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.     

Diabetes mellitus and COVID-19: Understanding the association in light of current evidence

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have posed a problematic healthcare situation worldwide since December 2019. Diabetes mellitus is associated with an increased risk and severity of coronavirus disease 2019 (COVID-19). While interacting with various other risk factors, high blood sugar was found to reduce immunity and increase the replication of SARS-CoV-2. Oxidative stress and the release of pro-inflammatory cytokines are greater in diabetic individuals than in healthy people, worsening the outcome of SARS-CoV-2 infection in diabetics. Increased expression of furin and angiotensin converting enzyme 2 (ACE-2) receptor in the hyperglycemic environment may promote the entry of SARS-CoV-2 in the host cell. COVID-19 infection primarily modulates immune and inflammatory responses, and may cause a cytokine storm, resulting in possible lethal outcomes in diabetics. An experimental report suggests that ACE expressed in the pancreas and the SARS-CoV-2 virus invariably destroy β-cells which contain ACE-2 receptors and results in acute diabetes. Moreover, COVID-19 also causes hyperglycemia in an individual with diabetes which may be related to insulin resistance and destruction of β-cells during SARS-CoV-2 infection. Early observations also suggest a correlation between oral hypoglycemic agents and the risk of COVID-19. This review focused on the possible cause and mechanism involved in SARS-CoV-2 infection in diabetics and the role of antidiabetic drugs in COVID-19.     

Pharmaconutrition strategy to resolve SARS-CoV-2-induced inflammatory cytokine storm in non-alcoholic fatty liver disease: Omega-3 long-chain polyunsaturated fatty acids

Inflammation is one of the primary factors associated with the causation and/or progression of several lifestyle disorders, including obesity, type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). NAFLD is a spectrum of disorders, and starts with simple steatosis, progresses to non-alcoholic steatohepatitis, and then advances to fibrosis, cirrhosis and finally, hepatocellular carcinoma, due to perpetual cycles of insults caused by inflammation and other cellular stress. Emerging evidence has documented that patients with NAFLD have severe coronavirus disease 2019 (COVID-19), and patients with COVID-19 have a higher liver injury and mortality. Although the exact cause or mechanism is not known, inflammatory cytokine storm is a characteristic feature of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and is known to be associated with higher mortality among COVID-19 patients. Therefore, the COVID-19 pandemic seems to be a major concern in NAFLD patients, who have contracted SARS-CoV-2 infection and develop COVID-19. This is evident in patients at any stage of the NAFLD spectrum, as the inflammatory cytokine storm may cause and/or aggravate the progression or severity of NAFLD. Thus, there is a need for resolution of the inflammatory cytokine storm in these patients. A large body of evidence has demonstrated the efficacy of omega-3 long-chain polyunsaturated fatty acids (ω-3 LCPUFA) in NAFLD conditions, due to their anti-inflammatory, immunomodulatory and anti-viral properties. Therefore, intervention with ω-3 LCPUFA, an effective pharmaconutrient along with the standard treatment for COVID-19 may be useful in the management of the NAFLD spectrum in COVID-19 patients with pre-existing NAFLD conditions by resolving the inflammatory cytokine storm and thereby attenuating its progression. Although there are challenges in implementation, optimistically they can be circumvented and the pharmaconutrition strategy may be potentially helpful in tackling both the pandemics; NAFLD and COVID-19 at least in this subset of patients.     

Liver injury in COVID-19: A minireview

In December 2019, an outbreak of unexplained pneumonia was reported in Wuhan, China. The World Health Organization officially named this disease as novel coronavirus disease 2019 (COVID-19). Liver injury was observed in patients with COVID-19, and its severity varied depending on disease severity, geographical area, and patient age. Systemic inflammatory response, immune damage, ischemia-reperfusion injury, viral direct damage, drug induce, mechanical ventilation, and underlying diseases may contribute to liver injury. Although, in most cases, mild liver dysfunction is observed, which is usually temporary and does not require special treatment, the importance of monitoring liver injury should be emphasized for doctors. The risk of COVID-19 infection of liver transplantation recipients caused more and more concerns. In this article, we aimed to review the available literature on liver injury in COVID-19 to highlight the importance of monitoring and treating liver injury in COVID-19.     

