Fibrosis-4 (FIB-4) Index and mortality in COVID-19 patients admitted to the emergency department.

Liver damage worsens the prognosis of coronavirus 19 disease (COVID-19). However, the best strategy to stratify mortality risk according to liver damage has not been established. The aim of this study is to test the predictive value of the validated Fibrosis-4 (FIB-4) Index and compared it to liver transaminases and to the AST-to-Platelet ratio index (APRI). Multicenter cohort study including 992 consecutive COVID-19 patients admitted to the Emergency Department. FIB-4 > 3.25 and APRI > 0.7 were used to define liver damage. Multivariable Cox regression and ROC curve analysis for mortality were performed. Secondary endpoints were (1) need for high-flow oxygen and (2) mechanical ventilation. 240 (24.2%) patients had a FIB-4 > 3.25. FIB-4 > 3.25 associated with an increased mortality (n = 119, log-rank test p < 0.001 and adjusted hazard ratio (HR) 1.72 (95% confidence interval [95%CI] 1.14-2.59, p = 0.010). ROC analysis for mortality showed that FIB-4 (AUC 0.734, 95% CI 0.705-0.761) had a higher predictive value than AST (p = 0.0018) and ALT (p < 0.0001). FIB-4 > 3.25 was also superior to APRI > 0.7 (AUC 0.58, 95% CI 0.553-0.615, p = 0.0008). Using an optimized cut-off > 2.76 (AUC 0.689, 95% CI 0.659-0.718, p < 0.0001), FIB-4 was superior to FIB-4 > 3.25 (p = 0.0302), APRI > 0.7 (p < 0.0001), AST > 51 (p = 0.0119) and ALT > 42 (p < 0.0001). FIB-4 was also associated with high-flow oxygen use (n = 255, HR 1.69, 95% CI 1.25-2.28, p = 0.001) and mechanical ventilation (n = 39, HR 2.07, 95% CI 1.03-4.19, p = 0.043). FIB-4 score predicts mortality better than liver transaminases and APRI score. FIB-4 score may be an easy tool to identify COVID-19 patients at worse prognosis in the emergency department.

Clinical Utility of Midregional Proadrenomedullin in Patients with COVID-19.

OBJECTIVE: The aim of the study was to assess the role of midregional proadrenomedullin (MR-proADM) in patients with COVID-19. METHODS: We included 110 patients hospitalized for COVID-19. Biochemical biomarkers, including MR-proADM, were measured at admission. The association of plasma MR-proADM levels with COVID-19 severity, defined as a requirement for mechanical ventilation or in-hospital mortality, was evaluated. RESULTS: Patients showed increased levels of MR-proADM. In addition, MR-proADM was higher in patients who died during hospitalization than in patients who survived (median, 2.59 nmol/L; interquartile range, 2.3-2.95 vs median, 0.82 nmol/L; interquartile range, 0.57-1.03; P <.0001). Receiver operating characteristic curve analysis showed good accuracy of MR-proADM for predicting mortality. A MR-proADM value of 1.73 nmol/L was established as the best cutoff value, with 90% sensitivity and 95% specificity (P <.0001). CONCLUSION: We found that MR-proADM could represent a prognostic biomarker of COVID-19.

A meta-regression study of the clinical significance of serum aminotransferases in COVID-19.

OBJECTIVE: The aim of the study was to appraise the capacity of serum aminotransferases to discriminate between hepatic and other extra-pulmonary COVID-19-related manifestations and, potentially, to serve as predictors of poor clinical outcomes. MATERIALS AND METHODS: Ninety-eight studies were identified (79% from China), including 43,554 patients (57% males), 9,983 (62% males) with poor outcomes and 33,571 (50% males) with favorable outcomes. After splitting studies depending on whether serum alanine aminotransferase (ALT) concentrations were statistically different between patients with poor vs. favorable outcomes, the 35 'hepatic involvement' articles (p<0.05) included 28,510 patients (51% males), 5,279 (66% males) and 23,231 subjects (48% males) with poor and favorable outcomes, respectively. The 63 'extra-hepatic involvement' studies (p>0.05) included 15,044 patients (54% males), 4,704 (60% males) with poor outcomes and 10,340 (51% males) with favorable outcomes. RESULTS: The meta-analysis shows that serum aspartate aminotransferase (AST) concentrations were significantly higher in patients with poor outcomes than those with favorable outcomes (WMD 12.5 UI/L, 95% CI 10.9 to 14.1 p<0.001). Similarly, AST concentrations were significantly higher in the 'hepatic involvement' studies (WMD 16.3 UI/L, 95% CI 13.4 to 19.2 p<0.001) and in the 'extra-hepatic involvement' studies (WMD 10.3 UI/L, 95% CI 8.6 to 12.0 p<0.001). CONCLUSIONS: The different association of serum AST concentrations with some clinical, demographic, and biochemical factors in the two clusters suggests that in COVID-19 patients, serum AST elevation is not necessarily linked to real liver damage.

