Liver injury during highly pathogenic human coronavirus infections

The severe acute respiratory syndrome coronavirus 2 (SARS‐Cov‐2), the pathogen of 2019 novel coronavirus disease (COVID‐19), has posed a serious threat to global public health. The WHO has declared the outbreak of SARS‐CoV‐2 infection an international public health emergency. Lung lesions have been considered as the major damage caused by SARS‐CoV‐2 infection. However, liver injury has also been reported to occur during the course of the disease in severe cases. Similarly, previous studies have shown that liver damage was common in the patients infected by the other two highly pathogenic coronavirus – severe acute respiratory syndrome coronavirus (SARS‐CoV) and the Middle East respiratory syndrome coronavirus (MERS‐CoV), and associated with the severity of diseases. In this review, the characteristics and mechanism of liver injury caused by SARS‐CoV, MERS‐CoV as well as SARS‐CoV‐2 infection were summarized, which may provide help for further studies on the liver injury of COVID‐19.     

Low prevalence and disease severity of COVID‐19 in post‐liver transplant recipients—A single centre experience

Coronavirus disease 2019 (COVID‐19) caused by a novel coronavirus called severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) is driving a present day global pandemic. Immunosuppressed patients are regarded as a high‐risk cohort. The following is a short report on COVID‐19 in liver transplant recipients (n = 5) from a high volume UK liver transplant unit with a large follow‐up cohort (n = 4500). Based on this limited data, liver transplant recipients appear to have a low incidence of COVID‐19, with less severe symptoms than expected, when compared with the general population and other solid organ recipients. This possibly could be related to self‐isolation adherence and/or the ‘ideal’ level of immunosuppression that favourably modulates the immune response to COVID‐19.     

Cardiac and arrhythmic complications in patients with COVID‐19

In December 2019, the world started to face a new pandemic situation, the severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2). Although coronavirus disease (COVID‐19) clinical manifestations are mainly respiratory, major cardiac complications are being reported. Cardiac manifestations etiology seems to be multifactorial, comprising direct viral myocardial damage, hypoxia, hypotension, enhanced inflammatory status, ACE2‐receptors downregulation, drug toxicity, endogenous catecholamine adrenergic status, among others. Studies evaluating patients with COVID‐19 presenting cardiac injury markers show that it is associated with poorer outcomes, and arrhythmic events are not uncommon. Besides, drugs currently used to treat the COVID‐19 are known to prolong the QT interval and can have a proarrhythmic propensity. This review focus on COVID‐19 cardiac and arrhythmic manifestations and, in parallel, makes an appraisal of other virus epidemics as SARS‐CoV, Middle East respiratory syndrome coronavirus, and H1N1 influenza.     

Digestive system involvement of novel coronavirus infection: Prevention and control infection from a gastroenterology perspective

An epidemic of an acute respiratory syndrome caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) in Wuhan, China, now known as coronavirus disease 2019 (COVID‐19), beginning in December 2019, has attracted an intense amount of attention worldwide. As the natural history and variety of clinical presentations of this disease unfolds, extrapulmonary symptoms of COVID‐19 have emerged, especially in the digestive system. While the respiratory mode of transmission is well known and is probably the principal mode of transmission of this disease, a possibility of the fecal‐oral route of transmission has also emerged in various case series and clinical scenarios. In this review article, we summarize four different aspects in published studies to date: (a) gastrointestinal manifestations of COVID‐19; (b) microbiological and virological investigations; (c) the role of fecal‐oral transmission; and (d) prevention and control of SARS‐CoV‐2 infection in the digestive endoscopy room. A timely understanding of the relationship between the disease and the digestive system and implementing effective preventive measures are of great importance for a favorable outcome of the disease and can help climnicians to mitigate further transmission by taking appropriate measures.     

