Liver in the limelight in the corona (COVID-19) time

The novel coronavirus, severe acute respiratory syndrome-corona virus-2 (SARS-CoV-2), is a topic of great interest currently in the medical field due to the significant morbidity and mortality associated with it. There is immense curiosity about this virus as knowledge about it is limited from pathogenesis, host related factors and the variable effect it has on different patient populations. Though it has claimed fame due to its ability to compromise the respiratory system, it possess the capability to infect other organs as well including the liver. It is important for clinicians to recognize that the virus can result in multi-organ dysfunction as well. Presentation with gastrointestinal symptoms and involvement of the liver can be subtle and can be misdiagnosed. Those with pre-existing liver disease may be more susceptible as well as those who are immunosuppressed or have other co-morbidities. This review article provides a brief overview of some of the information that is available so far with regards to how the liver is impacted by the coronavirus.     

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.     

Risk Factors for Mortality in Patients with COVID-19: The Kuwait Experience

ObjectivesTo describe the baseline characteristics and to evaluate the risk factors for in-hospital mortality in patients admitted to hospitals with coronavirus disease (COVID-19) in Kuwait.Subjects and MethodsThis retrospective cohort study analyzed data of patients admitted to two hospitals in Kuwait with COVID-19. The outcome was assessed by using multivariable analysis of factors affecting survival and mortality.ResultsIn 962 patients, the case fatality ratio was 9.04%. The mean age of nonsurvivors was 63.5 ± 14.8 years, and most deaths occurred in males (80.5%). For the whole sample, the source of transmission was significantly related to mortality and the median duration of in-hospital stay was 15 days (interquartile range: 2–52 days). In patients with high oxygen requirements, the case fatality rate was 96.6%. Multivariable analysis identified age, hypertension, cardiovascular disease (CVD), and dyspnea on presentation as independent risk factors for COVID-19 mortality.ConclusionsThe mortality rate was higher in older patients with comorbidities such as hypertension and CVD. Early recognition of high-risk patients may help to improve care and reduce mortality.     

COVID-19: Acing the Treatment

Angiotensin converting enzyme 2 is the functional receptor that the SARS-Cov-2 virus requires to enter cells and cause dysregulated inflammatory conditions that contribute towards acute lung injuries. The renin-angiotensin-aldosterone system with its physiological surveillance and regulation system can be implicated in both harm and therapeutic benefit. The initial observational studies suggesting the discontinuation of angiotensin converting enzyme inhibitors and angiotensin receptor blockers have been firmly rebutted by international societies. On the contrary, these therapeutics may confer a survival benefit in COVID-19 infections. Understanding the biological plausibility of this pathway alongside the emerging therapeutic evidence may yield new modes of treatment. Such developments appear fundamentally important in the battle against the inevitable emergence of new variants and their potential to drive future waves of COVID-19 pandemics.     

Circulating angiotensin converting enzyme 2 and COVID-19

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has triggered a widespread outbreak since December 2019. The SARS-CoV-2 infection-related illness has been dubbed the coronavirus disease 2019 (COVID-19) by the World Health Organization. Asymptomatic and subclinical infections, a severe hyper-inflammatory state, and mortality are all examples of clinical signs. After attaching to the angiotensin converting enzyme 2 (ACE2) receptor, the SARS-CoV-2 virus can enter cells through membrane fusion and endocytosis. In addition to enabling viruses to cling to target cells, the connection between the spike protein (S-protein) of SARS-CoV-2 and ACE2 may potentially impair the functionality of ACE2. Blood pressure is controlled by ACE2, which catalyzes the hydrolysis of the active vasoconstrictor octapeptide angiotensin (Ang) II to the heptapeptide Ang-(1-7) and free L-Phe. Additionally, Ang I can be broken down by ACE2 into Ang-(1-9) and metabolized into Ang-(1-7). Numerous studies have demonstrated that circulating ACE2 (cACE2) and Ang-(1-7) have the ability to restore myocardial damage in a variety of cardiovascular diseases and have anti-inflammatory, antioxidant, anti-apoptotic, and anti-cardiomyocyte fibrosis actions. There have been some suggestions for raising ACE2 expression in COVID-19 patients, which might be used as a target for the creation of novel treatment therapies. With regard to this, SARS-CoV-2 is neutralized by soluble recombinant human ACE2 (hrsACE2), which binds the viral S-protein and reduces damage to a variety of organs, including the heart, kidneys, and lungs, by lowering Ang II concentrations and enhancing conversion to Ang-(1-7). This review aims to investigate how the presence of SARS-CoV-2 and cACE2 are related. Additionally, there will be discussion of a number of potential therapeutic approaches to tip the ACE/ACE-2 balance in favor of the ACE-2/Ang-(1-7) axis.     