Dynamic changes in liver function parameters in patients with coronavirus disease 2019: a multicentre, retrospective study.

BACKGROUND: Liver injuries have been reported in patients with coronavirus disease 2019 (COVID-19). This study aimed to investigate the clinical role played by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: In this multicentre, retrospective study, the parameters of liver function tests in COVID-19 inpatients were compared between various time-points in reference to SARS-CoV-2 shedding, and 3 to 7 days before the first detection of viral shedding was regarded as the reference baseline. RESULTS: In total, 70 COVID-19 inpatients were enrolled. Twenty-two (31.4%) patients had a self-medication history after illness. At baseline, 10 (14.3%), 7 (10%), 9 (12.9%), 2 (2.9%), 15 (21.4%), and 4 (5.7%) patients already had abnormal alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), albumin, and total bilirubin (TBIL) values, respectively. ALT and AST abnormal rates and levels did not show any significant dynamic changes during the full period of viral shedding (all p > 0.05). The GGT abnormal rate (p = 0.008) and level (p = 0.033) significantly increased on day 10 of viral shedding. Meanwhile, no simultaneous significant increases in abnormal ALP rates and levels were observed. TBIL abnormal rates and levels significantly increased on days 1 and 5 of viral shedding (all p < 0.05). Albumin abnormal decrease rates increased, and levels decreased consistently from baseline to SARS-CoV-2 clearance day (all p < 0.05). Thirteen (18.6%) patients had chronic liver disease, two of whom died. The ALT and AST abnormal rates and levels did not increase in patients with chronic liver disease during SARS-CoV-2 shedding. CONCLUSIONS: SARS-CoV-2 does not directly lead to elevations in ALT and AST but may result in elevations in GGT and TBIL; albumin decreased extraordinarily even when SARS-CoV-2 shedding ended.

Elevated liver enzymes in hospitalized patients with COVID-19 in Singapore.

ABSTRACT: Liver dysfunction in patients with COVID-19 (coronavirus disease 2019) has been described. However, it is not clear if the presence of abnormal liver function tests at presentation was related to underlying undiagnosed liver disease, or a result of the viral infection.We retrospectively examined the first 554 consecutive polymerase chain reaction positive SARS-CoV-2 patients admitted from February 2020 to April 2020 to our academic medical centre. We reviewed their clinical data, chest radiography and laboratory studies obtained within 24 hour of admission.Despite similar hemodynamic parameters, we found significant aspartate transaminase elevation (64 ±â€Š141 vs 35 ±â€Š23 U/L, P < .001) in those with pneumonia compared to those without. Elevated liver enzymes were seen in 102 patients (18.4%). They presented with higher temperatures (38.5 ±â€Š0.9 vs 37.5 ±â€Š0.8 degC, P = .011), higher total white cell counts (6.95 ±â€Š2.29 vs 6.39 ±â€Š2.19 x109/L, P = .021), serum ferritin (240 ±â€Š274 vs 165 ±â€Š198 ng/ml, P = .002) and lactate dehydrogenase (632 ±â€Š912 vs 389 ±â€Š107 U/L, P < .001). These patients were more likely to require intensive care (6.9% vs 2.7% P = .036) and mechanical ventilation (5.9% vs 2.2%, P = .046). Migrant workers from dormitories had a higher rate of baseline liver function test abnormalities (88/425 vs 14/129, P = .01), which were more likely to persist at the time of discharge.Despite relatively mild COVID-19 disease, there was a significant prevalence of liver dysfunction, particularly amongst migrant workers. Elevated liver enzymes were associated with more severe disease, despite similar haemodynamic characteristics. Future studies should explore whether pre-existing liver disease may predispose to more severe COVID-19 disease.

