新型冠状病毒肺炎心血管并发症研究现状

新型冠状病毒肺炎是由严重急性呼吸综合征冠状病毒2引起的一种传染性疾病,目前的临床证据表明,新型冠状病毒肺炎合并基础心血管系统疾病的患者死亡风险明显增加,大部分患者在病程中会发生心肌炎、心肌损伤、心律失常和心肌病等。该文主要阐述新型冠状病毒肺炎心血管并发症的研究现状。     

Molecular mechanisms implicated in SARS-CoV-2 liver tropism

The coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Hepatic involvement is common in SARS-CoV-2-infected individuals. It is currently accepted that the direct and indirect hepatic effects of SARS-CoV-2 infection play a significant role in COVID-19. In individuals with pre-existing infectious and non-infectious liver disease, who are at a remarkably higher risk of developing severe COVID-19 and death, this pathology is most medically relevant. This review emphasizes the current pathways regarded as contributing to the gastrointestinal and hepatic ailments linked to COVID-19-infected patients due to an imbalanced interaction among the liver, systemic inflammation, disrupted coagulation, and the lung.     

COVID-19 and its effects on the digestive system

Coronavirus disease 2019 (COVID-19) is caused by infection of the coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with typical respiratory symptoms. SARS-CoV-2 invades not only the respiratory system, but also other organs expressing the cell surface receptor angiotensin converting enzyme 2. In particular, the digestive system is a susceptible target of SARS-CoV-2. Gastrointestinal symptoms of COVID-19 include anorexia, nausea, vomiting, diarrhea, abdominal pain, and liver damage. Patients with digestive damage have a greater chance of progressing to severe or critical illness, a poorer prognosis, and a higher risk of death. This paper aims to summarize the digestive system symptoms of COVID-19 and discuss fecal-oral contagion of SARS-CoV-2. It also describes the characteristics of inflammatory bowel disease patients with SARS-CoV-2 infection and discusses precautions for preventing SARS-CoV-2 infection during gastrointestinal endoscopy procedures. Improved attention to digestive system abnormalities and gastrointestinal symptoms of COVID-19 patients may aid health care providers in the process of clinical diagnosis, treatment, and epidemic prevention and control.     

新型冠状病毒肺炎研究进展

2019年12月底,中国暴发了一场不明微生物引发的病毒性肺炎。经研究确认,该不明微生物为一种新的冠状病毒,即严重急性呼吸综合征冠状病毒2（severe acute respiratory syndrome coronavirus 2, SARS-CoV-2）,2020年2月,WHO将SARS-CoV-2感染的肺炎正式命名为新型冠状病毒肺炎（coronavirus disease-2019, COVID-19）。随着对SARS-CoV-2及其引发肺炎研究的深入,SARS-CoV-2特点、COVID-19临床及流行病学特征、临床诊治技术等研究内容陆续在国内外杂志报道。本文对已开展的COVID-19研究工作梳理总结,围绕溯源分析、检测手段、临床表现、药物研发、病毒传播等5个方面进行综述,以期对临床及科研工作者提供帮助。     

Markers Associated with COVID-19 Susceptibility,Resistance, and Severity

In December 2019, the latest member of the coronavirus family, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in Wuhan, China, leading to the outbreak of an unusual viral pneumonia known as coronavirus disease 2019 (COVID-19). COVID-19 was then declared as a pandemic in March 2020 by the World Health Organization (WHO). The initial mortality rate of COVID-19 declared by WHO was 2%; however, this rate has increased to 3.4% as of 3 March 2020. People of all ages can be infected with SARS-CoV-2, but those aged 60 or above and those with underlying medical conditions are more prone to develop severe symptoms that may lead to death. Patients with severe infection usually experience a hyper pro-inflammatory immune reaction (i.e., cytokine storm) causing acute respiratory distress syndrome (ARDS), which has been shown to be the leading cause of death in COVID-19 patients. However, the factors associated with COVID-19 susceptibility, resistance and severity remain poorly understood. In this review, we thoroughly explore the correlation between various host, viral and environmental markers, and SARS-CoV-2 in terms of susceptibility and severity.     

