To compare the incidence and drivers of major adverse kidney events (MAKEs) between COVID-19 and non-COVID-19 acute respiratory distress syndrome (ARDS) patients, with a focus on long-term kidney outcomes.

Retrospective cohort study.

Single-centre intensive care unit in the Midlands, UK.

708 ARDS patients (458 COVID-19, 250 non-COVID-19).

The primary outcome was MAKE at 365 days (MAKE-365), defined as new renal replacement therapy (RRT), estimated glomerular filtration rate (eGFR) <75% of baseline or all-cause mortality. Secondary analyses examined non-mortality MAKE components.

The incidence of MAKE-365 was significantly higher in the non-COVID-19 group compared with the COVID-19 group (66% vs 39%, p<0.001), primarily driven by increased RRT initiation, followed by mortality and eGFR decline (p=0.055). Independent predictors of MAKE-365 included lower eGFR and elevated bilirubin in both groups. Age (p<0.001) and diabetes (p=0.041) were additional predictors in the COVID-19 cohort, while lower albumin (p=0.002) was significant in the non-COVID-19 group. Excluding mortality, RRT and eGFR decline remained significant drivers of MAKE outcomes in the non-COVID-19 cohort.

Non-COVID-19 ARDS patients face a greater risk of MAKE-365 and adverse kidney outcomes due to higher RRT requirements and mortality rates. These findings underscore the importance of tailored interventions and long-term nephrology follow-up, particularly for patients with reduced eGFR, elevated bilirubin and comorbidities like diabetes and hypoalbuminaemia.

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) binds to Angiotensin Converting Enzyme - 2 (ACE2) receptor targeting various organs including liver. Liver injury is a common feature of SARS-CoV-2 acute infection. A few studies have also described chronic hepatic alterations in patients with previous COVID-19. We hypothesize that steatosis seen in COVID-19 patients reflects their metabolic profile and is not caused by persistent inflammation sustained by SARS-CoV-2.

We conducted a prospective study to evaluate long-term changes in liver function and structure in patients hospitalized for COVID-19. Patients without a prior known hepatic disease with mild to moderate COVID-19 were enrolled during hospitalization and reevaluated during a follow-up visit at a medium 16 months. Complete blood panels with metabolic profile, BMI, alcohol consumption and physical activity were compared between baseline and follow-up. Specific ultrasound scans were obtained during hospital stay and at follow-up to quantify steatosis using Steatoscore2.0.

Among 55 eligible patients, 33 were included in the analysis and only 3 (9 %) had a new diagnosis of steatosis at follow-up. Steatoscore2.0 did not change significantly from baseline to follow-up (1.7 vs 1.73, p = 0.348), while changes occurred in body mass index and physical activity estimated by IPAQ questionnaire (26.3 vs 26.6 kg/m2, p = 0.005; 540 vs. 480, p = 0.015, respectively). There was a statistically significant increase in total cholesterol (144.5 vs 187.0 mg/dl, p = 0.003) and low-density lipoprotein-cholesterol (73.8 vs 113.9 mg/dl, p = 0.003). Inflammatory markers normalized at follow-up, including C-reactive protein (41.1 vs. 0.8 mg/L, p < 0.001), and ferritin (410.0 vs. 91.0 ng/dl, p < 0.001). Four patients had a 3-time rise in liver transaminase levels at baseline, and this was not confirmed at follow-up. Change in Steatoscore2.0 correlated significantly with Triglyceride-glucose index as a surrogate of insulin resistance.

In our study, long term functional and structural changes were not observed in patients with previous SARS-CoV-2 infection. There was a significant deterioration of metabolic profile post COVID-19.

The people living with HIV with abnormal immune responses have been identified as a population that is particularly susceptibility to contracting COVID-19. We explored the correlation between gene polymorphisms of IL-17A, IL-17F, and IL-6, and the susceptibility to COVID-19 in individuals with HIV infection.

In this cross-sectional study, 337 HIV-positive patients were included. Serological and molecular tests were done using ELISA and PCR-RFLP methods. Allelic frequency, haplotype analyses, linkage disequilibrium were calculated. A linear regression model was used to analyze the interleukin SNP genotypes in HIV patients with and without COVID-19.

A total of 337 PLWH were recruited for this study, with 170 having COVID-19 and 167 not having it. The mean age and laboratory indicators showed no significant differences between the two groups (P > 0.05). The allele frequency analysis found no significant difference in the IL-17A rs2275913 polymorphism between case and control groups. However, the IL-17F rs763780 and IL-6 rs1800795 had significantly greater frequencies of specific alleles in the case group compared to the control group. The A-A haplotype of IL-17 in SNPs-rs 2,275,913 and rs763780 rising the risk of COVID-19 infection in PLWH by up to 2.398 times compared with the other haplotypes, and the A-G and G-A haplotypes have a protective role against the incidence of COVID-19 infection.

This study is the first to show a significant correlation between the prevalence of COVID-19 and variety polymorphism at IL-17 and IL-6, which suggests that genetic changes in interleukin genes may relate to COVID-19 distribution.

Steatotic liver diseases (SLD) have become more prevalent over the last decade and are associated not only with cardiometabolic diseases but also with psychological symptoms (depression, fatigue). These symptoms are also common in post-COVID syndrome (PCS). Therefore, the aim of the study was to analyze the burden of SLD in PCS patients.

We systematically screened all PCS patients from our post-COVID outpatient clinic using transient elastography, structured questionnaires for neurocognitive evaluation and blood sample analysis. Controls without PCS and without known liver diseases were also recruited and assessed with the same approach.

560 PCS patients and 103 healthy controls were included. The overall prevalence of SLD was high in both cohorts (57 vs. 53%). PCS patients with SLD were more frequently male (41 vs. 24%), older (52 vs. 44 years) and had more cardiometabolic diseases (87.0 vs. 46.4%). Cognitive impairment was more related to SLD in PCS patients than in the no-SLD group (OR: 1.68, CI: 1.14-2.46, p = 0.008). The presence of SLD was related to severe COVID-19 with hospitalization (OR: 2.91, CI: 1.85-4.56, p < 0.001). Within 1 year of the follow-up, 152 of 289 patients described a resolution in PCS irrespective of the presence or absence of SLD (log-rank p = 0.96).

SLD is associated with severe COVID-19 and cognitive dysfunction in PCS. Longitudinal studies are needed to assess the role of hepatic steatosis, development of post-acute infection regulation (e.g., SARS-CoV-2) and to differentiate between SLD-associated symptoms and PCS.