The Associations of Lymphocyte Ratio and Neutrophil Ratio on Liver Dysfunction in COVID-19 Patients.

Data on the impact of lymphocytes and neutrophils on the incidence of liver dysfunction in COVID-19 patients are limited. This study aimed to investigate the lateral and longitudinal associations of lymphocyte ratio (LR) and neutrophil ratio (NR) on liver dysfunction in COVID-19 patients. We tested 1,409 blood samples from 245 COVID-19 patients in China between January 2020 and June 2021. The lateral U-shaped relationships, determined by smooth curve fitting and the piecewise-linear mixed-effect model, were observed between LR, NR, and AST and the incidence of AST-linked liver dysfunction, with the threshold cutoffs of 26.1 and 62.0, respectively. Over the 1,409 tests, the LR ≤ 26.1 and NR ≥ 62.0 related to the occurrence of mild liver dysfunction (HR: 1.36; 95% CI: 1.01, 1.82), moderate liver dysfunction (HR: 1.37; 95% CI: 1.01, 1.85), and severe liver dysfunction (HR: 1.72; 95% CI: 1.02, 2.90). For the patients with preexisting AST ≥ 35 U/L, the baseline LR ≤ 26.1 and NR ≥ 62.0 (b.LLCHN) groups had a fully adjusted 8.85-, 7.88-, and 5.97-fold increased risk of mild and moderate liver dysfunction after being hospitalized of 3, 6, and 9 days compared to the baseline LR > 26.1 and NR < 62.0 (b.normal) groups. Severe liver dysfunction only presents significant differences after being adjusted for age, sex, and BMI. Consistently, Kaplan-Meier analyses showed that b.LLCHN reflects a better predictive value for different subsequent magnitude liver dysfunctions after admission of 3 and 6 days. To improve liver function in patients with preexisting AST ≥35 U/L, future management strategies should pay more attention to baseline LR ≤ 26.1 and NR ≥ 62.0 patients.

Artificial Intelligence Predicts Severity of COVID-19 Based on Correlation of Exaggerated Monocyte Activation, Excessive Organ Damage and Hyperinflammatory Syndrome: A Prospective Clinical Study.

Background: Prediction of the severity of COVID-19 at its onset is important for providing adequate and timely management to reduce mortality. Objective: To study the prognostic value of damage parameters and cytokines as predictors of severity of COVID-19 using an extensive immunologic profiling and unbiased artificial intelligence methods. Methods: Sixty hospitalized COVID-19 patients (30 moderate and 30 severe) and 17 healthy controls were included in the study. The damage indicators high mobility group box 1 (HMGB1), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), extensive biochemical analyses, a panel of 47 cytokines and chemokines were analyzed at weeks 1, 2 and 7 along with clinical complaints and CT scans of the lungs. Unbiased artificial intelligence (AI) methods (logistic regression and Support Vector Machine and Random Forest algorithms) were applied to investigate the contribution of each parameter to prediction of the severity of the disease. Results: On admission, the severely ill patients had significantly higher levels of LDH, IL-6, monokine induced by gamma interferon (MIG), D-dimer, fibrinogen, glucose than the patients with moderate disease. The levels of macrophage derived cytokine (MDC) were lower in severely ill patients. Based on artificial intelligence analysis, eight parameters (creatinine, glucose, monocyte number, fibrinogen, MDC, MIG, C-reactive protein (CRP) and IL-6 have been identified that could predict with an accuracy of 83-87% whether the patient will develop severe disease. Conclusion: This study identifies the prognostic factors and provides a methodology for making prediction for COVID-19 patients based on widely accepted biomarkers that can be measured in most conventional clinical laboratories worldwide.

Risk factors for secondary hemophagocytic lymphohistiocytosis in severe coronavirus disease 2019 adult patients.

