Abnormalities in liver biochemistry are common in COVID-19 patients. Hepatic vein Doppler waveform, typically triphasic, may become biphasic or monophasic in cirrhosis, correlating with liver dysfunction, fibrosis, inflammation, and portal hypertension. This study investigates liver ultrasound (US) features in COVID-19 patients, correlating hepatic vein Doppler waveform and portal vein velocity (PVV) with inflammatory indexes and clinical outcomes.

Fifty-seven patients with SARS-CoV-2 infection participated in a crosssectional study. Bedside upper abdomen US evaluations, including B-mode and Doppler, were conducted using a convex probe. Hepatic vein Doppler waveforms were classified as triphasic, biphasic, or monophasic, and the hepatic vein waveform index (HVWI) was calculated. PVV was measured over three cardiac cycles. Tracings were blindly analyzed by three operators to ensure consistency.

Low HVWI and high PVV correlated with elevated LDH, ALT, D-dimer, and ferritin (p < 0.05). HVWI showed significant negative correlations with ferritin, D-dimer, and ALT (p < 0.05). D-Dimer and ferritin were higher in patients with biphasic/monophasic waveforms (p < 0.05). High PVV and larger spleen diameters predicted worse respiratory outcomes, including CPAP and tracheal intubation (p < 0.05). Optimal cut-off values for PVV (21.7 cm/s) and spleen diameter (9.84 cm) maximized sensitivity and specificity for predicting these outcomes. FIB-4 scores did not correlate with respiratory outcomes or hepatic hemodynamics (p > 0.05). Hemodynamic alterations were not significantly influenced by the presence of SLD (Steatotic Liver Disease).

COVID-19 patients exhibit altered intrahepatic hemodynamics, with hepatic vein waveform abnormalities potentially reflecting liver inflammation and fibrosis. PVV and spleen diameter may serve as non-invasive predictors of respiratory outcomes.

The global pandemic of novel coronavirus pneumonia (COVID-19) has resulted in millions of deaths over the past three years. As one of the most commonly affected extra-pulmonary organs, numerous studies have reported varying degrees of liver injury in a significant proportion of patients with COVID-19, particularly in severe and critically ill patients. Early prediction of liver dysfunction in hospitalized patients would facilitate the clinical management of COVID-19 and improve clinical prognosis, but reliable and valid predictive models are still lacking.MethodsWe collected data from 286 patients with RT-PCR confirmed COVID-19 admitted to various ICUs from the case system. These patients were randomly divided into a training cohort (50%) and a validation cohort (50%). In the training cohort, we first used ROC curves to measure the predictive efficiency of each of the variables for the development of liver damage during hospitalization in patients with COVID-19, followed by LASSO regression analysis to screen the variables for predictive models and logistic regression analysis to identify relevant risk factors. A nomogram based on these variables was created following the above model. Finally, the efficiency of the prediction models in the training and validation cohorts was assessed using AUC, consistency index (C index), calibration curves and Decision Curve Analysis.ResultsOut of a total of 80 parameters for COVID-19 patients admitted to the ICUs, 10 were determined to be significantly associated with the occurrence of liver dysfunction during hospitalization. Based on these predictors, further prediction models were used to construct and develop a nomogram that was offered for practical clinical application. The C-index of the column line graphs for the training and validation cohorts was 0.956 and 0.844 respectively. in addition, the calibration curves for the model showed a high degree of agreement between the predicted and actual incidence of liver dysfunction in patients with COVID-19.ConclusionBy developing a predictive model and associated nomogram, we predicted the incidence of liver dysfunction during hospitalization in patients with COVID-19 in the ICU. The model's predictive performance was determined in both the training and validation cohorts, contributing to the clinical management of COVID-19.

SARS-CoV-2 disease (COVID-19) has had an enormous health and economic impact globally. Although primarily a respiratory illness, multi-organ involvement is common in COVID-19, with evidence of vascular-mediated damage in the heart, liver, kidneys and brain in a substantial proportion of patients following moderate-to-severe infection. The pathophysiology and long-term clinical implications of multi-organ injury remain to be fully elucidated. Age, gender, ethnicity, frailty and deprivation are key determinants of infection severity, and both morbidity and mortality appear higher in patients with underlying comorbidities such as ischaemic heart disease, hypertension and diabetes. Our aim is to gain mechanistic insights into the pathophysiology of multiorgan dysfunction in people with COVID-19 and maximise the impact of national COVID-19 studies with a comparison group of COVID-negative controls.

COmorbidities and Sociodemographic factors on Multiorgan Injury following COVID-19 (COSMIC) is a prospective, multicentre UK study which will recruit 200 subjects without clinical evidence of prior COVID-19 and perform extensive phenotyping with multiorgan imaging, biobank serum storage, functional assessment and patient reported outcome measures, providing a robust control population to facilitate current work and serve as an invaluable bioresource for future observational studies.

Approved by the National Research Ethics Service Committee East Midlands (REC reference 19/EM/0295). Results will be disseminated via peer-reviewed journals and scientific meetings.

COSMIC is registered as an extension of C-MORE (Capturing Multi-ORgan Effects of COVID-19) on ClinicalTrials.gov (NCT04510025).

Acute kidney injury (AKI) and acute liver injury (ALI) were associated with poor outcomes during hospitalization, respectively. However, the clinical outcome of AKI combined with ALI (AKI-ALI) remains unknown. The current study aimed to describe AKI-ALI's incidences, risk factors, and outcomes.

The study population included patients aged 18-99 years with enough serum creatinine and liver testing hospitalized at 19 medical centers throughout China between 2000 and 2021. AKI was defined by Kidney Disease Improving Global Outcomes and ALI was defined by the change of liver enzymes based on Asia Pacific Association of Study of Liver consensus guidelines. Cox proportional hazard model was used to identify risk factors for AKI-ALI, and a time-dependent Cox proportional hazard regression model was used to estimate the association between AKI-ALI and in-hospital mortality.

Among the 18,461 patients with AKI, 1689 (9.1%) combined with ALI. Male patients or those who have used nonsteroidal anti-inflammatory drugs or vasopressors, and who have heart failure or shock, with higher AST or GGT values, were associated with an increased risk of AKI-ALI. Compared with AKI-nonALI, patients with AKI-ALI were at higher risk of in-hospitalized mortality (hazard ratio [HR] 1.76, 95% confidence interval [CI] 1.54, 2.00). In addition, a stronger association between AKI-ALI and in-hospital mortality was found in those with lower AKI grades (p for interaction = 0.037).

ALI was not uncommon among patients with AKI, especially in patients who used vasopressors and had shock. This study highlights the association between AKI-ALI and a significantly increased risk of mortality. It suggests that dynamic monitoring of liver function is essential, particularly in patients with AST and GGT exceeding the normal upper limit, to improve the in-hospital prognosis of AKI patients.

