Project description:Early identification of severe patients with coronavirus disease 2019 (COVID-19) is very important for individual treatment. We included 203 patients with COVID-19 by propensity score matching in this retrospective, case-control study. The effects of serum lactate dehydrogenase (LDH) at admission on patients with COVID-19 were evaluated. We found that serum LDH levels had a 58.7% sensitivity and 82.0% specificity, based on a best cut-off of 277.00 U/L, for predicting severe COVID-19. And a cut-off of 359.50 U/L of the serum LDH levels resulted in a 93.8% sensitivity, 88.2% specificity for predicting death of COVID-19. Additionally, logistic regression analysis and Cox proportional hazards model respectively indicated that elevated LDH level was an independent risk factor for the severity (HR: 2.73, 95% CI: 1.25-5.97; P=0.012) and mortality (HR: 40.50, 95% CI: 3.65-449.28; P=0.003) of COVID-19. Therefore, elevated LDH level at admission is an independent risk factor for the severity and mortality of COVID-19. LDH can assist in the early evaluating of COVID-19. Clinicians should pay attention to the serum LDH level at admission for patients with COVID-19.
Project description:Coronavirus disease 2019 (COVID-19) infection has now reached a pandemic state, affecting more than a million patients worldwide. Predictors of disease outcomes in these patients need to be urgently assessed to decrease morbidity and societal burden. Lactate dehydrogenase (LDH) has been associated with worse outcomes in patients with viral infections. In this pooled analysis of 9 published studies (n = 1532 COVID-19 patients), we evaluated the association between elevated LDH levels measured at earliest time point in hospitalization and disease outcomes in patients with COVID-19. Elevated LDH levels were associated with a ~6-fold increase in odds of developing severe disease and a ~16-fold increase in odds of mortality in patients with COVID-19. Larger studies are needed to confirm these findings.
Project description:SARS-CoV-2 (COVID-19) patients who develop acute respiratory distress syndrome (ARDS) can suffer acute lung injury, or even death. Early identification of severe disease is essential in order to control COVID-19 and improve prognosis. Oxidative stress (OS) appears to play an important role in COVID-19 pathogenesis; we therefore conceived a study of the potential discriminative ability of serum biomarkers in patients with ARDS and those with mild to moderate disease (non-ARDS). 60 subjects were enrolled in a single-centre, prospective cohort study of consecutively admitted patients: 29 ARDS/31 non-ARDS. Blood samples were drawn and marker levels analysed by spectrophotometry and immunoassay techniques. C-reactive protein (CRP), lactate dehydrogenase (LDH), and ferritin were significantly higher in ARDS versus non-ARDS cases at hospital admission. Leukocytes, LDH, ferritin, interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-α) were also significantly elevated in ARDS compared to non-ARDS patients during the hospital stay. Total thiol (TT) was found to be significantly lower in ARDS. Conversely, D-dimer, matrix metalloproteinase-9 (MMP-9) and advanced glycosylated end products (AGE) were elevated. Leukocytes, LDH, CRP, ferritin and IL-6 were found to be significantly higher in non-survivors. However, lymphocyte, tumour necrosis factor beta (TGF-β), and TT were lower. In summary, our results support the potential value of TT, ferritin and LDH as prognostic biomarkers for ARDS development in COVID-19 patients, distinguishing non-ARDS from ARDS (AUCs = 0.92; 0.91; 0.89) in a fast and cost-effective manner. These oxidative/inflammatory parameters appear to play an important role in COVID-19 monitoring and can be used in the clinical management of patients.
Project description:Viral infections activate the innate immune response and the secretion of inflammatory cytokines. They also alter oxidative stress markers, which potentially can have an involvement in the pathogenesis of the disease. The aim of this research was to study the role of the oxidative stress process assessed through lactate dehydrogenase (LDH) on the severity of COVID-19 measured by oxygen saturation (SaO2) and the putative interaction with inflammation. The investigation enrolled 1808 patients (mean age of 68 and 60% male) with COVID-19 from the HM Hospitals database. To explore interactions, a regression model and mediation analyses were performed. The patients with lower SaO2 presented lymphopenia and higher values of neutrophils-to-lymphocytes ratio and on the anisocytosis coefficient. The regression model showed an interaction between LDH and anisocytosis, suggesting that high levels of LDH (>544 U/L) and an anisocytosis coefficient higher than 10% can impact SaO2 in COVID-19 patients. Moreover, analysis revealed that LDH mediated 41% (p value = 0.001) of the effect of anisocytosis on SaO2 in this cohort. This investigation revealed that the oxidative stress marker LDH and the interaction with anisocytosis have an important role in the severity of COVID-19 infection and should be considered for the management and treatment of the oxidative phenomena concerning this within a precision medicine strategy.
Project description:Lactate dehydrogenase (LDH) levels are inversely related with response to checkpoint inhibitors. Elevated LDH levels are the product of enhanced glycolytic activity of the tumor and tumor necrosis due to hypoxia, the latter being associated with high tumor burden. In this review, we elucidate the effects of glycolysis and hypoxia on antitumor immunity and set forth ways to improve response to immunotherapy in cancer patients with elevated LDH levels. We discuss the current knowledge on combining immunotherapy with glycolysis inhibitors, anti-acidifying drugs, anti-angiogenic or cytoreductive therapy.
