Clinical features and potential mechanism of coronavirus disease 2019-associated liver injury

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, has posed a serious threat to global public health security. With the increase in the number of confirmed cases globally, the World Health Organization has declared the outbreak of COVID-19 an international public health emergency. Despite atypical pneumonia as the primary symptom, liver dysfunction has also been observed in many clinical cases and is associated with the mortality risk in patients with COVID-19, like severe acute respiratory syndrome and Middle East respiratory syndrome. Here we will provide a schematic overview of the clinical characteristics and the possible mechanisms of liver injury caused by severe acute respiratory syndrome coronavirus 2 infection, which may provide help for optimizing the management of liver injury and reducing mortality in COVID-19 patients.     

COVID-19 in gastroenterology and hepatology: Lessons learned and questions to be answered

BACKGROUNDAlthough coronavirus disease 2019 (COVID-19) presents primarily as a lower respiratory tract infection, increasing data suggests multiorgan, including the gastrointestinal (GI) tract and liver, involvement in patients who are infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).AIMTo provide a comprehensive overview of COVID-19 in gastroenterology and hepatology.METHODSRelevant studies on COVID-19 related to the study aim were undertaken through a literature search to synthesize the extracted data.RESULTSWe found that digestive symptoms and liver injury are not uncommon in patients with COVID-19 and varies in different individuals. The most common GI symptoms reported are diarrhea, nausea, vomiting, and abdominal discomfort. Other atypical GI symptoms, such as loss of smell and taste and GI bleeding, have also been reported along with the evolvement of COVID-19. Liver chemistry abnormalities mainly include elevation of aspartate transferase, alanine transferase, and total bilirubin. It is postulated to be related to the binding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus to the angiotensin converting enzyme-2 receptor located on several different human cells. CONCLUSIONStandardized criteria should be established for diagnosis and grading of the severity of GI symptoms in COVID-19 patients. Gastroenterology and hepatology in special populations, such as children and elderly, should be the focus of further research. Future long-term data regarding GI symptoms should not be overlooked.     

COVID-19 and gastroenteric manifestations

Coronavirus disease 2019 (COVID-19), caused by the infection of a novel coronavirus [severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)], has become a pandemic. The infection has resulted in about one hundred million COVID-19 cases and millions of deaths. Although SARS-CoV-2 mainly spreads through the air and impairs the function of the respiratory system, it also attacks the gastrointestinal epithelial cells through the same receptor, angiotensin converting enzyme 2 receptor, which results in gastroenteric symptoms and potential fecal-oral transmission. Besides the infection of SARS-CoV-2, the treatments of COVID-19 also contribute to the gastroenteric manifestations due to the adverse drug reactions of anti-COVID-19 drugs. In this review, we update the clinical features, basic studies, and clinical practices of COVID-19-associated gastroenteric manifestations.     

Surgical intervention for acute pancreatitis in the COVID-19 era

Approximately 15%-19% of patients with severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infections develop gastrointestinal symptoms. Acute pancreatitis (AP) has been reported in 0.1% of patients with coronavirus disease 2019 (COVID-19). Biliary AP was most common (78.4%) before the COVID-19 pandemic; idiopathic AP is most common in patients with COVID-19 (up to 57.1%). The number of emergency department presentations decreased by 23.3% during the pandemic and many governments made national recommendations to delay nonurgent endoscopic procedures, leading to decrements of 22% in combined esophagogastroduodenoscopy (EGD) and colonoscopy and 20% in EGD after the COVID-19 pandemic. The symptoms and signs of COVID-19-related AP are fever (63%), abdominal pain (58%), respiratory symptoms (40%), nausea and vomiting (39%), and headache (4%). Approximately 5-10% of patients develop necrotizing or hemorrhagic AP, and patients who required surgical intervention had a higher mortality risk. Compared to 2019, the rates of elective surgery decreased by 41.8% in 2020; including cholecystectomy (40.1% decrease) and pancreas (111.1% decrease). Surgical volumes also decreased by 18.7% in 2020; device-assisted laparoscopic and robot-assisted procedures reduced by 45.4% and 61.9% during the COVID-19 Lockdown in 2020.     