SARS‐CoV‐2 infection in patients with a normal or abnormal liver

Severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2), a novel coronavirus causing coronavirus disease 19 (COVID‐19), with an estimated 22 million people infected worldwide so far although involving primarily the respiratory tract, has a remarkable tropism for the liver and the biliary tract. Patients with SARS‐CoV‐2 infection and no antecedent liver disease may display evidence of cytolytic liver damage, proportional to the severity of COVID‐19 but rarely of clinical significance. The mechanism of hepatocellular injury is unclear and possibly multifactorial. The clinical impact of SARS‐CoV‐2 infection in patients with underlying chronic liver disease, a cohort whose global size is difficult to estimate, has been assessed appropriately only recently and data are still evolving. Patients with cirrhosis are at higher risk of developing severe COVID‐19 and worse liver‐related outcomes as compared to those with non‐cirrhotic liver disease. OLT patients have an intermediate risk. Specific interventions in order to reduce the risk of transmission of infection among this high‐risk population have been outlined by international societies, together with recommendations for modified treatment and follow‐up regimens during the COVID‐19 pandemic. When a vaccine against SARS‐CoV‐2 becomes available, patients with fibrotic liver disease and those with OLT should be considered as prime targets for prophylaxis of COVID‐19, as all other highly susceptible subjects.     

Understanding immunopathological fallout of human coronavirus infections including COVID‐19: Will they cross the path of rheumatologists?

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection causing coronavirus disease 2019 (COVID‐19) is the biggest pandemic of our lifetime to date. No effective treatment is yet in sight for this catastrophic illness. Several antiviral agents and vaccines are in clinical trials, and drug repurposings as immediate and alternative choices are also under consideration. Immunomodulatory agents like hydroxychloroquine (HCQ) as well as biological disease‐modifying anti‐rheumatic drugs (bDMARDs) such as tocilizumab and anakinra received worldwide attention for treatment of critical patients with COVID‐19. This is of interest to rheumatologists, who are well versed with rational use of these agents. This brief review addresses the understandings of some of the common immunopathogenetic mechanisms in the context of autoimmune rheumatic diseases like systemic lupus erythematosus (SLE) and COVID‐19. Apart from demographic comparisons, the role of type I interferons (IFN), presence of antiphospholipid antibodies and finally mechanism of action of HCQ in both the scenarios are discussed here. High risks for fatal disease in COVID‐19 include older age, metabolic syndrome, male gender, and individuals who develop delayed type I IFN response. HCQ acts by different mechanisms including prevention of cellular entry of SARS‐CoV‐2 and inhibition of type I IFN signaling. Recent controversies regarding efficacy of HCQ in management of COVID‐19 warrant more studies in that direction. Autoantibodies were also reported in severe acute respiratory syndrome (SARS) as well as in COVID‐19. Rheumatologists need to wait and see whether SARS‐CoV‐2 infection triggers development of autoimmunity in patients with COVID‐19 infection in the long run.     

Insight into the pediatric and adult dichotomy of COVID‐19: Age‐related differences in the immune response to SARS‐CoV‐2 infection

The difference in morbidity and mortality between adult and pediatric coronavirus disease 2019 infections is dramatic. Understanding pediatric‐specific acute and delayed immune responses to severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is critical for the development of vaccination strategies, immune‐targeted therapies, and treatment and prevention of multisystem inflammatory syndrome in children. The goal of this review is to highlight research developments in the understanding of the immune responses to SARS‐CoV‐2 infections, with a specific focus on age‐related immune responses.     

Management of heart failure patients with COVID‐19: a joint position paper of the Chinese Heart Failure Association & National Heart Failure Committee and the Heart Failure Association of the European Society of Cardiology

The coronavirus disease 2019 (COVID‐19) pandemic of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection is causing considerable morbidity and mortality worldwide. Multiple reports have suggested that patients with heart failure (HF) are at a higher risk of severe disease and mortality with COVID‐19. Moreover, evaluating and treating HF patients with comorbid COVID‐19 represents a formidable clinical challenge as symptoms of both conditions may overlap and they may potentiate each other. Limited data exist regarding comprehensive management of HF patients with concomitant COVID‐19. Since these issues pose serious new challenges for clinicians worldwide, HF specialists must develop a structured approach to the care of patients with COVID‐19 and be included early in the care of these patients. Therefore, the Heart Failure Association of the European Society of Cardiology and the Chinese Heart Failure Association & National Heart Failure Committee conducted web‐based meetings to discuss these unique clinical challenges and reach a consensus opinion to help providers worldwide deliver better patient care. The main objective of this position paper is to outline the management of HF patients with concomitant COVID‐19 based on the available data and personal experiences of physicians from Asia, Europe and the United States.     

