Plasminogen activator inhibitor-1 levels as an indicator of severity and mortality for COVID-19

OBJECTIVE Coronavirus disease-19 (COVID-19) is a multisystemic disease that can cause severe illness and mortality by exacerbating symptoms such as thrombosis, fibrinolysis, and inflammation. Plasminogen activator inhibitor-1 (PAI-1) plays an important role in regulating fibrinolysis and may cause thrombotic events to develop. The goal of this study is to examine the relationship between PAI-1 levels and disease severity and mortality in relation to COVID-19. METHODS A total of 71 hospitalized patients were diagnosed with COVID-19 using real time-polymerase chain reaction tests. Each patient underwent chest computerized tomography (CT). Data from an additional 20 volunteers without COVID-19 were included in this single-center study. Each patient's PAI-1 data were collected at admission, and the CT severity score (CT-SS) was then calculated for each patient. RESULTS The patients were categorized into the control group (n=20), the survivor group (n=47), and the non-survivor group (n=24). In the non-survivor group, the mean age was 75.3±13.8, which is higher than in the survivor group (61.7±16.9) and in the control group (59.5±11.2), (p=0.001). When the PAI-1 levels were compared between each group, the non-survivor group showed the highest levels, followed by the survivor group and then the control group (p<0.001). Logistic regression analysis revealed that age, PAI-1, and disease severity independently predicted COVID-19 mortality rates. In this study, it was observed that PAI-1 levels with >10.2 ng/mL had 83% sensitivity and an 83% specificity rate when used to predict mortality after COVID-19. Then, patients were divided into severe (n=33) and non-severe (n=38) groups according to disease severity levels. The PAI-1 levels found were higher in the severe group (p<0.001) than in the non-severe group. In the regression analysis that followed, high sensitive troponin I and PAI-1 were found to indicate disease severity levels. The CT-SS was estimated as significantly higher in the non-survivor group compared to the survivor group (p<0.001). When comparing CT-SS between the severe group and the non-severe group, this was significantly higher in the severe group (p<0.001). In addition, a strong statistically significant positive correlation was found between CT-SS and PAI-1 levels (r: 0.838, p<0.001). CONCLUSION Anticipating poor clinical outcomes in relation to COVID-19 is crucial. This study showed that PAI-1 levels could independently predict disease severity and mortality rates for patients with COVID-19.

Prognostic significance of HDL-C on long-term mortality in patients with COVID-19 pneumonia in the Turkish population: A potential mechanism for population differences.

Coronavirus disease 2019 (COVID-19) is diagnosed by the evidence of the presence of multiple phenotypes, including thrombosis, inflammation, and alveolar and myocardial damage, which can cause severe illness and mortality. High-density lipoprotein cholesterol (HDL-C) has pleiotropic properties, including anti-inflammatory, anti-infectious, antithrombotic, and endothelial cell protective effects. The aim of this study was to investigate the HDL-C levels and one-year mortality after the first wave of patients with COVID-19 were hospitalized. Data from 101 patients with COVID-19 were collected for this single-center retrospective study. Lipid parameters were collected on the admission. The relationship between lipid parameters and long-term mortality was investigated. The mean age of the non-survivor group (n = 38) was 68.8 ± 14.1 years, and 55% were male. The HDL-C levels were significantly lower in the non-survivors group compared with the survivors (26.9 ± 9.5 vs 36.8 ± 12.8 mg/dl, respectively p < 0.001). Multivariate regression analysis determined that age, C-reactive protein, D-dimer, hypertension, and HDL-C as independent predictors for the development of COVID-19 mortality. HDL-C levels <30.5 mg/dl had 71% sensitivity and 68% specificity to predict one-year mortality after COVID-19. The findings of this study showed that HDL-C is a predictor of one-year mortality in Turkish patients with COVID-19. COVID-19 is associated with decreased lipid levels, and it is an indicator of the inflammatory burden and increased mortality rate. The consequences of long-term metabolic dysregulations in patients that have recovered from COVID-19 still need to be understood.

Coronary microvascular dysfunction is common in patients hospitalized with COVID-19 infection.

BACKGROUND AND AIMS: Microvascular disease is considered as one of the main drivers of morbidity and mortality in severe COVID-19, and microvascular dysfunction has been demonstrated in the subcutaneous and sublingual tissues in COVID-19 patients. The presence of coronary microvascular dysfunction (CMD) has also been hypothesized, but direct evidence demonstrating CMD in COVID-19 patients is missing. In the present study, we aimed to investigate CMD in patients hospitalized with COVID-19, and to understand whether there is a relationship between biomarkers of myocardial injury, myocardial strain and inflammation and CMD. METHODS: 39 patients that were hospitalized with COVID-19 and 40 control subjects were included to the present study. Biomarkers for myocardial injury, myocardial strain, inflammation, and fibrin turnover were obtained at admission. A comprehensive echocardiographic examination, including measurement of coronary flow velocity reserve (CFVR), was done after the patient was stabilized. RESULTS: Patients with COVID-19 infection had a significantly lower hyperemic coronary flow velocity, resulting in a significantly lower CFVR (2.0 ± 0.3 vs. 2.4 ± 0.5, p < .001). Patients with severe COVID-19 had a lower CFVR compared to those with moderate COVID-19 (1.8 ± 0.2 vs. 2.2 ± 0.2, p < .001) driven by a trend toward higher basal flow velocity. CFVR correlated with troponin (p = .003, r: -.470), B-type natriuretic peptide (p < .001, r: -.580), C-reactive protein (p < .001, r: -.369), interleukin-6 (p < .001, r: -.597), and d-dimer (p < .001, r: -.561), with the three latter biomarkers having the highest areas-under-curve for predicting CMD. CONCLUSIONS: Coronary microvascular dysfunction is common in patients with COVID-19 and is related to the severity of the infection. CMD may also explain the "cryptic" myocardial injury seen in patients with severe COVID-19 infection.

