Molecular mechanisms underlying SARS-CoV-2 hepatotropism and liver damage

In coronavirus disease 2019(COVID-19),severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)primarily targets the respiratory system,but evidence suggests extrapulmonary organ involvement,notably in the liver.Viral RNA has been detected in hepatic tissues,and in situ hybridization revealed virions in blood vessels and endothelial cells.Electron microscopy confirmed viral particles in hepatocytes,emphasizing the need for understanding hepatotropism and direct cytopathic effects in COVID-19-related liver injury.Various factors contribute to liver injury,including direct cytotoxicity,vascular changes,inflammatory responses,immune reactions from COVID-19 and vaccinations,and druginduced liver injury.Although a typical hepatitis presentation is not widely documented,elevated liver biochemical markers are common in hospitalized COVID-19 patients,primarily showing a hepatocellular pattern of elevation.Long-term studies suggest progressive cholestasis may affect 20%of patients with chronic liver disease post-SARS-CoV-2 infection.The molecular mechanisms underlying SARS-CoV-2 infection in the liver and the resulting liver damage are complex.This“Editorial”highlights the expression of the Angiotensin-converting enzyme-2 receptor in liver cells,the role of inflammatory responses,the impact of hypoxia,the involvement of the liver's vascular system,the infection of bile duct epithelial cells,the activation of hepatic stellate cells,and the contribution of monocyte-derived macrophages.It also mentions that pre-existing liver conditions can worsen the outcomes of COVID-19.Understanding the interaction of SARS-CoV-2 with the liver is still evolving,and further research is required.

Acute pancreatitis as a complication of acute COVID-19 in kidney transplant recipients

BACKGROUND Acute pancreatitis is a rare extrapulmonary manifestation of coronavirus disease 2019(COVID-19)but its full correlation with COVID-19 infection remains unknown.AIM To identify acute pancreatitis’occurrence,clinical presentation and outcomes in a cohort of kidney transplant recipients with acute COVID-19.METHODS A retrospective observational single-centre cohort study from a transplant centre in Croatia for all adult renal transplant recipients with a functioning kidney allograft between March 2020 and August 2022 to record cases of acute pancreatitis during acute COVID-19.Data were obtained from hospital electronic medical records.Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection was proven by a positive SARS-CoV-2 real-time reverse transcriptase-polymerase chain reaction on the nasopharyngeal swab.RESULTS Four hundred and eight out of 1432(28.49%)patients who received a renal allograft developed COVID-19 disease.The analyzed cohort included 321 patients(57%males).One hundred and fifty patients(46.7%)received at least one dose of the anti-SARS-CoV-2 vaccine before the infection.One hundred twenty-five(39.1%)patients required hospitalization,141(44.1%)developed pneumonia and four patients(1.3%)required mechanical ventilation.Treatment included immunosuppression modification in 233 patients(77.1%)and remdesivir in 53 patients(16.6%),besides the other supportive measures.In the study cohort,only one transplant recipient(0.3%)developed acute pancreatitis during acute COVID-19,presenting with abdominal pain and significantly elevated pancreatic enzymes.She survived without complications with a stable kidney allograft function.CONCLUSION Although rare,acute pancreatitis may complicate the course of acute COVID-19 in kidney transplant recipients.The mechanism of injury to the pancreas and its correlation with the severity of the COVID-19 infection in kidney transplant recipients warrants further research.

Physical activity and mental well-being during COVID-19 pandemic

The corona virus disease 2019(COVID-19)pandemic has resulted in most nations deciding upon self-isolation and social distancing policies for their citizens to control the pandemic and reduce hospital admission.This review aimed at evaluating the effect of physical activity on mental well-being during the COVID-19 pandemic.It was concluded that the COVID-19 pandemic may lead to augmented levels of angiotensin-converting enzyme(ACE)-2 that led to cardiovascular and neurological disorders associated with highly inflammatory effects of viral infection affecting the brain tissues leading to damage of the nervous system and resulting in cognition dysfunction,insulin sensitivity reduction,and behavioral impairments.Anxiety and depression may lead to negative effects on various quality of life domains,such as being physically inactive.Regular physical activities may reduce inflammatory responses,improve ACE-2 responses,and improve mental well-being during self-isolation and social distancing policies related to the COVID-19 pandemic.Further studies should be conducted to assess the different intensities of physical activities on cardiovascular function,and mental well-being during the COVID-19 pandemic.