Ten key points about COVID‐19 in children: The shadows on the wall

The pandemic of the new coronavirus disease‐2019 (COVID‐19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), initially described in China, is challenging the health care systems of all countries. Every emerging disease raises many questions with a scarcity of answers since all its characteristics are still being discovered. In the case of SARS‐CoV‐2, most of the literature comes from adult patients. Children seem to be less affected. Pediatric patients diagnosed with COVID‐19 disease usually suffer a mild illness, with a low risk of complications, or mortality. Defining the role of children in the transmission of SARS‐CoV‐2 is critical as some national infection control decisions involving children, such as school closures or social distancing, will probably impact the dynamics of the virus. To aid in the knowledge of COVID‐19 in children, this study presents an expert review of the literature published from 1 January to 28 May 2020, including peer‐reviewed and preprint nonpeer‐reviewed studies, along with some relevant articles afterward, summarizing ten key points that characterize the disease in children.     

COVID‐19 and the clinical hematology laboratory

The ongoing COVID‐19 pandemic originated in Wuhan, Hubei Province, China, in December 2019. The etiologic agent is a novel coronavirus of presumed zoonotic origin with structural similarity to the viruses responsible for severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). Like SARS and MERS, COVID‐19 infection manifests most frequently with lower respiratory symptoms. A minority of patients progress to acute respiratory distress syndrome/ diffuse alveolar damage. In addition to its central role in the diagnosis of COVID‐19 infection, the clinical laboratory provides critical information to clinicians regarding prognosis, disease course, and response to therapy. The purpose of this review is to (a) provide background context about the origins and course of the pandemic, (b) discuss the laboratory's role in the diagnosis of COVID‐19 infection, (c) summarize the current state of biomarker analysis in COVID‐19 infection, with an emphasis on markers derived from the hematology laboratory, (d) comment on the impact of COVID‐19 on hematology laboratory safety, and (e) describe the impact the pandemic has had on organized national and international educational activities worldwide.     

Influence of immunosuppression on seroconversion against SARS‐CoV‐2 in two kidney transplant recipients

Solid organ transplant recipients are at risk for infectious complications due to chronic immunosuppression. The outbreak of coronavirus disease 2019 (COVID‐19) in the United States has raised growing concerns for the transplant patient population. We seek to add to the current limited literature on COVID‐19 in transplant recipients by describing the clinical course of two kidney transplant recipients with SARS‐CoV‐2 infection monitored by both RT‐PCR and serology. Through careful adjustment of their immunosuppression regimen, both patients had excellent recovery with intact graft function and development of anti‐SARS‐CoV‐2 antibodies.     

The renin–angiotensin–aldosterone system as a link between obesity and coronavirus disease 2019 severity

Coronavirus disease 2019 (COVID‐19), caused by the severe acute respiratory distress coronavirus 2 (SARS‐CoV2), is a rapidly evolving pandemic challenging the world and posing unprecedented public health issues. Current data show that COVID‐19 is associated with increased disease severity in individuals with obesity. Obesity is usually associated with dysregulated renin–angiotensin–aldosterone (RAAS) axis. RAAS has also been implicated in acute lung injury as well as myocardial injury and has thus attracted interest as a potential regulator of COVID‐19 severity. Whilst research all over the world is still struggling to provide a detailed characterization of the biology of SARS‐CoV2 and its associated disease profile, it has become evident that SARS‐CoV2 uses the membrane‐bound form of angiotensin‐converting enzyme 2 (ACE2) as a receptor for cell internalization. ACE2 is a protective component of the RAAS axis and is downregulated after SARS‐CoV2 infection. The RAAS axis could thus be a link between obesity and COVID‐19 severity; therefore, more accurate understanding of the underlying mechanisms would be needed with the hope of proposing efficient therapeutic interventions.     