Project description:The causative organism, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), exhibits a wide spectrum of clinical manifestations in disease-ridden patients. Differences in the severity of COVID-19 ranges from asymptomatic infections and mild cases to the severe form, leading to acute respiratory distress syndrome (ARDS) and multiorgan failure with poor survival. MiRNAs can regulate various cellular processes, including proliferation, apoptosis, and differentiation, by binding to the 3′UTR of target mRNAs inducing their degradation, thus serving a fundamental role in post-transcriptional repression. Alterations of miRNA levels in the blood have been described in multiple inflammatory and infectious diseases, including SARS-related coronaviruses. We used microarrays to delineate the miRNAs and snoRNAs signature in the peripheral blood of severe COVID-19 cases (n=9), as compared to mild (n=10) and asymptomatic (n=10) patients, and identified differentially expressed transcripts in severe versus asymptomatic, and others in severe versus mild COVID-19 cases. A cohort of 29 male age-matched patients were selected. All patients were previously diagnosed with COVID-19 using TaqPath COVID-19 Combo Kit (Thermo Fisher Scientific, Waltham, Massachusetts), or Cobas SARS-CoV-2 Test (Roche Diagnostics, Rotkreuz, Switzerland), with a CT value < 30. Additional criterion for selection was age between 35 and 75 years. Participants were grouped into severe, mild and asymptomatic. Classifying severe cases was based on requirement of high-flow oxygen support and ICU admission (n=9). Whereas mild patients were identified based on symptoms and positive radiographic findings with pulmonary involvement (n=10). Patients with no clinical presentation were labelled as asymptomatic cases (n=10).
Project description:Background: In this study, we investigated the relationship between serum lactate dehydrogenase (LDH) level and disease progression and prognosis of patients with COVID-19. Methods: We retrospectively reviewed the information of 1,751 patients with COVID-19 from Leishenshan Hospital in Wuhan, China. Univariate and multivariate Cox regression analyses as well as Logistics regression analyses, and Kaplan-Meier curves were used to determine the association between LDH levels and the prognosis of COVID-19 patients. Results: LDH was an independent risk factor for in-hospital death no matter it was taken as classified variable and continuous variable (all P = 0.001) but not for severe or critical illness status. The Kaplan-Meier curves for LDH level showed that an elevated level of LDH was associated with in-hospital death. Conclusions: In patients with COVID-19, the increased LDH level is associated with a higher risk of negative clinical prognosis and higher mortality. This will provide a reference for clinicians and researchers to understand, diagnose, and treat patients with COVID-19. Further prospective studies with larger sample sizes are needed to verify these findings.
Project description:Serum lactate dehydrogenase (LDH) has been established as a prognostic indicator given its differential expression in COVID-19 patients. However, the molecular mechanisms underneath remain poorly understood. In this study, 144 COVID-19 patients were enrolled to monitor the clinical and laboratory parameters over 3 weeks. Serum LDH was shown elevated in the COVID-19 patients on admission and declined throughout disease course, and its ability to classify patient severity outperformed other biochemical indicators. A threshold of 247 U/L serum LDH on admission was determined for severity prognosis. Next, we classified a subset of 14 patients into high- and low-risk groups based on serum LDH expression and compared their quantitative serum proteomic and metabolomic differences. The results showed that COVID-19 patients with high serum LDH exhibited differentially expressed blood coagulation and immune responses including acute inflammatory responses, platelet degranulation, complement cascade, as well as multiple different metabolic responses including lipid metabolism, protein ubiquitination and pyruvate fermentation. Specifically, activation of hypoxia responses was highlighted in patients with high LDH expressions. Taken together, our data showed that serum LDH levels are associated with COVID-19 severity, and that elevated serum LDH might be consequences of hypoxia and tissue injuries induced by inflammation.
Project description:OBJECTIVE:The dramatic worldwide CoVID-19 infection requires the identification of a reliable and inexpensive tool to quickly discriminate patients with a more unfavorable outcome. METHODS:We performed routine laboratory tests suitable to identify tissue damage and inflammatory status in 123 consecutive CoVID-19 patients admitted to the Emergency Department of the hospital of Piacenza (Emilia-Romagna, Northern Italy). The results were correlated with patients' respiratory function evaluated by the partial pressure of arterial oxygen to fraction of inspired oxygen ratio (PaO2/FiO2). RESULTS:The most common laboratory abnormalities were lymphocytopenia and elevated values of C-reactive protein (CRP) and lactate dehydrogenase (LDH). Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and creatine kinase (CK) were also increased. The respiratory performance (PaO2/FiO2) showed a strong inverse correlation with LDH (r = 0.62, r2 0.38, p value < 0.0001) and CRP (r = 0.55, r2 0.31, p value < 0.0001). PaO2/FiO2 values also showed a significant inverse correlation with age (r = -0.37, p < 0.0001), AST (r = -0.31, p < 0.01), WBC (r = -0.49, p < 0.0001), neutrophils count (r = -0.5, p < 0.001). ROC curves showed a sensitivity of 75% and specificity of 70% for the LDH cut-off value of 450 U/L and a sensitivity of 72% and specificity of 71% for the CRP cut-off value of 11 mg/dl in identifying CoVID-19 with moderate-severe ARDS. CONCLUSIONS:LDH and CRP may be related to respiratory function (PaO2/FiO2) and be a predictor of respiratory failure in CoVID-19 patients. LDH and CRP should be considered a useful test for the early identification of patients who require closer respiratory monitoring and more aggressive supportive therapies to avoid poor prognosis.