COVID-19 encompasses a wide clinical spectrum, from mild influenza-like illness to severe pneumonia and systemic complications. There is emerging literature on hepatobiliary involvement in COVID-19, especially elevation in liver enzymes as surrogate markers of liver injury. Angiotensin-converting enzyme 2 receptors within the hepatobiliary system are a portal of entry for SARS-CoV-2, after which injury may be perpetuated through hypoxia and cytokine storms. This literature review covers studies published before 2024 from databases such as PubMed, Google Scholar, Springer, and BMC Library. The keywords used were "COVID-19", "liver", "SARS-CoV-2", "chronic liver disease", and other relevant terms to ensure a wide scope of investigation. The most common liver enzymes elevated among COVID-19 patients include aspartate transaminase, alanine transaminase, and alkaline phosphatase, all of which are associated with the severity of the disease. Chronic liver disease (CLD) and hepatocellular carcinoma (HCC) patients have worse outcomes with increased ICU admission rates and increased mortality. COVID-19 vaccination in CLD and liver transplant recipients is very often associated with suboptimal antibody responses, adding to the risks. SARS-CoV-2 causes liver involvement through direct viral cytopathic effects, immune-mediated injury, and systemic hypoxia. Individuals with CLD are particularly vulnerable to severe illness.

After secondary respiratory failure, liver failure is often reported in the literature on coronavirus disease 2019 infection. Angiotensin-converting enzyme 2 receptors in hepatocytes make the liver directly susceptible to the severe acute respiratory syndrome coronavirus 2 virus. An exacerbated immune response, drug-induced hepatotoxicity, and hypoxia secondary to respiratory failure are further possible causes of hepatocytolysis in coronavirus disease 2019 patients. Pre-existing infection with the hepatitis B virus can aggravate coronavirus disease 2019 or be aggravated/reactivated by it. This case report describes unusually severe liver damage in a coronavirus disease 2019 patient with well controlled hepatitis B, where the evidence points to coronavirus disease 2019-related factors as the main causes of hepatic cytolysis.

A 70 year-old patient of Romanian ethnicity with a 5-year history of chronic hepatitis B presented to the emergency department complaining of fever, chills, and marked physical asthenia with an onset of 2 weeks. Blood tests revealed an inflammatory syndrome and incipient liver cytolysis. Low-intensity opacities were visible on chest X-ray, and the severe acute respiratory syndrome coronavirus 2 polymerase chain reaction test was positive, so the patient was transferred to the infectious diseases hospital. His condition then aggravated atypically, with increasingly severe hepatic cytolysis that was not noted in other coronavirus disease 2019 patients with hepatitis B.

The patient's history of well-controlled hepatitis B suggests that, in this case, liver dysfunction was secondary to coronavirus disease 2019 manifestations such as the cytokine storm, respiratory failure, and drug-induced hepatotoxicity. The patient eventually recovered, and there was no demonstrable reactivation of hepatitis B after discharge. Coronavirus disease 2019 can thus affect liver function severely and primarily, yet without necessarily interacting with adequately managed hepatitis B.

There is conflicting evidence regarding the impact of chronic hepatitis B virus (HBV) on SARS-CoV-2 outcomes. Additionally, the impact of SARS-CoV-2 vaccination and variant periods on outcomes in HBV/SARS-CoV-2 coinfection remain unexplored.

We utilized the TriNetX database to compare adults with HBV/SARS-CoV-2 (vs SARS-CoV-2 alone) across 97 US healthcare systems from 2020 to 2023. We assessed the odds of all inpatient hospitalizations, intensive care unit admissions, mechanical ventilation, 30-day, 90-day, and overall mortality. In sensitivity analyses, we excluded HIV, hepatitis C virus, and transplant cases and stratified the HBV/SARS-CoV-2 cohort by cirrhosis status. We applied propensity score matching to address confounding and reported odds ratios (OR) with 95% confidence intervals (CI).

Of 4 206 774 individuals with SARS-CoV-2, about 0.2% (8293) were HBV/SARS-CoV-2. Individuals with HBV/SARS-CoV-2 (vs SARS-CoV-2 alone) had higher odds of intensive care unit admissions (OR, 1.18; 95% CI, 1.02-1.36), 90-day (OR, 1.22; 95% CI, 1.01-1.41) and overall mortality (OR, 1.18; 95% CI, 1.06-1.33). In sensitivity analyses, those with HBV/SARS-CoV-2 and cirrhosis had a 2.0- to 2.50-fold higher odds of adverse outcomes. Notably, even individuals with HBV/SARS-CoV-2 without cirrhosis had higher odds of mortality. Vaccinated (vs unvaccinated) individuals with HBV/SARS-CoV-2 had 57%, 54%, and 29% reduction in 30-day, 90-day, and overall mortality, respectively. The pre-Delta variant period was associated with higher odds of hospitalization compared to the Omicron but not the Delta period.

Chronic HBV was associated with worse SARS-CoV-2 outcomes, whereas SARS-CoV-2 vaccination reduced the likelihood of adverse outcomes.

The impact of coronavirus disease 2019 (COVID-19) on patients with acute-on-chronic liver failure (ACLF) remains unclear. To investigate the clinical characteristics of patients with ACLF complicated with COVID-19 in order to provide evidence for the precise treatment of this patient population.

A total of 34 ACLF patients with COVID-19 admitted to these three hospitals from December 2022 to August 2023 were included as the ACLF+COVID-19 group. Additionally, 34 age-, gender-, etiology-, and Model for End-Stage Liver Disease-Sodium (MELD-Na) score-matched ACLF patients were screened from 286 ACLF patients as the ACLF group. From 382 COVID-19 patients, 34 were selected as the COVID-19 group, matching the ACLF+COVID-19 group in age, gender, and illness severity. Clinical features of these three groups were compared, with the primary measure being the 28-day mortality rate in the ACLF patients and the secondary measures including clinical symptoms, laboratory tests, comorbidities, and complications in three groups.

Compared with the ACLF group, the ACLF+COVID-19 group had significantly higher incidence rates of fever, cough, sputum production, fatigue, and hypoxemia (all p<0.01). Patients in the ACLF+COVID-19 group were more likely to have hepatic encephalopathy (p=0.015), lower platelet count (p=0.016) and elevated IL-6 level (p=0.026), and higher MELD-Na score (p=0.041) one week after admission, but without a significant increase in 28-day mortality rate (p=0.16).

ACLF patients with COVID-19 have increased risk for thrombocytopenia, more obvious inflammatory response, and rapid disease progression 1 week after admission, but the 28-day mortality rate is similar to that of ACLF patients without COVID-19.

Liver involvement is a common complication of coronavirus disease 2019 (COVID-19), especially in hospitalized patients. However, the underlying mechanisms involved are not fully understood.