BACKGROUND: Secondary hemophagocytic lymphohistiocytosis (sHLH) is a life-threatening hyperinflammatory event and a fatal complication of viral infections. Whether sHLH may also be observed in patients with a cytokine storm induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is still uncertain. We aimed to determine the incidence of sHLH in severe COVID-19 patients and evaluate the underlying risk factors. METHOD: Four hundred fifteen severe COVID-19 adult patients were retrospectively assessed for hemophagocytosis score (HScore). A subset of 7 patients were unable to be conclusively scored due to insufficient patient data. RESULTS: In 408 patients, 41 (10.04%) had an HScore ≥169 and were characterized as "suspected sHLH positive". Compared with patients below a HScore threshold of 98, the suspected sHLH positive group had higher D-dimer, total bilirubin, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, serum creatinine, triglycerides, ferritin, interleukin-6, C-reactive protein, procalcitonin, lactate dehydrogenase, creatine kinase isoenzyme, troponin, Sequential Organ Failure Assessment (SOFA) score, while leukocyte, hemoglobin, platelets, lymphocyte, fibrinogen, pre-albumin, albumin levels were significantly lower (all P < 0.05). Multivariable logistic regression revealed that high ferritin (>1922.58 ng/mL), low platelets (<101 × 109/L) and high triglycerides (>2.28 mmol/L) were independent risk factors for suspected sHLH in COVID-19 patients. Importantly, COVID-19 patients that were suspected sHLH positive had significantly more multi-organ failure. Additionally, a high HScore (>98) was an independent predictor for mortality in COVID-19. CONCLUSIONS: HScore should be measured as a prognostic biomarker in COVID-19 patients. In particular, it is important that HScore is assessed in patients with high ferritin, triglycerides and low platelets to improve the detection of suspected sHLH.

Using Unsupervised Machine Learning to Identify Age- and Sex-Independent Severity Subgroups Among Patients with COVID-19: Observational Longitudinal Study.

BACKGROUND: Early detection and intervention are the key factors for improving outcomes in patients with COVID-19. OBJECTIVE: The objective of this observational longitudinal study was to identify nonoverlapping severity subgroups (ie, clusters) among patients with COVID-19, based exclusively on clinical data and standard laboratory tests obtained during patient assessment in the emergency department. METHODS: We applied unsupervised machine learning to a data set of 853 patients with COVID-19 from the HM group of hospitals (HM Hospitales) in Madrid, Spain. Age and sex were not considered while building the clusters, as these variables could introduce biases in machine learning algorithms and raise ethical implications or enable discrimination in triage protocols. RESULTS: From 850 clinical and laboratory variables, four tests-the serum levels of aspartate transaminase (AST), lactate dehydrogenase (LDH), C-reactive protein (CRP), and the number of neutrophils-were enough to segregate the entire patient pool into three separate clusters. Further, the percentage of monocytes and lymphocytes and the levels of alanine transaminase (ALT) distinguished cluster 3 patients from the other two clusters. The highest proportion of deceased patients; the highest levels of AST, ALT, LDH, and CRP; the highest number of neutrophils; and the lowest percentages of monocytes and lymphocytes characterized cluster 1. Cluster 2 included a lower proportion of deceased patients and intermediate levels of the previous laboratory tests. The lowest proportion of deceased patients; the lowest levels of AST, ALT, LDH, and CRP; the lowest number of neutrophils; and the highest percentages of monocytes and lymphocytes characterized cluster 3. CONCLUSIONS: A few standard laboratory tests, deemed available in all emergency departments, have shown good discriminative power for the characterization of severity subgroups among patients with COVID-19.

Positive Epstein-Barr virus detection in coronavirus disease 2019 (COVID-19) patients.