Since the start of the pandemic, considerable advancements have been made in our understanding of the effects of SARS-CoV-2 infection and the associated COVID-19 on the hepatic system. There is a broad range of clinical symptoms for COVID-19. It affects multiple systems and has a dominant lung illness depending on complications. The progression of COVID-19 in people with pre-existing chronic liver disease (CLD) has also been studied in large multinational groups. Notably, SARS-CoV-2 infection is associated with a higher risk of hepatic decompensation and death in patients with cirrhosis. In this review, the source, composition, mechanisms, transmission characteristics, clinical characteristics, therapy, and prevention of SARS-CoV-2 were clarified and discussed, as well as the evolution and variations of the virus. This review briefly discusses the causes and effects of SARS-CoV-2 infection in patients with CLD. As part of COVID-19, In addition, we assess the potential of liver biochemistry as a diagnostic tool examine the data on direct viral infection of liver cells, and investigate potential pathways driving SARS-CoV-2-related liver damage. Finally, we explore how the pandemic has had a significant impact on patient behaviors and hepatology services, which may increase the prevalence and severity of liver disease in the future. The topics encompassed in this review encompass the intricate relationships between SARS-CoV-2, liver health, and broader health management strategies, providing valuable insights for both current clinical practice and future research directions.

Liver fibrosis is a chronic pathological condition lacking specific clinical treatments. Stem cells, with notable potential in regenerative medicine, offer promise in treating liver fibrosis. However, stem cell therapy is hindered by potential immunological rejection, carcinogenesis risk, efficacy variation, and high cost. Stem cell secretome-based cell-free therapy offers potential solutions to address these challenges, but it is limited by low delivery efficiency and rapid clearance. Herein, an innovative approach for in situ implantation of smart microneedle (MN) arrays enabling precisely controlled delivery of multiple therapeutic agents directly into fibrotic liver tissues is developed. By integrating cell-free and platinum-based nanocatalytic combination therapy, the MN arrays can deactivate hepatic stellate cells. Moreover, they promote excessive extracellular matrix degradation by more than 75%, approaching normal levels. Additionally, the smart MN arrays can provide hepatocyte protection while reducing inflammation levels by ≈70-90%. They can also exhibit remarkable capability in scavenging almost 100% of reactive oxygen species and alleviating hypoxia. Ultimately, this treatment strategy can effectively restrain fibrosis progression. The comprehensive in vitro and in vivo experiments, supplemented by proteome and transcriptome analyses, substantiate the effectiveness of the approach in treating liver fibrosis, holding immense promise for clinical applications.

We evaluated glycemia and triglyceride, hepatic, muscular, and renal damage markers, redox profile, and leptin and ghrelin hormone levels in COVID-19 patients. We also conducted statistical analysis to verify the potential of biomarkers to predict poor prognosis and the correlation between them in severe cases. We assessed glycemia and the levels of triglycerides, hepatic, muscular, and renal markers in automatized biochemical analyzer. The leptin and ghrelin hormones were assessed by the ELISA assay. Severe cases presented high glycemia and triglyceride levels. Hepatic, muscular, and renal biomarkers were altered in severe patients. Oxidative stress status was found in severe COVID-19 patients. Severe cases also had increased levels of leptin. The ROC curves indicated many biomarkers as poor prognosis predictors in severe cases. The Spearman analysis showed that biomarkers correlate between themselves. Patients with COVID-19 showed significant dysregulation in the levels of several peripheral biomarkers. We bring to light that a robust panel of peripheral biomarkers and hormones predict poor prognosis in severe cases of COVID-19 and biomarkers correlate with each other. Early monitoring of these biomarkers may lead to appropriate clinical interventions in patients infected by SARS-CoV2.

The recent use of artificial intelligence (AI) in medical research is noteworthy. However, most research has focused on medical imaging. Although the importance of laboratory tests in the clinical field is acknowledged by clinicians, they are undervalued in medical AI research. Our study aims to develop an early prediction AI model for pneumonia mortality, primarily using laboratory test results.

We developed a mortality prediction model using initial laboratory results and basic clinical information of patients with pneumonia. Several machine learning (ML) models and a deep learning method-multilayer perceptron (MLP)-were selected for model development. The area under the receiver operating characteristic curve (AUROC) and F1-score were optimized to improve model performance. In addition, an ensemble model was developed by blending several models to improve the prediction performance. We used 80,940 data instances for model development.

Among the ML models, XGBoost exhibited the best performance (AUROC = 0.8989, accuracy = 0.88, F1-score = 0.80). MLP achieved an AUROC of 0.8498, accuracy of 0.86, and F1-score of 0.75. The performance of the ensemble model was the best among the developed models, with an AUROC of 0.9006, accuracy of 0.90, and F1-score of 0.81. Several laboratory tests were conducted to identify risk factors that affect pneumonia mortality using the "Feature importance" technique and SHapley Additive exPlanations. We identified several laboratory results, including systolic blood pressure, serum glucose level, age, aspartate aminotransferase-to-alanine aminotransferase ratio, and monocyte-to-lymphocyte ratio, as significant predictors of mortality in patients with pneumonia.

Our study demonstrates that the ensemble model, incorporating XGBoost, CatBoost, and LGBM techniques, outperforms individual ML and deep learning models in predicting pneumonia mortality. Our findings emphasize the importance of integrating AI techniques to leverage laboratory test data effectively, offering a promising direction for advancing AI applications in medical research and clinical decision-making.

Coronaviruses have been the cause of 3 major outbreaks during the last 2 decades. Information on coronavirus diseases in pregnant women is limited, and even less is known about seriously ill pregnant women. Data are also lacking regarding the real burden of coronavirus disease 2019 (COVID-19) infection in pregnant women from low/middle-income countries. The aim of this study was to determine the characteristics and clinical course of COVID-19 in pregnant/puerperal women admitted to ICUs in Turkey.

This was a national, multicenter, retrospective study. The study population comprised all SARS-CoV-2-infected pregnant/puerperal women admitted to participating ICUs between 1 March 2020 and 1 January 2022. Data regarding demographics, comorbidities, illness severity, therapies, extrapulmonary organ injuries, non-COVID-19 infections, and maternal and fetal/neonatal outcomes were recorded. LASSO logistic regression and multiple logistic regression analyses were used to identify predictive variables in terms of ICU mortality.