Liver injury in the era of COVID-19

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has undoubtedly revolutionized the whole globe and given a new point of view on respiratory tract infections. Nevertheless, coronavirus disease 2019 (COVID-19) cannot be perceived as a disease limited only to pneumonia with diverse severity. More and more reports have demonstrated a wide range of possible systemic symptoms, including hepatic complications. Liver injury has been observed in a significant proportion of patients, especially in those with a severe or critical illness. COVID-19 might provoke a deterioration of liver function in patients with already diagnosed chronic liver diseases and without pre-existing liver disorders. The deterioration of liver function worsens the prognosis, increases the risk of a severe course of SARS-CoV-2 infection and prolongs the hospital stay. In general, patients who develop liver dysfunction in COVID-19 are mainly males, elderly people, and those with higher body mass index. The underlying mechanisms for hepatic failure in patients infected with SARS-CoV-2 are still unclear, nevertheless liver damage appears to be directly connected with virus-induced cytopathic effects. A liver injury observed during hospitalization might be simultaneously caused by the use of potentially hepatotoxic drugs, mainly antiviral agents. This minireview focuses on a possible relationship between COVID-19 and the liver, potential molecular mechanisms of liver damage, the characteristics of liver injury and suggested factors predisposing to hepatic manifestations in COVID-19 patients.     

SARS-CoV-2 variants: A continuing threat to global health

Coronavirus disease 2019 (COVID-19) is an acute respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 pandemic ha...     

COVID-19 and hepatic injury: cellular and molecular mechanisms in diverse liver cells

The coronavirus disease 2019(COVID-19) represents a global health and economic challenge. Hepatic injuries have been approved to be associated with severe acute respiratory syndrome coronavirus(SARS-CoV-2) infection. The viral tropism pattern of SARS-CoV-2 can induce hepatic injuries either by itself or by worsening the conditions of patients with hepatic diseases. Besides, other factors have been reported to play a crucial role in the pathological forms of hepatic injuries induced by SARS-CoV-2...     

Characterization of the SARS-CoV-2 Host Response in Primary Human Airway Epithelial Cells from Aged Individuals

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19), a global pandemic characterized by an exaggerated immune response and respiratory illness. Age (>60 years) is a significant risk factor for developing severe COVID-19. To better understand the host response of the aged airway epithelium to SARS-CoV-2 infection, we performed an in vitro study using primary human bronchial epithelial cells from donors >67 years of age differentiated on an air–liquid interface culture. We demonstrate that SARS-CoV-2 infection leads to early induction of a proinflammatory response and a delayed interferon response. In addition, we observed changes in the genes and pathways associated with cell death and senescence throughout infection. In summary, our study provides new and important insights into the temporal kinetics of the airway epithelial innate immune response to SARS-CoV-2 in older individuals.     

Sustained coronavirus disease 2019-related organizing pneumonia successfully treated with corticosteroid

A 70-year-old Japanese man contracted severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and required oxygen to maintain oxygen saturation (>90%), 5 weeks after onset of coronavirus disease 2019 (COVID-19) symptoms. Transbronchial lung cryobiopsy revealed pathological features of organizing pneumonia with alveolar epithelial injury, and prednisolone administration led to alleviation of respiratory symptoms and recovery of respiratory function. This case report is the first to demonstrate the use of corticosteroids to successfully treat post-COVID-19 respiratory failure in a patient with biopsy-proven organizing pneumonia. We propose that steroid treatment be considered for patients with persistent respiratory dysfunction as COVID-19 pneumonia sequelae.     

COVID-19 and liver injury: An ongoing challenge

The new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in December 2019, in Wuhan, China. The virus was rapidly spread worldwide, causing coronavirus disease 2019 (COVID-19) pandemic. Although COVID-19 is presented, usually, with typical respiratory symptoms (i.e., dyspnea, cough) and fever, extrapulmonary manifestations are also encountered. Liver injury is a common feature in patients with COVID-19 and ranges from mild and temporary elevation of liver enzymes to severe liver injury and, even, acute liver failure. The pathogenesis of liver damage is not clearly defined; multiple mechanisms contribute to liver disorder, including direct cytopathic viral effect, cytokine storm and immune-mediated hepatitis, hypoxic injury, and drug-induced liver toxicity. Patients with underlying chronic liver disease (i.e., cirrhosis, non-alcoholic fatty liver disease, alcohol-related liver disease, hepatocellular carcinoma, etc.) may have greater risk to develop both severe COVID-19 and further liver deterioration, and, as a consequence, certain issues should be considered during disease management. The aim of this review is to present the prevalence, clinical manifestation and pathophysiological mechanisms of liver injury in patients with SARS-CoV-2 infection. Moreover, we overview the association between chronic liver disease and SARS-CoV-2 infection and we briefly discuss the management of liver injury during COVID-19.     

