Vaccination against SARS-CoV-2 has become a central public health issue, primarily for vulnerable populations such as individuals with Chronic Liver Disease (CLD). Increased COVID-19-related mortality and disease severity has been noted in this subgroup of patients. Severe COVID-19 tends to further deregulate liver function in patients with chronic liver failure or cirrhosis and even reactivate hepatitis in people living with HBV or HCV. In addition, impaired hepatic function leads to several limitations in possible therapeutic interventions. Chronic hepatic dysregulation, along with the underlying cirrhosis-associated immune dysfunction (CAID), leads to a decreased immune response to vaccination that, in turn, may result in reduced efficacy rates and lowered lasting protection. According to current guidelines, timely vaccination and frequent booster shot administration are deemed necessary in this context. Vaccination-related adverse events are mostly mild in nature and similar to those reported in the general population, whereas the incidence of liver injury following vaccination is relatively rare. We aimed to review available evidence and recommendations associated with COVID-19 vaccination in patients with chronic liver disease, and provide insight to current issues and future directions.

/pdf/covid-19-vaccination-in-patients-with-chronic-liver-disease-27xwp85l.pdf

COVID-19 Vaccination in Patients with Chronic Liver Disease

There are limited data on the performance of laboratory-derived biomarkers in kidney transplant recipients (KTR) with COVID-19. This observational study enrolled 65 KTR with COVID-19 who were treated at the University Hospital of Split up to March 2022. Laboratory-derived biomarkers (neutrophile-to-lymphocyte (NLR) ratio, platelet-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, De Ritis ratio, C-reactive protein (CRP)-to-albumin ratio, lactate dehydrogenase (LDH)-to-hemoglobin ratio, CRP-to-lymphocyte ratio, red cell distribution width-to-albumin ratio, platelet-to-albumin ratio, D-Dimer-to-albumin ratio, D-Dimer-to-NLR ratio, LDH-to-albumin ratio, and LDH-to-white blood cell (WBC) ratio) were calculated, and their performance with regard to 30-day mortality was determined. Mortality events occurred in 12 patients (18.5%), which was significantly associated with increased De Ritis (HR 3.83, 95% CI 1.57–9.35, p = 0.003), CRP-to-albumin (HR 1.36, 95% CI 1.13–1.64, p = 0.001), LDH-to-hemoglobin (HR 1.44, 95% CI 1.07–1.92, p = 0.015), CRP-to-lymphocyte (HR 1.03, 95% CI 1.01–1.07, p = 0.003), D-dimer-to-albumin (HR 4.94, 95% CI 1.38–7.24, p = 0.038), LDH-to-albumin (HR 1.20, 95% CI 1.05–1.36, p = 0.008), and LDH-to-WBC (HR 1.03 95% CI 1.01–1.05, p = 0.024) ratios. Out of these, the best area-under-the-curve (AUC) values were achieved with De Ritis (AUC 0.691), CRP-to-albumin (AUC 0.764), LDH-to-hemoglobin (AUC 0.877), CRP-to-lymphocyte (AUC 0.739), and LDH-to-albumin (AUC 0.827) ratios, while the best discrimination displayed LDH-to-hemoglobin ratio (Harrell’s C 0.808 and Somers’ D 0.616). The overall calibration was satisfactory for all models. Derived laboratory biomarkers such as the de Ritis, CRP-to-albumin, LDH-to-hemoglobin, CRP-to-lymphocyte, and LDH-to-albumin ratios show significant association and discrimination with all-cause mortality in KTR with COVID-19, suggesting its potential risk stratification role.

/pdf/performance-of-derived-laboratory-biomarkers-with-regard-to-1dllvjhy.pdf

Performance of Derived Laboratory Biomarkers with Regard to 30-Day Mortality in Kidney Transplant Recipients with COVID-19

Patients with Coronavirus disease 2019 (COVID-19) often have elevations in markers of liver injury, particularly serum aspartate transaminase (AST) and alanine transaminase (ALT). Such alterations may affect the AST/ALT ratio (De Ritis ratio) and, potentially, clinical outcomes. We conducted an updated systematic review and meta-analysis of the association between the De Ritis ratio and COVID-19 severity and mortality in hospitalized patients. PubMed, Web of Science, and Scopus were searched between 1 December 2019 and 15 February 2023. The Joanna Briggs Institute Critical Appraisal Checklist and the Grading of Recommendations, Assessment, Development, and Evaluation were used to assess the risk of bias and the certainty of the evidence, respectively. Twenty-four studies were identified. The De Ritis ratio on admission was significantly higher in patients with severe disease and non-survivors vs. patients with non-severe disease and survivors (15 studies, weighted mean difference = 0.36, 95% CI 0.24 to 0.49, p < 0.001). The De Ritis ratio was also associated with severe disease and/or mortality using odds ratios (1.83, 95% CI 1.40 to 2.39, p ˂ 0.001; nine studies). Similar results were observed using hazard ratios (2.36, 95% CI 1.17 to 4.79, p = 0.017; five studies). In six studies, the pooled area under the receiver operating characteristic curve was 0.677 (95% CI 0.612 to 0.743). In our systematic review and meta-analysis, higher De Ritis ratios were significantly associated with severe disease and mortality in COVID-19 patients. Therefore, the De Ritis ratio can be useful for early risk stratification and management in this patient group (PROSPERO registration number: CRD42023406916).