A total of 597 patients (341 pregnant women, 255 puerperal women) from 59 ICUs in 44 hospitals were included and of these patients, 87.1% were unvaccinated. The primary reason for ICU admission was acute hypoxemic respiratory failure in 522 (87.4%), acute hypoxemic respiratory failure plus shock in 14 (2.3%), ischemic cerebrovascular accident (CVA) in 5 (0.8%), preeclampsia/eclampsia/HELLP syndrome in 6 (1.0%), and post-caesarean follow-up in 36 (6.0%). Nonsurvivors were sicker than survivors upon ICU admission, with higher APACHE II (p < 0.001) and SOFA scores (p < 0.001). A total of 181 (30.3%) women died and 280 (46.6%) had received invasive mechanical ventilation (IMV). Myocardial injury, the highest SOFA score during ICU stay, LDH levels on admission, the highest levels of AST during ICU stay, average daily dose of corticosteroids, IMV, prophylactic dose anticoagulation (compared with therapeutic dose anticoagulation), PaO2/FiO2 ratio <100, pulmonary embolism, and shock were identified as predictors of mortality. Rates of premature birth (46.4%), cesarean section (53.7%), fetal distress (15.3%), stillbirth (6.5%), and low birth weight (19.4%) were high. Rates of neonatal death (8%) and respiratory distress syndrome (21%) were also high among live-born infants.

Severe/critical COVID-19 infection during the pregnancy/puerperal period was associated with high maternal mortality and fetal/neonatal complication rates in Turkey.

Background: Steatotic liver disease (SLD) has been linked to more exacerbated inflammatory responses in various scenarios. The relationship between SLD and COVID-19 prognosis remains unclear. Our aim was to investigate the impact of SLD on the outcome of COVID-19. Methods: Patients hospitalized with confirmed COVID-19 and who underwent laboratory tests and chest CT scans were included. SLD was assessed by measuring the attenuation coefficient on CT scans. The relationship between SLD, the severity of COVID-19 clinical presentation and in-hospital mortality were assessed. Results: A total of 610 patients were included (mean age 62 ± 16 years, 64% male). The prevalence of SLD was 30%, and the overall in-hospital mortality rate was 19%. Patients with SLD were younger (58 ± 13 vs. 64 ± 16 years, p < 0.001) and had a higher BMI (32 ± 5 vs. 28 ± 4 kg/m2, p = 0.014). Admission AST values were higher in patients with SLD (82 ± 339 vs. 50 ± 37, p = 0.02), while D-dimer (1112 ± 2147 vs. 1959 ± 8509, p = 0.07), C-reactive protein (12 ± 9 vs. 11 ± 8, p = 0.27), ALT (67 ± 163 vs. 47 ± 90, p = 0.11), ALP (83 ± 52 vs. 102 ± 125, p = 0.27), and GGT (123 ± 125 vs. 104 ± 146, p = 0.61) did not significantly differ compared to patients without SLD. No difference was observed regarding lung parenchyma involvement >50% (20% vs. 17%, p = 0.25), hospital length of stay (14 ± 19 vs. 16 ± 23 days, p = 0.20), hemodialysis support (14% vs. 16%, p = 0.57), use of mechanical ventilation (20% vs. 20%, p = 0.96), and in-hospital mortality (17% vs. 20%, p = 0.40) when comparing patients with and without SLD. Conclusions: SLD showed no significant association with morbidity and mortality in patients with COVID-19.

During the coronavirus disease 2019 (COVID-19) pandemic, clinical prevention, early diagnosis, and hematological monitoring were challenging areas. This study aims to compare risk factors and hematological and biochemical data in non-survivor group patients with COVID-19 versus survivor group patients. A total of 204 patients with COVID-19 were selected as research subjects from December 2022 to January 2023. We analyzed the age, sex, time from onset to admission, and laboratory test indicators upon admission. The differences between surviving and deceased patients and mortality-related risk factors were examined. Among the 204 patients, 168 survived, whereas 36 died during hospitalization. Significant differences were observed between the two groups with COVID-19 across various factors, including age (p < 0.0001), WBC count (p < 0.0001), RBC count (p < 0.05), neutrophils (p < 0.0001), lymphocytes (p < 0.05), mean corpuscular hemoglobin concentration (MCHC) (p < 0.0001), RBC distribution width-standard deviation (RDW-SD) (p < 0.0001), RBC distribution width coefficient of variation (RDW-CV) (p < 0.0001), aspartate aminotransferase (AST) (p < 0.05), albumin (ALB) (p < 0.0001), creatinine (CR) (p < 0.0001), uric acid (UA) (p < 0.0001), blood urea nitrogen (BUN) (p < 0.0001), plasma thrombin time (TT) (p < 0.05), prothrombin time (PT) (p < 0.0001), and D-dimer (p < 0.0001). Multivariate logistic analysis revealed that older age, CR, UA, and ALB were independent factors associated with death (p < 0.05). Elderly patients with underlying diseases, abnormal routine blood test indices, and abnormal renal function and coagulation indices are at an increased worse prognosis and should be identified early. Age, UA, CR, and ALB can be used as predictors to assess the worse prognosis in the hospital.

The coronavirus disease 2019 (COVID-19) pandemic has caused changes in the global health system, causing significant setbacks in healthcare systems worldwide. This pandemic has also shown resilience, flexibility, and creativity in reacting to the tragedy. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection targets most of the respiratory tract, resulting in a severe sickness called acute respiratory distress syndrome that may be fatal in some individuals. Although the lung is the primary organ targeted by COVID-19 viruses, the clinical aspect of the disease is varied and ranges from asymptomatic to respiratory failure. However, due to an unorganized immune response and several affected mechanisms, the liver may also experience liver cell injury, ischemic liver dysfunction, and drug-induced liver injury, which can result in respiratory failure because of the immune system's disordered response and other compromised processes that can end in multisystem organ failure. Patients with liver cirrhosis or those who have impaired immune systems may be more likely than other groups to experience worse results from the SARS-CoV-2 infection. We thus intend to examine the pathogenesis, current therapy, and consequences of liver damage concerning COVID-19.

Blood is critical for health, supporting key functions like immunity and oxygen transport. While studies have found links between common blood clinical indicators and COVID-19, they cannot provide causal inference due to residual confounding and reverse causality. To identify indicators affecting COVID-19, we analyzed clinical data (n = 2,293, aged 18-65 years) from Guangzhou Medical University's first affiliated hospital (2022-present), identifying 34 significant indicators differentiating COVID-19 patients from healthy controls. Utilizing bidirectional Mendelian randomization analyses, integrating data from over 2.46 million participants from various large-scale studies, we established causal links for six blood indicators with COVID-19 risk, five of which is consistent with our observational findings. Specifically, elevated Troponin I and Platelet Distribution Width levels are linked with increased COVID-19 susceptibility, whereas higher Hematocrit, Hemoglobin, and Neutrophil counts confer a protective effect. Reverse MR analysis confirmed four blood biomarkers influenced by COVID-19, aligning with our observational data for three of them. Notably, COVID-19 exhibited a positive causal relationship with Troponin I (Tnl) and Serum Amyloid Protein A, while a negative association was observed with Plateletcrit. These findings may help identify high-risk individuals and provide further direction on the management of COVID-19.

