Impact of SARS-CoV-2 infection on liver disease.

Introduction: Abnormal liver biochemistry is not a rare finding in the context of SARS-CoV-2 infection, regardless of patients having pre-existing chronic disease or not. Content: This review examines the current body of knowledge on the relationship between COVID-19 and liver injury, which is frequently found in this setting. Summary: Although the pathogenesis of liver injury is not fully understood, it has been suggested to be the result of a combination of multiple factors. These include direct injury caused by the virus, immune system hyperactivation, ischemic and drug-induced injury. The prognostic valor of these alterations is also the subject of intense research. Due to their potential impact, these alterations require proper management and treatment, especially in patients with chronic liver disease or liver transplant recipients. Outlook: Some aspects associated with liver injury during COVID-19, especially in severe presentations, are not well understood. Studies assessing the clinical impact of COVID-19 on the healthy or diseased liver may help adjust treatment and immunization guidelines to the profile of the patient.

Impact of SARS-CoV-2 infection on liver disease.

Introduction: Abnormal liver biochemistry is not a rare finding in the context of SARS-CoV-2 infection, regardless of patients having pre-existing chronic disease or not. Content: This review examines the current body of knowledge on the relationship between COVID-19 and liver injury, which is frequently found in this setting. Summary: Although the pathogenesis of liver injury is not fully understood, it has been suggested to be the result of a combination of multiple factors. These include direct injury caused by the virus, immune system hyperactivation, ischemic and drug-induced injury. The prognostic valor of these alterations is also the subject of intense research. Due to their potential impact, these alterations require proper management and treatment, especially in patients with chronic liver disease or liver transplant recipients. Outlook: Some aspects associated with liver injury during COVID-19, especially in severe presentations, are not well understood. Studies assessing the clinical impact of COVID-19 on the healthy or diseased liver may help adjust treatment and immunization guidelines to the profile of the patient.

Recovery of serum testosterone levels is an accurate predictor of survival from COVID-19 in male patients.

BACKGROUND: SARS-CoV-2 infection portends a broad range of outcomes, from a majority of asymptomatic cases to a lethal disease. Robust correlates of severe COVID-19 include old age, male sex, poverty, and co-morbidities such as obesity, diabetes, and cardiovascular disease. A precise knowledge of the molecular and biological mechanisms that may explain the association of severe disease with male sex is still lacking. Here, we analyzed the relationship of serum testosterone levels and the immune cell skewing with disease severity in male COVID-19 patients. METHODS: Biochemical and hematological parameters of admission samples in 497 hospitalized male and female COVID-19 patients, analyzed for associations with outcome and sex. Longitudinal (in-hospital course) analyses of a subcohort of 114 male patients were analyzed for associations with outcome. Longitudinal analyses of immune populations by flow cytometry in 24 male patients were studied for associations with outcome. RESULTS: We have found quantitative differences in biochemical predictors of disease outcome in male vs. female patients. Longitudinal analyses in a subcohort of male COVID-19 patients identified serum testosterone trajectories as the strongest predictor of survival (AUC of ROC = 92.8%, p < 0.0001) in these patients among all biochemical parameters studied, including single-point admission serum testosterone values. In lethal cases, longitudinal determinations of serum luteinizing hormone (LH) and androstenedione levels did not follow physiological feedback patterns. Failure to reinstate physiological testosterone levels was associated with evidence of impaired T helper differentiation and augmented circulating classical monocytes. CONCLUSIONS: Recovery or failure to reinstate testosterone levels is strongly associated with survival or death, respectively, from COVID-19 in male patients. Our data suggest an early inhibition of the central LH-androgen biosynthesis axis in a majority of patients, followed by full recovery in survivors or a peripheral failure in lethal cases. These observations are suggestive of a significant role of testosterone status in the immune responses to COVID-19 and warrant future experimental explorations of mechanistic relationships between testosterone status and SARS-CoV-2 infection outcomes, with potential prophylactic or therapeutic implications.

Soluble Angiotensin-Converting Enzyme 2 as a Prognostic Biomarker for Disease Progression in Patients Infected with SARS-CoV-2.

Predicting disease severity in patients infected with SARS-CoV-2 is difficult. Soluble angiotensin-converting enzyme 2 (sACE2) arises from the shedding of membrane ACE2 (mACE2), which is a receptor for SARS-CoV-2 spike protein. We evaluated the predictive value of sACE2 compared with known biomarkers of inflammation and tissue damage (CRP, GDF-15, IL-6, and sFlt-1) in 850 patients with and without SARS-CoV-2 with different clinical outcomes. For univariate analyses, median differences between biomarker levels were calculated for the following patient groups (classified by clinical outcome): RT-PCR-confirmed SARS-CoV-2 positive (Groups 1-4); RT-PCR-confirmed SARS-CoV-2 negative following previous SARS-CoV-2 infection (Groups 5 and 6); and 'SARS-CoV-2 unexposed' patients (Group 7). Median levels of CRP, GDF-15, IL-6, and sFlt-1 were significantly higher in hospitalized patients with SARS-CoV-2 compared with discharged patients (all p < 0.001), whereas levels of sACE2 were significantly lower (p < 0.001). ROC curve analysis of sACE2 provided cut-offs for predicting hospital admission (≤0.05 ng/mL (positive predictive value: 89.1%) and ≥0.42 ng/mL (negative predictive value: 84.0%)). These findings support further investigation of sACE2, as a single biomarker or as part of a panel, to predict hospitalization risk and disease severity in patients with SARS-CoV-2 infection.