COVID-19 Susceptibility in chronic obstructive pulmonary disease

In barely nine months, the pandemic known as COVID-19 has spread over 200 countries, affecting more than 22 million people and causing over than 786 000 deaths. Elderly people and patients with previous comorbidities such as hypertension and diabetes are at an increased risk to suffer a poor prognosis after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Although the same could be expected from patients with chronic obstructive pulmonary disease (COPD), current epidemiological data are conflicting. This could lead to a reduction of precautionary measures in these patients, in the context of a particularly complex global health crisis. Most COPD patients have a long history of smoking or exposure to other harmful particles or gases, capable of impairing pulmonary defences even years after the absence of exposure. Moreover, COPD is characterized by an ongoing immune dysfunction, which affects both pulmonary and systemic cellular and molecular inflammatory mediators. Consequently, increased susceptibility to viral respiratory infections have been reported in COPD, often worsened by bacterial co-infections and leading to serious clinical outcomes. The present paper is an up-to-date review that discusses the available research regarding the implications of coronavirus infection in COPD. Although validation in large studies is still needed, COPD likely increases SARS-CoV-2 susceptibility and increases COVID-19 severity. Hence, specific mechanisms to monitor and assess COPD patients should be addressed in the current pandemic.     

Acute myocardial injury in patients with COVID-19: Possible mechanisms and clinical implications

Severe acute respiratory syndrome coronavirus 2 infection affects not only the lungs, but also the cardiovascular system, having a major impact on patients’ outcomes. Myocardial injury (MI) occurs in the context of coronavirus infectious disease 2019 (COVID-19) and is associated with a higher risk of severe clinical outcome and mortality. COVID-19-related MI can have various clinical manifestations, of which the main ones are myocarditis, stress cardiomyopathy, acute coronary syndrome, and pulmonary embolism. The exact mechanisms of how MI occurs in these patients are not yet fully known. Direct injury, through direct viral myocardial invasion, and indirect injury, through interaction with angiotensin I converting enzyme 2, increased inflammation, and thrombocyte and endothelial dysfunction, could be involved in acute MI in patients with COVID-19. A better understanding of these multiple potential mechanisms may help to develop new targeted therapeutic strategies. The purpose of this review is to provide the current understanding of the potential mechanisms involved in MI induced by COVID-19 and to discuss the current progress in the therapeutic strategies.     

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.     

Pernio (Chilblains), SARS-CoV-2, and COVID Toes Unified Through Cutaneous and Systemic Mechanisms

Pernio or chilblains is characterized by erythema and swelling at acral sites (eg, toes and fingers), typically triggered by cold exposure. Clinical and histopathologic features of pernio are well described, but the pathogenesis is not entirely understood; vasospasm and a type I interferon (IFN-I) immune response are likely involved. During the coronavirus disease 2019 (COVID-19) pandemic, dermatologists have observed an increase in pernio-like acral eruptions. Direct causality of pernio due to COVID-19 has not been established in many cases because of inconsistent testing methods (often negative results) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, a form of COVID-19?associated pernio (also called COVID toes) is probable because of increased occurrence, frequently in young patients with no cold exposure or a history of pernio, and reports of skin biopsies with positive SARS-CoV-2 immunohistochemistry. PubMed was searched between January 1, 2020, and December 31, 2020 for publications using the following keywords: pernio, chilblain, and acral COVID-19. On the basis of our review of the published literature, we speculate that several unifying cutaneous and systemic mechanisms may explain COVID-19?associated pernio: (1) SARS-CoV-2 cell infection occurs through the cellular receptor angiotensin-converting enzyme 2 mediated by transmembrane protease serine 2, subsequently affecting the renin-angiotensin-aldosterone system with an increase in the vasoconstricting, pro-inflammatory, and prothrombotic angiotensin II pathway. (2) Severe acute respiratory syndrome coronavirus 2 cell infection triggers an immune response with robust IFN-I release in patients predisposed to COVID-19?associated pernio. (3) Age and sex discrepancies correlated with COVID-19 severity and manifestations, including pernio as a sign of mild disease, are likely explained by age-related immune and vascular differences influenced by sex hormones and genetics, which affect susceptibility to viral cellular infection, the renin-angiotensin-aldosterone system balance, and the IFN-I response.     

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.     