COVID-19, which was first identified in 2019 in Wuhan, China, is a respiratory illness caused by a virus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although some patients infected with COVID-19 can remain asymptomatic, most experience a range of symptoms that can be mild to severe. Common symptoms include fever, cough, shortness of breath, fatigue, loss of taste or smell and muscle aches. In severe cases, complications can arise including pneumonia, acute respiratory distress syndrome, organ failure and even death, particularly in older adults or individuals with underlying health conditions. Treatments for COVID-19 include remdesivir, which has been authorised for emergency use in some countries, and dexamethasone, a corticosteroid used to reduce inflammation in severe cases. Biological drugs including monoclonal antibodies, such as casirivimab and imdevimab, have also been authorised for emergency use in certain situations. While these treatments have improved the outcome for many patients, there is still an urgent need for new treatments. Medicinal plants have long served as a valuable source of new drug leads and may serve as a valuable resource in the development of COVID-19 treatments due to their broad-spectrum antiviral activity. To date, various medicinal plant extracts have been studied for their cellular and molecular interactions, with some demonstrating anti-SARS-CoV-2 activity in vitro. This review explores the evaluation and potential therapeutic applications of these plants against SARS-CoV-2. This review summarises the latest evidence on the activity of different plant extracts and their isolated bioactive compounds against SARS-CoV-2, with a focus on the application of plant-derived compounds in animal models and in human studies.

Liver dysfunction is common during coronavirus disease 2019 (COVID-19), while its clinical impact and association with chronic hepatitis B (CHB) remain uncertain. We aimed to investigate liver dysfunction in COVID-19 patients and its impacts on those with/without CHB.

We conducted a retrospective cohort study of COVID-19 patients at National Taiwan University Hospital, stratified according to hepatitis B surface antigen (HBsAg) serostatus, with demographics, laboratory data, and hospitalization course reviewed, and clinical outcomes compared through multivariable analyses.

We enrolled 109 COVID-19 patients unvaccinated against SARS-CoV-2 by August 2021. The HBsAg-positive group (n = 34) had significantly higher alanine aminotransferase (ALT) (26 vs. 16 U/L, P = 0.034), platelet (224 vs. 183 k/μL, P = 0.010) and longer hospitalizations (17 vs. 13 days, P = 0.012) compared with HBsAg-negative group (n = 75), while percentages of hepatitis (2-fold ALT elevation), oxygen supplementation, ventilators usage, COVID-specific treatment, intensive care unit (ICU) admission and mortality were comparable. Older age (odds ratio [OR]: 1.04, 95 % confidence interval [CI]: 1.00-1.08, P = 0.032) and higher aspartate aminotransferase (AST) (OR: 1.08, 95 % CI: 1.004-1.16, P = 0.038) were associated with oxygen supplementation according to multivariable analyses. Higher AST predicted ICU admission (OR: 1.11, 95 % CI: 1.03-1.19, P = 0.008). Oxygen usage (OR: 5.64, 95 % CI: 1.67-19.09, P = 0.005) and shock (OR: 5.12, 95 % CI: 1.14-22.91, P = 0.033) were associated with liver dysfunction.

CHB patients had higher ALT levels and longer hospitalizations during COVID-19. Higher AST levels predict severe COVID-19 and ICU admission.

The novel disease produced by SARS-CoV-2 mainly harms the respiratory tract, but it has shown the capacity to affect multiple organs. Epidemiologic evidence supports the relationship between Coronavirus Disease 2019 (COVID-19) and pancreatic and hepatic injury development, identified by alterations in these organ function markers. In this regard, it is important to ascertain how the current prevalence of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) might affect COVID-19 evolution and complications. Although it is not clear how SARS-CoV-2 affects both the pancreas and the liver, a multiplicity of potential pathophysiological mechanisms seem to be implicated; among them, a direct viral-induced injury to the organ involving liver and pancreas ACE2 expression. Additionally, immune system dysregulation, coagulopathies, and drugs used to treat the disease could be key for developing complications associated with the patient's clinical decline. This review aims to provide an overview of the available epidemiologic evidence regarding developing liver and pancreatic alterations in patients with COVID-19, as well as the possible role that NAFLD/NASH might play in the pathophysiological mechanisms underlying some of the complications associated with COVID-19. This review employed a comprehensive search on PubMed using relevant keywords and filters. From the initial 126 articles, those aligning with the research target were selected and evaluated for their methodologies, findings, and conclusions. It sheds light on the potential pathophysiological mechanisms underlying this relationship. As a result, it emphasises the importance of monitoring pancreatic and hepatic function in individuals affected by COVID-19.

The pathogenesis of COVID-19 involves a complex interplay between host factors and the SARS-CoV-2 virus, leading to a multitude of clinical manifestations beyond the respiratory system. This chapter provides an overview of the risk factors, genetic predisposition, and multisystem manifestations of COVID-19, shedding light on the underlying mechanisms that contribute to extrapulmonary manifestations. The chapter discusses the direct invasion of SARS-CoV-2 into various organs as well as the indirect mechanisms such as dysregulation of the renin-angiotensin-aldosterone system (RAAS), immune response dysfunctions within the innate and adaptive immune systems, endothelial damage, and immunothrombosis. Furthermore, the multisystem manifestations of COVID-19 across different organ systems, including the cardiovascular, renal, gastrointestinal, hepatobiliary, nervous, endocrine and metabolic, ophthalmic, ear-nose-throat, reproductive, hematopoietic, and immune systems are discussed in detail. Each system exhibits unique manifestations that contribute to the complexity of the disease.

SARS-CoV-2 unsparingly impacts all areas of medicine. Pregnant women are particularly affected by the pandemic and COVID-19 related liver damage seems to be another threat to maternal and fetal health. The aim of this study is to define liver damage profile including bile acids serum levels in COVID-19 pregnant patients and to determine predictors of disease aggravation and poor obstetrics outcomes.

This study has been carried out in the Obstetrics and Gynecology Department, at the National Medical Institute in Warsaw, Poland between 01.02.2021 and 01.11.2022 The study cohort comprises 148 pregnant patients with COVID-19 and 102 pregnant controls who has been tested negative for SARS-CoV-2.

COVID-19 pregnant patients presented liver involvement at admission in 41,9%. Hepatotoxic damage accounted for 27 (19.85%), cholestatic type was diagnosed in 11 (8.09%) and mixed type of liver injury was presented in 19 (13.97%) of patients. Higher serum levels of AST, ALT, GGT, total bilirubin and bile acids as well as mixed type of liver injury at admission were correlated with severe form of an illness. AST and ALT above upper reference limit as well as hepatotoxic type of liver damage predisposed pregnant patients with COVID-19 to poor obstetrics outcomes.

Hepatic damage in pregnant women with COVID-19 is a common, mild, transaminase-dominant, or mixed type of injury, and often correlates with elevated inflammatory markers. SARS-CoV-2 test should be performed as a part of differential diagnosis in elevated liver function tests. Although bile acids serum levels were commonly elevated they seems to be clinically irrelevant in terms of pregnancy outcomes. Video Abstract.