Immunohistochemistry (IHC) staining of SARS-CoV-2 spike (S) and nucleocapsid (N) proteins was conducted on liver tissues from six patients with COVID-19. The 10x Genomics Visium CytAssist Spatial Gene Assay was designed to analyze liver transcriptomics. TCR CDR3 sequences were analyzed in DNA from liver tissues. Liver function indicators were retrospectively studied in 650 hospitalized patients with COVID-19.

SARS-CoV-2 proteins were initially detected in the livers of naturally infected golden (Syrian) hamsters, prompting us to investigate the situation in clinical cases. Thus, we collected liver tissues from patients with abnormal liver biochemical values. Viral S and N proteins were detected in the livers of severe and deceased patients but not in those of moderate patients. We further demonstrated that hepatocytes and erythroid cells in hepatic sinusoids are major cells targeted by SARS-CoV-2. Immune cells, especially T cells, were enriched in surviving severe patients, characterized by enhanced CDR3α clonality and novel CDR3β recombination of the T-cell receptor. In contrast, hepatocyte apoptosis was triggered, and the transcription of albumin (ALB) was obviously impaired in the deceased patients. We then performed a retrospective study including patients with COVID-19. Serum aspartate aminotransferase (AST) and ALB levels at baseline significantly differed in the deceased cohort. However, AST regression did not decrease the risk of death. ALB recovery indicated clinical improvement, and declining or low serum ALB concentrations were associated with death.

This study provides clinical evidence for liver infection with SARS-CoV-2, insight into the impact of SARS-CoV-2 on the liver, and a potential way to evaluate the risk of death via assessing serum ALB concentration fluctuations in patients with COVID-19.

National Key R&D Program of China (2021YFC2300602), National Natural Science Foundation of China (92369110), National Natural Science Foundation of China (U23A20474), Shanghai Municipal Science and Technology Major Project (ZD2021CY001), Shanghai Jinshan District Medical and Health Technology Innovation Fund Project (2023-WS-31).

Objectives: This study aimed to assess the effectiveness of the COVID-19 vaccine on the outcomes of patients in three hospitals in Vietnam. Methods: An observational study involved 3102 confirmed COVID-19 patients from Vietnam. Participants were classified into unvaccinated, partially vaccinated (one dose) (PV), fully vaccinated (two doses) (FV), and boosted (three doses) groups. We used a regression model to assess the relationship between vaccine status and disease outcome, including mortality, persistent symptoms after treatment, and hospital duration. Results: The proportions of unvaccinated, PV, FV, and boosted groups were 43.39%, 4.63%, 43.93%, and 8.05%, respectively, and 48% of the participants had at least one comorbidity. The proportion of severe clinical disease was significantly higher in the unvaccinated compared with the vaccinated. Biomarkers of cellular injury and organ failure, e.g., aspartate aminotransferase (AST), ferritin, troponin T, proBNP, D-dimer, and urea plasma concentration were significantly higher in unvaccinated and PV patients compared with FV and boosted patients. Age was the most crucial predictor of critical illness, followed by vaccine status, hypertension, diabetes, heart disease, and chronic kidney disease. The unvaccinated group had the highest proportion of deaths (5.2% vs. 1.4% and 0.3% in FV and boosted groups, respectively). Conclusions: Vaccination reduced mortality and both hospitalization length and disease severity in COVID-19 survivors, especially the older and patients with chronic comorbidities.

Bacterial pneumonia is a prevalent respiratory disease and a primary cause of death among hospitalized patients. Ambroxol and loquat syrup are widely utilized pharmaceuticals for managing respiratory infections in China. This study investigates the potential application and efficacy of combining ambroxol with loquat syrup for treating bacterial pneumonia.

In this study, mice with P. aeruginosa-induced bacterial pneumonia were used to evaluate the therapeutic effects of ambroxol, loquat syrup, and their combination. A bacterial plate coating assay was performed to measure the P. aeruginosa content in saliva, lung tissue, and bronchoalveolar lavage fluid (BALF). A plate colony counting assay was conducted to assess the antibacterial activity of ambroxol and loquat syrup. Serum, BALF, and lung tissues were analyzed using qPCR, ELISA, immunohistochemistry, and hematoxylin-eosin staining to evaluate disease severity.

In this study, the experimental results demonstrate that, compared to treatment with ambroxol and/or loquat syrup alone, the combined administration of ambroxol and loquat syrup significantly increases the volume of saliva expectorated by mice infected with bacteria, concurrently augmenting bacterial presence in saliva while diminishing bacterial burden in the lungs, with significant differences observed (p<0.05). Furthermore, the combined therapy of ambroxol and loquat syrup achieved better therapeutic effects on P. aeruginosa pneumonia compared to ambroxol and/or loquat syrup alone (p<0.05), as evidenced by significantly reduced P. aeruginosa-induced lung injury, improved lung permeability, decreased inflammatory cell infiltration, and lower expression of inflammatory cytokines.

These findings suggest that the combination therapy of ambroxol and loquat syrup presents a safe and feasible new treatment strategy for bacterial pneumonia, offering promising benefits for ameliorating lung tissue damage and inflammation.

Continuous renal replacement therapies (CRRTs) and sequential extracorporeal blood purification (EBP) therapies can be used in patients with severe COVID-19 disease to support kidney failure and restore immune homeostasis. EBP prescription should be based on the patient's clinical needs and frequently re-evaluated during the intensive care unit (ICU) stay. Personalization of treatment at the bedside plays a fundamental role for patient recovery. This aim can be simplified by using both clinical and molecular data collected from a patient-individualized web registry. In this case report, we describe how we apply a sequential approach to EBP therapies following the rapid evolution of a critically ill COVID-19 patient with acute kidney injury. We show patient strategies and outcomes using bedside data from a registry-based method for the routine use of EBP. We explain the choice of specific hemofilter prescription, also focusing on dose and anticoagulation strategies. We describe the difficulties, uncertainties, and mistakes made during EBP prescription. Furthermore, we discuss the causes and workable solutions that can be adopted by the ICU physician for a better EBP prescription, considering the current lack of well-recognized indications. Trial Registration: ClinicalTrials.gov identifier: NCT03807414.

Coxsackievirus (CV) A6 has emerged as an important causative agent in global outbreaks of hand, foot, and mouth disease (HFMD), which typically presents as a mild illness with a large generalized rash, herpes. However, some patients can develop encephalitis, pneumonia, myocarditis and liver injury. Our previous study took the view that CVA6 could replicate in mouse liver, leading to acute liver injury; however, the precise underlying mechanism remains elusive.

10-day-old wild-type (WT, C57BL/6J) and NLRP3 knock-out (KO) mice were intraperitoneal (i.p.) inoculated with a lethal dose of the CVA6 strain. The muscle homogenate supernatant from normal mice was used to inoculate mock-infected mice. At 5 days post infection (dpi), the mouse liver was taken out for histopathological analyses and molecular biology experiments.