The objective of this study was to detect the Epstein-Barr virus (EBV) coinfection in coronavirus disease 2019 (COVID-19). In this retrospective single-center study, we included 67 COVID-19 patients with onset time within 2 weeks in Renmin Hospital of Wuhan University from January 9 to February 29, 2020. Patients were divided into EBV/SARS-CoV-2 coinfection group and SARS-CoV-2 infection alone group according to the serological results of EBV, and the characteristics differences between the two groups were compared. The median age was 37 years, with 35 (52.2%) females. Among these COVID-19 patients, thirty-seven (55.2%) patients were seropositive for EBV viral capsid antigen (VCA) IgM antibody. EBV/SARS-CoV-2 coinfection patients had a 3.09-fold risk of having a fever symptom than SARS-CoV-2 infection alone patients (95% CI 1.11-8.56; P = 0.03). C-reactive protein (CRP) (P = 0.02) and the aspartate aminotransferase (AST) (P = 0.04) in EBV/SARS-CoV-2 coinfection patients were higher than that in SARS-CoV-2 infection alone patients. EBV/SARS-CoV-2 coinfection patients had a higher portion of corticosteroid use than the SARS-CoV-2 infection alone patients (P = 0.03). We find a high incidence of EBV coinfection in COVID-19 patients. EBV/SARS-CoV-2 coinfection was associated with fever and increased inflammation. EBV reactivation may associated with the severity of COVID-19.

Serum syndecan-1 reflects organ dysfunction in critically ill patients.

Syndecan-1 (SDC-1) is found in the endothelial glycocalyx and shed into the blood during systemic inflammatory conditions. We investigated organ dysfunction associated with changing serum SDC-1 levels for early detection of organ dysfunction in critically ill patients. To evaluate the effect of SDC-1 on laboratory parameters measured the day after SDC-1 measurement with consideration for repeated measures, linear mixed effects models were constructed with each parameter as an outcome variable. A total of 94 patients were enrolled, and 831 samples were obtained. Analysis using mixed effects models for repeated measures with adjustment for age and sex showed that serum SDC-1 levels measured the day before significantly affected several outcomes, including aspartate aminotransferase (AST), alanine transaminase (ALT), creatinine (CRE), blood urea nitrogen (BUN), antithrombin III, fibrin degradation products, and D-dimer. Moreover, serum SDC-1 levels of the prior day significantly modified the effect between time and several outcomes, including AST, ALT, CRE, and BUN. Additionally, increasing serum SDC-1 level was a significant risk factor for mortality. Serum SDC-1 may be a useful biomarker for daily monitoring to detect early signs of kidney, liver and coagulation system dysfunction, and may be an important risk factor for mortality in critically ill patients.

Cardiac markers of multisystem inflammatory syndrome in children (MIS-C) in COVID-19 patients: A meta-analysis.

OBJECTIVE: A meta-analysis of laboratory cardiac markers for multisystem inflammatory syndrome in children (MIS-C) was performed in patients with coronavirus disease 2019 (COVID-19). METHODS: Eight databases were searched until April 10, 2021, for studies on cardiac markers, including B-type natriuretic peptide (BNP)/N-terminal pro-BNP (NT-proBNP), troponin, aspartate aminotransferase (AST), in MIS-C patients. RESULTS: Of the 2583 participants enrolled in 24 studies, 1613 patients were diagnosed with MIS-C. MIS-C patients exhibited higher BNP levels than patients with non-severe COVID-19 [SMD (95% CI): 1.13 (0.48, 1.77), p < 0.05]. No significant differences in BNP levels were observed between patients with MIS-C and severe COVID-19 [SMD (95% CI): 0.29 (-0.07, 0.65), p = 0.117]. Comparisons of MIS-C patients to all COVID-19 patients revealed no significant differences in levels of troponin [SMD (95% CI): 0.13 (-0.07, 0.32), p = 0.212] or AST [SMD (95% CI): 0.10 (-0.11, 0.31), p = 0.336]. Compared to patients with non-severe MIS-C, those with severe MIS-C exhibited higher levels of BNP [SMD (95% CI): 0.26 (0.04, 0.48), p < 0.05], but no differences in troponin [SMD (95% CI): 0.05 (-0.06, 0.16) p = 0.387] or AST [SMD (95% CI): 0.19 (-0.34, 0.71), p = 0.483] were observed. Moreover, there was no significant difference in BNP [SMD (95% CI): -0.21 (-1.07, 0.64), p = 0.624] or troponin [SMD (95% CI): -0.07 (-0.45, 0.31), p = 0.710] between MIS-C with and without coronary artery abnormality. Sensitivity analyses were performed to assess stability. No publication bias was detected based on Begg's test. CONCLUSIONS: The key cardiac marker that showed differences between patients with MIS-C/non-severe COVID-19 and between patients with severe/non-severe MIS-C was BNP. Other markers, such as troponin and AST, did not exhibit notable differences in indicating cardiac injury between patients with MIS-C and COVID-19.