Living with liver disease in the era of COVID-19-the impact of the epidemic and the threat to high-risk populations

The cardinal symptoms of severe acute respiratory syndrome coronavirus 2 infection as the pandemic began in 2020 were cough, fever, and dyspnea, thus characterizing the virus as a predominantly pulmonary disease. While it is apparent that many patients presenting acutely to the hospital with coronavirus disease 2019 (COVID-19) infection have complaints of respiratory symptoms, other vital organs and systems are also being affected. In fact, almost half of COVID-19 hospitalized patients were found to have evidence of some degree of liver injury. Incidence and severity of liver injury in patients with underlying liver disease were even greater. According to the Centers of Disease Control and Prevention, from August 1, 2020 to May 31, 2022 there have been a total of 4745738 COVID-19 hospital admissions. Considering the gravity of the COVID-19 pandemic and the incidence of liver injury in COVID-19 patients, it is imperative that we as clinicians understand the effects of the virus on the liver and conversely, the effect of underlying hepatobiliary conditions on the severity of the viral course itself. In this article, we review the spectrum of novel studies regarding COVID-19 induced liver injury, compiling data on the effects of the virus in various age and high-risk groups, especially those with preexisting liver disease, in order to obtain a comprehensive understanding of this disease process. We also provide an update of the impact of the new Omicron variant and the changing nature of COVID-19 pathogenesis.     

Non-pulmonary involvement in COVID-19: A systemic disease rather than a pure respiratory infection

During the early phase of the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), diagnosis was difficult due to the diversity in symptoms and imaging findings and the variability of disease presentation. Pulmonary manifestations are reportedly the main clinical presentations of COVID-19 patients. Scientists are working hard on a myriad of clinical, epidemiological, and biological aspects to better understand SARS-CoV-2 infection, aiming to mitigate the ongoing disaster. Many reports have documented the involvement of various body systems and organs apart from the respiratory tract including the gastrointestinal, liver, immune system, renal, and neurological systems. Such involvement will result in diverse presentations related to effects on these systems. Other presentations such as coagulation defects and cutaneous manifestation may also occur. Patients with specific comorbidities including obesity, diabetes, and hypertension have increased morbidity and mortality risks with COVID-19.     

ST Elevation in the COVID-19 Era: A Diagnostic Challenge

BackgroundSevere acute respiratory syndrome coronavirus 2 induces a marked prothrombotic state with varied clinical presentations, including acute coronary artery occlusions leading to ST-elevation myocardial infarction (STEMI). However, while STEMI on electrocardiogram (ECG) is not always associated with acute coronary occlusion, this diagnostic uncertainty should not delay cardiac catheterization.Case ReportsWe present 2 cases of patients with COVID-19 that presented with STEMI on ECG. While both patients underwent cardiac catheterization, a delay in time to intervention in the patient found to have acute coronary artery occlusion may have contributed to a poor outcome.Why Should an Emergency Physician Be Aware of This?These cases highlight the fact that while not all COVID-19 patients with STEMI on ECG will have acute coronary artery occlusions, there is continued need for prompt percutaneous coronary intervention during the severe acute respiratory syndrome coronavirus 2 pandemic.     

COVID-19 and the heart

An outbreak of coronavirus disease 2019 (COVID-19) occurred in December 2019 due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is a strain of SARS-CoV. Patients infected with the virus present a wide spectrum of manifestations ranging from mild flu-like symptoms, cough, fever and fatigue to severe lung injury, appearing as bilateral interstitial pneumonia or acute respiratory failure. Although SARS-CoV-2 infection predominantly offends the respiratory system, it has been associated with several cardiovascular complications as well. For example, patients with COVID-19 may either develop type 2 myocardial infarction due to myocardial oxygen demand and supply imbalance or acute coronary syndrome resulting from excessive inflammatory response to the primary infection. The incidence of COVID-19 related myocarditis is estimated to be accountable for an average of 7% of all COVID-19 related fatal cases, whereas heart failure (HF) may develop due to infiltration of the heart by inflammatory cells, destructive action of pro-inflammatory cytokines, micro-thrombosis and new onset or aggravated endothelial and respiratory failure. Lastly, SARS-CoV-2 can engender arrhythmias through direct myocardial damage causing acute myocarditis or through HF decompensation or secondary, through respiratory failure or severe respiratory distress syndrome. In this comprehensive review we summarize the COVID-19 related cardiovascular complications (acute coronary syndromes, myocarditis, HF, arrhythmias) and discuss the main underlying pathophysiological mechanisms.     