Our in vivo experiments demonstrated that CVA6 caused severe liver injury in mice, as evidenced by pathological changes in liver slices, elevated liver injury markers (e.g., AST, ALT, LDH) and pro-inflammatory cytokines (e.g., IL-6, MCP-1, TNF-α, IL-1β). Further results revealed the activation of NLRP3 inflammasome characterized by the increase in the expression of NLRP3, Cleaved-Casp-1 (p20), mature IL-1β and IL-18. Importantly, upon CVA6 infection, NLRP3 KO mice exhibited attenuated pathological damage and reduced levels of pro-inflammatory cytokines production (e.g., TNF-α and IL-1β) compared with WT mice. Finally, increased levels of blood ALT, AST, LDH were strongly correlated with the severity of CVA6 patients.

Collectively, our findings suggest that the activation of NLRP3 inflammasome is involved in CVA6 infection-induced acute liver injury, providing novel insights into CVA6 infection associated adverse clinical outcomes.

This review explores the mechanisms, diagnostic approaches, and management strategies for COVID-19-induced liver injury, with a focus on its impact on patients with pre-existing liver conditions, liver cancer, and those undergoing liver transplantation.

A comprehensive literature review included studies on clinical manifestations of liver injury due to COVID-19. Key areas examined were direct viral effects, drug-induced liver injury, cytokine storms, and impacts on individuals with chronic liver diseases, liver transplants, and the role of vaccination. Data were collected from clinical trials, observational studies, case reports, and review literature.

COVID-19 can cause a spectrum of liver injuries, from mild enzyme elevations to severe hepatic dysfunction. Injury mechanisms include direct viral invasion, immune response alterations, drug toxicity, and hypoxia-reperfusion injury. Patients with chronic liver conditions (such as alcohol-related liver disease, nonalcoholic fatty liver disease, cirrhosis, and hepatocellular carcinoma) face increased risks of severe outcomes. The pandemic has worsened pre-existing liver conditions, disrupted cancer treatments, and complicated liver transplantation. Vaccination remains crucial for reducing severe disease, particularly in chronic liver patients and transplant recipients. Telemedicine has been beneficial in managing patients and reducing cross-infection risks.

This review discusses the importance of improved diagnostic methods and management strategies for liver injury caused by COVID-19. It emphasizes the need for close monitoring and customized treatment for high-risk groups, advocating for future research to explore long-term effects, novel therapies, and evidence-based approaches to improve liver health during and after the pandemic.

Hepatocellular carcinoma (HCC) is a highly heterogeneous malignancy with poor prognosis and a common cause of cancer-related death worldwide, and despite ongoing therapeutic breakthroughs, patient survival benefits are limited. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19) and poses a major threat to humanity worldwide. As the epidemic continues to develop, more and more people are infected with SARS-CoV-2, including patients with HCC. However, the relationship between COVID-19 and HCC has not yet been fully elucidated. Our study aimed to identify the shared genetic characteristics and molecular mechanisms between COVID-19 and HCC. The data involved in this study come from Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression(GTEx), and Cancer Cell Line Encyclopedia(CCLE) databases. We used differentially expressed genes to perform enrichment analysis to reveal the biological landscape of COVID-19 combined with HCC. In addition, weighted gene co-expression network analysis (WGCNA) was used to study the co-expression network related to COVID-19 and HCC. We then combined the validation datasets to screen out immunoglobulin superfamily member 1 (IGSF1) as the most important core gene. Finally, we extensively studied the functional expression of IGSF1 in tumor samples, normal tissues, and cancer cell lines. The molecular mechanisms related to COVID-19 and HCC are rarely studied. Our study identifies IGSF1 as a potential therapeutic target and immune-related biomarker for patients with COVID-19 and HCC.

Although the pediatric population has largely remained free of severe COVID-19 symptoms, in some cases, SARS-CoV-2 infection has been associated with complications such as multiple inflammatory syndrome in children (MIS-C). We identified another a unique form of hepatitis occurring subsequent to asymptomatic SARS-CoV-2 infection, designated by us as COVID-19-associated hepatitis in children (CAH-C), in a subset of children who presented with hepatitis.

Our study describes the clinical presentations, temporal association, and viral parameters of the CAH-C cases and compares them to those of MIS-C cases or other known forms of hepatitis in children.

In an ambispective (retrospective and follow-up) observational study, records from April to July 2021 were reviewed for all children aged ≤14 years who were previously healthy and presented with a sudden onset of hepatitis, elevated transaminases, and nonobstructive jaundice. After performing all routine tests, those lacking marked inflammatory responses and without evidence of (1) other known causes of acute hepatitis or previous underlying liver disease and (2) multisystem involvement were classified as having CAH-C. Their characteristics were compared to those of children with MIS-C or other known forms of hepatitis.

Among the 5539 children tested for SARS-CoV-2, a total of 475 (8.6%) tested positive and 47 (0.8%) presented with hepatitis. Among the 47 children with hepatitis, 37 (79%) had features of CAH-C: having symptoms of hepatitis only, without protracted illness (mean length of stay 5 d), and an uneventful recovery following supportive treatment. In contrast, the remaining 10 (21%) had features of MIS-C-associated hepatitis: multiple system involvement; protracted illness (mean length of stay 8 d); and requiring admission to critical care, with a mortality rate of 30% (3/10).

Our data suggest that CAH-C might be one of the new clinical complications associated with the emergence of newer variants of concern of SARS-CoV-2, which often result in changing presentations. Our findings should facilitate its early identification and thorough workup and aid its differentiation from other emerging syndromes in children, which would help initiate appropriate measures, enable better resource prioritization, and thus limit adversities.

Data on cholestasis and biliary injury in patients with COVID-19 are scarce. The primary aim of this study was to evaluate the prevalence of cholestasis and factors associated with its development and outcome in critically ill patients with COVID-19 associated acute respiratory distress syndrome (ARDS). In this retrospective exploratory study, COVID-19 patients with ARDS admitted to an intensive care unit (ICU) at the Medical University of Vienna were evaluated for the development of cholestasis defined as an alkaline phosphatase level of 1.67x upper limit of normal for at least three consecutive days. Simple and multiple logistic regression analysis was used to evaluate parameters associated with development of cholestasis and survival. Of 225 included patients 119 (53%) developed cholestasis during ICU stay. Patients with cholestasis had higher peak levels of alkaline phosphatase, gamma-glutamyl transferase, bilirubin and inflammation parameters. Factors independently associated with cholestasis were extracorporeal membrane oxygenation support, ketamine use, high levels of inflammation parameters and disease severity. Presence of cholestasis and peak ALP levels were independently associated with worse ICU and 6-month survival. Development of cholestasis is a common complication in critically ill COVID-19 patients and represents a negative prognostic marker for survival. It is associated with disease severity and specific treatment modalities of intensive care.