Elevated transaminases and hypoalbuminemia in Covid-19 are prognostic factors for disease severity.

Prognostic markers are needed to understand the disease course and severity in patients with Covid-19. There is evidence that Covid-19 causes gastrointestinal symptoms and abnormalities in liver enzymes. We aimed to determine if hepatobiliary laboratory data could predict disease severity in patients with Covid-19. In this retrospective, single institution, cohort study that analyzed patients admitted to a community academic hospital with the diagnosis of Covid-19, we found that elevations of Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphatase (AP) at any time during hospital admission increased the odds of ICU admission by 5.12 (95% CI: 1.55-16.89; p = 0.007), 4.71 (95% CI: 1.51-14.69; p = 0.01) and 4.12 (95% CI: 1.21-14.06, p = 0.02), respectively. Hypoalbuminemia found at the time of admission to the hospital was associated with increased mortality (p = 0.02), hypotension (p = 0.03), and need for vasopressors (p = 0.02), intubation (p = 0.01) and hemodialysis (p = 0.002). Additionally, there was evidence of liver injury: AST was significantly elevated above baseline in patients admitted to the ICU (54.2 ± 15.70 U/L) relative to those who were not (9.2 ± 4.89 U/L; p = 0.01). Taken together, this study found that hypoalbuminemia and abnormalities in hepatobiliary laboratory data may be prognostic factors for disease severity in patients admitted to the hospital with Covid-19.

Cytokine storm in severe COVID-19 pneumonia.

In this study, laboratorial parameters of hospitalized novel coronavirus (COVID-19) patients, who were complicated with severe pneumonia, were compared with the findings of cytokine storm developing in macrophage activation syndrome (MAS)/secondary hemophagocytic lymphohistiocytosis (sHLH). Severe pneumonia occurred as a result of cytokine storm in some patients who needed intensive care unit (ICU), and it is aimed to determine the precursive parameters in this situation. Also in this study, the aim is to identify laboratory criteria that predict worsening disease and ICU intensification, as well as the development of cytokine storm. This article comprises a retrospective cohort study of patients admitted to a single institution with COVID-19 pneumonia. This study includes 150 confirmed COVID-19 patients with severe pneumonia. When they were considered as severe pneumonia patients, the clinic and laboratory parameters of this group are compared with H-score criteria. Patients are divided into two subgroups; patients with worsened symptoms who were transferred into tertiary ICU, and patients with stable symptoms followed in the clinic. For the patients with confirmed COVID-19 infection, after they become complicated with severe pneumonia, lymphocytopenia (55.3%), anemia (12.0%), thrombocytopenia (19.3%), hyperferritinemia (72.5%), hyperfibrinogenemia (63.7%) and elevated lactate dehydrogenase (LDH) (90.8%), aspartate aminotransaminase (AST) (31.3%), alanine aminotransaminase (ALT) (20.7%) are detected. There were no significant changes in other parameters. Blood parameters between the pre-ICU period and the ICU period (in which their situation had been worsened and acute respiratory distress syndrome [ARDS] was developed) were also compared. In the latter group lymphocyte levels were found significantly reduced (p = 0.01), and LDH, highly sensitive troponin (hs-troponin), procalcitonin, and triglyceride levels were significantly increased (p < 0.05). In addition, there was no change in hemoglobin, leukocyte, platelet, ferritin, and liver function test levels, including patients who developed ARDS, similar to the cytokine storm developed in MAS/sHLH. COVID-19 pneumonia has similar findings as hyperinflammatory syndromes but does not seem to have typical features as in cytokine storm developed in MAS/sHLH. In the severe patient group who has started to develop ARDS signs, a decrease in lymphocyte level in addition to the elevated LDH, hs-troponin, procalcitonin, and triglyceride levels can be a predictor in progression to ICU admission and could help in the planning of anti-cytokine therapy.