Prevention,diagnostic evaluation,management and prognostic implications of liver disease in critically ill patients with COVID-19

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, broke out in December 2019 in Wuhan city of China and spread rapidly worldwide. Therefore, by March 2020, the World Health Organization declared the disease a global pandemic. Apart from the respiratory system, various other organs of the human body are also seriously affected by the virus. Liver injury in patients with a severe form of COVID-19 is estimated to be 14.8%-53.0%. Elevated levels of total bilirubin, aspartate aminotransferase and alanine aminotransferase and low levels of serum albumin and prealbumin are the main laboratory findings. Patients with pre-existing chronic liver disease and cirrhosis are much more prone to develop severe liver injury. This literature review presented the recent scientific findings regarding the pathophysiological mechanisms responsible for liver injury in critically ill patients with COVID-19, the various interactions between drugs used to treat the disease and the function of the liver and the specific tests providing the possibility of early diagnosis of severe liver injury in these patients. Moreover, it highlighted the burden that COVID-19 put on health systems worldwide and its effect on transplant programs and the care provided to critically ill patients in general and particularly to those with chronic liver disease.     

Thymosin as a possible therapeutic drug for COVID-19: A case report

BACKGROUNDThere are no effective antiviral therapies for coronavirus disease 2019 (COVID-19) at present. Although most patients with COVID-19 have a mild or moderate course of disease, up to 5%-10% of patients may have a serious and potentially life-threatening condition, indicating an urgent need for effective therapeutic drugs. The therapeutic effect of thymosin on COVID-19 has not been previously studied. In this paper, for the first time we report a case of thymosin treatment of COVID-19.CASE SUMMARYA 51-year-old man with imported COVID-19 was admitted with definite symptoms of chest tightness, chest pain, and fatigue. The polymerase chain reaction results for severe acute respiratory syndrome coronavirus 2 were negative. The antibody test was positive, confirming the diagnosis of COVID-19. As many orally administered drugs were not well tolerated due to gastrointestinal symptoms, an emergency use of thymosin, a polypeptide consisting of 28 amino acids, was administered by injection. Finally, after the implementation of the treatment program, symptoms and lung imaging improved significantly.CONCLUSIONIn this case report, it is confirmed that thymosin may help alleviate the severity of COVID-19 symptoms.     

COVID-19 and the digestive system: A comprehensive review

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is spreading at an alarming rate, and it has created an unprecedented health emergency threatening tens of millions of people worldwide. Previous studies have indicated that SARS-CoV-2 ribonucleic acid could be detected in the feces of patients even after smear-negative respiratory samples. However, demonstration of confirmed fecal-oral transmission has been difficult. Clinical studies have shown an incidence rate of gastrointestinal (GI) symptoms ranging from 2% to 79.1% in patients with COVID-19. They may precede or accompany respiratory symptoms. The most common GI symptoms included nausea, diarrhea, and abdominal pain. In addition, some patients also had liver injury, pancreatic damage, and even acute mesenteric ischemia/thrombosis. Although the incidence rates reported in different centers were quite different, the digestive system was the clinical component of the COVID-19 section. Studies have shown that angiotensin-converting enzyme 2, the receptor of SARS-CoV-2, was not only expressed in the lungs, but also in the upper esophagus, small intestine, liver, and colon. The possible mechanism of GI symptoms in COVID-19 patients may include direct viral invasion into target cells, dysregulation of angiotensin-converting enzyme 2, immune-mediated tissue injury, and gut dysbiosis caused by microbiota. Additionally, numerous experiences, guidelines, recommendations, and position statements were published or released by different organizations and societies worldwide to optimize the management practice of outpatients, inpatients, and endoscopy in the era of COVID-19. In this review, based on our previous work and relevant literature, we mainly discuss potential fecal-oral transmission, GI manifestations, abdominal imaging findings, relevant pathophysiological mechanisms, and infection control and prevention measures in the time of COVID-19.     