(1) Background: Liver damage is an important component of acute COVID-19, and the advancement of preexisting liver disease is associated with a worse prognosis; (2) Methods: A nationwide retrospective study including 7444 patients aimed to evaluate levels of selected markers of liver damage and disease advancement and their association with mortality and mechanical ventilation (MV); (3) Results: Elevation of the following markers in multivariate models were associated with increased odds of mortality: Alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyltransferase (GGT), lactate dehydrogenase (LDH), fibrosis-4 score (FIB-4), AST-to-platelet ratio index (APRI), and decreased levels of platelet count (PLT). Elevated levels of AST, LDH, APRI, FIB-4, and the AST/ALT ratio and decreased levels of PLT were associated with increased odds of MV in multivariate models. The best predictive accuracy against mortality was achieved with FIB-4 with AUC = 0.733 (95% CI, 0.718-0.749) at the optimal cut-off point of 2.764, while against MV was achieved with LDH with AUC = 0.753 (95% CI, 0.727-0.778) at the optimal cut-off point of 449.5 IU/L. (4) Conclusions: Our study confirms that the advancement of liver damage contributes to a worse prognosis in COVID-19 patients. Markers for liver damage and the advancement of liver disease can provide predictive value in clinical practice among COVID-19 patients.

The SARS-CoV-2 virus caused a pandemic in the 2020s, which affected almost every aspect of life. As the world is recovering from the effect of the coronavirus, the concept of post-COVID-19 syndrome has emerged. Multiple organ systems have been implicated, including the liver. We aim to identify and analyze the reported cases of severe and long-term parenchymal liver injury post-COVID-19 infection. Several databases were used to conduct a comprehensive literature search to target studies reporting cases of severe and long-term parenchymal liver injury post-COVID-19 infection. Screening, data extraction, and cross checking were performed by two independent reviewers. Only 22 studies met our inclusion criteria. Our results revealed that liver steatosis, non-alcoholic fatty liver disease (NAFLD), and cirrhosis were the most reported liver associated complications post-COVID-19 infection. Moreover, complications like acute liver failure, hepatitis, and liver hemorrhage were also reported. The mechanism of liver injury post-COVID-19 infection is not fully understood. The leading proposed mechanisms include the involvement of the angiotensin-converting enzyme-2 (ACE-2) receptor expressed in the liver and the overall inflammatory state caused by COVID-19 infection. Future studies should incorporate longer follow-up periods, spanning several years, for better insight into the progression and management of such diseases.

Many studies have revealed a link between non-alcoholic fatty liver disease (NAFLD) and coronavirus disease 2019 (COVID-19), making understanding the relationship between these two conditions an absolute requirement.

To provide a qualitative synthesis on the currently present data evaluating COVID-19 and NAFLD.

This systematic review was conducted in accordance with the guidelines provided by preferred reporting items for systematic reviews and meta-analyses and the questionnaire utilized the population, intervention, comparison, and outcome framework. The search strategy was run on three separate databases, PubMed/MEDLINE, Scopus, and Cochrane Central, which were systematically searched from inception until March 2024 to select all relevant studies. In addition, ClinicalTrials.gov, Medrxiv.org, and Google Scholar were searched to identify grey literature.

After retrieval of 11 studies, a total of 39282 patients data were pooled. Mortality was found in 11.5% and 9.4% of people in NAFLD and non-NAFLD groups. In all, 23.2% of NAFLD patients and 22% of non-NAFLD admissions diagnosed with COVID-19 were admitted to the intensive care unit, with days of stay varying. Ventilatory support ranged from 5% to 40.5% in the NAFLD cohort and from 3.1% to 20% in the non-NAFLD cohort. The incidence of acute liver injury showed significance. Clinical improvement on days 7 and 14 between the two classifications was significant. Hospitalization stay ranged from 9.6 days to 18.8 days and 7.3 days to 16.4 days in the aforementioned cohorts respectively, with 73.3% and 76.3% of patients being discharged. Readmission rates varied.

Clinical outcomes except mortality consistently showed a worsening trend in patients with NAFLD and concomitant COVID-19. Further research in conducting prospective longitudinal studies is essential for a more powerful conclusion.

The limited literature on the clinical course of COVID-19 among patients with underlying liver disease (LD) is available from India. The present study aimed to evaluate the clinical and mutational profile of SARS-CoV-2 among LD cases. This was a retrospective study including admitted LD cases in whom SARS-CoV-2 RT-PCR testing was performed. Complete demographic and clinical details were retrieved from Hospital Information System. Detailed mutational analysis was performed by comparing LD COVID-19 positive study group, i.e. LD-CoV(+) with COVID-19 positive outpatients without any underlying LD as control, i.e. NLD-CoV(+). Out of 232 enrolled LD cases, 137 (59.1%) were LD-CoV(+). LD cases with existing co-morbidities were affected more (P = 0.002) and had 2.29 times (OR 2.29, CI 95%, 1.25-4.29) higher odds of succumbing to COVID-19 (P = 0.006). On multivariate regression analysis, ascites (P = 0.05), severe COVID-19 pneumonia (P = 0.046), and an increased levels of bilirubin (P = 0.005) and alkaline phosphatase (P = 0.003) were found to be associated with adverse outcome in LD-CoV(+).On mutational analysis, we found certain differences between LD- and NLD-CoV(+) infected with Delta [LD- and NLD-CoV (+ /D)] and Omicron [LD- and NLD-CoV(+/O)]. More mutations were shared between LD- and NLD-CoV(+/O) compared to LD- and NLD-CoV(+/D). There were differences in prevalence of indel mutations specific to LD-CoV ( +) for both Delta and Omicron. Moreover, we also reported an interesting genic bias between LD- and NLD-CoV( +) in harbouring deleterious/tolerated mutations. To conclude, LD cases with comorbidities were affected more and had higher odds of mortality due to COVID-19. The definite difference between LD- and NLD-CoV(+) groups with respect to frequency of harboured mutations and an inherent genic bias between them is of noteworthy importance.