Remarkable gastrointestinal and liver manifestations of COVID-19: A clinical and radiologic overview

The coronavirus disease 2019 (COVID-19) raging around the world still has not been effectively controlled in most countries and regions. As a severe acute respiratory syndrome coronavirus, in addition to the most common infectious pneumonia, it can also cause digestive system disease such as diarrhea, nausea, vomiting, liver function damage, etc. In medical imaging, it manifests as thickening of the intestinal wall, intestinal perforation, pneumoperitoneum, ascites and decreased liver density. Angiotensin-converting enzyme 2 has great significance in COVID-19-related digestive tract diseases. In this review, we summarized the data on the clinical and imaging manifestations of gastrointestinal and liver injury caused by COVID-19 so far and explored its possible pathogenesis.     

The cardiovascular aspect of COVID-19

The coronavirus disease-2019 (COVID-19), an infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2(SARS-CoV-2), has hit the world very hard by affecting millions of people across countries hence posing a major health threat on a global scale. This novel virus is thought to enter and cause infection in its host through the attachment of its structural protein known as the S-glycoprotein to angiotensin-converting enzyme 2 (ACE2). Given the rapid spread of COVID-19 with its consequences globally, it is mandatory that health caregivers and researchers across all disciplines abreast themselves with the potential effects that this novel virus may have on their fields and the medical society at large. During the infection, the cardiovascular system is affected by unknown pathomechanistic processes, hence accounting for an increased prevalence of cardiovascular diseases (CVDs) among COVID-19 patients. As cardiovascular researchers, we are more concerned about the cardiovascular aspect of SARS-CoV-2/COVID-19. Hence, this concise review addresses these aspects where CVD as a risk factor of COVID-19, the prevalence of CVDs in COVID-19, and the potential cardiovascular disorders which may evolve owing to COVID-19 are discussed. A better understanding of these issues will be pivotal to improve cardiovascular health during this SARS-CoV-2/COVID-19 pandemic and beyond.     

新型冠状病毒肺炎相关性急性胰腺炎：证据，挑战与思考

由新型冠状病毒（SARS-CoV-2）感染引起的新型冠状病毒肺炎（COVID-19）自2019年12月发病以来,现已全球大流行。COVID-19除影响呼吸系统外,还可造成全身多系统、多脏器的损害。目前关于COVID-19累及胰腺的证据十分有限,COVID-19患者中急性胰腺炎（AP）的发病率存在不确定性,其临床特征和发病机制也存在诸多疑问。在全球COVID-19流行仍未得到完全控制的背景下,由于目前对COVID-19与AP之间相互作用知之甚少,我们必须警惕他们之间可能存在的联系。临床上诸多治疗程序需要合理化,应采取有效的防护措施,在科学诊治患者的同时有效避免医护人员SARS-CoV-2感染。     

Liver manifestations in COVID-19 patients: A review article

The coronavirus disease 2019 (COVID-19) initially presented as a disease that affected the lungs. Then, studies revealed that it intricately affected disparate organs in the human body, with the liver being one of the most affected organs. This review aimed to assess the association between COVID-19 and liver function, shedding light on its clinical implication. However, its exact pathophysiology remains unclear, involving many factors, such as active viral replication in the liver cells, direct cytotoxic effects of the virus on the liver or adverse reactions to viral antigens. Liver symptoms are mild-to-moderate transaminase elevation. In some patients, with underlying liver disease, more serious outcomes are observed. Thus, liver function should be meticulously considered in patients with COVID-19.     

