• Humans
• APACHE
• Critical Illness/mortality
• Male
• Female
• Middle Aged
• Prognosis
• Tuberculosis/mortality
• Retrospective Studies
• Intensive Care Units
• Aged
• China/epidemiology
• Adult
• Nutrition Assessment
• Risk Factors

• Immunology
• Public health
• Respiratory medicine

• Artificial intelligence
• COVID-19
• Classification algorithms
• DERGA
• Genetic
• SARS-CoV2
• hematological markers

• Humans
• COVID-19/diagnosis
• COVID-19/blood
• Machine Learning
• Male
• Female
• Middle Aged
• Intensive Care Units
• Prognosis
• Aged
• Severity of Illness Index
• Algorithms
• SARS-CoV-2
• Ferritins/blood
• Neural Networks, Computer
• Neutrophils
• Adult
• L-Lactate Dehydrogenase/blood

• C-reactive protein
• COVID-19
• SARS CoV-2
• complete blood count
• transaminases

• ICU
• Omicron infection
• abnormal liver function
• end stage kidney disease
• inflammation
• neutrophil-to-lymphocyte ratio
• platelet-albumin-bilirubin score

• Humans
• Female
• Aged
• Polycystic Ovary Syndrome
• Blood Glucose
• COVID-19 Drug Treatment
• COVID-19/complications
• COVID-19/epidemiology
• Comorbidity

• COVID-19
• arginine
• fatigue
• persistent symptoms
• post-acute COVID-19 syndrome

• The Article Processing Charges were funded by BIESSEN Pharma, Romania. BIESSEN Pharma

• 3-maleimido-PROXYL
• COVID-19
• EPR
• ROS
• TEMPOL
• hypoalbuminemia

Coronavirus disease 2019 (COVID-19) is primarily a respiratory disease with multi-organ involvement, including impaired liver function. It has been noticed that a significant proportion of COVID-19 patients have liver dysfunction, especially those with a more severe disease course. The coronavirus causes direct damage to the liver using the angiotensin-converting enzyme 2, a cell-surface receptor for cellular entry, that is expressed in the liver. According to previous research, liver enzyme abnormalities were observed in a considerable proportion of COVID-19 patients, and elevated liver transaminases were found in about 20% of these patients, alkaline phosphatase in 6.1%, and gamma-glutamyl transferase in 21.1%. COVID-19 might trigger a deterioration of liver function in patients with pre-existing chronic liver diseases (CLDs) and also in those without previous liver disorders. The majority of COVID-19 patients who develop liver injury are men, the elderly, and those with a higher body mass index. Compared to the general population, COVID-19 is associated with significant morbidity and mortality in patients with liver disease (cirrhosis and liver transplantation recipients). However, some studies indicate that CLDs have a lesser role in determining patient progression towards higher disease severity.

• Liver disease
• COVID-19
• Mortality
• Prognosis
• Liver function

• Male
• Humans
• Female
• Aged
• COVID-19
• SARS-CoV-2
• Liver Diseases
• Liver Cirrhosis/epidemiology

• COVID-19
• Liver enzymes
• mortality

• ARDS
• COVID-19
• SARS-CoV-2
• hCPAP
• non-invasive ventilation
• prognosis

• Artificial intelligence
• Artificial neural networks
• COVID-19
• Laboratory indices
• SARS-CoV2

Carbohydrate antigen 125 (CA125) is an indicator of inflammation, immune response, and impaired cardiac function. The aim was to investigate whether CA125 behaves as a biomarker of severity and poor clinical outcomes in hospitalized patients with coronavirus disease 2019 (COVID-19).

Serum CA125 [Elecsys CA125 II assay-(Roche Diagnostics GmbH)] was measured in stored biobank samples from COVID-19 hospitalized patients between 01 March 2020 and 17 October 2021. Multiple logistic regression models were built to explore the association between CA125 and clinical outcomes [in-hospital all-cause mortality, need for invasive mechanical ventilation (IMV), or non-invasive respiratory support (non-IRS)], estimating odds ratios (ORs; 95% CI). The gradient of risk of CA125 was evaluated by fractional polynomials.