Abnormal liver function was frequently observed in nonalcoholic fatty liver disease (NAFLD) patients infected with SARS-CoV-2. Our aim was to explore the effect of SARS-CoV-2 inactivated vaccines on liver function abnormality among NAFLD patients with COVID-19.

The multi-center retrospective cohort included 517 NAFLD patients with COVID-19 from 1 April to 30 June 2022. Participants who received 2 doses of the vaccine (n = 274) were propensity score matched (PSM) with 243 unvaccinated controls. The primary outcome was liver function abnormality and the secondary outcome was viral shedding duration. Logistic and Cox regression models were used to calculate the odds ratio (OR) and hazard ratio (HR) for the outcomes. Sensitivity analysis was conducted to assess robustness.

PSM identified 171 pairs of vaccinated and unvaccinated patients. Liver function abnormality was less frequent in the vaccinated group (adjusted OR, 0.556 [95% CI (confidence interval), 0.356-0.869], p = 0.010). Additionally, the vaccinated group demonstrated a lower incidence of abnormal bilirubin levels (total bilirubin: adjusted OR, 0.223 [95% CI, 0.072-0.690], p = 0.009; direct bilirubin: adjusted OR, 0.175 [95% CI, 0.080-0.384], p < 0.001) and shorter viral shedding duration (adjusted HR, 0.798 [95% CI, 0.641-0.994], p = 0.044) than the unvaccinated group. Further subgroup analysis revealed similar results, while the sensitivity analyses indicated consistent findings.

SARS-CoV-2 vaccination in patients with NAFLD may reduce the risk of liver dysfunction during COVID-19. Furthermore, vaccination demonstrated beneficial effects on viral shedding in the NAFLD population.

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Baicalin (BA) is a natural product extract with anti-inflammatory, antioxidant, and hepatoprotective properties. Given that the exact underlying mechanisms responsible for the impact of BA on liver cirrhosis remain ambiguous, a detailed investigation is sorely needed. Accordingly, a rat liver cirrhosis model was established via the intraperitoneal injection of diethyl nitrosamine (DEN, 100 mg/kg). Following the modeling, these rats were given BA (100 mg/kg) or N-acetylcysteine (NAC, 150 mg/kg) alone or in combination. The pathological morphology of rat liver tissues in each group was observed by hematoxylin and eosin staining and Masson's trichrome staining. The expression of fibrosis-related proteins was evaluated by Western blot, and the levels of liver function-related biochemical indexes, oxidative stress-related indexes, and inflammatory factors in the serum by enzyme-linked immunosorbent assays (ELISA). The level of mitochondrial reactive oxygen species was measured by flow cytometry. The results depicted that in the rat model of DEN-induced liver cirrhosis, BA reduced the expression of fibrosis-related proteins (collagen type I alpha 1, α-smooth muscle actin, and transforming growth factor-β1), thereby alleviating the structural fibrosis of liver tissue. Furthermore, BA could diminish the level of mitochondrial reactive oxygen species, and the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA), interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), and monocyte chemotactic protein-1 (MCP-1), while promoting albumin, superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) levels. Notably, all these effects of BA above were strengthened following the combined treatment of BA and NAC. On the whole, BA suppresses liver fibrosis by inhibiting oxidative stress and inflammation, thereby exerting a hepatoprotective effect.

Severe COVID-19 pneumonia is a principal cause of death due to cascade of hyper inflammatory condition that leading to lung damage. Therefore, an effective therapy to countercurrent the surge of uncontrolled inflammation is mandatory to propose. Anti-interlukin-6 receptor antagonist monoclonal therapy, tocilizumab (TCZ) showed potential results in COVID-19 patients. This study aimed to emphasize the factors associated with mortality in COVID-19 patients that treated with tocilizumab and may influence the level of serum IL-6. A retrospective cohort study included all patients with clinical parameters that pointed to presence of cytokines storm and treated with one or more doses of TCZ beside the regular protocol of COVID-19 pneumonia. The factors that influence the mortality in addition to the level of serum IL-6 were analyzed. A total of 377 patients were included, 69.5 % of them received only one dose of TCZ which started mainly at the third day of admission. The mortality rate was 29.44 %. Regardless the time of starting TCZ, just one dose was fair enough to prevent bad consequence; OR = 0.04, P = 0.001.However, in spite of protective action of TCZ, older age and female sex were significant risk factors for mortality, P = 0.001 and 0.01 respectively, as well heart disease. Moreover, increasing the level of neutrophil, AST and IL-6 were associated with bad prognosis. In the same line, treatment with ivermectin, chloroquine and remdesivir inversely affect the level of IL-6. Early treatments of COVID-19 pneumonia with at least one dose of tocilizumab minimized the fatality rate.

The aim of this study was to ascertain patient characteristics, outcomes, and liver injuries in patients infected with different SARS-CoV-2 variants. Data from consecutive adult patients with severe/critical COVID-19 admitted to our hospital during the peak month of the Delta wave were compared to the ancestral, Alpha, and Omicron waves. The dataset of 551 hospitalized patients was similar in the Delta/non-Delta waves. At admission and discharge, the median aminotransferase levels were normal or slightly increased. During the Delta wave (172 vs. 379 non-Delta patients), more patients died (OR 1.69, 95%CI 1.09-2.56) or had liver injury at discharge (alanine aminotransferase, ALT ≥ 2 ULN) (OR 1.97, 95%CI 1.08-3.54). In-hospital mortality was associated with age, lung injury, intensive care unit admission, number of and cardiovascular comorbidities, diabetes, chronic kidney disease, and all inflammatory biomarkers. Serious liver injury at admission (ALT ≥ 5 × ULN) was significantly associated with in-hospital mortality (OR = 7.9, 95%CI 2-28.9). At discharge, drug-induced liver injury (DILI) was found in patients treated with remdesivir, ALT ≥ 2 ULN (OR = 2.62, 95%CI 1.22-5.75). Treatment with dexamethasone, remdesivir, and immunomodulators showed improved survival, OR = 0.50 (95%CI 0.33-0.77). Regardless of the variant and treatment options, less than 2% of patients displayed serious liver injury, which was not found to be a death predictor in multivariable analysis.