/pdf/an-updated-systematic-review-and-meta-analysis-of-the-1msi67it.pdf

An Updated Systematic Review and Meta-Analysis of the Association between the De Ritis Ratio and Disease Severity and Mortality in Patients with COVID-19



Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a disease newly discovered in December 2019 which affects coagulation cascade and liver functions. The aim of this study was to investigate the potential of hemostatic and liver function parameters as severity markers in COVID-19 patients. This study was an observational analytic with cohort retrospective design using total sampling method. Data were retrieved from medical record of COVID-19 patients admitted to provincial hospital in Banda Aceh, Indonesia from March 2020 to March 2022. There were 1208 data eligible for the study after applying certain criteria. Mann–Whitney, logistic regression, and receiving operating characteristic (ROC) analyses were used to analysis the data. Thrombocyte count (p<0.001), prothrombin time (p<0.001), activated partial thromboplastin time (p<0.001), D-dimer (p<0.001), fibrinogen (p<0.001), aspartate aminotransferase (p<0.001), and alanine transaminase (p<0.001) significantly increased in severe compared to mild COVID-19 patients. After being adjusted, age (odds ratio (OR); 1.026 (95% confidence interval (CI): 1.016–1.037) was the most significant factor in predicting COVID-19 severity. Fibrinogen (cut-off 526.5 mg/L) was the best parameter associated with COVID-19 severity with 70% sensitivity and 66.4% specificity. Meanwhile, D-dimer (cut-off 805 ng/mL) had a sensitivity of 72.3% and specificity of 66.4%. Combining the parameters resulted in improved sensitivity to 82.0% with a slight decline of specificity to 65.5%. In conclusion, fibrinogen and D-dimer level on admission could be used as biomarkers in predicting COVID-19 prognosis. Routine monitoring and evaluation of laboratory testing especially D-dimer and fibrinogen could be implemented in order to reduce morbidity and mortality rate of COVID-19.



pdf/hemostatic-and-liver-function-parameters-as-covid-19-tmwwgpmnrd.pdf

Hemostatic and liver function parameters as COVID-19 severity markers

(1) Background: Respiratory co-infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other viruses are common, but data on clinical outcomes and laboratory biomarkers indicative of disease severity are limited. We aimed to compare clinical outcomes and laboratory biomarkers of patients with SARS-CoV-2 alone to those of patients with SARS-CoV-2 and either rhinovirus or adenovirus. (2) Methods: Hospitalized patients co-infected with SARS-CoV-2 and rhinovirus and patients co-infected with SARS-CoV-2 and adenovirus were matched to patients infected with SARS-CoV-2 alone. Outcomes of interest were the cumulative incidences of mechanical ventilation use, intensive care unit (ICU) admission, 30-day all-cause mortality, and 30-day all-cause readmission from the day of discharge. We also assessed differences in laboratory biomarkers from the day of specimen collection. (3) Results: Patients co-infected with SARS-CoV-2 and rhinovirus, compared with patients infected with SARS-CoV-2, had significantly greater 30-day all-cause mortality (8/23 (34.8%) vs. 8/69 (11.6%), p = 0.02). Additionally, median alanine transaminase (13 IU/L vs. 24 IU/L, p = 0.03), aspartate transaminase (25 IU/L vs. 36 IU/L, p = 0.04), and C-reactive protein (34.86 mg/L vs. 94.68 mg/L, p = 0.02) on day of specimen collection were significantly lower in patients co-infected with SARS-CoV-2 and rhinovirus in comparison to patients infected with SARS-CoV-2 alone. Clinical outcomes and laboratory markers did not differ significantly between patients with SARS-CoV-2 and adenovirus co-infection and patients with SARS-CoV-2 mono-infection. (4) Conclusion: SARS-CoV-2 and rhinovirus co-infection, compared with SARS-CoV-2 mono-infection alone, is positively associated with 30-day all-cause mortality among hospitalized patients. However, our lack of significant findings in our analysis of patients with SARS-CoV-2 and adenovirus co-infection may suggest that SARS-CoV-2 co-infections have variable significance, and further study is warranted.

/pdf/clinical-outcomes-associated-with-sars-cov-2-co-infection-3s6fxbs7.pdf

Clinical Outcomes Associated with SARS-CoV-2 Co-Infection with Rhinovirus and Adenovirus in Adults—A Retrospective Matched Cohort Study

Background: Coronavirus disease 2019 (COVID-19) has evolved into a pandemic. We hypothesized that biochemical indicators of liver function may help determine the prognosis of COVID-19 patients. Methods: Patient information was collected from the Wuhan-Leishenshan hospital. Logistic and Cox regression analyses, Kaplan-Meier curves, and Curve fitting were used to determine the correlation between elevated levels of aspartate transaminase (AST), alanine transaminase (ALT), and AST/ALT and severity of disease/mortality. Results: Logistic and Cox regression analyses and Kaplan-Meier survival curves showed that COVID-19 progression correlated with elevated levels of AST and AST/ALT. The odds ratios for elevated levels of AST and AST/ALT in patients were 0.818 (95% confidence interval [CI]: 0.274-2.441, P = 0.035) and 2.055 (95% CI: 1.269-3.327, P = 0.003), respectively; the hazard ratios were 4.195 (95% CI: 1.219-14.422, P = 0.023) and 3.348 (95% CI: 1.57-7.139, P = 0.002), respectively. The Kaplan-Meier survival curves demonstrated that patients with elevated AST and AST/ALT levels had a higher risk of developing severe COVID-19. Conclusion: Elevated AST and AST/ALT levels correlated with severity of COVID-19 and mortality. Liver function tests may help clinicians in determining the prognosis of patients undergoing treatment for COVID-19.

Prognostic Potential of Liver Enzymes in Patients With COVID-19 at the Leishenshan Hospital in Wuhan

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Prognostic Potential of Liver Enzymes in Patients With COVID-19 at the Leishenshan Hospital in Wuhan