority for vaccination for this category of patients.


Subject(s)
COVID-19 Vaccines , COVID-19 , Immunization Programs , Liver Diseases , Risk Adjustment/methods , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines/classification , COVID-19 Vaccines/pharmacology , Humans , Immunization Programs/methods , Immunization Programs/organization & administration , Immunosuppressive Agents/therapeutic use , Italy/epidemiology , Liver Diseases/immunology , Liver Diseases/therapy , Liver Transplantation , Patient Safety , Patient Selection , Risk Assessment , SARS-CoV-2/immunology , Transplant Recipients , Treatment Outcome
5.
J Hepatol ; 74(4): 944-951, 2021 04.
Article in English | MEDLINE | ID: covidwho-1065333

ABSTRACT

According to a recent World Health Organization estimate, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, which originated in China in 2019, has spread globally, infecting nearly 100 million people worldwide by January 2021. Patients with chronic liver diseases (CLD), particularly cirrhosis, hepatobiliary malignancies, candidates for liver transplantation, and immunosuppressed individuals after liver transplantation appear to be at increased risk of infections in general, which in turn translates into increased mortality. This is also the case for SARS-CoV-2 infection, where patients with cirrhosis, in particular, are at high risk of a severe COVID-19 course. Therefore, vaccination against various pathogens including SARS-CoV-2, administered as early as possible in patients with CLD, is an important protective measure. However, due to impaired immune responses in these patients, the immediate and long-term protective response through immunisation may be incomplete. The current SARS-CoV-2 pandemic has led to the exceptionally fast development of several vaccine candidates. A small number of these SARS-CoV-2 vaccine candidates have already undergone phase III, placebo-controlled, clinical trials in healthy individuals with proof of short-term safety, immunogenicity and efficacy. However, although regulatory agencies in the US and Europe have already approved some of these vaccines for clinical use, information on immunogenicity, duration of protection and long-term safety in patients with CLD, cirrhosis, hepatobiliary cancer and liver transplant recipients has yet to be generated. This review summarises the data on vaccine safety, immunogenicity, and efficacy in this patient population in general and discusses the implications of this knowledge on the introduction of the new SARS-CoV-2 vaccines.


Subject(s)
Biliary Tract Neoplasms , COVID-19 Vaccines/pharmacology , COVID-19 , Liver Diseases , Liver Transplantation , Biliary Tract Neoplasms/epidemiology , Biliary Tract Neoplasms/therapy , COVID-19/epidemiology , COVID-19/prevention & control , Humans , Immunocompromised Host , Liver Diseases/epidemiology , Liver Diseases/immunology , Liver Diseases/therapy , Liver Transplantation/methods , Liver Transplantation/statistics & numerical data , Risk Adjustment , SARS-CoV-2 , Vaccination/methods
7.
Respir Physiol Neurobiol ; 283: 103548, 2021 01.
Article in English | MEDLINE | ID: covidwho-779595

ABSTRACT

BACKGROUND: Globally, the current medical emergency for novel coronavirus 2019 (COVID-19) leads to respiratory distress syndrome and death. PURPOSE: This review highlighted the effect of COVID-19 on systemic multiple organ failure syndromes. This review is intended to fill a gap in information about human physiological response to COVID-19 infections. This review may shed some light on other potential mechanisms and approaches in COVID -19 infections towards systemic multiorgan failure syndromes. FINDING: SARS-CoV-2 intervened mainly in the lung with progression to pneumonia and acute respiratory distress syndrome (ARDS) via the angiotensin-converting enzyme 2(ACE2) receptor. Depending on the viral load, infection spread through the ACE2 receptor further to various organs such as heart, liver, kidney, brain, endothelium, GIT, immune cell, and RBC (thromboembolism). This may be aggravated by cytokine storm with the extensive release of proinflammatory cytokines from the deregulating immune system. CONCLUSION: The widespread and vicious combinations of cytokines with organ crosstalk contribute to systemic hyper inflammation and ultimately lead to multiple organ dysfunction (Fig. 1). This comprehensive study comprises various manifestations of different organs in COVID-19 and may assist the clinicians and scientists pertaining to a broad approach to fight COVID 19.


Subject(s)
Coronavirus Infections/immunology , Cytokine Release Syndrome/immunology , Multiple Organ Failure/immunology , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/immunology , Respiratory Distress Syndrome/immunology , Spike Glycoprotein, Coronavirus/metabolism , Acute Kidney Injury/immunology , Acute Kidney Injury/physiopathology , Angiotensin-Converting Enzyme 2 , Arrhythmias, Cardiac/immunology , Arrhythmias, Cardiac/physiopathology , Betacoronavirus/metabolism , COVID-19 , Coronavirus Infections/physiopathology , Cytokine Release Syndrome/physiopathology , Cytokines/immunology , Endothelium, Vascular/metabolism , Erythrocytes/metabolism , Gastrointestinal Diseases/immunology , Gastrointestinal Diseases/physiopathology , Gastrointestinal Tract/metabolism , Heart Failure/immunology , Heart Failure/physiopathology , Humans , Inflammation/immunology , Kidney/metabolism , Liver/metabolism , Liver Diseases/immunology , Liver Diseases/physiopathology , Lung/metabolism , Multiple Organ Failure/physiopathology , Myocardium/metabolism , Pandemics , Pneumonia, Viral/physiopathology , Respiratory Distress Syndrome/physiopathology , SARS-CoV-2 , Thromboembolism/immunology , Thromboembolism/physiopathology , Viral Load
8.
Scand J Immunol ; 93(3): e12977, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-760191

ABSTRACT

In the natural history of SARS-CoV-2 infection, liver injury is frequent but quite mild and it is defined as any liver damage occurring during disease progression and treatment of infection in patients with or without pre-existing liver diseases. The underlying mechanisms for hepatic injury in patients with COVID-19 are still unclear but the liver damage in SARS-CoV-2 infection seems to be directly caused by virus-induced cytopathic effects. In this review, we will summarize all data of updated literature, regarding the relationship between SARS-CoV-2 infection, acute response and liver involvement. An overview will be given on liver injury, liver transplant and the possible consequences of COVID-19 in patients with pre-existing liver diseases.