In the midst of the coronavirus disease 2019 (COVID-19) pandemic, intensive care units (ICUs) around the world have been pushed to their limits as they grapple with the effects of the severe acute respiratory syndrome coronavirus 2 virus. Identifying prognostic factors that influence mortality in COVID-19 patients admitted to the ICU could offer valuable insights for clinicians seeking to prevent disease progression. A retrospective analysis was conducted on COVID-19 patients admitted to the ICU between January and September 2020. The analysis considered patient demographics, comorbidities, neurological and non-neurological symptoms, as well as laboratory markers. The multivariate logistic regression analysis aims to uncover associations between these factors and patient outcomes. Of the 387 patients included in this study, nearly half (48.5%) of the ICU patients succumbed to COVID-19. Factors that contributed to increased mortality included being 60 years of age or older, impaired consciousness, lung disease, elevated international normalized ratio (INR), and elevated blood urea nitrogen (BUN) levels. Surprisingly, symptoms such as dizziness/lightheadedness, myalgia, and headache were associated with a higher likelihood of survival. In addition, elevated D-dimer and aspartate aminotransferase (AST) levels, as well as lymphopenia, were more commonly observed in deceased patients. The study concluded that those who died in the ICU tended to be older, white, and burdened with more comorbidities and impaired consciousness. With the intriguing link between specific symptoms and survival, further research is essential to uncover the underlying pathophysiological mechanisms that influence ICU patient outcomes in the context of COVID-19.

With evolving pandemic, a substantial proportion of patients are presenting with liver dysfunction as an extra-pulmonary manifestation of COVID-19 illness. We planned this study to evaluate the incidence of liver dysfunction in COVID-19 pneumonia and find an association between abnormal liver function and the severity of the disease.

We retrospectively analysed the hospital records of 344 patients with moderate to severe COVID-19 illness admitted to a Dedicated COVID Hospital in North India.

Out of 344 patients included in the study, 59.9% were males. The abnormal liver functions were present in 78.49% of patients at admission. Mean age of the patient with liver dysfunction was 53.41 ± 15.71 years. The incidence of elevated aspartate aminotransferase (AST), alanine aminotransferase (ALT), and hypoalbuminemia was 82.96%, 74.91%, and 69.7%, respectively, in patients with COVID-19 at admission. A positive correlation was found between the levels of AST, ALT and hypoalbuminemia with severity of disease. Mortality was 33% in patients with liver dysfunction in comparison to 18.9% in patients with normal liver functions.

More than 75% of the patient had abnormal liver functions at admission, and mortality was also high in this group. Mortality can be effectively reduced if laboratory parameters such as elevated AST and ALT and hypoalbuminemia are closely monitored at admission and during hospital stay in patients with risk factors like male, age <55 years and HTN.

Hepatic stellate cell hyperactivation is a central link in liver fibrosis development, transforming growth factor β1 (TGF-β1) is a key activator of HSCs.

This study investigated whether anlotinib attenuates CCl4 induced liver fibrosis in mice and explored its antifibrotic mechanism.

We used the human hepatic stellate cell line LX-2 for in vitro assays and used TGF-β1 to induce hepatic fibrosis in LX-2 cells. We analyzed cytotoxicity using a cell-counting kit-8 and transwell chambers to detect the migratory ability of LX-2 cells. Western blotting was used to detect the protein levels of collagen type I, α-smooth muscle actin, and p-Smad3. In addition, mice with CCl4-induced hepatic fibrosis were used as in vivo models. Histopathological examination was performed using H&E staining, Masson's trichrome staining, and immunohistochemistry.

Anlotinib significantly reversed TGF-β1-induced protein levels of Col I, α-SMA and p-Smad3 and inhibits migratory and proliferative abilities in vitro using LX-2 cells. CCl4 cause F4 grade (Ishak) hepatic fibrosis, liver inflammatory scores ranged from 12 to 14 (Ishak), a mean ALT measurement of 130 U/L and a mean measurement AST value of 119 U/L in mice. However, the CCl4-induced changes were markedly attenuated by anlotinib treatment, which returned to F2 grade (Ishak) hepatic fibrosis, liver inflammatory scores ranged from 4 to 6 (Ishak), a mean ALT measurement of 40 U/L and a mean measurement AST value of 56 U/L in mice.

Our results suggest that anlotinib-mediated suppression of liver fibrosis is related to the inhibition of TGF-β1 signaling pathway. Hepatic stellate cell hyper activation is a central link in liver fibrosis development, transforming growth factor β1 is a key activator of HSCs. Anlotinib is a multi-targeted tyrosine kinase inhibitor that has similar targets to nintedanib, a clinically used anti-pulmonary fibrosis drug. Our study demonstrates an FDA-approved drug-anlotinib-that could prevent liver fibrosis and inflammation. Experiments in cell cultures and mice show that anlotinib can inhibit the activation of hepatic stellate cells by down-regulating the TGFβ1/smad3 pathway, thereby reversing liver fibrosis. In animal experiments, anlotinib showed protective effects on the CCl4-induced liver damage, including ameliorating liver inflammation, reversing liver fibrosis and reducing liver enzymes. This is a very good signal, anlotinib may be useful for halting or reversing the progression of liver fibrosis and could be employed in the development of novel therapeutic drugs for the management of chronic liver diseases.

Since 2019, the COVID-19 pandemic wreaked havoc all over the world. Early in the course of the pandemic, multiple hepatic manifestations of COVID-19 were noted. We aim to categorize hepatic dysfunction and its outcome in COVID-19 infection.

This is a review article based on a literature search in PubMed and Medline databases for articles detailing short-term and long-term outcomes of COVID-19 related liver dysfunction.

The most common hepatic manifestation of COVID-19 was aspartate amino transferase (AST) predominant transaminase elevation. Transaminases improve once the COVID-19 infection resolves. In addition, COVID-19 cholangiopathy, autoimmune hepatitis associated COVID-19, and splanchnic venous thrombosis triggered by COVID-19 are other manifestations. Patients with preexisting liver disease, especially those with cirrhosis, have poor prognosis with COVID-19 infections compared to the general population. Elevations in liver tests were associated with severe COVID-19 infections. Patients with chronic liver disease have a higher risk of morbidity and mortality from COVID-19 infection. Among patients with chronic liver disease, decompensated liver cirrhosis, hepatocellular carcinoma and alcohol-associated liver disease were associated with an increased risk of severity and mortality from COVID-19 infection. Interactions between antiviral therapy for COVID-19 and hepatitis B/hepatitis C medications must be considered in patients with chronic viral hepatitis and COVID-19 infection. COVID-19 vaccination-related hepatic dysfunction has been reported.

COVID-19 is here to stay. Hepatic dysfunction in COVID-19 signals severe COVID-19 infections. Patients with chronic liver disease have higher mortality from COVID-19 than general population. It is important to remember the lessons learned throughout the covid pandemic to take care of patients with COVID-19 now and in the future. Further studies are needed to document long-term outcomes in patients with COVID-19 who developed hepatic dysfunction.