Multiple modifications of metabolic syndrome diagnostic criteria have been made-NCEP: ATP III (from 2001, modified in 2004), IDF (2005), IDF Consortium (2009), or Polish Scientific Society Consortium standards (2022) are now frequently in use. Hepatosteatosis and hepatofibrosis are commonly mentioned aspects of metabolic syndrome that greatly increase the likelihood of developing complications. The objective of the study was to assess different diagnostic criteria for metabolic syndrome based on the prevalence of liver steatosis and fibrosis. A retrospective analysis was conducted on the medical data of 2102 patients. Out of all the single criteria, meeting the obesity criterion based on waist circumference showed the highest increase in the risk of hepatosteatosis (by 64-69%, depending on the definition used)-hypertriglyceridemia increased the risk of hepatofibrosis by 71%. Regardless of the specific criteria used, patients with metabolic syndrome had a 34-36% increased likelihood of developing hepatosteatosis-the probability of hepatofibrosis varied between 42% and 47% for the criteria established in 2004, 2005, and 2009, while the Polish 2022 criteria were not statistically significant (p = 0.818). It seems appropriate to establish consistent metabolic syndrome diagnostic criteria-the 2009 IDF guidelines are the most effective in assessing hepatosteatosis and fibrosis risk.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), presents diverse clinical manifestations and multi-organ involvement. This study aimed to evaluate the extra-pulmonary histopathological patterns underpinning COVID-19-induced lesions in cardiac, hepatic, renal, brainstem, and splenic tissues.

The research involved conventional forensic autopsies conducted between April 2020 and April 2021 on individuals with confirmed SARS-CoV-2 infection in Cluj-Napoca, Romania. Tissues were processed and stained for histological examination. Differences in patients with and without diffuse alveolar damage (DAD) were evaluated.

In our study of 79 COVID-19 autopsies conducted on unvaccinated patients besides lung involvement, the patients had histological changes in at least two out of five (brain, heart, liver, kidney, and spleen) organs. Notable findings include hepatitis observed in 46.8 % of cases, 21.5 % with lobular hepatitis, and 41.8 % with liver steatosis. Additionally, 69.6 % exhibited acute tubular necrosis, and 55.7 % had varying degrees of splenic lymphocyte depletion. Almost 41 % of cases had pericardial effusion, 36.7 % myocarditis, 24.1 % myocardial infarction, and 12.7 % of cases had encephalitis. Acute tubular necrosis (78.6 %) was the most frequent histopathological finding observed in patients with DAD. Myocarditis was described in 45.9 % of the patients without DAD.

The autopsy findings in our cohort of COVID-19 victims align with international scientific literature. Distinguishing viral-induced myocarditis, encephalitis, hepatitis, or systemic inflammatory syndrome remains challenging.

Post-mortem analysis identified lesions associated with SARS-CoV-2 in multiple organs, highlighting the systemic nature of the virus and emphasizing the need for continued research into organ-specific damage and long-term sequelae of COVID-19.

Coronavirus disease 2019 (COVID-19) is characterized by an acute respiratory infection with multisystem involvement and the association of its severity to liver function abnormalities is not well characterized. The aim of this study was to assess the association between the severity of COVID-19 patients and liver function abnormalities. This retrospective study included adult patients with confirmed COVID-19, which were classified as non-severe or severe according to World Health Organization guidelines. Liver function test results were compared between the severity groups. A total of 339 patients were included of which 150 (44.25%) were severe cases. The male-to-female ratio was 0.9:1 and 3:2 in the non-severe and severe groups, respectively (p=0.031). Aspartate aminotransferase (AST), alanine transaminase (ALT), and total bilirubin levels and acute liver injury (ALI) incidence were significantly higher in the severe group compared to non-severe group (p<0.001, p<0.001, p=0.025, p=0.014, respectively). In contrast, albumin levels were significantly lower (p=0.001). Multivariate analysis showed that ALI was significantly associated with human immunodeficiency virus (HIV) infection (odds ratio (OR): 5.275; 95% confidence interval (CI): 1.165-23.890, p=0.031), hemoglobin level (OR: 1.214; 95%CI: 1.083-1.361, p=0.001), and hypoalbuminemia (OR: 2.627; 95%CI: 1.283-5.379, p=0.008). Pre-existing liver diseases were present in 6.5% of patients. No significant differences were observed between the groups based on COVID-19 severity and ALI presence. Liver function test abnormalities, including ALI, are more prevalent in patients with severe COVID-19 infection. HIV infection, high hemoglobin levels, and hypoalbuminemia may be potential risk factors for ALI.

The coronavirus disease (COVID-19) is a widely spread viral infectious disease, which can impact multiple organs, including the liver. Elevated liver enzymes have been reported in COVID-19 patients; however, potential changes in liver stiffness following the viral infection remain uncertain. The main aim of this pilot study was to determine if there is a significant difference in liver stiffness between individuals who have never been infected with COVID-19 and those who had been infected with COVID-19 <6 months, experiencing only mild symptoms. The secondary aim was to compare the liver stiffness between participants infected with COVID-19 depending on the elapsed time since infection.

Two-dimensional shear wave elastography (2D-SWE) was performed prospectively on 68 participants. Thirty-four participants had been infected with COVID-19 (all for <6 months) (COVID-19 group), and another 34 had never been infected with COVID-19 (control group). The mean 2D-SWE measurements of both the COVID-19 group and the control group were compared using an independent t-test. The mean 2D-SWE measurements of the COVID-19 subgroups A (<2 months), B (2 to <4 months) and C (4 to <6 months) were compared using a one-way ANOVA test (P < 0.05).

The (mean ± standard deviation) liver stiffness (kPa) of the COVID-19 group (5.26 ± 1.63 kPa) was significantly higher than the control group (4.30 ± 0.96 kPa) (P = 0.005). There was no significant difference in liver stiffness among subgroups A (5.20 ± 1.79 kPa), B (4.70 ± 1.53 kPa) and C (5.96 ± 1.48 kPa) (P = 0.143) respectively.

The mean liver stiffness of 4.30  ±  0.96k Pa in the control group showed a high probability of being normal as per guidelines. Conversely, the mean liver stiffness of 5.26  ±  1.63 kPa in the COVID-19 group exhibited a statistically significant increase compared to the control group. However, compensated advanced chronic liver disease was ruled out without other known clinical signs, as per guidelines.

A statistically significant increase in liver stiffness value was observed in the post-COVID-19 infection group compared to the group who had never been infected. This highlights the potential for short-term impact on liver stiffness associated with COVID-19 infection. However, it is unclear if these changes in liver stiffness are associated with liver injury. Further study is warranted to investigate the effects of COVID-19 infection and its long-term impact on the liver.

Total plasma protein N-glycosylation (TPNG) changes are a hallmark of many diseases. Here, we analyzed the TPNG of 169 COVID-19 patients and 12 healthy controls, using mass spectrometry, resulting in the relative quantification of 85 N-glycans. We found a COVID-19 N-glycomic signature, with 59 glycans differing between patients and controls, many of them additionally differentiating between severe and mild COVID-19. Tri- and tetra-antennary N-glycans were increased in patients, showing additionally elevated levels of antennary α2,6-sialylation. Conversely, bisection of di-antennary, core-fucosylated, nonsialylated glycans was low in COVID-19, particularly in severe cases, potentially driven by the previously observed low levels of bisection on antibodies of severely diseased COVID-19 patients. These glycomic changes point toward systemic changes in the blood glycoproteome, particularly involvement of acute-phase proteins, immunoglobulins and the complement cascade. Further research is needed to dissect glycosylation changes in a protein- and site-specific way to obtain specific functional leads.