Evaluation of serum hepatic enzyme activities in different COVID-19 phenotypes.

Coronavirus disease 2019 (COVID-19) is a newly emerging infectious disease. Our understanding of the clinical characteristics of liver damage and the relationship with disease severity in COVID-19 is still limited. To investigate the serum hepatic enzyme activities in different phenotypes of COVID-19 patients, evaluate their relationship with the illness severity and analyze the correlation of glycyrrhizin treatment and abnormal liver enzyme activities, one hundred and forty-seven patients with COVID-19 were enrolled in a retrospective study that investigated hepatic dysfunction. Liver alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactic dehydrogenase (LDH), Y-glutamyl transferase (GGT), superoxide dismutase (SOD), and alkaline phosphatase (ALP) were analyzed in these patients. Patients with diammonium glycyrrhizinate (DG) treatment were further investigated. Of the 147 patients, 56 (38.1%) had abnormal ALT activity and 80 (54.4%) had abnormal AST activity. The peak of abnormal hepatic enzyme activities occurred at 3 to 6 days after on admission. Serum AST and LDH levels were elevated, while the SOD level was decreased in severe and critical patients, compared with mild cases. DG treatment may alleviate the abnormal liver enzyme activities in non-critical COVID-19 patients. Abnormal liver functions may be observed in patients with COVID-19, and were associated with SARS-CoV-2-induced acute liver damage. Glycyrrhizin treatment may be an effective therapeutic approach for the outcome of abnormal hepatic enzyme activities in severe COVID-19 cases. Serum hepatic enzyme tests may reflect the illness severity and should be monitored.

Risk factors associated with the need for oxygen therapy in patients with COVID-19.

ABSTRACT: Respiratory failure is the major cause of death in patients with coronavirus disease (COVID-19). Data on factors affecting the need for oxygen therapy in early-stage COVID-19 are limited. This study aimed to evaluate the factors associated with the need for oxygen therapy in patients with COVID-19.This is a retrospective study of consecutive COVID-19 patients who were hospitalized between February 27 and June 28, 2020, in South Korea. Logistic regression analyses were performed to identify the factors associated with the need for oxygen therapy.Of the 265 patients included in the study, 26 (9.8%) received oxygen therapy, and 7 of these patients (29.2%) were transferred to a step-up facility, and 3 (11.5%) died. The median age of all patients was 46 years (IQR, 30-60 years), and the median modified early warning score at admission was 1 (IQR, 1-2). In a multivariate logistic regression analysis, being a current smoker (odds ratio [OR] 7.641, 95% confidence interval [CI] 1.686-34.630, P = .008), heart rate (OR 1.053, 95% CI 1.010-1.097, P = .014), aspartate aminotransferase values (OR 1.049, 95% CI 1.008-1.092, P = .020), blood urea nitrogen levels (OR 1.171, 95% CI 1.073-1.278, P < .001), and chest radiographic findings (OR 3.173, 95% CI 1.870-5.382, P < .001) were associated with oxygen therapy.In patients with less severe COVID-19, the need for oxygen therapy is affected by smoking and elevated values of aspartate aminotransferase and blood urea nitrogen. Further research is warranted on the risk factors for deterioration in COVID-19 to efficiently allocate medical resources.

Hepatic Manifestations of Nonhepatotropic Infectious Agents Including Severe Acute Respiratory Syndrome Coronavirus-2, Adenovirus, Herpes Simplex Virus, and Coxiella burnetii.

Nonhepatotropic viruses such as adenovirus, herpes simplex virus, flaviviruses, filoviruses, and human herpes virus, and bacteria such as Coxiella burnetii, can cause liver injury mimicking acute hepatitis. Most of these organisms cause a self-limited infection. However, in immunocompromised patients, they can cause severe hepatitis or in some cases fulminant hepatic failure requiring an urgent liver transplant. Hepatic dysfunction is also commonly seen in patients with severe acute respiratory syndrome coronavirus-2 infection. Patients with preexisting liver diseases are likely at risk for severe coronavirus disease 2019 (COVID-19) and may be associated with poor outcomes.