Effect of prone position on clinical outcomes of nonintubated patients with COVID-19: A randomised clinical trial

BackgroundProne positioning (PP) is a well-known respiratory support approach. Limited data are available for the use of PP in nonintubated patients with COVID-19.AimThis study aims to investigate the effect of PP on the clinical outcomes of patients with COVID-19 pneumonia.MethodsIn this clinical trial, the participants in the PP group (n = 41) were asked to lie comfortably in a PP for 90 min. In the supine position (SP) group (n = 41), the participants were asked to lie comfortably in a SP for 90 min. Clinical data such as oxygen saturation, respiratory rate (RR), the severity of dyspnoea, mean arterial pressure (MAP), and pulse rate were assessed at 0 (immediately before), 30, 60, and 90 min after the start of the intervention, and 30 min after resuming the SP. The participants in the PP group were then asked to intermittently stay in a PP for a total of 8 h per 24 h of hospitalisation. The participants in the control group were asked to remain in their usual positions during the hospital stay. Finally, the length of hospital stay, intubation rate, and survival were assessed.FindingsPP was associated with significant improvement in oxygen saturation (P = 0.001), RR (P = 0.004), the severity of dyspnoea (P = 0.014), and MAP (P = 0.027). There was no significant difference between the two groups in terms of pulse rate (P = 0.890), hospital stay (P = 0.994), intubation rate (P = 0.324), and survival (P = 0.091).DiscussionOur results demonstrated that PP showed marked improvement in some short-term clinical outcomes in nonintubated patients with COVID-19.ConclusionPP can be considered an inexpensive, accessible, and simple measure in awake nonintubated patients with COVID-19.     

Emergency Nursing Care of Patients With Novel Coronavirus Disease 2019

Novel coronavirus disease 2019 is the disease caused by the novel coronavirus originally from Wuhan, China. Its pathophysiology is poorly understood, but it is known to be contagious and deadly. Multiple symptoms and complications from the disease have been described, with the most common complaints being respiratory. Nursing care of patients with novel coronavirus disease 2019 is largely supportive, but it should include a strong focus on mitigating the spread of infection to staff, other patients, and the community.     

Having Children Is Associated with a Higher Prevalence of COVID-19 among Young Adults in Kuwait

ObjectivesThe role of children in the transmission of coronavirus disease 2019 (COVID-19) remains unclear. We investigated whether having children is associated with self-reported COVID-19 among adults.Subjects and MethodsA web-based cross-sectional study enrolled adults living in Kuwait (n = 2,355; aged ≥21 years). Prior COVID-19 diagnosis and having children were self-reported. Associations were assessed using Poisson regression, and adjusted prevalence ratios (aPRs) and 95% confidence intervals (CIs) were estimated.ResultsOf the 2,355 participants (1,595 female subjects), 744 (31.6%) and 605 (25.7%) were of age 21–29 and 30–39 years, respectively. Overall, 4.8% (114/2,355) of the participants reported having had COVID-19, with 4.8% of females and 5.1% of males reporting prior COVID-19 diagnosis. In the total study sample, having children showed a trend for association with having had COVID-19 (aPR: 1.46, 95% CI: 0.99–2.14, p = 0.056). Among participants aged 21–29 years, having children was associated with an increased prevalence of COVID-19 (aPR: 2.50, 95% CI: 1.21–5.20, p = 0.014). Such an association was not detected in adults aged ≥30 years.ConclusionsOur epidemiological findings highlight the possible role of children in spreading COVID-19. Hence, preventive measures should consider the role of children.     

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.     

A patient with human coronavirus NL63 falsely diagnosed with COVID-19; Lesson learned for the importance of definitive diagnosis

The gold standard for the diagnosis of coronavirus disease 2019 (COVID-19) is a nucleic acid detection test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which may occasionally reveal false-positive or false-negative results. Herein, we describe a case of a patient infected with human coronavirus NL63 (HCoV-NL63) who was falsely diagnosed with COVID-19 using the Ampdirect? 2019-nCoV detection kit (Shimadzu Corporation, Japan) and SARS-CoV-2 Detection Kit (TOYOBO co., ltd.), and was admitted to a COVID-19 hospital ward. We suspected a cross-reaction between HCoV-NL63 and SARS-CoV-2; however, the reported genome sequences of HCoV-NL63 and N1/N2 primers for SARS-CoV-2 do not correspond. Thus, the PCR result was supposed to be a false positive possibly due to contamination or human error. Although the issue of a false-negative result has been the focus of much attention to prevent the spread of the disease, a false positive is fraught with problems as well. Physicians should recognize that unnecessary isolation violates human rights and a careful diagnosis is indispensable when the results of laboratory testing for COVID-19 are unclear. Generally, in cases such as a duplicate PCR test was partially positive, either N1 or N2 alone was positive, PCR testing for two or more target regions resulted in a positive only for single region, a high cycle threshold >35 was obtained, a false positive should be suspected. Especially, when these conditions coincide, we should recognize the high likelihood of a false positive.     