COVID-19 is a multisystem disease with many clinical manifestations, including liver damage and inflammation. The objective of this study is to analyze inflammation biomarkers in relation to the clinical outcome and respiratory symptoms of COVID-19. This is a retrospective cohort of patients with COVID-19 admitted to the Hospital Regional do Baixo Amazonas from 2020 to 2022. Data were collected from electronic medical records from admission to the 30th day of hospitalization and soon after hospital discharge. A total of 397 patients were included in the study. In the longitudinal follow-up of liver markers, a significant difference was found for AST on day 14, with a higher median in the death group. Among the hematological markers, lymphopenia was observed throughout the follow-up, with the death group having the most altered values. When comparing the evolution of biomarkers in the Non-Invasive Ventilation (NIV) and Invasive Mechanical Ventilation (IMV) groups, AST showed a significant difference only on day 14 and GGT on day 1, being greater in the IMV group, and indirect bilirubin on day 7 being more altered in the NIV group. In conclusion, death during hospitalization or a more severe form of COVID-19 was related to significant changes in liver and inflammatory biomarkers.

COVID-19 has affected millions worldwide, causing significant morbidity and mortality. While predominantly involving the respiratory tract, SARS-CoV-2 has also caused systemic illnesses involving other sites. Liver injury due to COVID-19 has been variably reported in observational studies. It has been postulated that liver damage may be due to direct damage by the SARS-CoV-2 virus or multifactorial secondary to hepatotoxic therapeutic options, as well as cytokine release syndrome and sepsis-induced multiorgan dysfunction. The approach to a COVID-19 patient with liver injury requires a thorough evaluation of the pattern of hepatocellular injury, along with the presence of underlying chronic liver disease and concurrent medications which may cause drug-induced liver injury. While studies have shown uneventful recovery in the majority of mildly affected patients, severe COVID-19 associated liver injury has been associated with higher mortality, prolonged hospitalization, and greater morbidity in survivors. Furthermore, its impact on long-term outcomes remains to be ascertained as recent studies report an association with metabolic-fatty liver disease. This present review provides insight into the subject by describing the postulated mechanism of liver injury, its impact in the presence of pre-existing liver disease, and its short- and long-term clinical implications.

Coronavirus disease 2019 (COVID-19), caused by the highly pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily impacts the respiratory tract and can lead to severe outcomes such as acute respiratory distress syndrome, multiple organ failure, and death. Despite extensive studies on the pathogenicity of SARS-CoV-2, its impact on the hepatobiliary system remains unclear. While liver injury is commonly indicated by reduced albumin and elevated bilirubin and transaminase levels, the exact source of this damage is not fully understood. Proposed mechanisms for injury include direct cytotoxicity, collateral damage from inflammation, drug-induced liver injury, and ischemia/hypoxia. However, evidence often relies on blood tests with liver enzyme abnormalities. In this comprehensive review, we focused solely on the different histopathological manifestations of liver injury in COVID-19 patients, drawing from liver biopsies, complete autopsies, and in vitro liver analyses. We present evidence of the direct impact of SARS-CoV-2 on the liver, substantiated by in vitro observations of viral entry mechanisms and the actual presence of viral particles in liver samples resulting in a variety of cellular changes, including mitochondrial swelling, endoplasmic reticulum dilatation, and hepatocyte apoptosis. Additionally, we describe the diverse liver pathology observed during COVID-19 infection, encompassing necrosis, steatosis, cholestasis, and lobular inflammation. We also discuss the emergence of long-term complications, notably COVID-19-related secondary sclerosing cholangitis. Recognizing the histopathological liver changes occurring during COVID-19 infection is pivotal for improving patient recovery and guiding decision-making.

To determine the incidence of newly diagnosed liver disorders (LD) up to 3.5-year post-acute COVID-19, and risk factors associated with new LD.

We analyzed 54,699 COVID-19 patients and 1,409,547 non-COVID-19 controls from March-11-2020 to Jan-03-2023. New liver disorders included abnormal liver function tests, advanced liver failure, alcohol and non-alcohol related liver disorders, and cirrhosis. Comparisons were made with ambulatory non-COVID-19 patients and patients hospitalized for other lower respiratory tract infections (LRTI). Demographics, comorbidities, laboratory data, incomes, insurance status, and unmet social needs were tabulated. The primary outcome was new LD at least two weeks following COVID-19 positive test.

Incidence of new LD was not significantly different between COVID-19 and non-COVID-19 cohorts (incidence:1.99% vs 1.90% p>0.05, OR = 1.04[95%CI: 0.92,1.17], p = 0.53). COVID-19 patients with new LD were older, more likely to be Hispanic and had higher prevalence of diabetes, hypertension, chronic kidney disease, and obesity compared to patients without new LD. Hospitalized COVID-19 patients had no elevated risk of LD compared to hospitalized LRTI patients (2.90% vs 2.07%, p>0.05, OR = 1.29[0.98,1.69], p = 0.06). Among COVID-19 patients, those who developed LD had fewer patients with higher incomes (14.18% vs 18.35%, p<0.05) and more with lower incomes (21.72% vs 17.23%, p<0.01), more Medicare and less Medicaid insurance, and more patients with >3 unmet social needs (6.49% vs 2.98%, p<0.001) and fewer with no unmet social needs (76.19% vs 80.42%, p<0.001).

Older age, Hispanic ethnicity, and obesity, but not COVID-19 status, posed increased risk for developing new LD. Lower socioeconomic status was associated with higher incidence of new LD.

The objective of this research was to create a machine learning predictive model that could be easily interpreted in order to precisely determine the risk of premature death in patients receiving intensive care after pulmonary inflammation.

In this study, information from the China intensive care units (ICU) Open Source database was used to examine data from 2790 patients who had infections between January 2019 and December 2020. A 7:3 ratio was used to randomly assign the whole patient population to training and validation groups. This study used six machine learning techniques: logistic regression, random forest, gradient boosting tree, extreme gradient boosting tree (XGBoost), multilayer perceptron, and K-nearest neighbor. A cross-validation grid search method was used to search the parameters in each model. Eight metrics were used to assess the models' performance: accuracy, precision, recall, F1 score, area under the curve (AUC) value, Brier score, Jordon's index, and calibration slope. The machine methods were ranked based on how well they performed in each of these metrics. The best-performing models were selected for interpretation using both the Shapley Additive exPlanations (SHAP) and Local interpretable model-agnostic explanations (LIME) interpretable techniques.