Effective Reduction of SARS-CoV-2 RNA Levels Using a Tailor-Made Oligonucleotide-Based RNA Inhibitor

In only two years, the coronavirus disease 2019 (COVID-19) pandemic has had a devastating effect on public health all over the world and caused irreparable economic damage across all countries. Due to the limited therapeutic management of COVID-19 and the lack of tailor-made antiviral agents, finding new methods to combat this viral illness is now a priority. Herein, we report on a specific oligonucleotide-based RNA inhibitor targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It displayed remarkable spontaneous cellular uptake, >94% efficiency in reducing RNA-dependent RNA polymerase (RdRp) RNA levels in transfected lung cell lines, and >98% efficiency in reducing SARS-CoV-2 RNA levels in samples from patients hospitalized with COVID-19 following a single application.     

Liver dysfunction during COVID-19 pandemic: Contributing role of associated factors in disease progression and severity

In December 2019, a new strain of coronavirus was discovered in China, and the World Health Organization declared it a pandemic in March 2020. The majority of people with coronavirus disease 19 (COVID-19) exhibit no or only mild symptoms such as fever, cough, anosmia, and headache. Meanwhile, approximately 15% develop a severe lung infection over the course of 10 d, resulting in respiratory failure, which can lead to multi-organ failure, coagulopathy, and death. Since the beginning of the pandemic, it appears that there has been consideration that pre-existing chronic liver disease may predispose to deprived consequences in conjunction with COVID-19. Furthermore, extensive liver damage has been linked to immune dysfunction and coagulopathy, which leads to a more severe COVID-19 outcome. Besides that, people with COVID-19 frequently have abnormal liver function, with more significant elevations in alanine aminotransferase and aspartate aminotransferase in patients with severe COVID-19 compared to those with mild/moderate disease. This review focuses on the pathogenesis of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in the liver, as well as the use of liver chemistry as a prognostic tool during COVID-19. We also evaluate the findings for viral infection of hepatocytes, and look into the potential mechanisms behind SARS-CoV-2-related liver damage.     

Liver injury in COVID-19: The hepatic aspect of the respiratory syndrome — what we know so far

The 2019 novel coronavirus disease (COVID-19) pandemic due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed a serious threat to global public health. Although primarily, the infection causes lung injury, liver enzyme abnormalities have also been reported to occur during the course of the disease. We conducted an extensive literature review using the PubMed database on articles covering a broad range of issues related to COVID-19 and hepatic injury. The present review summarizes available information on the spectrum of liver involvement, the possible mechanisms and risk factors of liver injury due to SARS-CoV-2 infection, and the prognostic significance of the presence of liver injury. Hopefully, this review will enable clinicians, especially the hepatologists, to understand and manage the liver derangements they may encounter in these patients better and provide guidance for further studies on the liver injury of COVID-19.     

Atteintes du système cardiovasculaire chez les patients atteints de maladie à coronavirus 19

The coronavirus disease 2019 (COVID-19) outbreak has become a worldwide public health concern. Cardiovascular complications are relatively frequent, reaching 20% of COVID-19 patients and 43% of COVID-19 patients admitted in Intensive Care Unit. Cardiac injury mechanisms are multiple, including hyperinflammation, pro-coagulant and pro-thrombotic states, sepsis related cardiomyopathy, hypoxia in relation with lung severity, hemodynamic instability, cytokine storm, critically illness, direct myocardial insult by acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and stress cardiomyopathy. The authors report a narrative review about cardio-vascular complications and predictive factors of mortality in patients infected with COVID-19.     

Severe SARS-CoV-2 Infection in a Cat with Hypertrophic Cardiomyopathy

Coronavirus disease 19 (COVID-19), has claimed millions of human lives worldwide since the emergence of the zoonotic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China in December 2019. Notably, most severe and fatal SARS-CoV-2 infections in humans have been associated with underlying clinical conditions, including diabetes, hypertension and heart diseases. Here, we describe a case of severe SARS-CoV-2 infection in a domestic cat (Felis catus) that presented with hypertrophic cardiomyopathy (HCM), a chronic heart condition that has been described as a comorbidity of COVID-19 in humans and that is prevalent in domestic cats. The lung and heart of the affected cat presented clear evidence of SARS-CoV-2 replication, with histological lesions similar to those observed in humans with COVID-19 with high infectious viral loads being recovered from these organs. The study highlights the potential impact of comorbidities on the outcome of SARS-CoV-2 infection in animals and provides important information that may contribute to the development of a feline model with the potential to recapitulate the clinical outcomes of severe COVID-19 in humans.     