Association of Timing and Balance of Physical Activity and Rest/Sleep With Risk of COVID-19: A UK Biobank Study

Behavioral lifestyle factors are associated with cardiometabolic disease and obesity, which are risk factors for coronavirus disease 2019 (COVID-19). We aimed to investigate whether physical activity, and the timing and balance of physical activity and sleep/rest, were associated with SARS-CoV-2 positivity and COVID-19 severity. Data from 91,248 UK Biobank participants with accelerometer data and complete covariate and linked COVID-19 data to July 19, 2020, were included. The risk of SARS-CoV-2 positivity and COVID-19 severity—in relation to overall physical activity, moderate-to-vigorous physical activity (MVPA), balance between activity and sleep/rest, and variability in timing of sleep/rest—was assessed with adjusted logistic regression. Of 207 individuals with a positive test result, 124 were classified as having a severe infection. Overall physical activity and MVPA were not associated with severe COVID-19, whereas a poor balance between activity and sleep/rest was (odds ratio [OR] per standard deviation: 0.71; 95% confidence interval [CI], 0.62 to 0.81]). This finding was related to higher daytime activity being associated with lower risk (OR, 0.75; 95% CI, 0.61 to 0.93) but higher movement during sleep/rest being associated with higher risk (OR, 1.26; 95% CI, 1.12 to 1.42) of severe infection. Greater variability in timing of sleep/rest was also associated with increased risk (OR, 1.21; 95% CI, 1.08 to 1.35). Results for testing positive were broadly consistent. In conclusion, these results highlight the importance of not just physical activity, but also quality sleep/rest and regular sleep/rest patterns, on risk of COVID-19. Our findings indicate the risk of COVID-19 was consistently approximately 1.2-fold greater per approximately 40-minute increase in variability in timing of proxy measures of sleep, indicative of irregular sleeping patterns.     

Long-Term Effects of COVID-19

Coronavirus disease 2019 (COVID-19) is the third deadly coronavirus infection of the 21st century that has proven to be significantly more lethal than its predecessors, with the number of infected patients and deaths still increasing daily. From December 2019 to July 2021, this virus has infected nearly 200 million people and led to more than 4 million deaths. Our understanding of COVID-19 is constantly progressing, giving better insight into the heterogeneous nature of its acute and long-term effects. Recent literature on the long-term health consequences of COVID-19 discusses the need for a comprehensive understanding of the multisystemic pathophysiology, clinical predictors, and epidemiology to develop and inform an evidence-based, multidisciplinary management approach. A PubMed search was completed using variations on the term post-acute COVID-19. Only peer-reviewed studies in English published by July 17, 2021 were considered for inclusion. All studies discussed in this text are from adult populations unless specified (as with multisystem inflammatory syndrome in children). The preliminary evidence on the pulmonary, cardiovascular, neurological, hematological, multisystem inflammatory, renal, endocrine, gastrointestinal, and integumentary sequelae show that COVID-19 continues after acute infection. Interdisciplinary monitoring with holistic management that considers nutrition, physical therapy, psychological management, meditation, and mindfulness in addition to medication will allow for the early detection of post-acute COVID-19 sequelae symptoms and prevent long-term systemic damage. This review serves as a guideline for effective management based on current evidence, but clinicians should modify recommendations to reflect each patient's unique needs and the most up-to-date evidence. The presence of long-term effects presents another reason for vaccination against COVID-19.     

Surgically treated reactive arthritis of the ankle after COVID-19 infection: A case report

A 37-year-old man developed right ankle pain and swelling six days after being diagnosed with coronavirus disease (COVID-19). Despite conservative treatment, his ankle symptoms persisted. Magnetic resonance imaging and computed tomography showed synovial hypertrophy and bone erosion in the ankle. Following arthroscopic synovectomy, performed 69 days after the COVID-19 diagnosis, the pain improved significantly. The clinical course was consistent with that of reactive arthritis following severe acute respiratory syndrome coronavirus 2 infection. The pathological findings resembled rheumatoid nodules. The bone erosion may have originated from the inflammatory pathway, which resembles the mechanism of rheumatoid arthritis.     

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...     