A subset of the study cohort's patients (120/1668, or 7.19%) died in the hospital following screening for inclusion and exclusion criteria. Using a cross-validated grid search to evaluate the six machine learning techniques, XGBoost showed good discriminative ability, achieving an accuracy score of 0.889 (0.874-0.904), precision score of 0.871 (0.849-0.893), recall score of 0.913 (0.890-0.936), F1 score of 0.891 (0.876-0.906), and AUC of 0.956 (0.939-0.973). Additionally, XGBoost exhibited excellent performance with a Brier score of 0.050, Jordon index of 0.947, and calibration slope of 1.074. It was also possible to create an interactive internet page using the XGBoost model.

By identifying patients at higher risk of early mortality, machine learning-based mortality risk prediction models have the potential to significantly improve patient care by directing clinical decision making and enabling early detection of survival and mortality issues in patients with pulmonary inflammation disease.

SARS-CoV-2 is the causative virus of the devastating COVID-19 pandemic that results in an unparalleled global health and economic crisis. Despite unprecedented scientific efforts and therapeutic interventions, the fight against COVID-19 continues as the rapid emergence of different SARS-CoV-2 variants of concern and the increasing challenge of long COVID-19, raising a vast demand to understand the pathomechanisms of COVID-19 and its long-term sequelae and develop therapeutic strategies beyond the virus per se. Notably, in addition to the virus itself, the replication cycle of SARS-CoV-2 and clinical severity of COVID-19 is also governed by host factors. In this review, we therefore comprehensively overview the replication cycle and pathogenesis of SARS-CoV-2 from the perspective of host factors and host-virus interactions. We sequentially outline the pathological implications of molecular interactions between host factors and SARS-CoV-2 in multi-organ and multi-system long COVID-19, and summarize current therapeutic strategies and agents targeting host factors for treating these diseases. This knowledge would be key for the identification of new pathophysiological aspects and mechanisms, and the development of actionable therapeutic targets and strategies for tackling COVID-19 and its sequelae.

With the rapid global spread of COVID-19, it has become evident that the virus can lead to multisystem complications, leading to a significant increase in related publications. Bibliometrics serves as a valuable tool for identifying highly cited literature and research hotspots within specific areas.

The aim of this study is to identify current research hotspots and future trends in COVID-19 complications.

The dataset was obtained from the Web of Science Core Collection, covering COVID-19 complications from December 8, 2019, to October 31, 2022. Various aspects, including publication general information, authors, journals, co-cited authors, co-cited references, research hotspots, and future trends, were subjected to analysis. Visual analysis was conducted using VOSviewer, The Online Analysis Platform of Literature Metrology, and Charticulator.

There were 4597 articles in the study. The top three countries with the most published articles are the USA (n = 1350, 29.4 %), China (n = 765, 16.6 %), and Italy (n = 623, 13.6 %). USA and China have the closest collaborative relationship. The institute with the largest number of publications is Huazhong University of Science and Technology, followed by Harvard Medical School. Nevertheless, half of the top 10 institutes belong to the USA. "Rezaei, Nima" published 13 articles and ranked first, followed by "Yaghi, Shadi" with 12 articles and "Frontera, Jennifer" with 12 articles. The journal with the largest number of publications is "Journal of Clinical Medicine". The top 3 co-cited authors are "Zhou, Fei", "Guan, Wei-Jie", "Huang, Chaolin". The top 3 co-cited references addressed COVID-19's clinical features in China and noticed that COVID-19 patients had a wide range of complications. We also list four research hotspots.

This study conducted a bibliometric visual analysis of the literature on COVID-19 complications and summarized the current research hotspots. This study may provide valuable insights into the complications of COVID-19.

Liver dysfunction is a common manifestation of the COVID-19 infection. We aimed to study transaminase abnormalities through different waves of COVID-19 and their relations to disease severity or mortality.

A retrospective study included 521 Egyptian patients diagnosed with COVID-19. Data was retrieved from the medical records of patients who were admitted from April 2020 to October 2021 in Kasr Al-Ainy Hospitals, Cairo University, with categorization according to disease severity in correspondence to the four waves.

The median age was lower in the first wave compared to other waves, with male predominance across all waves. The most commonly encountered comorbidity overall was hypertension, followed by diabetes mellitus. White blood cells, ferritin, and interleukin-6 showed the highest median values in the second wave, with significantly higher median C-reactive protein on day 1 in the first wave. Forty percent of the patients showed elevated hepatic transaminases on admission in four waves, with no statistically significant difference between waves. On day 5, around half of the patients had elevated transaminases, with no significant difference between waves. Most CT findings were of moderate severity. Clinical severity was higher in the second wave. It was observed that the higher the disease severity, the greater the proportion of patients with elevated hepatic transaminases. The mortality rate was markedly high in cases who had elevated ALT or AST on day 5. The association between elevated enzymes on admission and mortality was seen in the first wave only, with a fatality rate of 22.5% in cases with increased baseline ALT and AST versus 5% in those with normal baseline enzymes.

There was no significant difference in transaminases between the four waves. Elevated transaminases were positively associated with increased mortality and severity, reflecting their prognostic value.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of coronavirus disease 2019 (COVID-19), has infected millions of individuals worldwide, which poses a severe threat to human health. COVID-19 is a systemic ailment affecting various tissues and organs, including the lungs and liver. Intrahepatic cholangiocarcinoma (ICC) is one of the most common liver cancer, and cancer patients are particularly at high risk of SARS-CoV-2 infection. Nonetheless, few studies have investigated the impact of COVID-19 on ICC patients.

With the methods of systems biology and bioinformatics, this study explored the link between COVID-19 and ICC, and searched for potential therapeutic drugs.

This study identified a total of 70 common differentially expressed genes (DEGs) shared by both diseases, shedding light on their shared functionalities. Enrichment analysis pinpointed metabolism and immunity as the primary areas influenced by these common genes. Subsequently, through protein-protein interaction (PPI) network analysis, we identified SCD, ACSL5, ACAT2, HSD17B4, ALDOA, ACSS1, ACADSB, CYP51A1, PSAT1, and HKDC1 as hub genes. Additionally, 44 transcription factors (TFs) and 112 microRNAs (miRNAs) were forecasted to regulate the hub genes. Most importantly, several drug candidates (Periodate-oxidized adenosine, Desipramine, Quercetin, Perfluoroheptanoic acid, Tetrandrine, Pentadecafluorooctanoic acid, Benzo[a]pyrene, SARIN, Dorzolamide, 8-Bromo-cAMP) may prove effective in treating ICC and COVID-19.

This study is expected to provide valuable references and potential drugs for future research and treatment of COVID-19 and ICC.