Dissecting the interaction between COVID‐19 and diabetes mellitus

Coronavirus disease 2019 (COVID‐19) is a global pandemic that is caused by a novel coronavirus, severe acute respiratory syndrome coronavirus‐2. Data from several countries have shown higher morbidity and mortality among individuals with chronic metabolic diseases, such as diabetes mellitus. In this review, we explore the contributing factors for poorer prognosis in these individuals. As a significant proportion of patients with COVID‐19 also have diabetes mellitus, this adds another layer of complexity to their management. We explore potential interactions between antidiabetic medications and renin–angiotensin–aldosterone system inhibitors with COVID‐19. Suggested recommendations for the use of antidiabetic medications for COVID‐19 patients with diabetes mellitus are provided. We also review pertinent clinical considerations in the management of diabetic ketoacidosis in COVID‐19 patients. In addition, we aim to increase clinicians’ awareness of the metabolic effects of promising drug therapies for COVID‐19. Finally, we highlight the importance of timely vaccinations for patients with diabetes mellitus.     

Practical management of inflammatory bowel disease patients during the COVID‐19 pandemic: expert commentary from the Gastroenterological Society of Australia Inflammatory Bowel Disease faculty

The COVID‐19 pandemic, caused by the novel coronavirus SARS‐CoV‐2, has emerged as a public health emergency and challenged healthcare systems globally. In a minority of patients, SARS‐CoV‐2 manifests with a severe acute respiratory illness and currently there are insufficient data regarding the virulence of COVID‐19 in inflammatory bowel disease patients taking immunosuppressive therapy. This review aims to summarise the current literature and provide guidance on the management of inflammatory bowel disease (IBD) patients in the context of the COVID‐19 pandemic in the Australasian setting.     

In‐hospital management of persons with haemophilia and COVID‐19: Practical guidance

A new disease (COVID‐19) caused by a coronavirus (SARS‐CoV‐2) that appeared in China at the end of 2019 is currently spreading globally. This emerging virus is mainly responsible for respiratory tract infections and potentially fatal pneumonia, mainly in more frail patients. Persons with haemophilia of variable severity and from all parts of the world will likely be infected and develop COVID‐19. We here propose practical guidance for the in‐hospital specific management of haemophilia persons with COVID‐19 including their possible transfer to the intensive care unit. Rapid identification of the haemophilia status, undelayed and regular liaison with the haemophilia team, proper therapy with factor concentrates or alternative treatments appear instrumental to prevent haemophilia‐related complications in this setting. Information of patients and their families about COVID‐19, psychological support and good appreciation of the impact of haemophilia on therapeutic decisions including end‐of‐life directives are also addressed.     

COVID‐19 and heart failure: from infection to inflammation and angiotensin II stimulation. Searching for evidence from a new disease

Patients with cardiovascular disease and, namely, heart failure are more susceptible to coronavirus disease 2019 (COVID‐19) and have a more severe clinical course once infected. Heart failure and myocardial damage, shown by increased troponin plasma levels, occur in at least 10% of patients hospitalized for COVID‐19 with higher percentages, 25% to 35% or more, when patients critically ill or with concomitant cardiac disease are considered. Myocardial injury may be elicited by multiple mechanisms, including those occurring with all severe infections, such as fever, tachycardia, adrenergic stimulation, as well as those caused by an exaggerated inflammatory response, endotheliitis and, in some cases, myocarditis that have been shown in patients with COVID‐19. A key role may be that of the renin–angiotensin–aldosterone system. Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infects human cells binding to angiotensin‐converting enzyme 2 (ACE2), an enzyme responsible for the cleavage of angiotensin II into angiotensin 1–7, which has vasodilating and anti‐inflammatory effects. Virus‐mediated down‐regulation of ACE2 may increase angiotensin II stimulation and contribute to the deleterious hyper‐inflammatory reaction of COVID‐19. On the other hand, ACE2 may be up‐regulated in patients with cardiac disease and treated with ACE inhibitors or angiotensin receptor blockers. ACE2 up‐regulation may increase the susceptibility to COVID‐19 but may be also protective vs. angiotensin II‐mediated vasoconstriction and inflammatory activation. Recent data show the lack of untoward effects of ACE inhibitors or angiotensin receptor blockers for COVID‐19 infection and severity. Prospective trials are needed to ascertain whether these drugs may have protective effects.     