Comparative profile for COVID-19 cases from China and North America: Clinical symptoms,comorbidities and disease biomarkers

BACKGROUNDLarge inter-individual and inter-population differences in the susceptibility to and outcome of severe acute respiratory syndrome coronavirus 2 or coronavirus disease 2019 (COVID-19) have been noted. Understanding these differences and how they influence vulnerability to infection and disease severity is critical to public health intervention. AIMTo analyze and compare the profile of COVID-19 cases between China and North America as two regions that differ in many environmental, host and healthcare factors related to disease risk.METHODSWe conducted a meta-analysis to examine and compare demographic information, clinical symptoms, comorbidities, disease severity and levels of disease biomarkers of COVID-19 cases from clinical studies and data from China (105 studies) and North America (19 studies). RESULTSCOVID-19 patients from North America were older than their Chinese counterparts and with higher male: Female ratio. Fever, cough, fatigue and dyspnea were the most common clinical symptoms in both study regions (present in about 30% to 75% of the cases in both regions). Meta-analysis for the prevalence of comorbidities (such as obesity, hypertension, diabetes, cardiovascular diseases, chronic obstructive pulmonary disease, cancer, and chronic kidney diseases) in COVID-19 patients were all significantly more prevalent in North America compared to China. Comorbidities were positively correlated with age but at a significantly younger age range in China compared to North American. The most prevalent infection outcome was acute respiratory distress syndrome which was 2-fold more frequent in North America than in China. Levels of C-reactive protein were 4.5-fold higher in the North American cases than in cases from China.CONCLUSIONThe differences in the profile of COVID-19 cases from China and North America may relate to differences in environmental-, host- and healthcare-related factors between the two regions. Such inter-population differences-together with intra-population variability-underline the need to characterize the effect of health inequities and inequalities on public health response to COVID-19 and can assist in preparing for the re-emergence of the epidemic.     

Post-COVID-19 interstitial lung disease presenting with profound hypoxemia: Report of three cases demonstrating a good response to high-dose corticosteroid therapy

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which leads to critical pneumonia, although the clinical courses vary. In some cases, COVID-19 pneumonia causes secondary pulmonary fibrosis, which can retain radiological changes and prolong respiratory symptoms. Interstitial lung disease (ILD) secondary to COVID-19 is thought to be caused by multiple pathologies, such as excessive cytokines and abnormal repair processes elaborated by lung cells (epithelium, mesenchyme, and alveolar macrophages) after lung injury rather than viral invasion itself. Immunosuppression therapy may improve chronic respiratory symptoms and radiological changes in post-COVID-19 ILD, although the treatment is not yet established. Herein, we report three patients with post-COVID-19 ILD who presented with profound hypoxemia that had a good response to high-dose corticosteroid therapy. Further and larger studies are needed to establish post-COVID-19 ILD.     

Manifestations and risk factors of COVID-19 and mucormycosis: A mini-review

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 has become a pandemic disease. It also increases the risk of co-infections. Mucormycosis is a severe fungal infectious disease and its causative agent, mucormycetes, belongs to an opportunist fungus Mucoraceae family. Mucormycosis in COVID-19 patients with mucormycosis presents an additional challenge worldwide. Mucormycosis shares certain risk factors and signs and symptoms with COVID-19. In this review, we summarize manifestations and risk factors of mucormycosis and COVID-19.     

COVID-19: Gastrointestinal manifestations,liver injury and recommendations

Coronavirus disease 2019 (COVID-19) has caused a pandemic that affected all countries with nearly 270 million patients and 5 million deaths, as of as of December, 2021. The severe acute respiratory syndrome coronavirus 2 virus targets the receptor, angiotensin-converting enzyme 2, which is frequently found in human intestinal epithelial cells, bile duct epithelial cells, and liver cells, and all gastrointestinal system organs are affected by COVID-19 infection. The aim of this study is to review the gastrointestinal manifestations and liver damage of COVID-19 infection and investigate the severe COVID-19 infection risk in patients that have chronic gastrointestinal disease, along with current treatment guidelines. A literature search was conducted on electronic databases of PubMed, Scopus, and Cochran Library, consisting of COVID-19, liver injury, gastrointestinal system findings, and treatment. Liver and intestinal involvements are the most common manifestations. Diarrhea, anorexia, nausea/vomiting, abdominal pain are the most frequent symptoms seen in intestinal involvement. Mild hepatitis occurs with elevated levels of transaminases. Gastrointestinal involvement is associated with long hospital stay, severity of the disease, and intensive care unit necessity. Treatments and follow-up of patients with inflammatory bowel diseases, cirrhosis, hepatocellular carcinoma, or liver transplant have been negatively affected during the pandemic. Patients with cirrhosis, hepatocellular carcinoma, auto-immune diseases, or liver transplantation may have a greater risk for severe COVID-19. Diagnostic or therapeutic procedures should be restricted with specific conditions. Telemedicine should be used in non-urgent periodic patient follow up. COVID-19 treatment should not be delayed in patients at the risk group. COVID-19 vaccination should be prioritized in this group.     