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.     

Effectiveness of prone position in acute respiratory distress syndrome and moderating factors of obesity class and treatment durations for COVID-19 patients: A meta-analysis

ObjectivesTo examine the effectiveness of prone positioning on COVID-19 patients with acute respiratory distress syndrome with moderating factors in both traditional prone positioning (invasive mechanical ventilation) and awake self-prone positioning patients (non-invasive ventilation).Research methodologyA comprehensive search was conducted in CINAHL, Cochrane library, Embase, Medline-OVID, NCBI SARS-CoV-2 Resources, ProQuest, Scopus, and Web of Science without language restrictions. All studies with prospective and experimental designs evaluating the effect of prone position patients with COVID-19 related to acute respiratory distress syndrome were included. Pooled standardised mean differences were calculated after prone position for primary (PaO₂/FiO₂) and secondary outcomes (SpO₂ and PaO₂)ResultsA total of 15 articles were eligible and included in the final analysis. Prone position had a statistically significant effect in improving PaO₂/FiO₂ with standardised mean difference of 1.10 (95%CI 0.60–1.59), SpO₂ with standardised mean difference of 3.39 (95% CI 1.30–5.48), and PaO₂ with standardised mean difference of 0.77 (95% CI 0.19–1.35). Patients with higher body mass index and longer duration/day are associated with larger standardised mean difference effect sizes for prone positioning.ConclusionsOur findings demonstrate that prone position significantly improved oxygen saturation in COVID-19 patients with acute respiratory distress syndrome in both traditional prone positioning and awake self-prone positioning patients. Prone position should be recommended for patients with higher body mass index and longer durations to obtain the maximum effect.     

Impact of colchicine on mortality and morbidity in COVID-19: a systematic review

IntroductionColchicine, because of its anti-inflammatory and possible anti-viral properties, has been proposed as potential therapeutic option for COVID-19. The role of colchicine to mitigate “cytokine storm” and to decrease the severity and mortality associated with COVID-19 has been evaluated in many studies.ObjectiveTo evaluate the role of colchicine on morbidity and mortality in COVID-19 patients.MethodsThis systematic review was conducted in accordance with the PRISMA recommendations. The literature search was conducted in 6 medical databases from inception to February 17, 2021 to identify studies evaluating colchicine as a therapeutic agent in COVID-19. All included studies were evaluated for risk of bias (ROB) using the Revised Cochrane ROB tool for randomised controlled trials (RCTs) and Newcastle-Ottawa Scale (NOS) for case-control and cohort studies.ResultsFour RCTs and four observational studies were included in the final analysis. One study evaluated colchicine in outpatients, while all others evaluated inpatient use of colchicine. There was significant variability in treatment protocols for colchicine and standard of care in all studies. A statistically significant decrease in all-cause mortality was observed in three observational studies. The risk of mechanical ventilation was significantly reduced only in one observational study. Length of hospitalisation was significantly reduced in two RCTs. Risk for hospitalisation was not significantly decreased in the study evaluating colchicine in outpatients. Very few studies had low risk of bias.ConclusionBased on the available data, colchicine shall not be recommended to treat COVID-19. Further high-quality and multi-center RCTs are required to assess the meaningful impact of this drug in COVID-19.

KEY MESSAGES

• Colchicine, an anti-inflammatory agent has demonstrated anti-viral properties in in-vitro studies by degrading the microtubules, as well as by inhibiting the production of pro-inflammatory cytokines.
• Colchicine has been studied as a potential therapeutic option for COVID-19, with variable results.
• Until further research can establish the efficacy of colchicine in COVID-19, the use of colchicine in COVID-19 shall be restricted to clinical trials.