Overview: The history and pediatric perspectives of severe acute respiratory syndromes: Novel or just like SARS

Many respiratory viral infections such as influenza and measles result in severe acute respiratory symptoms and epidemics. In the spring of 2003, an epidemic of coronavirus pneumonia spread from Guangzhou to Hong Kong and subsequently to the rest of the world. The WHO coined the acronym SARS (severe acute respiratory syndrome) and subsequently the causative virus as SARS‐CoV. In the summer of 2012, epidemic of pneumonia occurred again in Saudi Arabia which was subsequently found to be caused by another novel coronavirus. WHO coined the term MERS (Middle East respiratory syndrome) to denote the Middle East origin of the novel virus (MERS‐CoV). In the winter of 2019, another outbreak of pneumonia occurred in Wuhan, China which rapidly spread globally. Yet another novel coronavirus was identified as the culprit and has been named SARS‐CoV‐2 due to its similarities with SARS‐CoV, and the disease as coronavirus disease‐2019. This overview aims to compare and contrast the similarities and differences of these three major episodes of coronavirus outbreak, and conclude that they are essentially the same viral respiratory syndromes caused by similar strains of coronavirus with different names. Coronaviruses have caused major epidemics and outbreaks worldwide in the last two decades. From an epidemiological perspective, they are remarkably similar in the mode of spread by droplets. Special focus is placed on the pediatric aspects, which carry less morbidity and mortality in all three entities.     

Clinical characteristics of COVID‐19 in children: Are they similar to those of SARS?

Although the number of SARS‐CoV‐2 infections has been rising amid the current pandemic of COVID‐19, the low infection rate of SARS‐CoV‐2 in children has been low. By examining the clinical data available in the public domain, the present work clarifies the clinical presentations in children with COVID‐19 in China. Statistical significance tests and adjusted odds ratios estimation were performed on the children (age below 18) and adults (age 18 or above) cohorts in China. SARS‐CoV and SARS‐CoV‐2 shared similar clinical features. Lower respiratory tract infection was less prominent in children as evidenced by the relatively low prevalence in chest pain/discomfort and dyspnea. Similar to SARS, younger children had a less aggressive clinical course, compared with adolescents. While fewer symptoms were observed in children compared to adults, there is not yet sufficient evidence to conclude shorter hospital stay in children.     

Pathophysiological mechanisms of liver injury in COVID‐19

The recent outbreak of coronavirus disease 2019 (COVID‐19), caused by the Severe Acute Respiratory Syndrome Coronavirus‐2 (SARS‐CoV‐2) has resulted in a world‐wide pandemic. Disseminated lung injury with the development of acute respiratory distress syndrome (ARDS) is the main cause of mortality in COVID‐19. Although liver failure does not seem to occur in the absence of pre‐existing liver disease, hepatic involvement in COVID‐19 may correlate with overall disease severity and serve as a prognostic factor for the development of ARDS. The spectrum of liver injury in COVID‐19 may range from direct infection by SARS‐CoV‐2, indirect involvement by systemic inflammation, hypoxic changes, iatrogenic causes such as drugs and ventilation to exacerbation of underlying liver disease. This concise review discusses the potential pathophysiological mechanisms for SARS‐CoV‐2 hepatic tropism as well as acute and possibly long‐term liver injury in COVID‐19.     

Acute on chronic liver failure from novel severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)

The novel severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is a highly infectious viral disease that predominantly causes respiratory symptoms. Elevated liver enzymes have been reported during the course of disease and appear to be common. We present a 56‐year‐old woman with a history of decompensated alcoholic cirrhosis who presented with abdominal pain, fever and diarrhoea and was found to have acute on chronic liver failure secondary to SARS‐CoV‐2 infection. The patient was treated with empiric antibiotic and supportive care with subsequent improvement.