A total of 691 patients were included, median age of 63 years (50–76), men (57.2%), with high comorbidity. At admission, 85.8% had pneumonia. Median CA125 was 10.33 U/ml (7.48–15.50). The in-hospital mortality rate was 7.2%. After adjusting for confounding factors, CA125 ≥ 15.5 U/ml (75th percentile) showed an increased risk of death [OR 2.85(1.21–6.71)], as age ≥ 65 years, diabetes, and immunosuppression. Furthermore, CA125 as a continuous variable was positive and significantly associated with the risk of death after multivariate adjustment. The mean hospital stay of the patients with CA125 ≥ 15.5 U/ml was longer than the rest of the study population.

CA125 in the first 72 h of hospital admission seems a useful biomarker of mortality in hospitalized patients with moderate–severe COVID-19. If our findings are confirmed, the wide availability of this biomarker would make easy its widespread implementation in clinical practice.

Over hundreds of years, humans have faced multiple pandemics and have overcome many of them with scientific advancements. However, the recent coronavirus disease (COVID-19) has challenged the physical, mental, and socioeconomic aspects of human life, which has introduced a general sense of uncertainty among everyone. Although several risk profiles, such as the severity of the disease, infection rate, and treatment strategy, have been investigated, new variants from different parts of the world put humans at risk and require multiple strategies simultaneously to control the spread. Understanding the entire system with respect to the commonly involved or essential mechanisms may be an effective strategy for successful treatment, particularly for COVID-19. Any treatment for COVID-19 may alter the redox profile, which can be an effective complementary method for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry and further replication. Indeed, redox profiles are one of the main barriers that suddenly shift the immune response in favor of COVID-19. Fortunately, several redox components exhibit antiviral and anti-inflammatory activities. However, access to these components as support elements against COVID-19 is limited. Therefore, understanding redox-derived species and their nodes as a common interactome in the system will facilitate the treatment of COVID-19. This review discusses the redox-based perspectives of the entire system during COVID-19 infection, including how redox-based molecules impact the accessibility of SARS-CoV-2 to the host and further replication. Additionally, to demonstrate its feasibility as a viable approach, we discuss the current challenges in redox-based treatment options for COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a multi-organ damage that includes hepatic dysfunction, which has been observed in over 50% of COVID-19 patients. Liver injury in COVID-19 could be attributed to the cytopathic effects, exacerbated immune responses or treatment-associated drug toxicity. Herein we demonstrate that hepatocytes are susceptible to infection in different models: primary hepatocytes derived from humanized angiotensin-converting enzyme-2 mice (hACE2) and primary human hepatocytes. Pseudotyped viral particles expressing the full-length spike of SARS-CoV-2 and recombinant receptor binding domain (RBD) bind to ACE2 expressed by hepatocytes, promoting metabolic reprogramming towards glycolysis but also impaired mitochondrial activity. Human and hACE2 primary hepatocytes, where steatosis and inflammation were induced by methionine and choline deprivation, are more vulnerable to infection. Inhibition of the renin-angiotensin system increases the susceptibility of primary hepatocytes to infection with pseudotyped viral particles. Metformin, a common therapeutic option for hyperglycemia in type 2 diabetes patients known to partially attenuate fatty liver, reduces the infection of human and hACE2 hepatocytes. In summary, we provide evidence that hepatocytes are amenable to infection with SARS-CoV-2 pseudovirus, and we propose that metformin could be a therapeutic option to attenuate infection by SARS-CoV-2 in patients with fatty liver.

SARS-CoV-2 pseudovirus infects human hepatocytes leading to metabolic reprogramming towards glycolysis and impaired mitochondrial activity, and metformin can reduce infection under steatotic conditions.

Coronavirus disease 2019 (COVID-19) pneumonia outbreak started in December 2019. On March 12, 2020, the World Health Organization (WHO) declared that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) constitutes a pandemic, and as of May 2021, SARS-CoV-2 has infected over 167.3 million patients, including 3.4 million deaths, reported to WHO. In this review, we will focus on the relationship between SARS-CoV-2 infection and the liver. We will discuss how chronic liver diseases affect the COVID-19 disease course and outcomes. We will also discuss the SARS-CoV-2 effects on the liver, mechanisms of acute liver injury, and potential management plans.