Angiotensin converting enzymes inhibitors or angiotensin receptor blockers should be continued in COVID-19 patients with hypertension

BACKGROUND Recent studies have revealed that sustained ingestion of angiotensin converting enzymes inhibitors or angiotensin receptor blockers(ACEIs/ARBs)had no harmful effects on coronavirus disease 2019(COVID-19)patients complicated with hypertension.AIM To investigate the impact on COVID-19 patients complicated with hypertension who discontinued using ACEIs/ARBs.METHODS All COVID-19 patients complicated with hypertension admitted to our isolated unit were consecutively recruited in this study.Some patients switched from ACEIs/ARBs to calcium channel blocker(CCBs)after admission,while others continued using non-ACEIs/ARBs.We compared characteristics and clinical outcomes between these two groups of patients.RESULTS A total of 53 patients were enrolled,27 patients switched from ACEIs/ARBs to CCBs while 26 patients continued with non-ACEIs/ARBs.After controlling potential confounding factors using the Cox proportional hazards model,hospital stay was longer in patients who discontinued ACEIs/ARBs,with a hazard ratio of 0.424(95%confidence interval:0.187-0.962;P=0.040),upon discharge than patients using other anti-hypertensive drugs.A sub-group analysis showed that the effect of discontinuing use of ACEIs/ARBs was stronger in moderate cases[hazard ratio=0.224(95%confidence interval:0.005-0.998;P=0.0497)].CONCLUSION Patients in the discontinued ACEIs/ARBs group had longer hospital stays.Our findings suggest that COVID-19 patients complicated with hypertension should continue to use ACEIs/ARBs.

Current therapies and novel approaches for biliary diseases

Chronic liver diseases that inevitably lead to hepatic fibrosis, cirrhosis and/or hepatocellular carcinoma have become a major cause of illness and death worldwide. Among them, cholangiopathies or cholestatic liver diseases comprise a large group of conditions in which injury is primarily focused on the biliary system. These include congenital diseases(such as biliary atresia and cystic fibrosis), acquired diseases(such as primary sclerosing cholangitis and primary biliary cirrhosis), and those that arise from secondary damage to the biliary tree from obstruction, cholangitis or ischaemia. These conditions are associated with a specific pattern of chronic liver injury centered on damaged bile ducts that drive the development of peribiliary fibrosis and, ultimately, biliary cirrhosis and liver failure. For most, there is no established medical therapy and, hence, these diseases remain one of the most important indications for liver transplantation.As a result, there is a major need to develop new therapies that can prevent the development of chronic biliary injury and fibrosis. This mini-review briefly discusses the pathophysiology of liver fibrosis and its progression to cirrhosis.We make a special emphasis on biliary fibrosis and current therapeutic options,such as angiotensin converting enzyme-2(known as ACE2) over-expression in the diseased liver as a novel potential therapy to treat this condition.

Mechanism and potential treatments for gastrointestinal dysfunction in patients with COVID-19

The global coronavirus disease 2019(COVID-19)has become one of the biggest threats to the world since 2019.The respiratory and gastrointestinal tracts are the main targets for severe acute respiratory syndrome coronavirus 2 infection for they highly express angiotensin-converting enzyme-2 and transmembrane protease serine 2.In patients suffering from COVID-19,gastrointestinal symptoms have ranged from 12%to 61%.Anorexia,nausea and/or vomiting,diarrhea,and abdominal pain are considered to be the main gastrointestinal symptoms of COVID-19.It has been reported that the direct damage of intestinal mucosal epithelial cells,malnutrition,and intestinal flora disorders are involved in COVID-19.However,the underlying mechanisms remain unclear.Thus,in this study,we reviewed and discussed the correlated mechanisms that cause gastrointestinal symptoms in order to help to develop the treatment strategy and build an appropriate guideline for medical workers.

Underlying reasons for the decline in physical activity during COVID-19

The article not only successfully evaluated regular physical activities can improve mental well-being during self-isolation and social distancing policies related to the coronavirus disease 2019(COVID-19),but also concluded that the COVID-19 pandemic may lead to augmented levels of angiotensin-converting enzyme-2.By reading the article of Walid Kamal Abdelbasset,we have some questions and put forward some suggestions on the content of the article.

Prediction of Proteins Associated with COVID-19 Based Ligand Designing and Molecular Modeling

Current understanding about how the virus that causes COVID-19 spreads is largely based on what is known about similar coronaviruses.Some of the Natural products are suitable drugs against SARS-CoV-2 main protease.For recognizing a strong inhibitor,we have accomplished dock-ing studies on the major virus protease with 4 natural product species as anti COVID-19(SARS-CoV-2),namely“Vidarabine”,“Cytarabine”,“Gem-citabine”and“Matrine”which have been extracted fromGillan’s leaves plants.These are known as Chuchaq,Trshvash,Cote-Couto and Khlvash in Iran.Among these four studied compounds,Cytarabine appears as a suitable com-pound with high effectiveness inhibitors to this protease.Finally by this work we present a method on the Computational Prediction of Protein Structure Associated with COVID-19 Based Ligand Design and Molecular Modeling.By this investigation,auto dock software(iGEM-DOCK)has been used and via this tool,the suitable receptors can be distinguished in whole COVID-19 component structures for forming a complex.“iGEMDOCK”is suitable to define the binding site quickly.With docking simulation and NMR inves-tigation,we have demonstrated these compounds exhibit a suitable binding energy around 9 Kcal/mol with various ligand proteins modes in the bind-ing to COVID-19 viruses.However,these data need further evaluation for repurposing these drugs against COVID-19 viruses,in both vivo&vitro.