Gut microbiota and COVID-19: An intriguing pediatric perspective

Gastrointestinal (GI) involvement has been reported in approximately 50% of patients with coronavirus disease 2019 (COVID-19), which is due to the pathogenic role of inflammation and the intestinal function of the angiotensin-converting enzyme 2 and its receptor. Accumulating adult data has pointed out that gut dysbiosis might occur in these patients with a potential impact on the severity of the disease, however the role of gut microbiota in susceptibility and severity of COVID-19 disease in children is still poorly known. During the last decades, the crosstalk between gut and lung has been largely recognized resulting in the concept of “gut-lung axis” as a central player in modulating the development of several diseases. Both organs are involved in the common mucosal immune system (including bronchus-associated and gut-associated lymphoid tissues) and their homeostasis is crucial for human health. In this framework, it has been found that the role of GI dysbiosis is affecting the homeostasis of the gut-liver axis. Of note, a gut microbiome imbalance has been linked to COVID-19 severity in adult subjects, but it remains to be clarified. Based on the increased risk of inflammatory diseases in children with COVID-19, the potential correlation between gut microbiota dysfunction and COVID-19 needs to be studied in this population. We aimed to summarize the most recent evidence on this striking aspect of COVID-19 in childhood.     

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.     

Liver dysfunction-related COVID-19: A narrative review

The coronavirus 2019 disease (COVID-19) is caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2. This disease was designated by the World Health Organization as a pandemic on March 11, 2020, which is not seen before. There are no classical features among the cases of the disease owing to the involvement of nearly all body tissues by the virus. Hepatic involvement is one of the characteristics of the COVID-19 course. There are six possible mechanisms of such involvement: Direct virus injury, drug-induced effect, inflammatory cytokine storm, hypoxia-ischemic destruction, abnormalities in liver function tests, and pre-existing chronic liver diseases. Liver abnormalities are seen commonly in the severe or critical stage of COVID-19. Therefore, these abnormalities determine the COVID-19 severity and carry a high rate of morbidity and mortality. The elderly and patients with comorbidities like diabetes mellitus and hypertension are more vulnerable to liver involvement. Another issue that needs to be disclosed is the liver manifestations following the COVID-19 vaccination, such as autoimmune hepatitis. Of note, complete vaccination with third and fourth booster doses is necessary for patients with previous chronic liver diseases or those who have been subjected to liver transplantation. This review aims to explore the various aspects of liver dysfunction during the COVID-19 course regarding the epidemiological features, predisposing factors, pathophysiological mechanisms, hepatic manifestations due to COVID-19 or following vaccination, role of liver function tests in the assessment of COVID-19 severity, adverse effects of the therapeutic agents for the disease, and prognosis.     

肺功能成像在新型冠状病毒肺炎急性及康复期病变的研究进展

截至2022年11月4日，新型冠状病毒肺炎（coronavirus disease 2019, COVID-19）确诊病例超过6.28亿，死亡人数超过657万。肺是COVID-19最常累及的器官，主要表现为COVID-19肺炎、肺血栓栓塞等急性病变及康复期COVID-19相关小气道病变、肺间质纤维化。肺功能成像使用影像学成像技术对肺功能进行区域性可视化量化评估，并额外提供常规肺功能检查未涉及的区域分布及定位信息。为全面了解肺功能成像技术在COVID-19患者中的应用价值，本文归纳总结CT、MRI及核医学成像技术在COVID-19急性及康复期病变早期识别、诊断及随访中的初步应用，并展望各种成像模态及相关技术在未来更广泛的应用。     

Features of COVID-19 post-infectious cytokine release syndrome in children presenting to the emergency department

The 2019 coronavirus disease (COVID-19) has not appeared to affect children as severely as adults. However, approximately 1 month after the COVID-19 peak in New York City in April 2020, cases of children with prolonged fevers abruptly developing inflammatory shock-like states have been reported in Western Europe and the United States.This case series describes four previously healthy children with COVID-19 infection confirmed by serologic antibody testing, but negative by nasopharyngeal RT-PCR swab, presenting to the Pediatric Emergency Department (PED) with prolonged fever (5 or more days) and abrupt onset of hemodynamic instability with elevated serologic inflammatory markers and cytokine levels (IL-6, IL-8 and TNF-α).Emergency physicians must maintain a high clinical suspicion for this COVID-19 associated post-infectious cytokine release syndrome, with features that overlap with Kawasaki Disease (KD) and Toxic Shock Syndrome (TSS) in children with recent or current COVID-19 infection, as patients can decompensate quickly.