Elevated D-dimer levels on admission are associated with severity and increased risk of mortality in COVID-19: A systematic review and meta-analysis.

BACKGROUND: In this systematic review and meta-analysis, we aimed to investigate the correlation of D-dimer levels measured on admission with disease severity and the risk of death in patients with coronavirus disease 2019 (COVID-19) pneumonia. MATERIALS AND METHODS: We performed a comprehensive literature search from several databases. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed in abstracting data and assessing validity. Quality assessment was performed using the Newcastle-Ottawa quality assessment scale (NOS). D-dimer levels were pooled and compared between severe/non-severe and surviving/non-surviving patient groups. Weighted mean difference (WMD), risk ratios (RRs) and 95% confidence intervals (CIs) were analyzed. RESULTS: Thirty-nine studies reported on D-dimer levels in 5750 non-severe and 2063 severe patients and 16 studies reported on D-dimer levels in 2783 surviving and 697 non-surviving cases. D-dimer levels were significantly higher in patients with severe clinical status (WMD: 0.45 mg/L, 95% CI: 0.34-0.56; p < 0.0001). Non-surviving patients had significantly higher D-dimer levels compared to surviving patients (WMD: 5.32 mg/L, 95% CI: 3.90-6.73; p < 0.0001). D-dimer levels above the upper limit of normal (ULN) was associated with higher risk of severity (RR: 1.58, 95% CI: 1.25-2.00; p < 0.0001) and mortality (RR: 1.82, 95% CI: 1.40-2.37; p < 0.0001). CONCLUSION: Increased levels of D-dimer levels measured on admission are significantly correlated with the severity of COVID-19 pneumonia and may predict mortality in hospitalized patients.

Echocardiographic features of patients with COVID-19 infection: a cross-sectional study.

COVID-19 patients with cardiac involvement have a high mortality rate. The aim of this study was to investigate the echocardiographic features in COVID-19 patients between severe and non-severe groups. For this single-center study, data from patients who were treated for COVID-19 between March 25, 2020 and April 15, 2020 were collected. Two-dimensional echocardiography (2DE) images were obtained for all patients. Patients were divided into two groups based on the severity of their COVID-19 infections. 2DE parameters indicating right ventricular (RV) and left ventricular (LV) functions were compared between the two groups. A total of 90 patients hospitalized for COVID-19 were included in this study. The mean age of the severe group (n = 44) was 63.3 ± 15.7 years, and 54% were male. The mean age of non-severe group (n = 46) was 49.7 ± 21.4 years, and 47% were male. In the severe group, RV and LV diameters were larger (RV, 36.6 ± 5.9 mm vs. 33.1 ± 4.8 mm, p = 0.003; LV 47.3 ± 5.8 mm vs. 44.9 ± 3.8 mm, p = 0.023), the LE ejection fraction (LVEF) and the RV fractional area change (RV-FAC) were lower (LVEF, 54.0 ± 9.8% vs. 61.9 ± 4.8%, p < 0.001; RV-FAC, 41.4 ± 4.1% vs. 45.5 ± 4.5%, p < 0.001), and pericardial effusions were more frequent (23% vs. 0%) compared to patients in the non-severe group. A multiple linear regression analysis determined that LVEF, right atrial diameter, high-sensitivity troponin I, d-dimer, and systolic pulmonary artery pressure, were independent predictors of RV dilatation. The results demonstrate that both right and left ventricular functions decreased due to COVID-19 infection in the severe group. 2DE is a valuable bedside tool and may yield valuable information about the clinical status of patients and their prognoses.

Prognostic significance of cardiac injury in COVID-19 patients with and without coronary artery disease.

OBJECTIVE: COVID-19 is a disease with high mortality, and risk factors for worse clinical outcome have not been well-defined yet. The aim of this study is to delineate the prognostic importance of presence of concomitant cardiac injury on admission in patients with COVID-19. METHODS: For this multi-center retrospective study, data of consecutive patients who were treated for COVID-19 between 20 March and 20 April 2020 were collected. Clinical characteristics, laboratory findings and outcomes data were obtained from electronic medical records. In-hospital clinical outcome was compared between patients with and without cardiac injury. RESULTS: A total of 607 hospitalized patients with COVID-19 were included in the study; the median age was 62.5 ± 14.3 years, and 334 (55%) were male. Cardiac injury was detected in 150 (24.7%) of patients included in the study. Mortality rate was higher in patients with cardiac injury (42% vs. 8%; P < 0.01). The frequency of patients who required ICU (72% vs. 19%), who developed acute kidney injury (14% vs. 1%) and acute respiratory distress syndrome (71%vs. 18%) were also higher in patients with cardiac injury. In multivariate analysis, age, coronary artery disease (CAD), elevated CRP levels, and presence of cardiac injury [odds ratio (OR) 10.58, 95% confidence interval (CI) 2.42-46.27; P < 0.001) were found to be independent predictors of mortality. In subgroup analysis, including patients free of history of CAD, presence of cardiac injury on admission also predicted mortality (OR 2.52, 95% CI 1.17-5.45; P = 0.018). CONCLUSION: Cardiac injury on admission is associated with worse clinical outcome and higher mortality risk in COVID-19 patients including patients free of previous CAD diagnosis.