Impact of chronic liver disease on SARS-CoV-2 infection outcomes: Roles of stage,etiology and vaccination

Since the first identification in December of 2019 and the fast spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, it has represented a dramatic global public health concern. Though affecting mainly the respiratory system, SARS-CoV-2 disease, defined as coronavirus disease 2019 (COVID-19), may have a systemic involvement leading to multiple organ dysfunction. Experimental evidence about the SARS-CoV-2 tropism for the liver and the increasing of hepatic cytolysis enzymes during infection support the presence of a pathophysiological relationship between liver and SARS-CoV-2. On the other side, patients with chronic liver disease have been demonstrated to have a poor prognosis with COVID-19. In particular, patients with liver cirrhosis appear extremely vulnerable to infection. Moreover, the etiology of liver disease and the vaccination status could affect the COVID-19 outcomes. This review analyzes the impact of the disease stage and the related causes on morbidity and mortality, clinical outcomes during SARS-CoV-2 infection, as well as the efficacy of vaccination in patients with chronic liver disease.     

Endothelium Infection and Dysregulation by SARS-CoV-2: Evidence and Caveats in COVID-19

The ongoing pandemic of coronavirus disease 2019 (COVID-19) caused by the acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) poses a persistent threat to global public health. Although primarily a respiratory illness, extrapulmonary manifestations of COVID-19 include gastrointestinal, cardiovascular, renal and neurological diseases. Recent studies suggest that dysfunction of the endothelium during COVID-19 may exacerbate these deleterious events by inciting inflammatory and microvascular thrombotic processes. Although controversial, there is evidence that SARS-CoV-2 may infect endothelial cells by binding to the angiotensin-converting enzyme 2 (ACE2) cellular receptor using the viral Spike protein. In this review, we explore current insights into the relationship between SARS-CoV-2 infection, endothelial dysfunction due to ACE2 downregulation, and deleterious pulmonary and extra-pulmonary immunothrombotic complications in severe COVID-19. We also discuss preclinical and clinical development of therapeutic agents targeting SARS-CoV-2-mediated endothelial dysfunction. Finally, we present evidence of SARS-CoV-2 replication in primary human lung and cardiac microvascular endothelial cells. Accordingly, in striving to understand the parameters that lead to severe disease in COVID-19 patients, it is important to consider how direct infection of endothelial cells by SARS-CoV-2 may contribute to this process.     

Evolución clínica en un receptor de trasplante de hígado con la COVID-19: ¿Un efecto benéfico del tacrolimus?

Coronavirus disease 2019 (COVID-19) is a serious respiratory illness caused by SARS-CoV-2. There is controversy about whether their immunosuppressive status is a risk factor or a protective factor for developing severe disease.We report herein the clinical outcome of three family members that had COVID-19 infection, presenting with and without different risk factors that have been described in more severe disease. Paradoxically, the patient with more risks of developing a severe disease, a 64-year-old woman, 2-years liver transplant recipient under treatment with tacrolimus, presented a similar outcome compared to the two other members of the family. She showed shorter hospitalization time, similar clinical outcome with fewer oxygen needs.The present clinical observation raises the question about the possible beneficial effect of tacrolimus in patients with COVID-19. Indeed, tacrolimus (FK-506) have an inhibitory effect on human coronaviruses by: 1) an antiviral effect by binding to the FK-506-binding proteins (FKBP) with a subsequent inhibition of their peptidyl-prolyl cis/trans isomerase (PPIase) activity, which seems to be important for the coronavirus life cycle; and 2) regulating the immune response by the inhibition of the activity of the nuclear factor of activated T-cells (NFAT) required for immunosuppression.The present observation states that liver recipients’ patients with COVID-19 may not have worse outcomes when compared with other patients that have COVID-19 risk factors and puts in evidence the two mechanisms related to tacrolimus.