Diagnosis,treatment protocols,and outcomes of liver transplant recipients infected with COVID-19

Several cases of fatal pneumonia during November 2019 were linked initially to severe acute respiratory syndrome coronavirus 2, which the World Health Organization later designated as coronavirus disease 2019(COVID-19). The World Health Organization declared COVID-19 as a pandemic on March 11, 2020. In the general population, COVID-19 severity can range from asymptomatic/mild symptoms to seriously ill. Its mortality rate could be as high as 49%. The Centers for Disease Control and Prevention hav...     

2例新型冠状病毒肺炎粪便SARS-CoV-2核酸阳性临床启示

目前中国新型冠状病毒肺炎(COVID-19)疫情仍十分严峻,及时、早期地识别COVID-19患者是控制疫情的关键步骤。而新型冠状病毒(SARS-CoV-2)核酸检测作为诊断COVID-19的金标准,不但对检测技术提出更高的要求,同时对不同病程患者如何选择标本类型也是一个挑战。本文报道2例COVID-19确诊病例的诊疗经过,并分析采用不同类型标本检测SARS-CoV-2核酸的检出情况,为临床诊断COVID-19时如何选择标本类型和如何提高核酸检出率提供参考。     

One disease,many faces-typical and atypical presentations of SARS-CoV-2 infection-related COVID-19 disease

Since the appearance of the novel coronavirus (severe acute respiratory syndrome-coronavirus-2) and related coronavirus disease 2019 (COVID-19) in China in December 2019, a very high number of small and large patient series have been published in literature from around the world. Even though the classical presentation of COVID-19 is one with respiratory symptoms with or without pneumonia that can be self-limiting or evolve into severe respiratory distress syndrome with multiple organ failure, and secondary bacterial sepsis, a large body of evidence suggests a plethora of other types of clinical presentation. In this exhaustive review, we reviewed all of the published literature on COVID-19 to identify different types of clinical presentations affecting various organ systems, to provide an in-depth analysis that may prove useful for clinicians and health-workers on the frontline, battling the severe pandemic.     

Distinctive features of severe SARS-CoV-2 pneumonia

The coronavirus disease 2019 (COVID-19) pandemic is among the most important public health crises of our generation. Despite the promise of prevention offered by effective vaccines, patients with severe COVID-19 will continue to populate hospitals and intensive care units for the foreseeable future. The most common clinical presentation of severe COVID-19 is hypoxemia and respiratory failure, typical of the acute respiratory distress syndrome (ARDS). Whether the clinical features and pathobiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia differ from those of pneumonia secondary to other pathogens is unclear. This uncertainty has created variability in the application of historically proven therapies for ARDS to patients with COVID-19. We review the available literature and find many similarities between patients with ARDS from pneumonia attributable to SARS-CoV-2 versus other respiratory pathogens. A notable exception is the long duration of illness among patients with COVID-19, which could result from its unique pathobiology. Available data support the use of care pathways and therapies proven effective for patients with ARDS, while pointing to unique features that might be therapeutically targeted for patients with severe SARS-CoV-2 pneumonia.     

Clinical improvement in a patient with severe coronavirus disease 2019 after administration of hydroxychloroquine and continuous hemodiafiltlation with nafamostat mesylate

The number of people infected with severe acute respiratory syndrome coronavirus 2 is increasing globally, and some patients have a fatal clinical course. In light of this situation, the World Health Organization (WHO) declared coronavirus disease 2019 (COVID-19) a pandemic on March 11, 2020. While clinical studies and basic research on a treatment for COVID-19 are ongoing around the world, no treatment has yet been proven to be effective. Several clinical studies have demonstrated the efficacy of chloroquine phosphate and nafamostat mesylate with COVID-19. Here, we report the case of a Japanese patient with COVID-19 with severe respiratory failure who improved following the administration of hydroxychloroquine and continuous hemodiafiltlation with nafamostat mesylate. Hence, hydroxychloroquine with nafamostat mesylate might be a treatment option for severe COVID-19.