Microplastics (MPs) are a newly emerging type of pollutants. To date, MPs have been found in the atmosphere, soil, water, and even in human samples, posing a non-negligible threat to humans. Furthermore, multiple heavy metals have been found to co-exist with MPs or be absorbed by MPs. This leads to a widespread concern about their combined toxicity, which is currently elusive. Herein, we investigated the single or combined toxic effects of polystyrene MPs (PS-MPs) and cadmium chloride (CdCl2) on the liver and hepatocytes. After co-incubation, cadmium (Cd) can be absorbed by PS-MPs, resulting in physiochemical alterations of PS-MPs. In vivo and in vitro experiments revealed that PS-MPs solely or together with CdCl2 induced ferroptosis in hepatocytes, a newly defined programmed cell death characterized by lipid oxidation and iron accumulation. PS-MPs exerted more ferroptotic effect on hepatocytes than CdCl2, and combined exposure to PS-MPs and CdCl2 enhanced their ferroptotic effect, mainly by stimulating reactive oxygen species (ROS) production and inhibiting antioxidant activity. Upon single or combined exposure to PS-MPs and CdCl2, the induction of ferroptosis in hepatocytes can be inhibited by N-acetyl-cysteine (NAC, an ROS scavenger), deferoxamine (DFO, an iron chelator), and particularly ferrostatin-1 (Fer-1, a specific ferroptosis inhibitor). Fer-1 efficiently rescued the cell viability of hepatocytes upon exposure to PS-MPs and CdCl2 through enhancing the antioxidant system via upregulating GPX4 and SLC7A11. These findings would contribute to an in-depth understanding of the single and combined toxicity of microplastics and cadmium.

Since China's dynamic zero-COVID policy is cancelled on December 7, 2022, the rapidly growing number of patients has brought a major public health challenge. This study aimed to assess whether there were differences in the severity and mortality risk factors for patients hospitalized for COVID-19 pneumonia between the early wave and the very late stage of the pandemic.

A retrospective cross-sectional study was carried out using data from 223 hospitalized patients diagnosed with COVID-19 pneumonia during the Omicron surge in Xi'an People's Hospital (Xi'an Fourth Hospital) from December 8, 2022, to January 31, 2023. Univariable and multivariable logistic regression analyses were used to identify potential risk factors associated with the severity and mortality of COVID-19 pneumonia during the first wave of the pandemic after the dynamic zero-COVID policy was retracted. Differences in the severity and mortality risk factors were assessed at different stages of the pandemic, mainly from demographic, clinical manifestation, laboratory tests and radiological findings of patients on admission.

The mean age of the 223 participants was 71.2 ± 17.4. Compared with the patients in the initial stage of the pandemic, the most common manifestation among patients in this study was cough (90.6%), rather than fever (79.4%). Different from the initial stage of the pandemic, older age, chest tightness, elevated neutrophil-to-lymphocyte ratio (NLR), decreased albumin (ALB) level and ground glass opacification (GGO) in radiological finding were identified as severity risk factors, instead of mortality risk factors for COVID-19 patients in the very late stage of the pandemic. Arterial partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) ≤300 mmHg, cardiovascular disease and laboratory findings including elevated levels of D-dimer, α-hydroxybutyrate dehydrogenase (α-HBDH), total bilirubin (TBIL), alanine aminotransferase (ALT), urea nitrogen (BUN), creatinine (CR), fasting blood glucose (FBG) and decreased platelet count (PLT) were still associated with mortality in the very late stage of the pandemic.

Monitoring continuously differences in the severity and mortality risk factors for COVID-19 patients between different stages of the pandemic could provide evidence for exploring uncharted territory in the coming post-pandemic era.

Using a large dataset, we evaluated prevalence and severity of alterations in liver enzymes in COVID-19 and association with patient-centred outcomes.

We included hospitalized patients with confirmed or suspected SARS-CoV-2 infection from the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) database. Key exposure was baseline liver enzymes (AST, ALT, bilirubin). Patients were assigned Liver Injury Classification score based on 3 components of enzymes at admission: Normal; Stage I) Liver injury: any component between 1-3x upper limit of normal (ULN); Stage II) Severe liver injury: any component ≥3x ULN. Outcomes were hospital mortality, utilization of selected resources, complications, and durations of hospital and ICU stay. Analyses used logistic regression with associations expressed as adjusted odds ratios (OR) with 95% confidence intervals (CI).

Of 17,531 included patients, 46.2% (8099) and 8.2% (1430) of patients had stage 1 and 2 liver injury respectively. Compared to normal, stages 1 and 2 were associated with higher odds of mortality (OR 1.53 [1.37-1.71]; OR 2.50 [2.10-2.96]), ICU admission (OR 1.63 [1.48-1.79]; OR 1.90 [1.62-2.23]), and invasive mechanical ventilation (OR 1.43 [1.27-1.70]; OR 1.95 (1.55-2.45). Stages 1 and 2 were also associated with higher odds of developing sepsis (OR 1.38 [1.27-1.50]; OR 1.46 [1.25-1.70]), acute kidney injury (OR 1.13 [1.00-1.27]; OR 1.59 [1.32-1.91]), and acute respiratory distress syndrome (OR 1.38 [1.22-1.55]; OR 1.80 [1.49-2.17]).

Liver enzyme abnormalities are common among COVID-19 patients and associated with worse outcomes.

Coronavirus disease 2019 (COVID-19) is an infectious disease spreading rapidly worldwide. As it quickly spreads and can cause severe disease, early detection and treatment may reduce mortality. Therefore, the study aims to construct a risk model and a nomogram for predicting the mortality of COVID-19.

The original data of this study were from the article "Neurologic Syndromes Predict Higher In-Hospital Mortality in COVID-19." The database contained 4,711 multiethnic patients. In this secondary analysis, a statistical difference test was conducted for clinical demographics, clinical characteristics, and laboratory indexes. The least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression analysis were applied to determine the independent predictors for the mortality of COVID-19. A nomogram was conducted and validated according to the independent predictors. The area under the curve (AUC), the calibration curve, and the decision curve analysis (DCA) were carried out to evaluate the nomogram.

The mortality of COVID-19 is 24.4%. LASSO and multivariate logistic regression analysis suggested that risk factors for age, PCT, glucose, D-dimer, CRP, troponin, BUN, LOS, MAP, AST, temperature, O2Sats, platelets, Asian, and stroke were independent predictors of CTO. Using these independent predictors, a nomogram was constructed with good discrimination (0.860 in the C index) and internal validation (0.8479 in the C index), respectively. The calibration curves and the DCA showed a high degree of reliability and precision for this clinical prediction model.

An early warning model based on accessible variates from routine clinical tests to predict the mortality of COVID-19 were conducted. This nomogram can be conveniently used to facilitate identifying patients who might develop severe disease at an early stage of COVID-19. Further studies are warranted to validate the prognostic ability of the nomogram.

Oxidative stress refers to the imbalance between oxidants and antioxidants in organisms and often induces hepatic inflammation. Supplementing exogenous superoxide dismutase is an effective way to alleviate oxidative stress; however, the effects and mechanisms by which superoxide dismutase alleviates hepatic inflammation remain unclear.

This study established a Kunming mouse model to verify and investigate the oxidative stress and hepatic inflammation-alleviating effects of the superoxide dismutase oral supplement that was prepared by our research group in a previous study.