Subject(s)
COVID-19/immunology , Cytokine Release Syndrome/immunology , Liver Diseases/immunology , Liver/immunology , SARS-CoV-2/immunology , Antiviral Agents/immunology , Antiviral Agents/therapeutic use , COVID-19/epidemiology , COVID-19/virology , Cytokine Release Syndrome/metabolism , Cytokines/immunology , Cytokines/metabolism , Hepatocytes/immunology , Hepatocytes/metabolism , Hepatocytes/pathology , Humans , Liver/pathology , Liver/physiopathology , Liver Diseases/physiopathology , Liver Diseases/therapy , Pandemics/prevention & control , SARS-CoV-2/drug effects , SARS-CoV-2/physiology
9.
Eur J Gastroenterol Hepatol ; 33(3): 319-324, 2021 03 01.
Article in English | MEDLINE | ID: covidwho-528914

ABSTRACT

Coronavirus disease 2019 (COVID-19) is an infection caused by a novel coronavirus (SARS-CoV-2) originated in China in December 2020 and declared pandemic by WHO. This coronavirus mainly spreads through the respiratory tract and enters cells through angiotensin-converting enzyme 2 (ACE2). The clinical symptoms of COVID-19 patients include fever, cough, and fatigue. Gastrointestinal symptoms (diarrhea, anorexia, and vomiting) may be present in 50% of patients and may be associated with worst prognosis. Other risk factors are older age, male gender, and underlying chronic diseases. Mitigation measures are essential to reduce the number of people infected. Hospitals are a place of increased SARS-CoV-2 exposure. This has implications in the organization of healthcare services and specifically endoscopy departments. Patients and healthcare workers safety must be optimized in this new reality. Comprehension of COVID-19 gastrointestinal manifestations and implications of SARS-CoV-2 in the management of patients with gastrointestinal diseases, under or not immunosuppressant therapies, is essential. In this review, we summarized the latest research progress and major societies recommendations regarding the implications of COVID-19 in gastroenterology, namely the adaptations that gastroenterology/endoscopy departments and professionals must do in order to optimize the provided assistance, as well as the implications that this infection will have, in particularly vulnerable patients such as those with chronic liver disease and inflammatory bowel disease under or not immunosuppressant therapies.


Subject(s)
COVID-19/prevention & control , Endoscopy, Gastrointestinal , Gastroenterologists , Infection Control , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Infectious Disease Transmission, Professional-to-Patient/prevention & control , Liver Diseases/therapy , Practice Patterns, Physicians' , COVID-19/immunology , COVID-19/transmission , Clinical Decision-Making , Decision Support Techniques , Endoscopy, Gastrointestinal/adverse effects , Humans , Immunocompromised Host , Liver Diseases/diagnosis , Liver Diseases/immunology , Occupational Health , Patient Safety , Risk Assessment , Risk Factors
11.
Diabetes Metab Syndr ; 14(4): 665-669, 2020.
Article in English | MEDLINE | ID: covidwho-232720

ABSTRACT

BACKGROUND & AIM: As on date, no specific treatment is available for devastating COVID-19 (SARS-CoV-2) infection. This pandemic viral infection has affected over 200 countries within a very short time and created a calamitous situation across the globe. As per WHO guidelines, the treatment is mainly symptomatic and supportive. This clinical protocol has not proven sufficient to save the lives of COVID-19 patients suffering from diabetes or having underlying liver diseases; hence there is utmost need to tackle this situation by other means such as Convalescent Plasma (CP) therapy. METHODS: A comprehensive literature survey was carriedout using Elsevier, PubMed, Taylor & Francis, Springer, Nature and Google search engines. RESULTS: The patients suffering from diabetes or liver dysfunction or any other underlying diseases are at greatest risk of SARS-CoV-2 infection. From the study, it is proved that plasma collected from the recovered patients of viral infection has considerable potential to treat the viral disease without the occurrence of adverse effects. CONCLUSION: The CP therapy can be a possible life saving alternative to treat critical COVID-19 patients having diabetes or underlying liver dysfunction. Hence, randomised clinical trials are recommended at the earliest to save the lives of infected individuals of COVID-19.


Subject(s)
Coronavirus Infections/immunology , Coronavirus Infections/therapy , Diabetes Complications/physiopathology , Liver Diseases/complications , Pneumonia, Viral/immunology , Pneumonia, Viral/therapy , Betacoronavirus/immunology , COVID-19 , Clinical Protocols , Comorbidity , Diabetes Complications/immunology , Diabetes Complications/therapy , Humans , Immunization, Passive , Liver Diseases/immunology , Liver Diseases/physiopathology , Liver Diseases/therapy , Pandemics , Randomized Controlled Trials as Topic , SARS-CoV-2
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