• COIVD-19
• SARS-CoV-2
• Liver diseases
• Transaminases
• Non alcoholic fatty liver
• Hepatocellular carcinoma

To describe breakthrough COVID-19 infection in patients who needed hospitalization and the factors associated with poor outcomes.

We conducted a retrospective study on patients hospitalized with COVID-19 between December 27, 2020, and October 17, 2021, with either a complete vaccination (CV) scheme (diagnosed 2 weeks after the second dose of the Pfizer/Moderna/AstraZeneca or first dose of the Janssen vaccine was administered) or a partial vaccination (PV) scheme. The main outcomes were all-cause mortality and the need for invasive mechanical ventilation (IMV). The baseline factors associated with the outcomes were analyzed by multiple logistic regression to estimate the odds ratios (odds ratio [OR]; 95% confidence interval [CI]).

A total of 145 (101 CV) patients were included. The CV subgroup was mainly composed of older males with high comorbidity (Charlson Index ≥3, 72%; immunosuppression, 20%) and with bilateral pneumonia in 63.4%. Limited therapeutic effort (LTE) was agreed upon for 28% of the patients. In the CV subgroup, endotracheal intubation was required in 10.9% of patients, reaching 15.3% when excluding LTE patients; the global mortality was 22.8%, reaching 41.4% in the subgroup with LTE. Although the patients with PV were younger and had fewer comorbidities, the main outcomes did not differ significantly between the CV and PV groups. The predictors of poor outcomes were age ≥ 65 years, confusion, ferritin > 500 mg/L, extensive lung infiltrates, and a Charlson Index ≥ 3.

Patients with CV hospitalized because of breakthrough COVID-19 infection tend to be older persons, with comorbidities, and have a high mortality.

• COVID-19
• breakthrough infection
• hospitalization
• mortality
• risk factors
• vaccine effectiveness

The clinical spectrum of the SARS-CoV-2 infection is very broad, ranging from asymptomatic infection to severe pneumonia. However, the majority of fatalities related to COVID-19 have involved old, frail and patients with comorbidities, such as obesity, groups that also have high rates of a poor nutritional status. To assess the impact on clinical outcomes of the coexistence of any degree of obesity and low albumin levels on admission among patients with COVID-19.

This is a sub-analysis of a former study where 75 patients admitted due to COVID-19 were evaluated cross-sectionally. In this analysis, patients were divided in two groups, according to the presence of obesity and albumin levels on admission lower than 3.5 g/dl.

11 out 75 patients evaluated (14.7%) had obesity and albumin levels lower than 3.5 g/dl. Patients with obesity and hypoalbuminemia were older than patients without these two conditions (65.3 ± 7.7 vs 54.2 ± 17 years; p = 0.01). CRP (141.4 ± 47.9 vs 70.1 ± 60.6 mg/l; p = 0.002), D-dimer (2677.3 ± 2358.3 vs 521.7 ± 480.3 ng/ml; p = 0.001), fibrinogen (765.9 ± 123.9 vs 613.5 ± 158gr/L; p = 0.007) ferritin levels (903.1 ± 493 vs 531.4 ± 418.9 mcg/l; p = 0.01) and procalcitonin (3.5 ± 0.6 vs 1.1 ± 0.7 ng/ml; p = 0.009) were significantly higher in the group with obesity and hypoalbuminemia. Among patients with low albumin and obesity, length of hospital was higher (21.9 ± 18.7 vs 10.5 ± 9.5 days; p = 0.004) and the proportion of subjects admitted to ICU was greater (81.8% vs 11.5%; p < 0.0001). However, mortality rates were comparable between the two groups (3.8% vs 0%; p = 0.5).

The combination of obesity and hypoalbuminemia may worsen the prognosis of patients with a SARS-CoV-2 infection. Therefore, prompt identification and amelioration of nutritional status could be beneficial.

• Albumin
• COVID-19
• Hypoalbuminemia
• Obesity
• SARS-CoV-2

• COVID‐19
• bilirubin
• jaundice
• liver
• liver injury
• severe acute respiratory syndrome coronavirus 2

• T35 DK093430 NIDDK NIH HHS
• UL1 TR001873 NCATS NIH HHS
• National Center for Advancing Translational Sciences
• National Institute of Diabetes and Digestive and Kidney Diseases