The superoxide dismutase product significantly restored the body weight and liver alanine transaminase, aspartate aminotransferase, superoxide dismutase, catalase, glutathione, and glutathione peroxidase levels of oxidative stress induced mice. Moreover, exogenous superoxide dismutase significantly inhibited interleukin 1β and interleukin 6 mRNA expression in the livers of mice with hepatic inflammation. Transcriptomic analysis indicated that superoxide dismutase had a significant inhibitory effect on Endog expression, alleviating oxidative stress damage, and mediating liver cell apoptosis by regulating the expression of Rab5if, Hnrnpab, and Ifit1.

Our research verified the oxidative stress remediation effects of superoxide dismutase and its therapeutic role against hepatic inflammation. This study can lay a foundation for investigating the mechanism by which superoxide dismutase alleviates hepatic disease.

This study aimed to investigate the relationship between blood types and COVID-19 susceptibility and explore changes in blood variables, as well as their relationship with the occurrence of COVID-19. SARS-CoV-2 is a pandemic that has affected people's health and the global financial system. Since the initial confirmed case of COVID-19, people have been influenced worldwide with varying manifestations. Moreover, researchers have illustrated a link between ABO blood types and COVID-19 susceptibility and incidence. Research has also shown that ABO blood groups might play a role in estimating COVID-19 susceptibility and death. Our analysis revealed that blood type O might probably reduce vulnerability to the SARS-CoV-2 illness. On the contrary, people with blood type A are at a higher risk of SARS-CoV-2 infection. This study also evaluated liver biomarkers among COVID-19 patients, revealing significant abnormalities in the levels of alanine amino transferees, aspartate amino transferees, gamma-glutamyl transferees, and total bilirubin.

Convergence of the two pandemics: metabolic syndrome and COVID-19 over last two years has posed unprecedented challenges to individuals as well as healthcare systems. Epidemiological data suggest a close association between metabolic syndrome and COVID-19 while variety of possible pathogenic connections have been proposed while some have been proven. Despite the evidence of high risk for adverse COVID-19 outcomes in people with metabolic syndrome, little is known about the differences in efficacy and safety among people with metabolic syndrome and without. It is important to recognize that among people with metabolic syndrome This review summarizes the current knowledge and epidemiological evidence on the association between metabolic syndrome and adverse COVID-19 outcomes, pathogenic interrelationships, management considerations for acute COVID-19 and post-COVID sequalae and sustaining care of people living with metabolic syndrome with appraisal of evidence and gaps in knowledge.

Acute liver injury (ALI) in children, which commonly leads to acute liver failure (ALF) with the need for liver transplantation, is a devastating life-threatening condition. As the orchestrated regulation of immune hemostasis in the liver is essential for resolving excess inflammation and promoting liver repair in a timely manner, in this study we focused on the immune inflammation and regulation with the functional involvement of both innate and adaptive immune cells in acute liver injury progression. In the context of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic, it was also important to incorporate insights from the immunological perspective for the hepatic involvement with SARS-CoV-2 infection, as well as the acute severe hepatitis of unknown origin in children since it was first reported in March 2022. Furthermore, molecular crosstalk between immune cells concerning the roles of damage-associated molecular patterns (DAMPs) in triggering immune responses through different signaling pathways plays an essential role in the process of liver injury. In addition, we also focused on DAMPs such as high mobility group box 1 (HMGB1) and cold-inducible RNA-binding protein (CIRP), as well as on macrophage mitochondrial DNA-cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway in liver injury. Our review also highlighted novel therapeutic approaches targeting molecular and cellular crosstalk and cell-based therapy, providing a future outlook for the treatment of acute liver injury.

Coronavirus disease 2019 (COVID-19) typically presents with fever and respiratory symptoms in children. Most children develop an asymptomatic and mild illness, with a minority requiring specialist medical care. Gastrointestinal manifestations and liver injury can also occur in children following infection. The mechanisms of liver injury may include infection following direct viral hepatic tissue invasion, immune response, or medication effects. Affected children might develop mild liver dysfunction which has a benign course in most children with no pre-existing liver disease. However, the presence of non-alcoholic fatty liver disease or other pre-existing chronic liver disorders is associated with a higher risk of developing severe COVID-19 illness with poor outcomes. On the other hand, the presence of liver manifestations is associated with the severity of COVID-19 disease and is considered an independent prognostic factor. Respiratory, hemodynamic, and nutritional supportive therapies are the mainstay of management. Vaccination of children at increased risk of developing severe COVID-19 disease is indicated. This review describes the liver manifestations in children with COVID-19, detailing its epidemiology, basic mechanisms, clinical expression, management, and prognosis in those with and without pre-existing liver disease and also children who have had earlier liver transplantation.

COVID-19-infected individuals and those who recovered from the infection have been demonstrated to have elevated liver enzymes or abnormal liver biochemistries, particularly with preexisting liver diseases, liver metabolic disorders, viral hepatitis, and other hepatic comorbidities. However, possible crosstalk and intricate interplay between COVID-19 and liver disease severity are still elusive, and the available data are murky and confined. Similarly, the syndemic of other blood-borne infectious diseases, chemical-induced liver injuries, and chronic hepatic diseases continued to take lives while showing signs of worsening due to the COVID-19 crisis. Moreover, the pandemic is not over yet and is transitioning to becoming an epidemic in recent years; hence, monitoring liver function tests (LFTs) and assessing hepatic consequences of COVID-19 in patients with or without liver illnesses would be of paramount interest. This pragmatic review explores the correlations between COVID-19 and liver disease severity based on abnormal liver biochemistries and other possible mechanisms in individuals of all ages from the emergence of the COVID-19 pandemic to the post-pandemic period. The review also alludes to clinical perspectives of such interactions to curb overlapping hepatic diseases in people who recovered from the infection or living with long COVID-19.

Non-Coronavirus disease 2019 (COVID-19) pneumonia and COVID-19 have similar clinical features but last for different periods, and consequently, require different treatment protocols. Therefore, they must be differentially diagnosed. This study uses artificial intelligence (AI) to classify the two forms of pneumonia using mainly laboratory test data.

Various AI models are applied, including boosting models known for deftly solving classification problems. In addition, important features that affect the classification prediction performance are identified using the feature importance technique and SHapley Additive exPlanations method. Despite the data imbalance, the developed model exhibits robust performance.

eXtreme gradient boosting, category boosting, and light gradient boosted machine yield an area under the receiver operating characteristic of 0.99 or more, accuracy of 0.96-0.97, and F1-score of 0.96-0.97. In addition, D-dimer, eosinophil, glucose, aspartate aminotransferase, and basophil, which are rather nonspecific laboratory test results, are demonstrated to be important features in differentiating the two disease groups.

The boosting model, which excels in producing classification models using categorical data, excels in developing classification models using linear numerical data, such as laboratory tests. Finally, the proposed model can be applied in various fields to solve classification problems.